Surgery versus Carboplatin and Cisplatin followed by Radiotherapies and Surgery in Locally advanced Gastrointestinal tract Cancer

Surgery versus Carboplatin and Cisplatin followed by Radiotherapies and Surgery in Locally advanced Gastrointestinal tract Cancer | 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 Research Article Surgery versus Carboplatin and Cisplatin followed by Radiotherapies and Surgery in Locally advanced Gastrointestinal tract Cancer Xuxing Ye, Zhangqiang Wu, Weijun Teng, Yili Zhang, Yanping Chen, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5360326/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Gastrointestinal tract cancer is still prevalent in the world. Localized GI cancer treatment has greatly relied on surgery, even for locally advanced diseases. Aim and objectives: The goal of this study was to assess the prognosis of direct surgery and neoadjuvant chemoradiotherapy and surgery in patients with locally advanced GI tract cancers. Materials and Methods: A cross-sectional study was done on patients diagnosed with locally advanced GI cancers who were treated at Zhejiang Jinhua Guangfu Cancer Hospital between the period Jan 2021 to December 2023, total number of patients was 245. Patients were divided into two cohorts: DS of 107 and CRS of 138. Disease-free survival was the main predictor, while the others were considered secondary endpoints; these were overall survival, pathological complete response rate, postoperative complications, and R0 resection rate. Results: Disease-specific survival benefitted the CRS cohort relative to the DS cohort with a 2-year DFS of 76.81% compared to 65.42% (p= 0. 049). Median DFS also favored the CRS group (34. 7 months vs 28. 3 months, p = 0. 023). While not statistically significant, there was a trend towards improved OS in the CRS cohort (2-year OS rate: The results are as follows: 81. 16% versus 72. 90%, p=0.124. The CRS group had higher resection of R0 (92.8% vs 86.0%, p=0.082), and similarly, the local recurrence and distant metastases, although non-significant, were lower in this group. Conclusion: Locally advanced GI tract cancer appears to be improved from neoadjuvant-applied chemoradiotherapy followed by surgery rather than upfront surgery. Whereas, the trend about OS was in favor of the CRS approach, perhaps more time is required to observe these differences. The multimodal technique had reasonable presurgical toxicities and did not worsen the rate of postoperative complications. These findings support the consideration of neoadjuvant chemoradiotherapy can be recommended as a viable treatment approach for locally advanced GI tract cancers but future comparative prospective trials must be conducted to determine long-term survivals and quality of life patterns. neoadjuvant-applied chemoradiotherapy postoperative complications Gastrointestinal tract cancer GI cancer treatment multimodal technique Introduction Gastrointestinal (GI) tract cancers are a major health issue affecting millions of patients worldwide including a wide spectrum of neoplasms originating in organs of the digestive tract [ 1 ]. These cancers are; esophageal cancer, gastric cancer, colorectal, and anal cancer; they contribute significantly to morbidity and mortality from cancers around the world [ 2 ]. The therapy of locally advanced GI tract cancer has undergone dramatic changes in the last decades where emphasis has been given to the combination of surgery, chemotherapy, and radiotherapy [ 3 ]. In the past, the operation has remained the mainstay of therapy for locally advanced GI tract cancers [ 4 ]. But even assuming improvements in the surgical procedures and the management of the patients during the operation, the results of the patients who underwent surgery alone have been far from satisfactory, especially for those patients who have undergone surgery at an early stage of their diseases. Local recurrence and distant metastases continue to be major challenges in the management of colorectal cancer and the application of combined modality treatment that implies the integration of locoregional and systemic treatments for the comprehensive management of the disease [ 5 ]. Neoadjuvant therapy or pre-operative treatment aimed at performing