Tislelizumab plus short-course chemoradiotherapy perioperative treatment for HER2-negative, locally advanced gastroesophageal junction(GEJ) adenocarcinoma patients: study protocol for a prospective,single-arm phase 2 trail

Tislelizumab plus short-course chemoradiotherapy perioperative treatment for HER2-negative, locally advanced gastroesophageal junction(GEJ) adenocarcinoma patients: study protocol for a prospective,single-arm phase 2 trail | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Study protocol Tislelizumab plus short-course chemoradiotherapy perioperative treatment for HER2-negative, locally advanced gastroesophageal junction(GEJ) adenocarcinoma patients: study protocol for a prospective,single-arm phase 2 trail Xiangyu Meng, Ji Liu, Dong Yang, Jun Zhang, Yuanlin Liu, Chao Wang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7324963/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Background Locally advanced HER2-negative gastroesophageal junction (GEJ) adenocarcinoma has limited treatment options with suboptimal outcomes. While immunotherapy combined with chemotherapy shows promise in advanced gastric cancer, the role of short-course radiotherapy (SCRT) in perioperative regimens remains underexplored. This trial evaluates a novel approach integrating tislelizumab (PD-1 inhibitor), SCRT, and SOX chemotherapy (S-1+oxaliplatin) for resectable GEJ adenocarcinoma. Methods This prospective, single-arm, phase II trial (N=31) enrolls treatment-naive adults (18-75 years) with histologically confirmed, resectable Siewert type II/III GEJ adenocarcinoma (cT3-4aN+M0, AJCC 8th edition).Treatment Protocol: Neoadjuvant: 2 cycles of tislelizumab (200mg ivgtt, day 1)+SOX (S-1: BSA-based dose orally twice daily, days 1-14; oxaliplatin: 130mg/m 2 ivgtt, day 1; 21-day cycles). Short-course Radiotherapy: Intensity-modulated radiation therapy (IMRT; 25Gy/5f) to primary tumor and involved nodes, initiated 1-2 weeks post-chemotherapy. Consolidation: 2 additional cycles of tislelizumab+SOX within 11-18 days post-radiotherapy. Surgery: Radical gastrectomy with D2 lymphadenectomy 6-8 weeks after last neoadjuvant dose. Adjuvant: 4 cycles of SOX. Endpoints: Primary: Pathological complete response (pCR). Secondary: R0 resection rate, major pathological response (MPR), disease-free survival (DFS), overall survival (OS), safety (NCI CTCAE v5.0). Discussion This is the first trial to combine tislelizumab, SCRT, and SOX in perioperative GEJ adenocarcinoma. SCRT may enhance immunogenicity while reducing toxicity. If successful, it may expand treatment options for locally advanced HER2-negative GEJ adenocarcinoma. Limitations include single-arm design and small sample size. Trial Registration Chinese Clinical Trial Registry (ChiCTR2500105244) GEJ adenocarcinoma PD1 chemoradiotherapy perioperative short-course Figures Figure 1 Figure 2 Background Globally, gastroesophageal junction (GEJ) cancer has become increasingly prevalent in recent years, ranking as the fifth most common cancer overall and the fourth leading cause of cancer-related mortality[ 1 ]. Research indicates that GEJ cancer is associated with a poor prognosis, as evidenced by a 5 year survival rate of less than 25% largely due to the aggressive biological behavior of the tumor and the frequent late-stage diagnosis[ 2 – 4 ]. The special etiology leads to the fact that the biological behavior and recurrence pattern of GEJ cancer are different from esophagus cancer (EC) and those of other types of gastric cancer (GC)[ 5 – 7 ]. The MAGIC (15% GEJ) and FLOT4 (56% GEJ) trials established and refined perioperative chemotherapy regimens by introducing multimodal perioperative chemotherapy (ECF and FLOT) in Western populations with resectable G/GEJ cancer[ 8 , 9 ]. The KEYNOTE-585, MATTERNHORN and DANTE trials demonstrate that the combination of PD-L1 inhibitors with chemotherapy significantly enhance the pathological complete response (pCR) rate in patients with locally advanced G/GEJ adenocarcinoma compared to chemotherapy alone which have facilitated the transition from conventional chemotherapy to an integrated approach combining chemotherapy and immunotherapy for the management of advanced G/GEJ cancers during the perioperative period[ 10 – 12 ]. With the publication of the results from the Dragon IV and NEOSUMMIT-02 studies, the perioperative treatment paradigm for advanced G/GEJ cancer has progressively shifted from a combination of chemotherapy and immunotherapy to a more comprehensive regimen incorporating chemotherapy, immunotherapy, and targeted therapy. Short-term outcomes indicate that as the range of therapeutic modalities expands, the pCR rate among patients has significantly increased[ 13 , 14 ]. The treatment of advanced GC mentioned above has made considerable progress in reducing tumor staging, increasing the R0 resection rate, pCR rate and improving prognosis. However, current studies on perioperative treatment for advanced GC have not performed subgroup analyses specifically for GEJ cancer, and the representation of patients with GEJ cancer within the overall GC study populations remains relatively limited. Especially, there remains considerable controversy regarding the selection of surgical approaches and the extent of lymph node dissection for GEJ cancer across different Siewert classifications. Therefore, in the management of locally advanced GEJ cancer, there is ongoing debate regarding the optimal treatment strategy-specifically, whether perioperative chemotherapy alone or a combination of chemotherapy with other therapeutic modalities should be recommended. This has also led to growing academic interest in the treatment of GEJ cancer. Clinical trials that solely apply radiotherapy to locally advanced GEJ cancer are very rare. The existing evidence mainly refers to several studies on the safety and efficacy of neoadjuvant chemotherapy (NCT) in EC (including GEJ cancer).Compared with simple surgical treatment, the studies by Walsh et al. (34.5% GEJ) and CALGB-9781 (75% GEJ) have demonstrated that neoadjuvant chemoradiotherapy (NCRT) significantly improves the prognosis of patients with EC or GEJ cancer[ 15 ]. The subsequent findings from the CROSS trial (24% GEJ) further demonstrated that NRCT is more effective than surgery alone in the treatment of GEJ cancer, particularly in terms of enhancing the R0 resection rate and ensuring the safety of radiotherapy[ 16 ]. In addition to demonstrating greater efficacy than simple surgical intervention, NCRT also offers distinct advantages over NCT in the management of EC and GEJ cancer. The POET study is the first phase III clinical trial comparing induced chemotherapy followed by NCRT and surgery with NCT for GEJ cancer which indicated that patients undergoing NCRT had a higher rate of local recurrence-free survival (RFS; HR 0.37, 95% CI 0.16–0.85) as well as a higher rate of pCR (14.3% vs. 1.9%, p = 0.03) and a trend toward higher 5 year OS (39.5% vs. 24.4%, HR 0.65, 95% CI 0.42–1.01). Notably, the subgroup analysis suggested that patients with cardia cancers (Siewert type II) gained more benefits from NCRT relative to patients with Siewert type I cancers[ 17 ]. Immunotherapy has significantly transformed the treatment modality for patients with advanced G/GEJ cancer. As previously mentioned, the KEYNOTE-585, MATTERNHORN and DANTE studies are actively exploring perioperative treatment methods for advanced G/GEJ cancer with immunotherapy combined with chemotherapy[ 10 – 12 ]. In light of the therapeutic advantages demonstrated by NCRT over surgery alone or chemotherapy alone in the treatment of EC and GEJ cancer, the neoadjuvant approach that combines radiotherapy with immunotherapy and chemotherapy has increasingly garnered significant research interest. It is noteworthy that emerging evidence suggests radiotherapy possesses the capacity to elicit immune activation. By facilitating the release of tumor antigens, enhancing PD-L1 expression, and activating the cGAS-STING signaling pathway, radiotherapy can convert "cold tumors (CPS < 5)" into "hot tumors (CPS ≥ 5)", thereby enhancing the efficacy of immunotherapy in antitumor immune responses[ 18 – 20 ]. Several small-sample phase II clinical trials on GEJ cancer and meta-analyses have demonstrated that the integration of immunotherapy with chemoradiotherapy offers notable efficacy in improving the pCR rate and facilitating tumor downstaging[ 20 – 22 ]. However, it should be noted that long-course radiotherapy remained predominant in the neoadjuvant radiotherapy regimens of previous studies, and it did not demonstrate a clear advantage over short-course radiotherapy with respect to cost-effectiveness or treatment convenience in locally advanced rectal cancer[ 23 , 24 ]. Moreover, studies have suggested that escalating the radiation dose in the treatment of EC/GEJ cancer may not lead to an improved pCR rate of patients[ 25 ]. A phase I Trial on total neoadjuvant therapy with short course chemoradiotherapy followed by chemotherapy for patients with potentially resectable gastric cancer indicated that short-course radiotherapy is feasible and safe for neoadjuvant treatment of GC[ 26 ]. Thus, based on the current evidences, our study will assess a newly designed total neoadjuvant therapy comprising short course NCRT + immunotherapy for locally advanced GEJ adenocarcinoma. The objective of this trial is to evaluate the feasibility and safety of this treatment approach. The study aims to generate additional clinical evidence to support the implementation of novel neoadjuvant therapies. Methods Study design and objectives This study is a phase II, single-center, single-arm, prospective study aimed at evaluating the efficacy and safety of tislelizumab combined with perioperative chemoradiotherapy in patients with HER2-negative locally advanced resectable adenocarcinoma of the GEJ.The study protocol and the informed consent forms have been reviewed and approved by the Research Ethics Committee of the Liaoning Tumor Hospital & Institute (approval number 20231101). This study will be conducted in strict compliance with the ethical principles of the Declaration of Helsinki and the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) guidelines. All subjects enrolled in the study must provide written informed consent, and all data will be handled confidentially. The study has been prospectively registered at www.chictr.org.cn (ChiCTR2500105244). Patients diagnosed with locally advanced (stage cT3-4a or cN positive M0, according to the AJCC 8th edition) GEJ adenocarcinoma will be enrolled. Prior to enrollment, each patient will undergo gastroscopy, endoscopic ultrasound, and enhanced chest-abdomen-pelvis CT scans for tumor assessment and staging. A multidisciplinary team will screen and confirm eligibility for enrollment based on predefined criteria.The clinical T stage will be determined based on imaging findings and laparoscopic evaluation. The presence of metastatic regional lymph nodes will be assessed according to their size and biological characteristics. Following a thorough screening process, patients will receive NCRT as the initial treatment.Firstly, the patients will begin two courses of neoadjuvant immunotherapy combined with chemotherapy using tislelizuma plus the S-1 and oxaliplatin (SOX) regimen. Radiation therapy should be initiated within 1-2 weeks after the last dose of the combination regimen.The technique of Intensity-Modulated Radiation Therapy (IMRT) will be adopted in this trial, with a dose of 25Gy/5f to the planned target volume (PTV). Radiotherapy is followed by two cycles of tislelizuma plus the SOX regimen, preferably initiated within 11-18 days after the last radiotherapy, and at least within 4 weeks.Ultimately, the patient underwent surgical treatment 6 to 8 weeks after completing sequential chemoradiotherapy. Postoperatively, patients will receive 4 cycles of SOX regimen chemotherapy. A schematic diagram of the study design is shown in Figure 1. The primary objective is the assessment of a pCR, which is defined as no tumor cells in the primary tumor and metastatic regional lymph node. Secondary objectives include the DFS, OS, MPR, Objective Response Rate (ORR), assessing toxicities during NCRT and NCCT, surgical complications, and the R0 resection rate. Subgroup analysis based on the CPS and microsatellite status will also be evaluated. Recruitment began in August 2025 and is expected to be finished in August 2027. Eligibility criteria Patients meeting all of the following criteria were eligible:signed informed consent obtained prior to any study-specific procedures; aged 18–75 years;eastern cooperative oncology group (ECOG) performance status of 0 or 1; histologically confirmed (by enrolling center) adenocarcinoma of the GEJ, Siewert type II or III; clinical stage T3–4aN+M0 per the AJCC Staging System (8th Edition); HER2-Negative (HER2-negative defined as: IHC score 0 or 1+ on pretreatment endoscopic biopsy tissue; IHC 2+ requires confirmation of no gene amplification by in situhybridization); physical and organ function fitness to undergo planned surgical intervention; estimated life expectancy ≥6 months; no disease progression after sequential chemoradiotherapy; adequate Organ and Hematological Function(within 7 days prior to treatment initiation, without transfusion/growth factor support): absolute neutrophil count (ANC)≥1.5×10⁹/L; platelets ≥100×10⁹/L;hemoglobin ≥90 g/L; serum creatinine ≤1.5×ULN; calculated creatinine clearance (CrCl) ≥50 mL/min; total bilirubin ≤1.5×ULN; AST/ALT ≤3×ULN; serum albumin ≥28 g/L. The exclusion criteria included: patients aged 75 years; a history of prior anticancer treatment; pregnancy or lactation; metastatic disease; history of myocardial infarction or cerebral infarction within the preceding 6 months; active tuberculosis or hepatitis; and refusal to provide informed consent. Treatment The overall treatment includes two cycles of neoadjuvant chemotherapy combined with immunotherapy and neoadjuvant radiotherapy. After short-course radiotherapy, two more cycles of NCT combined with immunotherapy are administered, followed by radical surgery. Postoperatively, 4 cycles of adjuvant chemotherapy with the SOX regimen are given. Neoadjuvant chemotherapy combined with immunotherapy Two cycles of neoadjuvant tislelizumab plus SOX will be administered prior to short-course radiotherapy. Eligible patients will receive intravenous tislelizumab 200 mg on day 1 of each 21-day cycle. SOX chemotherapy consists of: S-1: Administered orally twice daily from day 1 to 14. Dose is BSA-dependent: BSA<1.25 m²: 40 mg twice daily (80 mg/day), BSA≥1.25 to<1.5 m²: 50 mg twice daily (100 mg/day), BSA≥1.5 m²: 60 mg twice daily (120 mg/day); Oxaliplatin: Administered intravenously at 130 mg/m² on day 1 of each cycle. Within 11 to 18 days after the last radiotherapy session, and at least within 4 weeks, two cycles of the neoadjuvant tislelizumab plus SOX should be administered again. Tislelizumab dose adjustments are not permitted. Dose reductions for S-1 and oxaliplatin are permitted for treatment-related adverse events (AEs) during the neoadjuvant/adjuvant phase. Neoadjuvant short-course radiotherapy Preoperative localization process:The patient should fast for 4-6 hours before CT localization. Position and fixation: Supine position, with both hands crossed and raised to the forehead; fixation with thermoplastic body mold. To reduce the difference in irradiation volume caused by gastric filling, the patient needs to take 250ml of semi-liquid containing contrast agent (such as yogurt) 5 minutes before CT scanning. Scanning range: The upper boundary of the scan should include the entire lung, and the lower boundary should include the entire abdomen; scan layer thickness 5mm; intravenous enhancement. The physicist will develop the target volume delineation and organ-at-risk (OAR) protection plan based on the chief physician's prescription. The target volumes typically include the gross tumor volume (GTV), clinical