chemotherapy and radiotherapy before resection of malignant tumors has been widely researched in GI tract cancers. This approach has several theoretical benefits on which it is based. First, neoadjuvant therapy can influence the tumour stage and size that can be removed by surgery fully. [ 6 ]. Second, it involves the possibility for the treatment of even tiny metastases, and thereby a chance to minimize the probability of the distant recurrence. [ 7 ]. Carboplatin and cisplatin platinum-containing regimens have become an important component of combined-modality treatment for GI tract cancers in the course of neoadjuvant therapy. [ 8 ]. These agents have shown effectiveness in many solid tumour types and there is evidence from many studies about synergy with other anticancer drugs as well as radiation. [ 8 ]. Carboplatin and cisplatin are the two main platinum-containing drugs used in chemotherapy. [ 9 ]; however, the choice between carboplatin and cisplatin can be influenced by tumour type, patient’s characteristics, side effects or toxicity profiles. The incorporation of radiotherapy in neoadjuvant modalities has additionally illuminated other prospects of local tumor control [ 10 ]. Improvements in radiation technology like IMRT and VMAT led to minimizing the dose to the healthy tissue and maximizing the dose to tumors [ 11 ]. This has made it possible to establish new approaches in dose escalation and find other ways of increasing the efficiency of combined modality treatments. There are several reasons why chemotherapy and radiotherapy may be given concurrently in a neoadjuvant strategy. Radiosensitivity can also be seen in chemotherapy treatment where it functions as an enhancer of radiation therapy [ 12 ]. Furthermore, the nonspecific cure of chemotherapy may also assist in eradicating micro metastases that may be out of the reach of localized radiotherapy [ 13 ]. The use of these modalities in combination might enhance local and distant disease control. Despite the possible advantages of neoadjuvant chemoradiotherapy, its application in the treatment of locally advanced GI tract cancer has undergone a lot of research and controversy [ 14 ]. The effects that neoadjuvant therapy has on the surgery is another subject that has to be studied. While neoadjuvant therapy may enhance the chance of negative surgical margin [ 15 ], these techniques may also change the tissue planes and may thus be much more technique-demanding intra-operatively [ 16 ]. To avoid postoperative complications and enhance the postoperative outcome it is significant to recognize and manage any possible negative consequences on it. However, the evaluation of the treatment response after providing neoadjuvant therapy has its strengths and weaknesses. Nevertheless, it remains difficult to predict and assess response to neoadjuvant therapy and ongoing efforts are being made to find better imaging modalities and molecular biomarkers. [ 17 ]. Other changes in GI tract cancer management are also applying the shift in oncology in general, including immunotherapy and target therapy. [ 18 ]. These techniques are not established in neoadjuvant protocols for GI tract cancers, although they have been utilized in several types of cancer [ 19 ]. Current research is underway trying to add new agents to the established chemoradiotherapy regimens to enhance survival rates. The perceptual aspects or ‘‘quality of life’’ issues are today considered important determinants in the management of cancer. This is very crucial in tract malignancies, as the treatments we offer impact features of life such as peristalsis, ingestion, and defecation. Therefore, the management of locally advanced GI tract cancers is dependent on several factors that call for a team effort from both medical professionals and patients. [ 20 ]. Multidisciplinary tumor boards containing surgeons, medical oncologists, radiation oncologists, radiologists, pathologists, and others are important in personalized medicine for cancer. Here some of the considerations are tumor location, stage, molecular characteristics, age, presence of the comorbidities, and, most importantly, preferences [ 21 , 22 ]. While advanced research progresses in revealing fundamental ideas as to the