target volume (CTV), and planning target volume (PTV). If lymph nodes are involved, the plan may also include GTVnd. The dose limitations of the organs at risk (OARs) will be as follows:Both lungs: V3≤20%, V12≤5%, average≤3 Gy; Liver: V18≤40%, V25≤30%, average≤13 Gy; Heart: V18≤40%, V25≤30%, average≤13 Gy; Spinal cord≤27 Gy; Both kidneys: V10≤3%. The treatment plan must be reviewed and approved by an experienced chief physician before treatment initiation. On the first day of treatment, the doctor, physicist and radiotherapy technician need to position the patient together. The patient should fast for 4 to 6 hours before radiotherapy. Five minutes before each treatment, the patient needs to orally take 250ml of semi-liquid food (such as yogurt). The cone beam computed tomography (CBCT) imaging will be conducted before each daily radiotherapy session to verify treatment accuracy. Additionally, laboratory tests including complete blood count, liver function, kidney function, blood glucose, serum electrolytes, and electrocardiogram (ECG) will be performed both before and after the completion of radiotherapy. Surgery Standard radical surgery will be performed 6 to 8 weeks after the completion of neoadjuvant tislelizumab combined with SOX chemotherapy. Laparoscopic resection will be the preferred approach. For Siewert II/III EGJ tumors, either proximal or total gastrectomy will be recommended. In terms of gastrointestinal reconstruction, single muscle flap, double muscle flap, or modified side-to-side overlap (mSOFY) gastroesophageal anastomosis will be performed following proximal gastrectomy, while Roux-en-Y reconstruction will be conducted after total gastrectomy. A D2 lymph node dissection will be performed, in accordance with the definitions provided by the NCCN guidelines. At least 16 or more lymph nodes should be examined during surgery. In cases of disease progression during neoadjuvant therapy, a multidisciplinary team (MDT) will be convened to determine the most appropriate subsequent treatment strategy. Tumor response and toxicity criteria Toxicity will be evaluated prior to each treatment cycle based on patient history, physical examination, and laboratory assessments, including complete blood count, liver function tests, and renal function tests. AEs will be classified according to the NCI CTCAE v5.0. Dose modifications will be determined by the type and severity of the observed toxicities. For chemotherapy-associated toxicities (e.g., myelosuppression, nausea, vomiting, diarrhea), concurrent dose reductions of S-1 will be applied. In cases of severe hematologic toxicity (e.g., grade≥3 neutropenia or thrombocytopenia), both S-1 and oxaliplatin will be reduced by one dose level, and treatment will be postponed until recovery if toxicity remains unresolved. The minimum recommended daily dose for S-1 is 60 mg, and the minimum dose for oxaliplatin is 85 mg/m². For fruquintinib-related toxicities (e.g., hand-foot syndrome, hypertension, fatigue, liver dysfunction), the recommended dose will be reduced to 3 mg/day in the event of grade≥3 toxicities, with a further reduction to 2 mg/day if clinically indicated. Temporary treatment interruptions may be necessary for persistent adverse events, and resumption of therapy will be contingent upon adequate recovery. When tislelizumab is administered, the following immune-related adverse events-such as pneumonitis, enteritis, hepatitis, nephritis, endocrine disorders, dermatitis, myocarditis, and neurotoxicity-are assessed as grade 2. In such cases, medication should be discontinued. Tislelizumab should be resumed in patients with improvement to grade 0-1 after tapering of corticosteroids or stabilization of hormone replacement therapy. Treatment was permanently discontinued in cases where any of these immune-related adverse effects reached grade 3 or higher, failed to improve to grade 0-1 within 12 weeks following the initiation of steroid therapy, or if prednisone could not be tapered to ≤10 mg per day (or equivalent) within the same time frame. For other toxicities that are difficult to classify, dose modifications will be guided by the investigator’s clinical judgment to ensure patient safety and continuity of treatment. Discontinuation of the study regimen will be considered if such toxicities persist despite two dose reductions, if intolerable adverse events recur, or if patients withdraw consent or demonstrate disease progression. Supportive care measures will include the use of antiemetics for nausea and vomiting, antihypertensive agents for elevated blood pressure, specialized dermatologic care for hand-foot syndrome, and general supportive interventions for fatigue and other associated symptoms. Sample size calculation In terms of research design, if the pCR rate is 15% (H0), the study will not be considered justified for further investigation. Conversely, a pCR rate of 35% (Ha) or higher will indicate the necessity for continued research. Based on these criteria, a Simon optimal two-stage design has been selected, with H0 = 0.15 versus Ha = 0.35, a one-sided significance level (α) of 0.05, and a statistical power of 80%. Under these parameters, the proposed study plan is structured as follows: Stage 1: A total of 15 patients will be enrolled. If two or more patients achieve pCR, the study will proceed to the second stage. If fewer than two patients exhibit pCR, the study will be terminated. Stage 2: An additional 13 patients will be enrolled, bringing the minimum total sample size to 28 patients. Considering an estimated dropout rate of 10%, the study aims to enroll a total of 31 patients to ensure sufficient statistical power. Statistical analysis Descriptive statistics will summarize baseline demographics and clinicopathological characteristics. Efficacy endpoints will be calculated with corresponding 95% confidence intervals (CIs) using Blaker’s binomial exact method. DFS and OS will be evaluated through Kaplan-Meier estimates, accompanied by 95% CIs. Primary analyses will utilize the intention-to-treat (ITT) population. Safety analyses will focus on patients receiving ≥1 dose of neoadjuvant therapy (safety population). Neoadjuvant-and adjuvant-related emergent AEs will be stratified by treatment phase due to regimen differences. Surgical outcomes (morbidity/mortality) will be assessed in the per-protocol population, defined as protocol-compliant patients undergoing surgery. Subgroup analysis of biomarkers: the pCR rates of patients with PD-L1 CPS≥5 vs <5, and MSI-H vs MSS were compared (Fisher's exact test), and the OR value and 95%CI were calculated. To mitigate missing data, proactive measures were implemented during trial design, including standardized data collection protocols. For participants with missing outcome data due to withdrawal or loss to follow-up, multiple imputation techniques will be employed. Follow-up After completing the prescribed treatment, patients will undergo the examinations on schedule. Follow-up evaluations will be conducted every 3 months during the first 3 years, every 6 months from year 4 to year 5, and annually thereafter. During the follow-up period, investigators will collect data on surgical complications, late toxicities, additional treatments, as well as disease recurrence and patient survival. The assessment and intervention schedule for the trial was shown in Table 1. Quality assurance The quality assurance (QA) team involved in this study will consist of experienced professionals in the fields of radiation oncology, dosimetry, medical physics, medicine, surgery, diagnostic imaging, pathology, and data monitoring. Diagnostic images obtained before and after neoadjuvant treatment will be centrally and independently reviewed by two radiologists. Data monitoring personnel will maintain communication with researchers and conduct periodic random checks to ensure the accuracy and consistency of data collection. Data collection and management One physician will be responsible for enrolling patients in the trial and coordinating patients’ treatment. Two physicians will be assigned to collect data and complete the Case Report Form (CRF). Any modifications made to the data must be accompanied by the researcher’s signature and the date of the change on the CRF. The CRF will serve as the source document, and all data contained therein will be archived electronically on a designated computer. All electronic files will be kept confidential, with access restricted to the data manager via a secure password. Only the project leader will have authorization to access the database; other researchers may access it only with prior permission. Discussion The definition of GEJ cancer is adenocarcinoma with the primary tumor (center) located within a 5 cm range above and below the esophagogastric junction[27]. Research indicates that the incidence of GEJ cancer has been rising steadily in comparison to other malignant tumors[28]. Obesity, gastroesophageal reflux and Barrett's esophagus are closely related to the occurrence of GEJ cancer[29]. According to the research findings of Siewert et al., GEJ cancer can be categorized into three distinct types: Siewert I, Siewert II, and Siewert III[30]. Although the advancements in radiotherapy, chemotherapy, and immunotherapy have significantly improved patient survival rates, surgical treatment continues to be the cornerstone for achieving a radical cure[31]. Thus,for locally resectable advanced GEJ cancer, comprehensive treatment centered on surgery is recommended by both the NCCN Guidelines, the Japanese Gastric Cancer Treatment Guidelines, and the CSCO Guidelines in China[32-34]. However, there is still considerable controversy regarding the comprehensive treatment model for GEJ cancer. The MAGIC[35] /FFCD9703[36] /FLOT4[9] study defined the significance of neoadjuvant chemotherapy in the management of advanced gastric cancer. Furthermore, the RESOLVE[37] and PRODIGY[38] studies have expanded the available options for perioperative chemotherapy regimens. Based on the findings of the INT-0116 study[39], the ARTIST study[40], and the CRITICS study[41] conducted at earlier stages, perioperative radiotherapy was primarily indicated for patients with gastric cancer or gastroesophageal junction cancer who exhibited less extensive lymph node dissection (D0 or D1), inadequate lymph node sampling (<15 nodes examined), or positive surgical margins following resection. In such cases, the administration of radiotherapy has been shown to improve clinical outcomes.However, postoperative radiotherapy continues to be associated with several limitations.For instance,postoperative radiotherapy may offer potential benefits to patients with G/GEJ cancer who have not undergone D2 radical resection. However, in the current era where D2 radical resection is widely adopted, postoperative radiotherapy has been associated with an increased risk of grade 3-4 toxicities[42], a reduced completion rate of adjuvant therapy[41], and an elevated likelihood of complications related to anastomotic integrity and organ protection due to the expanded postoperative target volume[39]. Therefore, with the continuous advancement and refinement of radiotherapy techniques and treatment protocols, NCRT has increasingly gained clinical acceptance and recognition. The POET study is the first phase III clinical trial comparing induced chemotherapy followed by NCRT and surgery with NCT. The results ultimately suggested that compared with the NCT group, patients in the NCRT group had a significantly higher pCR rate (14.3% vs 1.9%) and an advantage in 5-year OS[17]. The Dutch CROSS-trial also showed that the addition of NCRT to surgery led to an absolute 5-year OS benefit of 14 % without an increased risk of postoperative complications in patients with adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the esophagus and GEJ[43]. It is worth noting that the results of our meta-analysis show that compared with the NCT and surgery alone groups, NCRT can significantly improve the 2-year and 3-year OS of GEJ cancer[44]. To sum up,both perioperative chemotherapy and preoperative concurrent chemoradiotherapy are recommended for patients with locally advanced G/GEJ according to the National Comprehensive Cancer Network (NCCN) guidelines[32]. In the POET trial, limited by the constraints of radiotherapy dose and outdated chemotherapy regimens, further optimizing radiotherapy doses, methods, and medication regimens has become an urgent priority at present. The clinical trials including CheckMate 649[45], KEYNOTE-859[46],and RATIONALE-305[47] have demonstrated clinically meaningful survival benefits when combining immune checkpoint inhibitors with conventional chemotherapy in advanced G/GEJ adenocarcinoma. There is a 28% to 44% reduction in mortality risk. These findings establish immunotherapy as a standard component of current multimodal treatment strategies for advanced GC, particularly among patients with PD-L1-positive tumors.The latest findings from the MATTERHORN trial suggest that for patients with locally advanced G/GEJ cancers, the integration of perioperative immunotherapy not only leads to a higher pCR rate but also offers significant improvements in both event-free survival (EFS) and OS among individuals with locally advanced GC[48]. Furthermore, the DANTE study demonstrated that combining perioperative immunotherapy with chemotherapy results in greater clinical downstaging and a higher pCR rate compared to chemotherapy alone in patients with locally advanced GC. This benefit appears to be particularly prominent in patients exhibiting MSI-H status or a high CPS[12]. Thus, the incorporation of immunotherapy into the perioperative period or neoadjuvant treatment plays a significant role in enhancing therapeutic efficacy.Given the promising outcomes of chemoradiotherapy and immune combination chemotherapy in the neoadjuvant or perioperative management of GEJ cancer, the integration of immunotherapy with chemoradiotherapy has increasingly drawn the attention of oncology researchers. Sasaki et al.'s study demonstrates that the integration of immunotherapy into chemoradiotherapy treatment regimens can modulate the immune microenvironment by activating the cGAS-STING pathway, thereby enhancing the radiosensitivity in the management of advanced GC[49]. As presented in Table 2, all six studies investigated the safety and efficacy of immunotherapy in combination with chemoradiotherapy for locally resectable GEJ cancer[20, 21, 26, 50-52]. In the SHARED trial, the pCR rate was notably high at 38.2%, compared to 29% observed in the CROSS trial[16, 50]. Moreover, the research findings of Zhu et al. suggest that the pCR rate associated with the combination of immunotherapy and chemoradiotherapy in the treatment of GEJ cancer may be positively correlated with the CPS[21]. With regard to the assessment of the MPR rate, the SHARED study[50] and the research conducted by Ko et al.[52]reported rates of 79.4% and 62.5%, respectively. In addition, as evidenced by most studies, including the findings of Uboha et al.[20], the R0 resection rate generally exceeded 90% which is higher than the previously reported rates associated with neoadjuvant chemoradiotherapy alone[53]. The above data reflect the advantages of preoperative immunotherapy combined with chemoradiotherapy in terms of disease control in GEJ cancer. It is worth noting that in the Neo-PLANET study and the research by Badgwell et al, neoadjuvant immunotherapy combined with chemoradiotherapy achieved a 2-year overall survival rate of 76.1% and 85%, suggesting that the combination of immunotherapy may prolong survival[26, 51]. In terms of surgical safety assessment, the Neo-PLANET study[51] indicated that the incidence of surgery-related complications was consistent with historical data. It is also important to highlight certain issues identified across six distinct studies. Among the six studies reviewed, only the Badgwell study utilized a short-course radiotherapy regimen, whereas the remaining five employed long-course radiotherapy protocols. In GC, there is a relative paucity of comparative studies evaluating the efficacy and safety of long-course radiotherapy vs short-course radiotherapy, whereas such comparative analyses are more commonly reported in rectal cancer treatment. Although the long-course radiotherapy demonstrates superior efficacy in local control, the short-course radiotherapy also offers additional advantages in reducing distant metastasis rates, improving treatment efficiency, minimizing toxicity, and optimizing resource utilization[54-56]. In the study conducted by Ko et al.[52], the incidence of treatment-related adverse events (TRAEs) of grade 3 or higher reached 78.8% when long-course radiotherapy was combined with pharmacological therapy. During short-course radiotherapy, due to its short duration, the increase in drug toxicity caused by concurrent chemotherapy is avoided. According to the case report by Zhou et al. on the combination of immunotherapy with short-course chemoradiotherapy, short-course radiotherapy was well tolerated, and the patient ultimately achieved a TRG1 response[57]. In short-course radiotherapy, a single high-dose radiotherapy is more likely to induce immunogenic cell death, thereby enhancing the efficacy of immunotherapy[57]. Furthermore, it is imperative to optimize the current radiotherapy and chemotherapy protocols. Three studies utilized the paclitaxel and carboplatin combination regimen as part of concurrent chemoradiotherapy.In the study conducted by Uboha and Ko et al., the combination of paclitaxel and carboplatin within the comprehensive treatment model exhibited increased toxicity[20, 21, 52]. Therefore, based on the above data, we initiated this research. To our knowledge, this is the first clinical trial in locally resectable GEJ cancer evaluating the use of tislelizumab in combination with the SOX regimen as induction therapy, followed by short-course radiotherapy, subsequent continuation of tislelizumab combined with the SOX regimen for consolidation, and ultimately the administration of the SOX regimen as adjuvant chemotherapy post-surgery. The safety and effectiveness of this treatment model will be evaluated by us.If this phase II clinical trial achieves the anticipated results, we will conduct a large-sample, multicenter, and prospective study to more comprehensively evaluate the efficacy, safety, and biomarker (such CPS or MS status) benefit population of the treatment regimen used in the phase II trial. This study has several limitations inherent to its design. The research was a single-arm, single-center, small-sample study, with most survival data being short-term, and lacking long-term follow-up and a control group. In the future, there are several issues that warrant further consideration. For instance, in the research conducted by Zhu et al. and Uboha et al., immunotherapy alone was used as an adjuvant treatment plan, but their therapeutic effects were rather limited[20, 21]. Is long-term maintenance of immunotherapy necessary in the context of adjuvant treatment? Furthermore, Ko et al.'s research indicates that variations in the timing of immunotherapy intervention across the three groups may influence the therapeutic outcomes[52]. This suggests that the timing of immunotherapy administration is a critical factor. Should it be introduced during the induction phase, the synchronization phase, or the consolidation phase? Although concurrent immunotherapy can enhance the pCR rate, its associated toxicity risk and long-term survival benefits have not been fully established. In contrast, the sequential strategy appears to be safer; however, it may potentially miss the optimal window for immune activation.Thus, prospective, large-sample, multi-center studies are urgently needed. As presented in Table 3, numerous clinical trials investigating various combination strategies of immunotherapy integrated with chemoradiotherapy in the treatment of locally resectable advanced GEJ cancer are currently underway. It is anticipated that these studies will provide more robust references and clinical guidelines for the management of locally resectable advanced GEJ cancer in the future. Abbreviations AEs Adverse events ANC Absolute neutrophil count CBCT Cone beam computed tomography CIs Confidence intervals CPS Combined Positive Score CrCl calculated creatinine clearance CRF Case Report Form CTV Clinical target volume DFS Disease-free survival ECG Electrocardiogram ECOG Eastern cooperative oncology group EFS Event-free survival EC Esophagus cancer GC Gastric cancer GCP Good Clinical Practice GEJ Gastroesophageal junction GTV Gross tumor volume ICH International Council for Harmonization IMRT Intensity-Modulated Radiation Therapy ITT Intention-to-treat MPR Major pathological response NCCN National Comprehensive Cancer Network NCT Neoadjuvant chemotherapy NRCT Neoadjuvant chemoradiotherapy OAR Organs at risk ORR Objective Response Rate OS Overall survival pCR pathological complete response PTV Planned target volume QA Quality assurance RFS Recurrence-free survival SCRT Short-course radiotherapy TRAEs Treatment-related adverse events Declarations Acknowledgements The authors gratefully acknowledge the assistance provided by Professor Deyu Sun from the department of radiation oncology gastrointestinal and urinary and musculoskeletal Cancer, cancer hospital of China Medical University/Liaoning Cancer Hospital. Author contributions TZ and DYS conceived and designed the study protocol. XYM and JL drafted the initial manuscript. DY, JZ, YLL, CW, and JQY critically reviewed and revised the manuscript for important content. TZ and DYS contributed to clinical trial coordination. XYM, JL, and JQY provided methodological input and conducted the literature review. All authors reviewed and approved the final version of the manuscript. Funding This project is supported by the Beijing Hairun Public Welfare Foundation (Grant NO. BJ-HR-20230788), the Joint Program of Science and Technology Program of Liaoning Province (Natural Science Foundation-Doctoral Research Initiation Project) (Grant NO. 2024-BSLH-145), the Shenyang Science and Technology Program (Grant NO. 24-214-3-166), and the Shenyang Municipal Science and Technology Public Health Research and Development Special Project (Grant NO. 22-321-33-53). Data availability No datasets were generated or analysed during the current study. Ethics approval and consent to participate This research complies with the Helsinki declaration and has been approved by the Ethics committee of the Liaoning Tumor Hospital & Institute (approval number 20231101).Trial registration: Chinese Clinical Trial Registry:ChiCTR2500105244; Registered 1 July 2025. Signature of the informed consent will be obtained from all patients before inclusion in the study. Consent for publication Not applicable. Competing interests The authors declare no competing interests Author details Department of Gastric Surgery, Cancer Hospital of China Medical University/Liaoning Cancer Hospital, Shenyang, Liaoning, China Department of Radiation Oncology Gastrointestinal and Urinary and Musculoskeletal Cancer, Cancer Hospital of China Medical University/Liaoning Cancer Hospital, Shenyang, Liaoning, China Corresponding author Deyu Sun,Department of Radiation Oncology Gastrointestinal and Urinary and Musculoskeletal Cancer, Cancer Hospital of China Medical University/Liaoning Cancer Hospital, No.44 Xiaoheyan road, Dadong District, Shenyang 110042,Liaoning, China. E-mail: [email protected] ; Tao Zhang, Department of Gastric Surgery, Cancer Hospital of China Medical University/Liaoning Cancer Hospital, No.44 Xiaoheyan road, Dadong District, Shenyang 110042,Liaoning, China. 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Tables Table 1 Assessment and intervention schedule for the trial Screening Before NCIT During SRT Before NCIT Before Surgery Before ACT Follow up Year 1-3: every 3 months Year 4-5: every 6 months Year>5: every 1 months Physical examination √ × √ × √ × √ √ √ Blood routine √ × √ × √ × √ √ √ Urine routine √ × √ × √ × Stool routine √ × √ × √ × Biochemical test √ × √ × √ × √ √ √ CEA √ × √ × √ × √ √ √ AFP √ × √ × √ × √ √ √ CA125 √ × √ × √ × √ √ √ CA199 √ × √ × √ × √ √ √ NSE √ × √ × √ × √ √ √ Electrocardiogram √ √ √ Enhanced CT* √ √ √ √ √ √ √ Ultrasound √ √ Gastroscopy √ √ √ ○ ○ ○ Endoscopic ultrasound √ √ Pathology √ √ √ √: once, ×: triweekly, ○: once a year; NCIT: Neoadjuvant chemotherapy combined with immunotherapy; SRT: Short-course radiotherapy *scanning range: chest, abdomen and pelvis; ACT: Adjuvant chemotherapy **scanning range: neck and supraclavicular, echocardiography Table 2 Clinical trials that have released results on perioperative immunotherapy combined with chemoradiotherapy for resectable GEJ cancer. Author/year Title/No.of registration number Trail information No.of pts Stage Study design RT dose Drug regime Results Wei et al 2022 SHARED Single-arm II 34 cT3N2-3M0/ cT4aN+M0/ cT4bNanyM0 CI(1c)→cRCI(5w)→CI(1c)→S→CI(3c) 45Gy/25f Sintilimab:200mg ivgtt d1,3w S1:40mg/m2 PO d1-d14,3w Nab-p:100-120mg/m2 d1/d8,3w c: as above pCR: 38.2% MPR: 79.4% R0: 100% mDFS: 17.0m 1y-OS: 92.6% TRAEs≥3: 50.0% ORC: 38.2% Tang et al 2022 Neo-PLANET Single-arm II 36 cT3-4aN+M0 CI(1c)→cRCI(5w)→CI(1c)→I(1c)→S→C(4c) 45Gy/25f Camrelizumab:200mg ivgtt d1,3w Cape:850mg/m2 PO d1-d14,3w OXA:130mg/m2 ivgtt d1,3w c: Cape:850mg/m2 PO d1-d14,3w Camrelizumab:200mg ivgtt d1,3w pCR: 33.3% MPR: 44.4% R0: 91.7% 2y-PFS: 66.9% 2y-OS: 76.1% TRAEs≥3:77.8% ORC:39.4% Zhu et al 2022 NCT02730546 Single-arm Ib/II 31 cT1-3NanyM0 I(1c)→cRC(5w)→S→I(6c) 41.4Gy/23f Pembrolizumab:200mg ivgtt d1,3w c: PTX: 50mg/m2 ivgtt d1,1w Carboplatin: AUC 2 ivgtt,1w pCR: 22.6% R0: 90.3% mPFS: 19.6m 2y-OS: 66.3% Uboha et al 2024 NCT03490292 Single-arm I/II 24 cT1N1/ T2-3N0-2 cRCI(5w)→I(2c)→S→I(6c) 41.4Gy/23f Avelumab:10mg/kg ivgtt d1,2w PTX: 50mg/m2 ivgtt d1,1w Carboplatin: AUC 2 ivgtt,1w c: Avelumab:10mg/kg ivgtt d1,2w pCR: 26.0% R0: 79.0% 1y-RFS: 71.0% 1y-OS: 81.0% Badgwell et al 2024 NCT04523818 Single-arm I 24 ≥cT2/anyT+N+ csCRT(2w)→CT(2m)→S 30Gy/10f XELOX,3w/FLOT,2w c: Cape: 850mg/m2 5-Fu: 225–250 mg/m2/d pCR: 10.0% MPR: 35.0% R0: 95.0% ORC: 12.5% 1y-OS: 95% 2y-OS: 85% Ko et al 2025 NCT03165994 Single-arm II 33 cT1-3Nx A: s-mab(1c)→cRC+s-mab(5w)→s-mab(1c)→S B: s-mab(1c)→cRC+s-mab(5w)→S C: cRC(5w)+s-mab(w1,2,4,6)→S 50.4Gy/28f Sotigalimab:0.3mg/kg ivgtt d1,3w/(w1,2,4,6) PTX: 50mg/m2 ivgtt d1,1w Carboplatin: AUC 2 ivgtt,1w c: PTX: 130mg/m2 ivgtt d1,1w Carboplatin: AUC 2 ivgtt,1w pCR: 33.3% MPR: 62.5% R0: 83.3% TRAEs≥3: 78.8% ORC: 0% "c"TNM: clinical; "c"RCI: concurrent; 1"c": cycle; C: chemotherapy; I: immune checkpoint inhibitors; R: radiotherapy; s: short-course; T: treatment; w: weeks; m: mouth; s-mab: Sotigalimab; S: surgery; Cape: capecitabine; OXA: oxaliplatin; PTX: paclitaxel; ORC: operation-related complications; Table 3 Ongoing clinical trials involving perioperative immunotherapy combined with chemoradiotherapy for resectable GEJ cancer Author Title/No.of registration number Trail information No.of pts Stage Study design RT dose Drug regime Results Blum et al NCT03776487 Single-arm I/II 32 T1-4N0-3M0 C(4c)→cRCI(O+Y,3c→R+C,3c)→S→O(6c) 45Gy/25f OXA: 130mg/m 2 ivgtt d1,2w 5-Fu: 2400mg/m 2 48h iv,2w Nivolumab(O): 240mg ivgtt,2w Ipilimumab(Y): 1mg/kg,2w c: 5-Fu: 225mg/m 2 /d civ AEs ORR DFS Chung et al NCT04929392 Single-arm II 40-60 I-IVA cRCI(3w)→I+L(3w)→S 50.4Gy/28f Lenvatinib: 24mg/kg qd PO d1-21 Pembrolizumab: 200mg ivgtt d1,2w PTX: 50mg/m 2 ivgtt d1,1w Carboplatin: AUC 2 ivgtt,1w c: Pembrolizumab: 200mg ivgtt d1,2w PTX: 50mg/m2 ivgtt d1,1w Carboplatin: AUC 2 ivgtt,1w pCR cCR AEs DFS OS Wei et al NCT05687357 multicenter/ randomized/ open-label/IIb 140 T3-4aN+M0/ T4bNanyM0 A:I(2c)+cRCI(4w)(I(1c)+S1(25d))→CI(1c)→S →IC(I(16c)+C(6c) (6c:SOX/Nab-p+S1,3c;S1,3c)) B:cRCI (4w)(S1(25d))→C(1c)→S →C(6c)(6c:SOX/Nab-p+S1,3c;S1,3c)) C:C(6c)→S→C(6c) 45Gy/1.5f Tislelizumab:200mg ivgtt d1,3w OXA:130mg/m 2 ivgtt d1,3w Nab-p:100-120mg/m 2 ivgtt,3w S1:40-60mg bid PO d1-d14,3w c:S1:40-60mg bid PO d1-d25 pCR EFS OS Lin et al NCT05918419 Single-arm II 35 cT3-4aN+M0 CI(1c)→cRCI(CI,2c;R,4w)→S 45Gy/25f Serplulimab: 300mg ivgtt d1,3w OXA: 130mg/m 2 ivgtt d1,3w S1: 40-60mg bid PO d1-d14,3w c:OXA: 100mg/m 2 ivgtt d1,3w S1: 40-60mg bid PO d1-d14 pCR Jin et al NCT06250894 Single-arm II 32 cT3-4aNxM0 (Siewert II-III) cRCI(CI,3c;R,2w)→S→CI(3-5c) 36-40Gy/ 18-22f Sintilimab: 200mg ivgtt d1,3w OXA: 130mg/m 2 ivgtt d1,3w S1: 40-60mg bid PO d1-d14,3w c: as above pCR ORR MPR DFS OS AEs ORC Li et al NCT04061928 Single-arm I/II 45 cT3-4/N+M0 cRCI(CI,2c;R,6w)→I(2c)→S→CI(4c) 45-50.4Gy Toripalimab: 200mg ivgtt d1,3w Unusable chemotherapy regimens and dosages TRG AEs LC DFS Shitara et al NCT07018570 Single-arm II – T2-4NanyM0 CI(2c)→sR(5d)→CI(2c)→S 25Gy/5f Pembrolizumab: 200mg ivgtt d1,3w Docetaxel: 50mg/m 2 ivgtt d1,2w OXA: 85mg/m 2 ivgtt d1,2w leucovorin: 200mg/m 2 ivgtt d1,2w 5-Fu: 2600mg/m 2 ivgtt d1,2w 3y-EFS 3y-OS MPR R0 AEs Zhu et al NCT05505461 Single-arm II 26 cT3-4a/ N+M0 cRI(I,2c;R,5w)→CI(2c)→S→CI(4c) 45-50.4Gy PD1,3w OXA: 130mg/m 2 ivgtt d1,3w S1: 40-60mg bid PO d1-d14,3w c: PD1,3w pCR R0 PFS AEs ORC "c"TNM: clinical; "c"RCI: concurrent; 1"c": cycle; C: chemotherapy; I: immune checkpoint inhibitors; R: radiotherapy; w: weeks; S: surgery; OXA: oxaliplatin; PTX: paclitaxel; ORC: operation-related complications; AEs: Adverse events; LC: local control Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 05 Oct, 2025 Reviewers agreed at journal 17 Sep, 2025 Reviewers invited by journal 27 Aug, 2025 Editor assigned by journal 10 Aug, 2025 Submission checks completed at journal 10 Aug, 2025 First submitted to journal 08 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7324963","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Study protocol","associatedPublications":[],"authors":[{"id":506855695,"identity":"30607902-0d20-459d-821c-4715c0f52c03","order_by":0,"name":"Xiangyu Meng","email":"data:image/png;base64,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","orcid":"","institution":"Cancer Hospital of China Medical University, Liaoning Cancer Hospital","correspondingAuthor":true,"prefix":"","firstName":"Xiangyu","middleName":"","lastName":"Meng","suffix":""},{"id":506855696,"identity":"940e92ec-d348-47cc-aea0-af25a2fb1a3f","order_by":1,"name":"Ji Liu","email":"","orcid":"","institution":"Cancer Hospital of China Medical University, Liaoning Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ji","middleName":"","lastName":"Liu","suffix":""},{"id":506855697,"identity":"d6878089-a592-4c16-a187-e4a73af84224","order_by":2,"name":"Dong Yang","email":"","orcid":"","institution":"Cancer Hospital of China Medical University, Liaoning Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Dong","middleName":"","lastName":"Yang","suffix":""},{"id":506855698,"identity":"7dc31337-7408-4892-bcca-2e7d5c5cc0bd","order_by":3,"name":"Jun Zhang","email":"","orcid":"","institution":"Cancer Hospital of China Medical University, Liaoning Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jun","middleName":"","lastName":"Zhang","suffix":""},{"id":506855699,"identity":"894bf8e5-cd74-4fcb-ae06-0038d97cb719","order_by":4,"name":"Yuanlin Liu","email":"","orcid":"","institution":"Cancer Hospital of China Medical University, Liaoning Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuanlin","middleName":"","lastName":"Liu","suffix":""},{"id":506855700,"identity":"f6299d06-363d-4d19-affb-2581cbaee7e6","order_by":5,"name":"Chao Wang","email":"","orcid":"","institution":"Cancer Hospital of China Medical University, Liaoning Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chao","middleName":"","lastName":"Wang","suffix":""},{"id":506855701,"identity":"c4536675-b251-48a3-a890-2d351164fb42","order_by":6,"name":"Junqiao Yao","email":"","orcid":"","institution":"Cancer Hospital of China Medical University, Liaoning Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Junqiao","middleName":"","lastName":"Yao","suffix":""},{"id":506855702,"identity":"3037021e-db68-465a-b0d1-ae2e32200e7b","order_by":7,"name":"Deyu Sun","email":"","orcid":"","institution":"Cancer Hospital of China Medical University, Liaoning Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Deyu","middleName":"","lastName":"Sun","suffix":""},{"id":506855703,"identity":"7eb57976-ff6b-469f-9a53-929a134a1e99","order_by":8,"name":"Tao Zhang","email":"","orcid":"","institution":"Cancer Hospital of China Medical University, Liaoning Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tao","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2025-08-08 08:08:33","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7324963/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7324963/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90792077,"identity":"d00e2674-1205-4348-889a-f4f19d297505","added_by":"auto","created_at":"2025-09-08 08:25:05","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":135912,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of the research. MDT: Multiple Disciplinary Team\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7324963/v1/2a7217e7e4d29ec514895a48.jpeg"},{"id":90792089,"identity":"9455d10b-dbac-4704-9796-3dbfa188646b","added_by":"auto","created_at":"2025-09-08 08:25:10","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":321836,"visible":true,"origin":"","legend":"\u003cp\u003eSchematic diagram of this regimen. Neoadjuvant: 2 cycles of tislelizumab (200mg ivgtt, day 1)+SOX (S-1: BSA-based dose orally twice daily, days 1-14; oxaliplatin: 130mg/m2 ivgtt, day 1; 21-day cycles). Short-course Radiotherapy: Intensity-modulated radiation therapy (IMRT; 25Gy/5f) to primary tumor and involved nodes, initiated 1-2 weeks post-chemotherapy. Consolidation: 2 additional cycles of tislelizumab + SOX within 11-18 days post-radiotherapy. Surgery: Radical gastrectomy with D2 lymphadenectomy 6-8 weeks after last neoadjuvant dose. Adjuvant: 4 cycles of SOX.