progression, detailing cell reactions to therapies, and identification of individual patient attributes that define the likelihood of progression and responses, the ultimate aim is to enhance approaches to managing these intricate cancers. This study aims to provide useful information about these endeavours to try and achieve better survival and quality of life for those with locally advanced cancer of the GI tract. Materials and Methods Study Design and Population This study was a retrospective analysis conducted at Zhejiang Jinhua Guangfu Cancer Hospital. We reviewed the medical records of patients diagnosed with locally advanced gastrointestinal tract cancer who underwent treatment between January 2021, and December 2023. The study protocol was approved by the Institutional Review Board of Zhejiang Jinhua Guangfu Cancer Hospital, and the requirement for informed consent was waived due to the retrospective nature of the study. A total of 245 patients met the inclusion criteria and were included in the analysis. The inclusion criteria were as follows: Age ≥ 18 years, histologically confirmed locally advanced gastrointestinal tract cancer (including esophageal, gastric, colorectal, and anal cancers), Clinical stage II-III according to the 8 th edition of the American Joint Committee on Cancer (AJCC) TNM staging system, Adequate organ function. Exclusion criteria included: Distant metastases at the time of diagnosis, Previous history of malignancy within the past 5 years, Contraindications to surgery or chemotherapy, and Incomplete medical records. Treatment Groups Patients were divided into two cohorts based on their treatment approach: Direct Surgery (DS) cohort (n = 107): Patients who underwent upfront surgery without neoadjuvant therapy. Chemoradiotherapy followed by Surgery (CRS) cohort (n = 138): Patients who received neoadjuvant platinum-based chemotherapy followed by radiotherapy and then surgery. Treatment Protocols Direct Surgery (DS) Cohort: Patients in this group underwent standard surgical procedures appropriate for their specific gastrointestinal cancer type and location. The surgical approaches included: Esophagectomy for esophageal cancer, Gastrectomy (total or subtotal) for gastric cancer, Colectomy or low anterior resection for colorectal cancer, and Abdominoperineal resection for anal cancer. The extent of lymph node dissection was determined based on the tumor location and stage. All surgeries were performed by experienced surgical oncologists following standardized protocols. Chemoradiotherapy followed by Surgery (CRS) Cohort: Patients in this group received a multimodal treatment approach consisting of: Neoadjuvant Chemotherapy: Patients received either carboplatin or cisplatin-based chemotherapy regimens. The choice between carboplatin and cisplatin was made by the treating oncologist based on individual patient factors such as renal function, comorbidities, and potential toxicity profiles. Each patient received only one platinum drug throughout their treatment course. Common regimens included, For upper gastrointestinal cancers: a) Carboplatin (AUC 5) on day 1 + 5-fluorouracil (5-FU) 1000 mg/m2/day continuous infusion on days 1-4, every 3 weeks for 2-3 cycles OR b) Cisplatin 75 mg/m2 on day 1 + 5-FU 1000 mg/m2/day continuous infusion on days 1-4, every 3 weeks for 2-3 cycles. For colorectal and anal cancers: a) Carboplatin (AUC 5) on day 1 + capecitabine 1000 mg/m2 twice daily on days 1-14, every 3 weeks for 2-3 cycles OR b) Cisplatin 75 mg/m2 on day 1 + capecitabine 1000 mg/m2 twice daily on days 1-14, every 3 weeks for 2-3 cycles. Radiotherapy: Following neoadjuvant chemotherapy, patients underwent radiotherapy. The radiation dose and fractionation were tailored to the specific cancer type and location. For example, for Esophageal cancer it was 41.4-50.4 Gy in 23-28 fractions, for Gastric cancer it was 45 Gy in 25 fractions, for Rectal cancer it was 45-50.4 Gy in 25-28 fractions, and for Anal cancer, it was 50.4-54 Gy in 28-30 fractions. Intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) techniques were used to deliver the prescribed dose while minimizing exposure to surrounding healthy tissues. Surgery : Approximately 6-8 weeks after completing chemoradiotherapy, patients