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7324963/v1/4665d0e842e6d2f844de0040.jpeg"},{"id":90792894,"identity":"64083984-b429-4715-b58c-297b946b5aff","added_by":"auto","created_at":"2025-09-08 08:33:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1385297,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7324963/v1/f8030432-4e08-4499-a6bd-564b084c7eb2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Tislelizumab plus short-course chemoradiotherapy perioperative treatment for HER2-negative, locally advanced gastroesophageal junction(GEJ) adenocarcinoma patients: study protocol for a prospective,single-arm phase 2 trail","fulltext":[{"header":"Background","content":"\u003cp\u003eGlobally, gastroesophageal junction (GEJ) cancer has become increasingly prevalent in recent years, ranking as the fifth most common cancer overall and the fourth leading cause of cancer-related mortality[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Research indicates that GEJ cancer is associated with a poor prognosis, as evidenced by a 5 year survival rate of less than 25% largely due to the aggressive biological behavior of the tumor and the frequent late-stage diagnosis[\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The special etiology leads to the fact that the biological behavior and recurrence pattern of GEJ cancer are different from esophagus cancer (EC) and those of other types of gastric cancer (GC)[\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The MAGIC (15% GEJ) and FLOT4 (56% GEJ) trials established and refined perioperative chemotherapy regimens by introducing multimodal perioperative chemotherapy (ECF and FLOT) in Western populations with resectable G/GEJ cancer[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The KEYNOTE-585, MATTERNHORN and DANTE trials demonstrate that the combination of PD-L1 inhibitors with chemotherapy significantly enhance the pathological complete response (pCR) rate in patients with locally advanced G/GEJ adenocarcinoma compared to chemotherapy alone which have facilitated the transition from conventional chemotherapy to an integrated approach combining chemotherapy and immunotherapy for the management of advanced G/GEJ cancers during the perioperative period[\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. With the publication of the results from the Dragon IV and NEOSUMMIT-02 studies, the perioperative treatment paradigm for advanced G/GEJ cancer has progressively shifted from a combination of chemotherapy and immunotherapy to a more comprehensive regimen incorporating chemotherapy, immunotherapy, and targeted therapy. Short-term outcomes indicate that as the range of therapeutic modalities expands, the pCR rate among patients has significantly increased[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The treatment of advanced GC mentioned above has made considerable progress in reducing tumor staging, increasing the R0 resection rate, pCR rate and improving prognosis. However, current studies on perioperative treatment for advanced GC have not performed subgroup analyses specifically for GEJ cancer, and the representation of patients with GEJ cancer within the overall GC study populations remains relatively limited. Especially, there remains considerable controversy regarding the selection of surgical approaches and the extent of lymph node dissection for GEJ cancer across different Siewert classifications. Therefore, in the management of locally advanced GEJ cancer, there is ongoing debate regarding the optimal treatment strategy-specifically, whether perioperative chemotherapy alone or a combination of chemotherapy with other therapeutic modalities should be recommended. This has also led to growing academic interest in the treatment of GEJ cancer.\u003c/p\u003e\u003cp\u003eClinical trials that solely apply radiotherapy to locally advanced GEJ cancer are very rare. The existing evidence mainly refers to several studies on the safety and efficacy of neoadjuvant chemotherapy (NCT) in EC (including GEJ cancer).Compared with simple surgical treatment, the studies by Walsh et al. (34.5% GEJ) and CALGB-9781 (75% GEJ) have demonstrated that neoadjuvant chemoradiotherapy (NCRT) significantly improves the prognosis of patients with EC or GEJ cancer[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The subsequent findings from the CROSS trial (24% GEJ) further demonstrated that NRCT is more effective than surgery alone in the treatment of GEJ cancer, particularly in terms of enhancing the R0 resection rate and ensuring the safety of radiotherapy[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In addition to demonstrating greater efficacy than simple surgical intervention, NCRT also offers distinct advantages over NCT in the management of EC and GEJ cancer. The POET study is the first phase III clinical trial comparing induced chemotherapy followed by NCRT and surgery with NCT for GEJ cancer which indicated that patients undergoing NCRT had a higher rate of local recurrence-free survival (RFS; HR 0.37, 95% CI 0.16\u0026ndash;0.85) as well as a higher rate of pCR (14.3% vs. 1.9%, p\u0026thinsp;=\u0026thinsp;0.03) and a trend toward higher 5 year OS (39.5% vs. 24.4%, HR 0.65, 95% CI 0.42\u0026ndash;1.01). Notably, the subgroup analysis suggested that patients with cardia cancers (Siewert type II) gained more benefits from NCRT relative to patients with Siewert type I cancers[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eImmunotherapy has significantly transformed the treatment modality for patients with advanced G/GEJ cancer. As previously mentioned, the KEYNOTE-585, MATTERNHORN and DANTE studies are actively exploring perioperative treatment methods for advanced G/GEJ cancer with immunotherapy combined with chemotherapy[\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In light of the therapeutic advantages demonstrated by NCRT over surgery alone or chemotherapy alone in the treatment of EC and GEJ cancer, the neoadjuvant approach that combines radiotherapy with immunotherapy and chemotherapy has increasingly garnered significant research interest. It is noteworthy that emerging evidence suggests radiotherapy possesses the capacity to elicit immune activation. By facilitating the release of tumor antigens, enhancing PD-L1 expression, and activating the cGAS-STING signaling pathway, radiotherapy can convert \"cold tumors (CPS\u0026thinsp;\u0026lt;\u0026thinsp;5)\" into \"hot tumors (CPS\u0026thinsp;\u0026ge;\u0026thinsp;5)\", thereby enhancing the efficacy of immunotherapy in antitumor immune responses[\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Several small-sample phase II clinical trials on GEJ cancer and meta-analyses have demonstrated that the integration of immunotherapy with chemoradiotherapy offers notable efficacy in improving the pCR rate and facilitating tumor downstaging[\u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eHowever, it should be noted that long-course radiotherapy remained predominant in the neoadjuvant radiotherapy regimens of previous studies, and it did not demonstrate a clear advantage over short-course radiotherapy with respect to cost-effectiveness or treatment convenience in locally advanced rectal cancer[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Moreover, studies have suggested that escalating the radiation dose in the treatment of EC/GEJ cancer may not lead to an improved pCR rate of patients[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. A phase I Trial on total neoadjuvant therapy with short course chemoradiotherapy followed by chemotherapy for patients with potentially resectable gastric cancer indicated that short-course radiotherapy is feasible and safe for neoadjuvant treatment of GC[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Thus, based on the current evidences, our study will assess a newly designed total neoadjuvant therapy comprising short course NCRT\u0026thinsp;+\u0026thinsp;immunotherapy for locally advanced GEJ adenocarcinoma. The objective of this trial is to evaluate the feasibility and safety of this treatment approach. The study aims to generate additional clinical evidence to support the implementation of novel neoadjuvant therapies.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy design and objectives\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is a phase II, single-center, single-arm, prospective study aimed at evaluating the efficacy and safety of tislelizumab combined with perioperative chemoradiotherapy in patients with HER2-negative locally advanced resectable adenocarcinoma of the GEJ.The study protocol and the informed consent forms have been reviewed and approved by the Research Ethics Committee of the Liaoning Tumor Hospital \u0026amp; Institute (approval number 20231101). This study will be conducted in strict compliance with the ethical principles of the Declaration of Helsinki and the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) guidelines. All subjects enrolled in the study must provide written informed consent, and all data will be handled confidentially. The study has been prospectively registered at www.chictr.org.cn (ChiCTR2500105244). Patients diagnosed with locally advanced (stage cT3-4a or cN positive M0, according to the AJCC 8th edition) GEJ adenocarcinoma will be enrolled. Prior to enrollment, each patient will undergo gastroscopy, endoscopic ultrasound, and enhanced chest-abdomen-pelvis CT scans for tumor assessment and staging. A multidisciplinary team will screen and confirm eligibility for enrollment based on predefined criteria.The clinical T stage will be determined based on imaging findings and laparoscopic evaluation. The presence of metastatic regional lymph nodes will be assessed according to their size and biological characteristics. Following a thorough screening process, patients will receive NCRT as the initial treatment.Firstly, the patients will begin two courses of neoadjuvant immunotherapy combined with chemotherapy using tislelizuma plus the S-1 and oxaliplatin (SOX) regimen. Radiation therapy should be initiated within 1-2 weeks after the last dose of the combination regimen.The technique of Intensity-Modulated Radiation Therapy (IMRT) will be adopted in this trial, with a dose of 25Gy/5f to the planned target volume (PTV). Radiotherapy is followed by two cycles of tislelizuma plus the SOX regimen, preferably initiated within 11-18 days after the last radiotherapy, and at least within 4 weeks.Ultimately, the patient underwent surgical treatment 6 to 8 weeks after completing sequential chemoradiotherapy. Postoperatively, patients will receive 4 cycles of SOX regimen chemotherapy. A schematic diagram of the study design is shown in Figure 1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe primary objective is the assessment of a pCR, which is defined as no tumor cells in the primary tumor and metastatic regional lymph node. Secondary objectives include the DFS, OS, MPR, Objective Response Rate (ORR), assessing toxicities during NCRT and NCCT, surgical complications, and the R0 resection rate. Subgroup analysis based on the CPS and microsatellite status will also be evaluated. Recruitment began in August\u0026nbsp;2025 and is expected to be finished in August 2027.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEligibility criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients meeting all of the following criteria were eligible:signed informed consent obtained prior to any study-specific procedures; aged 18\u0026ndash;75 years;eastern cooperative oncology group (ECOG) performance status of 0 or 1; histologically confirmed (by enrolling center) adenocarcinoma of the GEJ, Siewert type II or III; clinical stage T3\u0026ndash;4aN+M0 per the AJCC Staging System (8th Edition); HER2-Negative (HER2-negative defined as: IHC score 0 or 1+ on pretreatment endoscopic biopsy tissue; IHC 2+ requires confirmation of no gene amplification by in situhybridization); physical and organ function fitness to undergo planned surgical intervention; estimated life expectancy \u0026ge;6 months; no disease progression after sequential chemoradiotherapy; adequate Organ and Hematological Function(within 7 days prior to treatment initiation, without transfusion/growth factor support): absolute neutrophil count (ANC)\u0026ge;1.5\u0026times;10⁹/L; platelets \u0026ge;100\u0026times;10⁹/L;hemoglobin \u0026ge;90 g/L; serum creatinine \u0026le;1.5\u0026times;ULN; calculated creatinine clearance (CrCl) \u0026ge;50 mL/min; total bilirubin \u0026le;1.5\u0026times;ULN; AST/ALT \u0026le;3\u0026times;ULN; serum albumin \u0026ge;28 g/L.\u003c/p\u003e\n\u003cp\u003eThe exclusion criteria included: patients aged\u0026lt;18 years or \u0026gt; 75 years; a history of prior anticancer treatment; pregnancy or lactation; metastatic disease; history of myocardial infarction or cerebral infarction within the preceding 6 months; active tuberculosis or hepatitis; and refusal to provide informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTreatment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe overall treatment includes two cycles of neoadjuvant chemotherapy combined with immunotherapy and neoadjuvant radiotherapy. After short-course radiotherapy, two more cycles of NCT combined with immunotherapy are administered, followed by radical surgery. Postoperatively, 4 cycles of adjuvant chemotherapy with the SOX regimen are given.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eNeoadjuvant chemotherapy combined with immunotherapy\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTwo cycles of neoadjuvant tislelizumab plus SOX will be administered prior to short-course radiotherapy. Eligible patients will receive intravenous tislelizumab 200 mg on day 1 of each 21-day cycle. SOX chemotherapy consists of: S-1: Administered orally twice daily from day 1 to 14. Dose is BSA-dependent: BSA\u0026lt;1.25 m\u0026sup2;: 40 mg twice daily (80 mg/day), BSA\u0026ge;1.25 to\u0026lt;1.5 m\u0026sup2;: 50 mg twice daily (100 mg/day), BSA\u0026ge;1.5 m\u0026sup2;: 60 mg twice daily (120 mg/day); Oxaliplatin: Administered intravenously at 130 mg/m\u0026sup2; on day 1 of each cycle. Within 11 to 18 days after the last radiotherapy session, and at least within 4 weeks, two cycles of the neoadjuvant tislelizumab plus SOX should be administered again. Tislelizumab dose adjustments are not permitted. Dose reductions for S-1 and oxaliplatin are permitted for treatment-related adverse events (AEs) during the neoadjuvant/adjuvant phase.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eNeoadjuvant short-course radiotherapy\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePreoperative localization process:The patient should fast for 4-6 hours before CT localization. Position and fixation: Supine position, with both hands crossed and raised to the forehead; fixation with thermoplastic body mold. To reduce the difference in irradiation volume caused by gastric filling, the patient needs to take 250ml of semi-liquid containing contrast agent (such as yogurt) 5 minutes before CT scanning. Scanning range: The upper boundary of the scan should include the entire lung, and the lower boundary should include the entire abdomen; scan layer thickness 5mm; intravenous enhancement. The physicist will develop the target volume delineation and organ-at-risk (OAR) protection plan based on the chief physician\u0026apos;s prescription.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe target volumes typically include the gross tumor volume (GTV), clinical target volume (CTV), and planning target volume (PTV). If lymph nodes are involved, the plan may also include GTVnd. The dose limitations of the organs at risk (OARs) will be as follows:Both lungs: V3\u0026le;20%, V12\u0026le;5%, average\u0026le;3 Gy; Liver: V18\u0026le;40%, V25\u0026le;30%, average\u0026le;13 Gy; Heart: V18\u0026le;40%, V25\u0026le;30%, average\u0026le;13 Gy; Spinal cord\u0026le;27 Gy; Both kidneys: V10\u0026le;3%. The treatment plan must be reviewed and approved by an experienced chief physician before treatment initiation. On the first day of treatment, the doctor, physicist and radiotherapy technician need to position the patient together. The patient should fast for 4 to 6 hours before radiotherapy. Five minutes before each treatment, the patient needs to orally take 250ml of semi-liquid food (such as yogurt). The cone beam computed tomography (CBCT) imaging will be conducted before each daily radiotherapy session to verify treatment accuracy. Additionally, laboratory tests including complete blood count, liver function, kidney function, blood glucose, serum electrolytes, and electrocardiogram (ECG) will be performed both before and after the completion of radiotherapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eSurgery\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStandard radical surgery will be performed 6 to 8 weeks after the completion of neoadjuvant tislelizumab combined with SOX chemotherapy. Laparoscopic resection will be the preferred approach. For Siewert II/III EGJ tumors, either proximal or total gastrectomy will be recommended. In terms of gastrointestinal reconstruction, single muscle flap, double muscle flap, or modified side-to-side overlap (mSOFY) gastroesophageal anastomosis will be performed following proximal gastrectomy, while Roux-en-Y reconstruction will be conducted after total gastrectomy. A D2 lymph node dissection will be performed, in accordance with the definitions provided by the NCCN guidelines. At least 16 or more lymph nodes should be examined during surgery. In cases of disease progression during neoadjuvant therapy, a multidisciplinary team (MDT) will be convened to determine the most appropriate subsequent treatment strategy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTumor response and\u0026nbsp;toxicity criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eToxicity will be evaluated prior to each treatment cycle based on patient history, physical examination, and laboratory assessments, including complete blood count, liver function tests, and renal function tests. AEs will be classified according to the NCI CTCAE v5.0. Dose modifications will be determined by the type and severity of the observed toxicities. For chemotherapy-associated toxicities (e.g., myelosuppression, nausea, vomiting, diarrhea), concurrent dose reductions of S-1 will be applied. In cases of severe hematologic toxicity (e.g., grade\u0026ge;3 neutropenia or thrombocytopenia), both S-1 and oxaliplatin will be reduced by one dose level, and treatment will be postponed until recovery if toxicity remains unresolved. The minimum recommended daily dose for S-1 is 60 mg, and the minimum dose for oxaliplatin is 85 mg/m\u0026sup2;. For fruquintinib-related toxicities (e.g., hand-foot syndrome, hypertension, fatigue, liver dysfunction), the recommended dose will be reduced to 3 mg/day in the event of grade\u0026ge;3 toxicities, with a further reduction to 2 mg/day if clinically indicated. Temporary treatment interruptions may be necessary for persistent adverse events, and resumption of therapy will be contingent upon adequate recovery. When tislelizumab is administered, the following immune-related adverse events-such as pneumonitis, enteritis, hepatitis, nephritis, endocrine disorders, dermatitis, myocarditis, and neurotoxicity-are assessed as grade 2. In such cases, medication should be discontinued. Tislelizumab should be resumed in patients with improvement to grade 0-1 after tapering of corticosteroids or stabilization of hormone replacement therapy. Treatment was permanently discontinued in cases where any of these immune-related adverse effects reached grade 3 or higher, failed to improve to grade 0-1 within 12 weeks following the initiation of steroid therapy, or if prednisone could not be tapered to \u0026le;10 mg per day (or equivalent) within the same time frame. For other toxicities that are difficult to classify, dose modifications will be guided by the investigator\u0026rsquo;s clinical judgment to ensure patient safety and continuity of treatment. Discontinuation of the study regimen will be considered if such toxicities persist despite two dose reductions, if intolerable adverse events recur, or if patients withdraw consent or demonstrate disease progression. Supportive care measures will include the use of antiemetics for nausea and vomiting, antihypertensive agents for elevated blood pressure, specialized dermatologic care for hand-foot syndrome, and general supportive interventions for fatigue and other associated symptoms.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSample size calculation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn terms of research design, if the pCR rate is 15% (H0), the study will not be considered justified for further investigation. Conversely, a pCR rate of 35% (Ha) or higher will indicate the necessity for continued research. Based on these criteria, a Simon optimal two-stage design has been selected, with H0 = 0.15 versus Ha = 0.35, a one-sided significance level (\u0026alpha;) of 0.05, and a statistical power of 80%. Under these parameters, the proposed study plan is structured as follows: Stage 1: A total of 15 patients will be enrolled. If two or more patients achieve pCR, the study will proceed to the second stage. If fewer than two patients exhibit pCR, the study will be terminated. Stage 2: An additional 13 patients will be enrolled, bringing the minimum total sample size to 28 patients. Considering an estimated dropout rate of 10%, the study aims to enroll a total of 31 patients to ensure sufficient statistical power.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDescriptive statistics will summarize baseline demographics and clinicopathological characteristics. Efficacy endpoints will be calculated with corresponding 95% confidence intervals (CIs) using Blaker\u0026rsquo;s binomial exact method. DFS and OS will be evaluated through Kaplan-Meier estimates, accompanied by 95% CIs. Primary analyses will utilize the intention-to-treat (ITT) population. Safety analyses will focus on patients receiving \u0026ge;1 dose of neoadjuvant therapy (safety population). Neoadjuvant-and adjuvant-related emergent AEs will be stratified by treatment phase due to regimen differences. Surgical outcomes (morbidity/mortality) will be assessed in the per-protocol population, defined as protocol-compliant patients undergoing surgery. Subgroup analysis of biomarkers: the pCR rates of patients with PD-L1 CPS\u0026ge;5 vs \u0026lt;5, and MSI-H vs MSS were compared (Fisher\u0026apos;s exact test), and the OR value and 95%CI were calculated. To mitigate missing data, proactive measures were implemented during trial design, including standardized data collection protocols. For participants with missing outcome data due to withdrawal or loss to follow-up, multiple imputation techniques will be employed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFollow-up\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter completing the prescribed treatment, patients will undergo the examinations on schedule. Follow-up evaluations will be conducted every 3 months during the first 3 years, every 6 months from year 4 to year 5, and annually thereafter. During the follow-up period, investigators will collect data on surgical complications, late toxicities, additional treatments, as well as disease recurrence and patient survival. The assessment and intervention schedule for the trial was shown in Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eQuality assurance\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe quality assurance (QA) team involved in this study will consist of experienced professionals in the fields of radiation oncology, dosimetry, medical physics, medicine, surgery, diagnostic imaging, pathology, and data monitoring. Diagnostic images obtained before and after neoadjuvant treatment will be centrally and independently reviewed by two radiologists. Data monitoring personnel will maintain communication with researchers and conduct periodic random checks to ensure the accuracy and consistency of data collection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData collection and management\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOne physician will be responsible for enrolling patients in the trial and coordinating patients\u0026rsquo; treatment. Two physicians will be assigned to collect data and complete the Case Report Form (CRF). Any modifications made to the data must be accompanied by the researcher\u0026rsquo;s signature and the date of the change on the CRF. The CRF will serve as the source document, and all data contained therein will be archived electronically on a designated computer. All electronic files will be kept confidential, with access restricted to the data manager via a secure password. Only the project leader will have authorization to access the database; other researchers may access it only with prior permission.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe definition of GEJ cancer is adenocarcinoma with the primary tumor (center) located within a 5 cm range above and below the esophagogastric junction[27]. Research indicates that the incidence of GEJ cancer has been rising steadily in comparison to other malignant tumors[28]. Obesity, gastroesophageal reflux and Barrett\u0026apos;s esophagus are closely related to the occurrence of GEJ cancer[29]. According to the research findings of Siewert et al., GEJ cancer can be categorized into three distinct types: Siewert I, Siewert II, and Siewert III[30]. Although the advancements in radiotherapy, chemotherapy, and immunotherapy have significantly improved patient survival rates, surgical treatment continues to be the cornerstone for achieving a radical cure[31]. Thus,for locally resectable advanced GEJ cancer, comprehensive treatment centered on surgery is recommended by both the NCCN Guidelines, the Japanese Gastric Cancer Treatment Guidelines, and the CSCO Guidelines in China[32-34]. However, there is still considerable controversy regarding the comprehensive treatment model for GEJ cancer. The MAGIC[35] /FFCD9703[36] /FLOT4[9] study defined the significance of neoadjuvant chemotherapy in the management of advanced gastric cancer. Furthermore, the RESOLVE[37] and PRODIGY[38] studies have expanded the available options for perioperative chemotherapy regimens.\u003c/p\u003e\n\u003cp\u003eBased on the findings of the INT-0116 study[39], the ARTIST study[40], and the CRITICS study[41] conducted at earlier stages, perioperative radiotherapy was primarily indicated for patients with gastric cancer or gastroesophageal junction cancer who exhibited less extensive lymph node dissection (D0 or D1), inadequate lymph node sampling (\u0026lt;15 nodes examined), or positive surgical margins following resection. In such cases, the administration of radiotherapy has been shown to improve clinical outcomes.However, postoperative radiotherapy continues to be associated with several limitations.For instance,postoperative radiotherapy may offer potential benefits to patients with G/GEJ cancer who have not undergone D2 radical resection. However, in the current era where D2 radical resection is widely adopted, postoperative radiotherapy has been associated with an increased risk of grade 3-4 toxicities[42], a reduced completion rate of adjuvant therapy[41], and an elevated likelihood of complications related to anastomotic integrity and organ protection due to the expanded postoperative target volume[39]. Therefore, with the continuous advancement and refinement of radiotherapy techniques and treatment protocols, NCRT has increasingly gained clinical acceptance and recognition. The POET study is the first phase III clinical trial comparing induced chemotherapy followed by NCRT and surgery with NCT. The results ultimately suggested that compared with the NCT group, patients in the NCRT group had a significantly higher pCR rate (14.3% vs 1.9%) and an advantage in 5-year OS[17]. The Dutch CROSS-trial also showed that the addition of NCRT to surgery led to an absolute 5-year OS benefit of 14 % without an increased risk of postoperative complications in patients with adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the esophagus and GEJ[43]. It is worth noting that the results of our meta-analysis show that compared with the NCT and surgery alone groups, NCRT can significantly improve the 2-year and 3-year OS of GEJ cancer[44]. To sum up,both perioperative chemotherapy and preoperative concurrent chemoradiotherapy are recommended for patients with locally advanced G/GEJ according to the National Comprehensive Cancer Network (NCCN) guidelines[32]. In the POET trial, limited by the constraints of radiotherapy dose and outdated chemotherapy regimens, further optimizing radiotherapy doses, methods, and medication regimens has become an urgent priority at present.\u003c/p\u003e\n\u003cp\u003eThe clinical trials including CheckMate 649[45], KEYNOTE-859[46],and RATIONALE-305[47] have demonstrated clinically meaningful survival benefits when combining immune checkpoint inhibitors with conventional chemotherapy in advanced G/GEJ adenocarcinoma. There is a 28% to 44% reduction in mortality risk. These findings establish immunotherapy as a standard component of current multimodal treatment strategies for advanced GC, particularly among patients with PD-L1-positive tumors.The latest findings from the MATTERHORN trial suggest that for patients with locally advanced G/GEJ cancers, the integration of perioperative immunotherapy not only leads to a higher pCR rate but also offers significant improvements in both event-free survival (EFS) and OS among individuals with locally advanced GC[48]. Furthermore, the DANTE study demonstrated that combining perioperative immunotherapy with chemotherapy results in greater clinical downstaging and a higher pCR rate compared to chemotherapy alone in patients with locally advanced GC. This benefit appears to be particularly prominent in patients exhibiting MSI-H status or a high CPS[12]. Thus, the incorporation of immunotherapy into the perioperative period or neoadjuvant treatment plays a significant role in enhancing therapeutic efficacy.Given the promising outcomes of chemoradiotherapy and immune combination chemotherapy in the neoadjuvant or perioperative management of GEJ cancer, the integration of immunotherapy with chemoradiotherapy has increasingly drawn the attention of oncology researchers. Sasaki et al.