underwent surgical resection following the same principles as the DS cohort. The timing of surgery was determined based on the patient's recovery from neoadjuvant therapy and restaging results. Outcome Measures The primary outcome measure was Disease-Free Survival (DFS), defined as the time from the date of surgery (for both cohorts) to the date of first recurrence, death from any cause, or last follow-up, whichever occurred first. Secondary outcome measures included: Overall Survival (OS): Time from the date of diagnosis to the date of death from any cause or last follow-up Pathological complete response rate in the CRS cohort Postoperative complication rates R0 resection rates (negative surgical margins) Statistical Analysis All statistical analyses were performed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± standard deviation or median (interquartile range) depending on the distribution of data. Categorical variables were presented as frequencies and percentages. A two-sided p-value < 0.05 was considered statistically significant for all analyses. Sample Size The sample size was determined based on the available patient population treated at Zhejiang Jinhua Guangfu Cancer Hospital during the specified period (2021-2023). With 245 patients (107 in the DS cohort and 138 in the CRS cohort). Ethical Considerations This study was conducted by the Declaration of Helsinki and Good Clinical Practice guidelines. The study protocol was approved by the Institutional Review Board of Zhejiang Jinhua Guangfu Cancer Hospital (approval number: ZJHGFCH-2024-001). Due to the retrospective nature of the study, the requirement for informed consent was waived. All patient data were de-identified and stored securely to ensure confidentiality. Results Patient Characteristics This retrospective analysis included 245 patients with locally advanced gastrointestinal tract cancer. The Direct Surgery (DS) cohort comprised 107 patients, while the Chemoradiotherapy followed by Surgery (CRS) cohort included 138 patients. There were no significant differences between the two groups in terms of age, sex, BMI, ECOG performance status, or cancer type distribution (Table 1 ). Table 1 Patient and treatment characteristics and comparison of demographic and tumor-related parameters of the patients Characteristic Direct Surgery (DS) Cohort (n = 107) Chemoradiotherapy followed by Surgery (CRS) Cohort (n = 138) p-value Age, years (mean ± SD) 62.5 ± 11.3 60.8 ± 10.7 0.230 Sex, n (%) 0.506 - Male 65 (60.7%) 78 (56.5%) - Female 42 (39.3%) 60 (43.5%) BMI, kg/m² (mean ± SD) 24.3 ± 3.8 23.9 ± 4.1 0.435 ECOG Performance Status, n (%) 0.777 0 45 (42.1%) 62 (44.9%) -1 52 (48.6%) 61 (44.2%) -2 10 (9.3%) 15 (10.9%) Cancer Type, n (%) 0.866 - Esophageal 28 (26.2%) 40 (29.0%) - Gastric 35 (32.7%) 48 (34.8%) - Colorectal 38 (35.5%) 42 (30.4%) - Anal 6 (5.6%) 8 (5.8%) Clinical Stage, n (%) 0.035* - II 49 (45.8%) 45 (32.6%) - III 58 (54.2%) 93 (67.4%) Type of Surgery, n (%) 0.866 -Esophagectomy 28 (26.2%) 40 (29.0%) -Gastrectomy 35 (32.7%) 48 (34.8%) -Colectomy/Low anterior resection 38 (35.5%) 42 (30.4%) -Abdominoperineal resection 6 (5.6%) 8 (5.8%) Operative time, minutes (mean ± SD) 245 ± 62 278 ± 71 0.001* Blood loss, mL (median [IQR]) 280 [150–450] 320 [180–520] 0.038* R0 resection rate , n (%) 92 (86.0%) 128 (92.8%) 0.082 Postoperative complications, n (%) 28 (26.2%) 42 (30.4%) 0.463 *Statistically significant (p < 0.05) SD: Standard Deviation; IQR: Interquartile Range However, the CRS cohort had a significantly higher proportion of patients with clinical stage III disease compared to the DS cohort (67.4% vs. 54.2%, p = 0.035). This difference in staging distribution should be considered when interpreting the outcomes. Treatment Outcomes: Surgical Outcomes: The CRS cohort had longer operative times (278 ± 71 min vs. 245 ± 62 min, p = 0.001) and higher intraoperative blood loss (median 320 mL vs. 280 mL, p = 0.038) compared to the DS cohort. Despite these differences, there was no significant difference in postoperative complication rates between the two groups (30.4% for CRS vs. 26.2% for DS, p = 0.463). The R0 resection rate was higher in the CRS group, although this difference did not reach statistical significance (92.8% vs. 86.0%, p = 0.082). Survival Outcomes: With a median follow-up of 28 months (range 12–48) in the DS cohort and 30 months (range 12–48) in the CRS cohort, the CRS group demonstrated improved survival outcomes (Table 2 ): Disease-Free Survival (DFS): The CRS cohort had a significantly higher 2-year DFS rate compared to the DS cohort (76.81% vs. 65.42%, p = 0.049). The median DFS was also significantly longer in the CRS group (34.7 months vs. 28.3 months, p = 0.023). Overall Survival (OS): Although not statistically significant, there was a trend towards improved OS in the CRS cohort. The 2-year OS rate was 81.16% in the CRS group compared to 72.90 in the DS group (p = 0.124). The median OS was 41.2 months in the CRS group versus 36.5 months in the DS group (p = 0.062). Recurrence Patterns: The CRS cohort showed lower rates of both local recurrence (10.1% vs. 16.8%, p = 0.124) and distant metastases (15.9% vs. 23.4%, p = 0.143) compared to the DS cohort, although these differences did not reach statistical significance. Toxicity: Tables 3 and 4 detail the acute toxicities observed during chemoradiotherapy and adjuvant chemotherapy in the CRS cohort. The most common grade 3–4 toxicities during chemoradiotherapy were neutropenia (5.8%), fatigue (5.8%), and nausea (5.1%). During adjuvant chemotherapy, the most frequent grade 3–4 toxicities were neutropenia (5.1%), fatigue (4.3%), and anemia (2.9%). No grade 4 toxicities were observed for most adverse events, indicating that the treatment was generally well-tolerated. This retrospective analysis suggests that a multimodal approach of neoadjuvant chemoradiotherapy followed by surgery may offer improved disease-free survival compared to upfront surgery in patients with locally advanced gastrointestinal tract cancer. While there was a trend towards improved overall survival with the multimodal approach, this difference did not reach statistical significance. The neoadjuvant approach was associated with acceptable toxicity profiles and did not significantly increase postoperative complications. Table 2 Local recurrence, distant metastases, overall survival, and disease-free survival rates of the patients Outcome Direct Surgery (DS) Cohort (n = 107) Chemoradiotherapy followed by Surgery (CRS) Cohort (n = 138) p-value Median follow-up, months (range) 28 (12–48) 30 (12–48) 0.624 Local recurrence, n (%) 18 (16.8%) 14 (10.1%) 0.124 Distant metastases, n (%) 25 (23.4%) 22 (15.9%) 0.143 2-year Overall Survival rate (%) 72.90% 81.16% 0.124 2-year Disease-Free Survival rate (%) 65.42% 76.81% 0.049* Median Overall Survival, months (95% CI) 36.5 (32.8–40.2) 41.2 (37.9–44.5) 0.062 Median Disease-Free Survival, months (95% CI) 28.3 (24.6–32.0) 34.7 (31.2–38.2) 0.023* *Statistically significant (p < 0.05) CI: Confidence Interval Table 3 The acute toxicity encountered during the chemoradiotherapy period for all patients Toxicity Grade 1 n (%) Grade 2 n (%) Grade 3 n (%) Grade 4 n (%) Hematological - Anemia 28 (20.3%) 15 (10.9%) 5 (3.6%) 0 (0%) - Neutropenia 35 (25.4%) 22 (15.9%) 8 (5.8%) 2 (1.4%) - Thrombocytopenia 20 (14.5%) 10 (7.2%) 3 (2.2%) 0 (0%) Gastrointestinal - Nausea 45 (32.6%) 25 (18.1%) 7 (5.1%) 0 (0%) - Vomiting 30 (21.7%) 18 (13.0%) 5 (3.6%) 0 (0%) - Diarrhea 25 (18.1%) 15 (10.9%) 4 (2.9%) 0 (0%) - Mucositis 22 (15.9%) 12 (8.7%) 3 (2.2%) 0 (0%) Other - Fatigue 50 (36.2%) 30 (21.7%) 8 (5.8%) 0 (0%) - Dermatitis 35 (25.4%) 20 (14.5%) 5 (3.6%) 0 (0%) - Nephrotoxicity 15 (10.9%) 8 (5.8%) 2 (1.4%) 0 (0%) Table 4 The acute toxicity related to the adjuvant chemotherapy period for the patients in the chemoradiotherapy + chemotherapy (CRT + CT) group Toxicity Grade 1 n (%) Grade 2 n (%) Grade 3 n (%) Grade 4 n (%) Hematological - Anemia 20 (14.5%) 12 (8.7%) 4 (2.9%) 0 (0%) - Neutropenia 25 (18.1%) 18 (13.0%) 7 (5.1%) 1 (0.7%) - Thrombocytopenia 15 (10.9%) 8 (5.8%) 2 (1.4%) 0 (0%) Gastrointestinal - Nausea 30 (21.7%) 20 (14.5%) 5 (3.6%) 0 (0%) - Vomiting 22 (15.9%) 15 (10.9%) 3 (2.2%) 0 (0%) - Diarrhea 18 (13.0%) 10 (7.2%) 2 (1.4%) 0 (0%) - Mucositis 15 (10.9%) 8 (5.8%) 1 (0.7%) 0 (0%) Other - Fatigue 35 (25.4%) 22 (15.9%) 6 (4.3%) 0 (0%) - Neuropathy 20 (14.5%) 12 (8.7%) 3 (2.2%) 0 (0%) - Nephrotoxicity 10 (7.2%) 5 (3.6%) 1 (0.7%) 0 (0%) Discussion This retrospective