\u0026apos;s study demonstrates that the integration of immunotherapy into chemoradiotherapy treatment regimens can modulate the immune microenvironment by activating the cGAS-STING pathway, thereby enhancing the radiosensitivity in the management of advanced GC[49]. As presented in Table 2, all six studies investigated the safety and efficacy of immunotherapy in combination with chemoradiotherapy for locally resectable GEJ cancer[20, 21, 26, 50-52]. In the SHARED trial, the pCR rate was notably high at 38.2%, compared to 29% observed in the CROSS trial[16, 50]. Moreover, the research findings of Zhu et al. suggest that the pCR rate associated with the combination of immunotherapy and chemoradiotherapy in the treatment of GEJ cancer may be positively correlated with the CPS[21]. With regard to the assessment of the MPR rate, the SHARED study[50] and the research conducted by Ko et al.[52]reported rates of 79.4% and 62.5%, respectively. In addition, as evidenced by most studies, including the findings of Uboha et al.[20], the R0 resection rate generally exceeded 90% which is higher than the previously reported rates associated with neoadjuvant chemoradiotherapy alone[53]. The above data reflect the advantages of preoperative immunotherapy combined with chemoradiotherapy in terms of disease control in GEJ cancer. It is worth noting that in the Neo-PLANET study and the research by Badgwell et al, neoadjuvant immunotherapy combined with chemoradiotherapy achieved a 2-year overall survival rate of 76.1% and 85%, suggesting that the combination of immunotherapy may prolong survival[26, 51]. In terms of surgical safety assessment, the Neo-PLANET study[51] indicated that the incidence of surgery-related complications was consistent with historical data.\u003c/p\u003e\n\u003cp\u003eIt is also important to highlight certain issues identified across six distinct studies. Among the six studies reviewed, only the Badgwell study utilized a short-course radiotherapy regimen, whereas the remaining five employed long-course radiotherapy protocols. In GC, there is a relative paucity of comparative studies evaluating the efficacy and safety of long-course radiotherapy vs short-course radiotherapy, whereas such comparative analyses are more commonly reported in rectal cancer treatment. Although the long-course radiotherapy demonstrates superior efficacy in local control, the short-course radiotherapy also offers additional advantages in reducing distant metastasis rates, improving treatment efficiency, minimizing toxicity, and optimizing resource utilization[54-56]. In the study conducted by Ko et al.[52], the incidence of treatment-related adverse events (TRAEs) of grade 3 or higher reached 78.8% when long-course radiotherapy was combined with pharmacological therapy. During short-course radiotherapy, due to its short duration, the increase in drug toxicity caused by concurrent chemotherapy is avoided. According to the case report by Zhou et al. on the combination of immunotherapy with short-course chemoradiotherapy, short-course radiotherapy was well tolerated, and the patient ultimately achieved a TRG1 response[57]. In short-course radiotherapy, a single high-dose radiotherapy is more likely to induce immunogenic cell death, thereby enhancing the efficacy of immunotherapy[57]. Furthermore, it is imperative to optimize the current radiotherapy and chemotherapy protocols. Three studies utilized the paclitaxel and carboplatin combination regimen as part of concurrent chemoradiotherapy.In the study conducted by Uboha and Ko et al., the combination of paclitaxel and carboplatin within the comprehensive treatment model exhibited increased toxicity[20, 21, 52].\u003c/p\u003e\n\u003cp\u003eTherefore, based on the above data, we initiated this research. To our knowledge, this is the first clinical trial in locally resectable GEJ cancer evaluating the use of tislelizumab in combination with the SOX regimen as induction therapy, followed by short-course radiotherapy, subsequent continuation of tislelizumab combined with the SOX regimen for consolidation, and ultimately the administration of the SOX regimen as adjuvant chemotherapy post-surgery. The safety and effectiveness of this treatment model will be evaluated by us.If this phase II clinical trial achieves the anticipated results, we will conduct a large-sample, multicenter, and prospective study to more comprehensively evaluate the efficacy, safety, and biomarker (such CPS or MS status) benefit population of the treatment regimen used in the phase II trial. This study has several limitations inherent to its design. The research was a single-arm, single-center, small-sample study, with most survival data being short-term, and lacking long-term follow-up and a control group. In the future, there are several issues that warrant further consideration. For instance, in the research conducted by Zhu et al. and Uboha et al., immunotherapy alone was used as an adjuvant treatment plan, but their therapeutic effects were rather limited[20, 21]. Is long-term maintenance of immunotherapy necessary in the context of adjuvant treatment? Furthermore, Ko et al.\u0026apos;s research indicates that variations in the timing of immunotherapy intervention across the three groups may influence the therapeutic outcomes[52]. This suggests that the timing of immunotherapy administration is a critical factor. Should it be introduced during the induction phase, the synchronization phase, or the consolidation phase? Although concurrent immunotherapy can enhance the pCR rate, its associated toxicity risk and long-term survival benefits have not been fully established. In contrast, the sequential strategy appears to be safer; however, it may potentially miss the optimal window for immune activation.Thus, prospective, large-sample, multi-center studies are urgently needed. As presented in Table 3, numerous clinical trials investigating various combination strategies of immunotherapy integrated with chemoradiotherapy in the treatment of locally resectable advanced GEJ cancer are currently underway. It is anticipated that these studies will provide more robust references and clinical guidelines for the management of locally resectable advanced GEJ cancer in the future.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"387\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eAEs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 302px;\"\u003e\n \u003cp\u003eAdverse events\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eANC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eAbsolute neutrophil count\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCBCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCone beam computed tomography\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCIs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eConfidence intervals\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCPS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCombined Positive Score\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCrCl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ecalculated creatinine clearance\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCRF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCase Report Form\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCTV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eClinical target volume\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eDFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eDisease-free survival\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eECG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eElectrocardiogram\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eECOG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eEastern cooperative oncology group\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eEFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eEvent-free survival\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eEC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eEsophagus cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eGC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eGastric cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eGCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eGood Clinical Practice\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eGEJ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eGastroesophageal junction\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eGTV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eGross tumor volume\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eICH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eInternational Council for Harmonization\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eIMRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eIntensity-Modulated Radiation Therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eITT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eIntention-to-treat\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eMPR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eMajor pathological response\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNCCN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNational Comprehensive Cancer Network\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNeoadjuvant chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNeoadjuvant chemoradiotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eOAR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eOrgans at risk\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eORR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eObjective Response Rate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eOS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eOverall survival\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003epCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003epathological complete response\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePTV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ePlanned target volume\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eQA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eQuality assurance\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eRFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eRecurrence-free survival\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSCRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eShort-course radiotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eTRAEs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eTreatment-related adverse events\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors gratefully acknowledge the assistance provided by Professor Deyu Sun from the department of radiation oncology gastrointestinal and urinary and musculoskeletal Cancer, cancer hospital of China Medical University/Liaoning Cancer Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTZ and DYS conceived and designed the study protocol. XYM and JL drafted the initial manuscript. DY, JZ, YLL, CW, and JQY critically reviewed and revised the manuscript for important content. TZ and DYS contributed to clinical trial coordination. XYM, JL, and JQY provided methodological input and conducted the literature review. All authors reviewed and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis project is supported by the Beijing Hairun Public Welfare Foundation (Grant NO. BJ-HR-20230788), the Joint Program of Science and Technology Program of Liaoning Province (Natural Science Foundation-Doctoral Research Initiation Project) (Grant NO. 2024-BSLH-145), the Shenyang Science and Technology Program (Grant NO. 24-214-3-166), and the Shenyang Municipal Science and Technology Public Health Research and Development Special Project (Grant NO. 22-321-33-53).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo datasets were generated or analysed during the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research complies with the Helsinki declaration and has been approved by the Ethics committee of the Liaoning Tumor Hospital \u0026amp; Institute (approval number 20231101).Trial registration: Chinese Clinical Trial Registry:ChiCTR2500105244; Registered 1 July 2025. Signature of the informed consent will be obtained from all patients before inclusion in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eDepartment of Gastric Surgery, Cancer Hospital of China Medical University/Liaoning Cancer Hospital, Shenyang, Liaoning, China\u003c/li\u003e\n \u003cli\u003eDepartment of Radiation Oncology Gastrointestinal and Urinary and Musculoskeletal Cancer, Cancer Hospital of China Medical University/Liaoning Cancer Hospital, Shenyang, Liaoning, China\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003eCorresponding author\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDeyu Sun,Department of Radiation Oncology Gastrointestinal and Urinary and Musculoskeletal Cancer, Cancer Hospital of China Medical University/Liaoning Cancer Hospital, No.44 Xiaoheyan road, Dadong District, Shenyang 110042,Liaoning, China. E-mail: [email protected];\u003c/p\u003e\n\u003cp\u003eTao Zhang, Department of Gastric Surgery, Cancer Hospital of China Medical University/Liaoning Cancer Hospital, No.44 Xiaoheyan road, Dadong District, Shenyang 110042,Liaoning, China. E-mail: [email protected];\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F: Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: a cancer journal for clinicians 2021, 71(3):209-249.\u003c/li\u003e\n\u003cli\u003eZhou Y, Tian M, Gungor C, Wang D: Neoadjuvant radiotherapy for locoregional Siewert type II gastroesophageal junction adenocarcinoma: A propensity scores matching analysis. PloS one 2021, 16(5):e0251555.\u003c/li\u003e\n\u003cli\u003eDeng HY, Wang WP, Wang YC, Hu WP, Ni PZ, Lin YD, Chen LQ: Neoadjuvant chemoradiotherapy or chemotherapy? 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European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 2019, 45(10):1796-1805.\u003c/li\u003e\n\u003cli\u003eAjani JA, D\u0026apos;Amico TA, Bentrem DJ, Chao J, Cooke D, Corvera C, Das P, Enzinger PC, Enzler T, Fanta P et al: Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network : JNCCN 2022, 20(2):167-192.\u003c/li\u003e\n\u003cli\u003eJapanese Gastric Cancer A: Japanese Gastric Cancer Treatment Guidelines 2021 (6th edition). Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2023, 26(1):1-25.\u003c/li\u003e\n\u003cli\u003eWang FH, Zhang XT, Tang L, Wu Q, Cai MY, Li YF, Qu XJ, Qiu H, Zhang YJ, Ying JE et al: The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023. Cancer communications (London, England) 2024, 44(1):127-172.\u003c/li\u003e\n\u003cli\u003eCunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ et al: Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. The New England journal of medicine 2006, 355(1):11-20.\u003c/li\u003e\n\u003cli\u003eYchou M, Boige V, Pignon JP, Conroy T, Bouche O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B et al: Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2011, 29(13):1715-1721.\u003c/li\u003e\n\u003cli\u003eZhang X, Liang H, Li Z, Xue Y, Wang Y, Zhou Z, Yu J, Bu Z, Chen L, Du Y et al: Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised controlled trial. The Lancet Oncology 2021, 22(8):1081-1092.\u003c/li\u003e\n\u003cli\u003eKang YK, Yook JH, Park YK, Lee JS, Kim YW, Kim JY, Ryu MH, Rha SY, Chung IJ, Kim IH et al: PRODIGY: A Phase III Study of Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 Versus Surgery and Adjuvant S-1 for Resectable Advanced Gastric Cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2021, 39(26):2903-2913.