study showed the respective survivals between the use of DS and neo-chemoradiotherapy with subsequent CRS in treating localized gastrointestinal tract malignancies. The examination of 245 patients (107 in the DS cohort and 138 in the CRS cohort) who received Zhejiang Jinhua Guangfu Cancer Hospital treatment from 2021 and 2023. The target patient population consisted of patients diagnosed with different types of GI Cancer, such as esophageal, gastric, colon, and anal cancer. There was no significant difference in the cancer distribution for the two groups such that each comparison was balanced. However, there is a noteworthy difference between the CRS and DS cohort regarding clinical stage: a higher proportion of patients in the CRS cohort were diagnosed with clinical stage III (67. 4% vs. 54. 2%, p = 0. 035). The importance of the understanding of the results is the difference in staging distribution, which indicates the fact that patients with more developed diseases were treated with neoadjuvant therapy. This approach is consistent with treatment plans in which there is a combination of therapy and medication for higher stages of GI cancers. The CRS group needed longer operative time than the DS group (278 ± 71 min vs 245 ± 62 min, p = 0.001) together with higher intraoperative blood loss; (Median, 320 mL vs 280 mL, p = 0.038). These results are comparable with the studies that have established that there is enhanced surgical invasiveness after neoadjuvant treatment. For example, [ 23 , 24 ] Discussed neoadjuvant chemoradiotherapy in rectal cancer where patients had similar prolongation of their operative time and a similar increase in blood loss as patients not treated with preoperative chemoradiotherapy. However, it has to be noted that there was no substantial difference in intraoperative parameters between the two groups, except for the duration of operation, which was shorter in the case of DS (278 ± 71 min vs. 245 ± 62 min, p < 0. 001). This leaves an impression that neoadjuvant therapy did not up the ante in terms of surgical morbidity thus it is significant in the safety compliance of the patients as well as their quality of life. This finding agrees with a large retrospective study by [ 25 ] on esophageal cancer where they also did not report a significant increase in postoperative complications following neoadjuvant chemoradiotherapy. Although this did not reach statistical significance, the clinically relevant increase of the R0 resection rate in the CRS group (92. 8% vs. 86. 0%, p = 0. 082). Furthermore, the percentage of T3/4 tumors did not differ significantly between both groups. Surgical margin status is one of the important predictors of long-term oncological results. The increased R0 resection rate observed in the CRS cohort fully corresponds with the results of other investigations of various GICTs. For instance, a study of esophageal cancer done by [ 26 ] that involved a randomized controlled trial showed that a combination of neoadjuvant chemoradiotherapy and surgery enhanced R0 resection as compared to surgery alone registering 92% as opposed to 69% p < 0.001 Another study that gave short-term adjuvant chemotherapy after CRS was able to demonstrate improved DFS in their CRS population. DFS, with a 2-year DFS rate of 76. 81% in the CRS group vs 65. 42% in the surgery group, p = 0. 049, median DFS of 34. 7 months in the CRS group vs 28. 3 months in the surgery group, p = 0.023. These results strengthen the argument that neoadjuvant chemoradiotherapy should be more frequently applied in locally advanced gastrointestinal cancers. The increase in DFS noted in this study has been registered in several major randomized controlled trials as well as meta-analyses in various kinds of gastrointestinal cancers. For example, in a CROSS trial randomized patients with esophageal cancer [ 27 ] observed a statistically significant increase in DFS with neoadjuvant chemoradiotherapy. Likewise, in rectal cancer, the German CAO/ARO/AIO-94 trial [ 27 ] confirmed significantly better DFS in patients with preoperative chemoradiation than in those with postoperative treatment. In the present study, a trend toward a better overall survival was observed in the CRS group with a 2-year overall survival of 81.16% compared to 72. 