\u003c/li\u003e\n\u003cli\u003eMacdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM et al: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. The New England journal of medicine 2001, 345(10):725-730.\u003c/li\u003e\n\u003cli\u003eLee J, Lim DH, Kim S, Park SH, Park JO, Park YS, Lim HY, Choi MG, Sohn TS, Noh JH et al: Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2012, 30(3):268-273.\u003c/li\u003e\n\u003cli\u003eCats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM et al: Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. The Lancet Oncology 2018, 19(5):616-628.\u003c/li\u003e\n\u003cli\u003eSmalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, Gunderson LL, Goldman B, Martenson JA, Jessup JM et al: Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. Journal of clinical oncology 2012, 30(19):2327‐2333.\u003c/li\u003e\n\u003cli\u003eShapiro J, van Lanschot JJB, Hulshof M, van Hagen P, van Berge Henegouwen MI, Wijnhoven BPL, van Laarhoven HWM, Nieuwenhuijzen GAP, Hospers GAP, Bonenkamp JJ et al: Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. The Lancet Oncology 2015, 16(9):1090-1098.\u003c/li\u003e\n\u003cli\u003eMeng X, Wang L, Zhao Y, Zhu B, Sun T, Zhang T, Gu X, Zheng Z: Neoadjuvant Chemoradiation Treatment for Resectable Esophago-Gastric Cancer: A Systematic Review and Meta-Analysis. Journal of Cancer 2019, 10(1):192-204.\u003c/li\u003e\n\u003cli\u003eJanjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, Wyrwicz L, Yamaguchi K, Skoczylas T, Campos Bragagnoli A et al: First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet (London, England) 2021, 398(10294):27-40.\u003c/li\u003e\n\u003cli\u003eRha SY, Oh DY, Yanez P, Bai Y, Ryu MH, Lee J, Rivera F, Alves GV, Garrido M, Shiu KK et al: Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial. The Lancet Oncology 2023, 24(11):1181-1195.\u003c/li\u003e\n\u003cli\u003eQiu MZ, Oh DY, Kato K, Arkenau T, Tabernero J, Correa MC, Zimina AV, Bai Y, Shi J, Lee KW et al: Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial. BMJ (Clinical research ed) 2024, 385:e078876.\u003c/li\u003e\n\u003cli\u003eJanjigian Y: Event-free survival (EFS) in MATTERHORN: A randomized, phase 3 study of durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel chemotherapy (FLOT) in resectable gastric/gastroesophageal junction cancer (GC/GEJC). Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2025, 43.\u003c/li\u003e\n\u003cli\u003eSasaki A, Nakamura Y, Togashi Y, Kuno H, Hojo H, Kageyama S, Nakamura N, Takashima K, Kadota T, Yoda Y et al: Enhanced tumor response to radiotherapy after PD-1 blockade in metastatic gastric cancer. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2020, 23(5):893-903.\u003c/li\u003e\n\u003cli\u003eWei J, Lu X, Liu Q, Fu Y, Liu S, Li L, Liu F, Fan X, Yang J, Yang Y et al: Efficacy and Safety of Sintilimab in Combination with Concurrent Chemoradiotherapy for Locally Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (SHARED): Study Protocol of a Prospective, Multi-Center, Single-Arm Phase 2 Trial. Cancer management and research 2022, 14:2007-2015.\u003c/li\u003e\n\u003cli\u003eTang Z, Wang Y, Liu D, Wang X, Xu C, Yu Y, Cui Y, Tang C, Li Q, Sun J et al: The Neo-PLANET phase II trial of neoadjuvant camrelizumab plus concurrent chemoradiotherapy in locally advanced adenocarcinoma of stomach or gastroesophageal junction. Nat Commun 2022, 13(1):6807.\u003c/li\u003e\n\u003cli\u003eKo AH, Chao J, Noel MS, Shankaran V, Sohal D, Crow M, Oberstein PE, Scott AJ, McRee AJ, Rocha Lima C et al: A Phase 2 Study of Sotigalimab, a CD40 Agonist Antibody, plus Concurrent Chemoradiation as Neoadjuvant Therapy for Esophageal and Gastroesophageal Junction Cancers. Cancer Res Commun 2025, 5(2):349-357.\u003c/li\u003e\n\u003cli\u003evan den Ende T, de Clercq NC, van Berge Henegouwen MI, Gisbertz SS, Geijsen ED, Verhoeven RHA, Meijer SL, Schokker S, Dings MPG, Bergman J et al: Neoadjuvant Chemoradiotherapy Combined with Atezolizumab for Resectable Esophageal Adenocarcinoma: A Single-arm Phase II Feasibility Trial (PERFECT). Clinical cancer research : an official journal of the American Association for Cancer Research 2021, 27(12):3351-3359.\u003c/li\u003e\n\u003cli\u003eDijkstra EA, Nilsson PJ, Hospers GAP, Bahadoer RR, Meershoek-Klein Kranenbarg E, Roodvoets AGH, Putter H, Berglund A, Cervantes A, Crolla R et al: Locoregional Failure During and After Short-course Radiotherapy Followed by Chemotherapy and Surgery Compared With Long-course Chemoradiotherapy and Surgery: A 5-Year Follow-up of the RAPIDO Trial. Annals of surgery 2023, 278(4):e766-e772.\u003c/li\u003e\n\u003cli\u003eBercz A, Park BK, Pappou E, Nemirovsky D, Sarkar R, Yamner M, Omer D, Verheij FS, Alvarez J, Atri P et al: Organ preservation after neoadjuvant long-course chemoradiotherapy versus short-course radiotherapy. Annals of oncology : official journal of the European Society for Medical Oncology 2024, 35(11):1003-1014.\u003c/li\u003e\n\u003cli\u003eConroy T, Bosset JF, Etienne PL, Rio E, Francois E, Mesgouez-Nebout N, Vendrely V, Artignan X, Bouche O, Gargot D et al: Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. The Lancet Oncology 2021, 22(5):702-715.\u003c/li\u003e\n\u003cli\u003eZhou ML, Xu RN, Tan C, Zhang Z, Wan JF: Advanced gastric cancer achieving major pathologic regression after chemoimmunotherapy combined with hypofractionated radiotherapy: A case report. World journal of gastrointestinal oncology 2023, 15(6):1096-1104.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cdiv align=\"\"\u003e\u0026nbsp;\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"875\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\" style=\"width: 875px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1\u0026nbsp;\u003c/strong\u003eAssessment and intervention schedule for the trial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"19\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eScreening\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eBefore NCIT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eDuring SRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eBefore NCIT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eBefore Surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eBefore ACT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\"\u003e\n \u003cp\u003eFollow up\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"19\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eYear 1-3: every \u0026nbsp; \u0026nbsp; \u0026nbsp; 3 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eYear 4-5: every \u0026nbsp; \u0026nbsp; \u0026nbsp; 6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eYear\u0026gt;5: every \u0026nbsp; \u0026nbsp; \u0026nbsp;1 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"56\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePhysical examination\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"19\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eBlood routine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"19\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eUrine routine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"19\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eStool routine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"19\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eBiochemical test\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"19\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCEA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"19\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAFP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"19\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCA125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"19\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCA199\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"19\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNSE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026times;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"19\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eElectrocardiogram\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"19\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eEnhanced CT*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"19\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eUltrasound\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"19\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eGastroscopy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e○\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e○\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e○\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"19\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eEndoscopic ultrasound\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"19\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePathology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"19\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\" rowspan=\"3\" style=\"width: 875px;\"\u003e\n \u003cp\u003e\u0026radic;: once,\u0026nbsp;\u0026times;: triweekly,\u0026nbsp;○: once a year; NCIT: Neoadjuvant chemotherapy combined with immunotherapy; SRT: Short-course radiotherapy\u003cbr\u003e\u0026nbsp;*scanning range: chest, abdomen and pelvis; ACT: Adjuvant chemotherapy\u003cbr\u003e\u0026nbsp;**scanning range: neck and supraclavicular, echocardiography\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"21\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd height=\"21\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd height=\"21\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"1282\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" style=\"width: 1282px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e Clinical trials that have released results on perioperative immunotherapy combined with chemoradiotherapy for resectable GEJ cancer.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"19\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003eAuthor/year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003eTitle/No.of registration number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003eTrail information\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003eNo.of pts\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 117px;\"\u003e\n \u003cp\u003eStage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 297px;\"\u003e\n \u003cp\u003eStudy design\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003eRT dose\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003eDrug regime\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 122px;\"\u003e\n \u003cp\u003eResults\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"56\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003eWei et al 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eSHARED\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eSingle-arm II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003ecT3N2-3M0/\u003cbr\u003e\u0026nbsp;cT4aN+M0/\u003cbr\u003e\u0026nbsp;cT4bNanyM0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 297px;\"\u003e\n \u003cp\u003eCI(1c)\u0026rarr;cRCI(5w)\u0026rarr;CI(1c)\u0026rarr;S\u0026rarr;CI(3c)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e45Gy/25f\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003eSintilimab:200mg ivgtt d1,3w\u003cbr\u003e\u0026nbsp;S1:40mg/m2 PO d1-d14,3w\u003cbr\u003eNab-p:100-120mg/m2 d1/d8,3w\u003cbr\u003ec: as above\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003epCR: 38.2%\u003cbr\u003e\u0026nbsp;MPR: 79.4%\u003cbr\u003e\u0026nbsp;R0: 100%\u003cbr\u003e\u0026nbsp;mDFS: 17.0m\u003cbr\u003e\u0026nbsp;1y-OS: 92.6%\u003cbr\u003e\u0026nbsp;TRAEs\u0026ge;3: 50.0%\u003cbr\u003e\u0026nbsp;ORC: 38.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"131\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003eTang et al 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eNeo-PLANET\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eSingle-arm II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003ecT3-4aN+M0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 297px;\"\u003e\n \u003cp\u003eCI(1c)\u0026rarr;cRCI(5w)\u0026rarr;CI(1c)\u0026rarr;I(1c)\u0026rarr;S\u0026rarr;C(4c)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e45Gy/25f\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003eCamrelizumab:200mg ivgtt d1,3w\u003cbr\u003e\u0026nbsp;Cape:850mg/m2 PO d1-d14,3w\u003cbr\u003eOXA:130mg/m2 ivgtt d1,3w\u003cbr\u003ec: Cape:850mg/m2 PO d1-d14,3w\u003cbr\u003eCamrelizumab:200mg ivgtt d1,3w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003epCR: 33.3%\u003cbr\u003e\u0026nbsp;MPR: 44.4%\u003cbr\u003e\u0026nbsp;R0: 91.7%\u003cbr\u003e\u0026nbsp;2y-PFS: 66.9%\u003cbr\u003e\u0026nbsp;2y-OS: 76.1%\u003cbr\u003e\u0026nbsp;TRAEs\u0026ge;3:77.8%\u003cbr\u003e\u0026nbsp;ORC:39.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"131\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003eZhu et al 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eNCT02730546\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eSingle-arm Ib/II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003ecT1-3NanyM0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 297px;\"\u003e\n \u003cp\u003eI(1c)\u0026rarr;cRC(5w)\u0026rarr;S\u0026rarr;I(6c)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e41.4Gy/23f\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003ePembrolizumab:200mg ivgtt d1,3w\u003cbr\u003e\u0026nbsp;c: PTX: 50mg/m2 ivgtt d1,1w\u003cbr\u003eCarboplatin: AUC 2 ivgtt,1w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003epCR: 22.6%\u003cbr\u003e\u0026nbsp;R0: 90.3%\u003cbr\u003e\u0026nbsp;mPFS: 19.6m\u003cbr\u003e\u0026nbsp;2y-OS: 66.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"75\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003eUboha et al 2024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eNCT03490292\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eSingle-arm I/II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003ecT1N1/\u003cbr\u003e\u0026nbsp;T2-3N0-2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 297px;\"\u003e\n \u003cp\u003ecRCI(5w)\u0026rarr;I(2c)\u0026rarr;S\u0026rarr;I(6c)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e41.4Gy/23f\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003eAvelumab:10mg/kg ivgtt d1,2w\u003cbr\u003e\u0026nbsp;PTX: 50mg/m2 ivgtt d1,1w\u003cbr\u003eCarboplatin: AUC 2 ivgtt,1w\u003cbr\u003ec: Avelumab:10mg/kg ivgtt d1,2w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003epCR: 26.0%\u003cbr\u003e\u0026nbsp;R0: 79.0%\u003cbr\u003e\u0026nbsp;1y-RFS: 71.0%\u003cbr\u003e\u0026nbsp;1y-OS: 81.