90% in the DS group, the difference was nevertheless not statistically significant (p = 0. 124). Similar trends were noted where the median overall survival (OS) was also numerically better in the CRS group (41. Even though we found a statistically significant improvement in DFS, we did not find a statistically significant improvement in OS, a situation that is not strange when analyzing the results of neoadjuvant treatment in gastrointestinal cancers. This pattern has been established in multiple trials among others being the CROSS trial in esophageal cancer whereby the up. The study also reported reduced rates of local recurrence in the CRS group (10. 1% vs 16. 8%; P = 0.124) and distant metastases (15. 9% vs 23. 4%; P = 0.143) as compared to the DS group but these were not statistically significant. Such findings indicate that neoadjuvant chemoradiotherapy may assist in the management of locoregional and systemic diseases hence improved DFS noted in the CRS group. The trend of less local recurrence in the CRS group is complemented by several works dedicated to various types of gastrointestinal cancers. For instance in rectal cancer, a Dutch TME trial [ 28 , 29 ] established a considerable decrease in local relapse in patients who received preoperative radiotherapy. Likewise in Gastric cancer, [ 30 ] reported better local control with perioperative chemotherapy. There are some potential decreases in distant metastases in this work; it seems that neoadjuvant therapy has not only the local effect on tumor bulk but also the systemic effect. Neoadjuvant therapy is thought to be advantageous for reasons, including control of micrometastases and enhanced drug delivery to the primary tumor site owing to vascular permeability, which gains support from this study. The study also offered the investigators explicit findings of acute toxicities during chemoradiotherapy and adjuvant chemotherapy in the CRS group. The incidence of grade 3–4 toxicities during chemoradiotherapy was neutropenia at 5.8%, and fatigue at 5. 8%, and nausea 5. 1%. When receiving adjuvant chemotherapy, the most common serious toxicity that occurred in the first cycle was neutropenia at 5.1%, fatigue 4. At 3%, and anemia 2.9%. The above-mentioned toxicity profiles are quite in tandem with other published reports of neoadjuvant chemoradiotherapy in gastrointestinal cancers. For example, the CROSS trial of chemoradiotherapy for esophageal cancer revealed similar toxicities of hematologic and gastrointestinal origins. The lack of grade 4 toxicities for most AEs in this study raises the idea that the neoadjuvant approach to the presented treatment regimen was spared from critical side effects. The study has however a few important limitations that merit consideration, among them is the fact that the long-term toxicities as well as the quality-of-life issues were not assessed within the study. Such factors are important factors to pronounce the overall advantage of neoadjuvant therapy and seem to be driven into prospective trial. This study possesses several advantages: a rather large patient cohort, multiple types of gastrointestinal cancer, a clear description of surgical results, and toxic effects. Performing the surgeries with standardized treatment plans and qualified surgical teams contributes to the credibility of the results. However, there are also important limitations that should be mentioned: selective inclusion of patients that created the risk of selection bias and confounding factors. The findings may not extend to other hospitals or clients. Although including multiple gastrointestinal cancers gives a wide view of the results, it may obscure the effects of cancer-specific treatment. The median follow-up of 28–30 months might have been insufficient to assess the survival rate, especially in patients with better prognosis about their cancer type. In this work, a posteriori, there is argumentation towards the use of neoadjuvant chemoradiotherapy and then surgery for locally advanced gastrointestinal tract cancers. The significant improvement in disease-free survival, the trend towards better overall survival, and the acceptable toxicity profile suggest that this multimodal approach may offer benefits