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"79\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003eBadgwell \u0026nbsp;et al 2024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eNCT04523818\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eSingle-arm I\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e\u0026ge;cT2/anyT+N+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 297px;\"\u003e\n \u003cp\u003ecsCRT(2w)\u0026rarr;CT(2m)\u0026rarr;S\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e30Gy/10f\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003eXELOX,3w/FLOT,2w\u003cbr\u003e\u0026nbsp;c: Cape: 850mg/m2\u003c/p\u003e\n \u003cp\u003e5-Fu: 225\u0026ndash;250 mg/m2/d\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003epCR: 10.0%\u003cbr\u003e\u0026nbsp;MPR: 35.0%\u003cbr\u003e\u0026nbsp;R0: 95.0%\u003cbr\u003e\u0026nbsp;ORC: 12.5%\u003cbr\u003e\u0026nbsp;1y-OS: 95%\u003cbr\u003e\u0026nbsp;2y-OS: 85%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"112\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003eKo et al 2025\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eNCT03165994\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eSingle-arm II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003ecT1-3Nx\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 297px;\"\u003e\n \u003cp\u003eA: s-mab(1c)\u0026rarr;cRC+s-mab(5w)\u0026rarr;s-mab(1c)\u0026rarr;S\u003cbr\u003e\u0026nbsp;B: s-mab(1c)\u0026rarr;cRC+s-mab(5w)\u0026rarr;S\u003cbr\u003e\u0026nbsp;C: cRC(5w)+s-mab(w1,2,4,6)\u0026rarr;S\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e50.4Gy/28f\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003eSotigalimab:0.3mg/kg ivgtt d1,3w/(w1,2,4,6)\u003cbr\u003e\u0026nbsp;PTX: 50mg/m2 ivgtt d1,1w\u003cbr\u003eCarboplatin: AUC 2 ivgtt,1w\u003cbr\u003ec: PTX: 130mg/m2 ivgtt d1,1w\u003cbr\u003eCarboplatin: AUC 2 ivgtt,1w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003epCR: 33.3%\u003cbr\u003e\u0026nbsp;MPR: 62.5%\u003cbr\u003e\u0026nbsp;R0: 83.3%\u003cbr\u003e\u0026nbsp;TRAEs\u0026ge;3: 78.8%\u003cbr\u003e\u0026nbsp;ORC: 0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"121\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" rowspan=\"4\" valign=\"top\" style=\"width: 1282px;\"\u003e\n \u003cp\u003e\u0026quot;c\u0026quot;TNM: clinical; \u0026quot;c\u0026quot;RCI: concurrent; 1\u0026quot;c\u0026quot;: cycle; C: chemotherapy; I: immune checkpoint inhibitors; R: radiotherapy; s: short-course; T: treatment; w: weeks; m: mouth; s-mab: Sotigalimab; S: surgery; Cape: capecitabine; OXA: oxaliplatin; PTX: paclitaxel; \u0026nbsp;ORC: operation-related complications;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"21\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd height=\"21\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd height=\"21\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd height=\"21\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cdiv align=\"center\"\u003e\u0026nbsp;\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"1155\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" style=\"width: 1155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 3\u0026nbsp;\u003c/strong\u003eOngoing clinical trials involving perioperative immunotherapy combined with chemoradiotherapy for resectable GEJ cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"19\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003eAuthor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003eTitle/No.of registration number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003eTrail information\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003eNo.of pts\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003eStage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 287px;\"\u003e\n \u003cp\u003eStudy design\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eRT dose\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 253px;\"\u003e\n \u003cp\u003eDrug regime\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eResults\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"56\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003eBlum et al\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eNCT03776487\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003eSingle-arm I/II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eT1-4N0-3M0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 287px;\"\u003e\n \u003cp\u003eC(4c)\u0026rarr;cRCI(O+Y,3c\u0026rarr;R+C,3c)\u0026rarr;S\u0026rarr;O(6c)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e45Gy/25f\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 253px;\"\u003e\n \u003cp\u003eOXA: 130mg/m\u003csup\u003e2\u003c/sup\u003e ivgtt d1,2w\u003cbr\u003e5-Fu: 2400mg/m\u003csup\u003e2\u0026nbsp;\u003c/sup\u003e48h iv,2w\u003cbr\u003e\u0026nbsp;Nivolumab(O): 240mg ivgtt,2w\u003cbr\u003e\u0026nbsp;Ipilimumab(Y): 1mg/kg,2w\u003cbr\u003ec: 5-Fu: 225mg/m\u003csup\u003e2\u003c/sup\u003e/d civ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eAEs\u003cbr\u003e\u0026nbsp;ORR\u003cbr\u003e\u0026nbsp;DFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"107\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003eChung et al\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eNCT04929392\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003eSingle-arm II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e40-60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eI-IVA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 287px;\"\u003e\n \u003cp\u003ecRCI(3w)\u0026rarr;I+L(3w)\u0026rarr;S\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e50.4Gy/28f\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 253px;\"\u003e\n \u003cp\u003eLenvatinib: 24mg/kg qd PO d1-21\u003cbr\u003e\u0026nbsp;Pembrolizumab: 200mg ivgtt d1,2w\u003cbr\u003ePTX: 50mg/m\u003csup\u003e2\u003c/sup\u003e ivgtt d1,1w\u003cbr\u003e\u0026nbsp;Carboplatin: AUC 2 ivgtt,1w\u003cbr\u003e\u0026nbsp;c: Pembrolizumab: 200mg ivgtt d1,2w\u003cbr\u003e\u0026nbsp; \u0026nbsp;PTX: 50mg/m2 ivgtt d1,1w\u003cbr\u003e\u0026nbsp; \u0026nbsp;Carboplatin: AUC 2 ivgtt,1w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003epCR\u003cbr\u003e\u0026nbsp;cCR\u003cbr\u003e\u0026nbsp;AEs\u003cbr\u003e\u0026nbsp;DFS\u003cbr\u003e\u0026nbsp;OS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"173\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003eWei et al\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eNCT05687357\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003emulticenter/\u003cbr\u003e\u0026nbsp;randomized/\u003cbr\u003e\u0026nbsp;open-label/IIb\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e140\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eT3-4aN+M0/\u003cbr\u003e\u0026nbsp;T4bNanyM0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 287px;\"\u003e\n \u003cp\u003eA:I(2c)+cRCI(4w)(I(1c)+S1(25d))\u0026rarr;CI(1c)\u0026rarr;S\u003cbr\u003e\u0026nbsp;\u0026rarr;IC(I(16c)+C(6c) (6c:SOX/Nab-p+S1,3c;S1,3c))\u003cbr\u003e\u0026nbsp;B:cRCI (4w)(S1(25d))\u0026rarr;C(1c)\u0026rarr;S\u003cbr\u003e\u0026nbsp;\u0026rarr;C(6c)(6c:SOX/Nab-p+S1,3c;S1,3c))\u003cbr\u003e\u0026nbsp;C:C(6c)\u0026rarr;S\u0026rarr;C(6c)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e45Gy/1.5f\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 253px;\"\u003e\n \u003cp\u003eTislelizumab:200mg ivgtt d1,3w\u003cbr\u003eOXA:130mg/m\u003csup\u003e2\u0026nbsp;\u003c/sup\u003eivgtt d1,3w\u003cbr\u003eNab-p:100-120mg/m\u003csup\u003e2\u003c/sup\u003e ivgtt,3w\u003cbr\u003e\u0026nbsp;S1:40-60mg bid PO d1-d14,3w\u003cbr\u003e\u0026nbsp;c:S1:40-60mg bid PO d1-d25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003epCR\u003cbr\u003e\u0026nbsp;EFS\u003cbr\u003e\u0026nbsp;OS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"103\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003eLin et al\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eNCT05918419\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003eSingle-arm II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003ecT3-4aN+M0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 287px;\"\u003e\n \u003cp\u003eCI(1c)\u0026rarr;cRCI(CI,2c;R,4w)\u0026rarr;S\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e45Gy/25f\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 253px;\"\u003e\n \u003cp\u003eSerplulimab: 300mg ivgtt d1,3w\u003cbr\u003eOXA: 130mg/m\u003csup\u003e2\u0026nbsp;\u003c/sup\u003eivgtt d1,3w\u003cbr\u003e\u0026nbsp;S1: 40-60mg bid PO d1-d14,3w\u003cbr\u003ec:OXA: 100mg/m\u003csup\u003e2\u003c/sup\u003e ivgtt d1,3w\u003cbr\u003e\u0026nbsp; \u0026nbsp;S1: 40-60mg bid PO d1-d14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003epCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"103\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003eJin et al\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eNCT06250894\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003eSingle-arm II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003ecT3-4aNxM0\u003cbr\u003e\u0026nbsp;(Siewert II-III)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 287px;\"\u003e\n \u003cp\u003ecRCI(CI,3c;R,2w)\u0026rarr;S\u0026rarr;CI(3-5c)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e36-40Gy/\u003cbr\u003e\u0026nbsp;18-22f\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 253px;\"\u003e\n \u003cp\u003eSintilimab: 200mg ivgtt d1,3w\u003cbr\u003eOXA: 130mg/m\u003csup\u003e2\u0026nbsp;\u003c/sup\u003eivgtt d1,3w\u003cbr\u003e\u0026nbsp;S1: 40-60mg bid PO d1-d14,3w\u003cbr\u003e\u0026nbsp;c: as above\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003epCR\u003cbr\u003e\u0026nbsp;ORR\u003cbr\u003e\u0026nbsp;MPR\u003cbr\u003e\u0026nbsp;DFS\u003cbr\u003e\u0026nbsp;OS\u003cbr\u003e\u0026nbsp;AEs\u003cbr\u003e\u0026nbsp;ORC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"131\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003eLi et al\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eNCT04061928\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003eSingle-arm I/II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003ecT3-4/N+M0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 287px;\"\u003e\n \u003cp\u003ecRCI(CI,2c;R,6w)\u0026rarr;I(2c)\u0026rarr;S\u0026rarr;CI(4c)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e45-50.4Gy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 253px;\"\u003e\n \u003cp\u003eToripalimab: 200mg ivgtt d1,3w\u003cbr\u003e\u0026nbsp;Unusable chemotherapy regimens and dosages\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eTRG\u003cbr\u003e\u0026nbsp;AEs\u003cbr\u003e\u0026nbsp;LC\u003cbr\u003e\u0026nbsp;DFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"75\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003eShitara et al\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eNCT07018570\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003eSingle-arm II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026ndash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eT2-4NanyM0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 287px;\"\u003e\n \u003cp\u003eCI(2c)\u0026rarr;sR(5d)\u0026rarr;CI(2c)\u0026rarr;S\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e25Gy/5f\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 253px;\"\u003e\n \u003cp\u003ePembrolizumab: 200mg ivgtt d1,3w\u003cbr\u003eDocetaxel: 50mg/m\u003csup\u003e2\u003c/sup\u003e ivgtt d1,2w\u003cbr\u003eOXA: 85mg/m\u003csup\u003e2\u003c/sup\u003e ivgtt d1,2w\u003cbr\u003eleucovorin: 200mg/m\u003csup\u003e2\u003c/sup\u003e ivgtt d1,2w\u003cbr\u003e5-Fu: 2600mg/m\u003csup\u003e2\u003c/sup\u003e ivgtt d1,2w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e3y-EFS\u003cbr\u003e\u0026nbsp;3y-OS\u003cbr\u003e\u0026nbsp;MPR\u003cbr\u003e\u0026nbsp;R0\u003cbr\u003e\u0026nbsp;AEs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"131\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003eZhu et al\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eNCT05505461\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003eSingle-arm II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003ecT3-4a/\u003cbr\u003e\u0026nbsp;N+M0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 287px;\"\u003e\n \u003cp\u003ecRI(I,2c;R,5w)\u0026rarr;CI(2c)\u0026rarr;S\u0026rarr;CI(4c)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e45-50.4Gy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 253px;\"\u003e\n \u003cp\u003ePD1,3w\u003cbr\u003eOXA: 130mg/m\u003csup\u003e2\u0026nbsp;\u003c/sup\u003eivgtt d1,3w\u003cbr\u003e\u0026nbsp;S1: 40-60mg bid PO d1-d14,3w\u003cbr\u003e\u0026nbsp;c: PD1,3w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003epCR\u003cbr\u003e\u0026nbsp;R0\u003cbr\u003e\u0026nbsp;PFS\u003cbr\u003e\u0026nbsp;AEs\u003cbr\u003e\u0026nbsp;ORC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"93\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" rowspan=\"3\" valign=\"top\" style=\"width: 1155px;\"\u003e\n \u003cp\u003e\u0026quot;c\u0026quot;TNM: clinical; \u0026quot;c\u0026quot;RCI: concurrent; 1\u0026quot;c\u0026quot;: cycle; C: chemotherapy; I: immune checkpoint inhibitors; R: radiotherapy; w: weeks; S: surgery; OXA: oxaliplatin; PTX: paclitaxel; \u0026nbsp;ORC: operation-related complications; AEs: Adverse events; \u0026nbsp; \u0026nbsp; LC: local control\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"21\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd height=\"21\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd height=\"21\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"GEJ adenocarcinoma, PD1, chemoradiotherapy, perioperative, short-course","lastPublishedDoi":"10.21203/rs.3.rs-7324963/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7324963/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground \u003c/strong\u003eLocally advanced HER2-negative gastroesophageal junction (GEJ) adenocarcinoma has limited treatment options with suboptimal outcomes. While immunotherapy combined with chemotherapy shows promise in advanced gastric cancer, the role of short-course radiotherapy (SCRT) in perioperative regimens remains underexplored. This trial evaluates a novel approach integrating tislelizumab (PD-1 inhibitor), SCRT, and SOX chemotherapy (S-1+oxaliplatin) for resectable GEJ adenocarcinoma.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods \u003c/strong\u003eThis prospective, single-arm, phase II trial (N=31) enrolls treatment-naive adults (18-75 years) with histologically confirmed, resectable Siewert type II/III GEJ adenocarcinoma (cT3-4aN+M0, AJCC 8th edition).Treatment Protocol: Neoadjuvant: 2 cycles of tislelizumab (200mg ivgtt, day 1)+SOX (S-1: BSA-based dose orally twice daily, days 1-14; oxaliplatin: 130mg/m\u003csup\u003e2 \u003c/sup\u003eivgtt, day 1; 21-day cycles). Short-course Radiotherapy: Intensity-modulated radiation therapy (IMRT; 25Gy/5f) to primary tumor and involved nodes, initiated 1-2 weeks post-chemotherapy. Consolidation: 2 additional cycles of tislelizumab+SOX within 11-18 days post-radiotherapy. Surgery: Radical gastrectomy with D2 lymphadenectomy 6-8 weeks after last neoadjuvant dose. Adjuvant: 4 cycles of SOX. Endpoints: Primary: Pathological complete response (pCR). Secondary: R0 resection rate, major pathological response (MPR), disease-free survival (DFS), overall survival (OS), safety (NCI CTCAE v5.0).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion \u003c/strong\u003eThis is the first trial to combine tislelizumab, SCRT, and SOX in perioperative GEJ adenocarcinoma. SCRT may enhance immunogenicity while reducing toxicity. If successful, it may expand treatment options for locally advanced HER2-negative GEJ adenocarcinoma. Limitations include single-arm design and small sample size.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial Registration \u003c/strong\u003eChinese Clinical Trial Registry (ChiCTR2500105244)\u003c/p\u003e","manuscriptTitle":"Tislelizumab plus short-course chemoradiotherapy perioperative treatment for HER2-negative, locally advanced gastroesophageal junction(GEJ) adenocarcinoma patients: study protocol for a prospective,single-arm phase 2 trail","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-08 08:24:07","doi":"10.21203/rs.3.rs-7324963/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-10-05T20:46:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"191793009540946215358347420264210521213","date":"2025-09-17T20:05:47+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-27T15:27:43+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-11T00:04:25+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-11T00:03:16+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2025-08-08T07:55:57+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"16f3595d-3c7c-45db-af30-694c60c52338","owner":[],"postedDate":"September 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-09-08T08:24:07+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-08 08:24:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7324963","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7324963","identity":"rs-7324963","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}