over upfront surgery alone. Conclusion The results of this study show the use of neoadjuvant chemoradiotherapy and then surgery as a viable approach to the management of locally advanced GI tract cancer. This approach seems to provide better disease control and yet results in little or no increase in the morbidity from the treatment. However, long-term prospective, randomized studies with better selection criteria, extended follow-up, and better definition of disease and quality of life parameters outcome need to be performed. Also, further study should involve the evaluation of patient populations that are most likely to benefit from this multimodal system and analysis of improvements to the neoadjuvant regime that can be made, including target therapies or immunotherapy. Declarations Funding: There is no source of funding for this study. Ethical Approved number The study protocol was approved by the Institutional Review Board of Zhejiang Jinhua Guangfu Cancer Hospital (approval number: ZJHGFCH-2024-001). Conflict Of Interest There is no conflict of Interest in this paper Author Contribution Xuxing Y and Zhangqiang Wu have contributed equally to this work and share the first authorship. Junmei Lin and Xiaobo Wang have contributed equally to this work and share the Correspondence author. Acknowledgement N/A References Vaes N, et al. Nerves in gastrointestinal cancer: from mechanism to modulations. Nat Reviews Gastroenterol Hepatol. 2022;19(12):768–84. Singh A. Global burden of five major types of gastrointestinal cancer. Gastroenterol Review/Przegląd Gastroenterologiczny, 2024. 19(1). Liang X, et al. Treatment strategies for metastatic gastric cancer: chemotherapy, palliative surgery or radiotherapy? Future Oncol. 2020;16(5):91–102. Rosenbaum MW, Gonzalez RS. Targeted therapy for upper gastrointestinal tract cancer: current and future prospects. Histopathology. 2021;78(1):148–61. Martin J, et al. Colorectal liver metastases: Current management and future perspectives. World J Clin Oncol. 2020;11(10):761. Byrd DR, et al. Current and future cancer staging after neoadjuvant treatment for solid tumors. Cancer J Clin. 2021;71(2):140–8. Body A, et al. Neoadjuvant therapy for locally advanced rectal cancer: recent advances and ongoing challenges. Clin Colorectal Cancer. 2021;20(1):29–41. Tsvetkova D, Ivanova S. Application of approved cisplatin derivatives in combination therapy against different cancer diseases. Molecules. 2022;27(8):2466. Ciarimboli G. Anticancer platinum drugs update . 2021, MDPI. p. 1637. Akakuru OU, et al. Chemotherapeutic nanomaterials in tumor boundary delineation: Prospects for effective tumor treatment. Acta Pharm Sinica B. 2022;12(6):2640–57. El-Sayed SM, et al. Stereotactic body radiation therapy for prostate cancer: a dosimetric comparison of IMRT and VMAT using flattening filter and flattening filter-free beams. Radiation and Environmental Biophysics; 2024. pp. 1–9. To NH, et al. Radiation therapy for triple-negative breast cancer: emerging role of microRNAs as biomarkers and radiosensitivity modifiers. A systematic review. Breast Cancer Res Treat. 2022;193(2):265–79. Kong X, et al. Nanomedicines inhibiting tumor metastasis and recurrence and their clinical applications. Nano Today. 2021;36:101004. Papaccio F, et al. Neoadjuvant chemotherapy in locally advanced rectal cancer. Cancers. 2020;12(12):3611. Devane LA, et al. The impact of neoadjuvant chemotherapy on margin re-excision in breast-conserving surgery. World J Surg. 2020;44:1547–51. Bray J, Eward W, Breen M. Defining the relevance of surgical margins. Part two: Strategies to improve prediction of recurrence risk. Vet Comp Oncol. 2023;21(2):145–58. Palumbo D, et al. Imaging in evaluation of response to neo-adjuvant treatment. Annals of Esophagus; 2020. p. 3. Kelly RJ et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of gastrointestinal cancer. J Immunother Cancer, 2023. 11(6). Petricevic B, et al. Neoadjuvant immunotherapy in gastrointestinal cancers–The new standard of care? Seminars in cancer biology. Elsevier; 2022. Shah MA, et al. Treatment of locally advanced esophageal carcinoma: ASCO guideline. J Clin Oncol. 2020;38(23):2677–94. Jeon SK, et al. Role of dedicated subspecialized radiologists in multidisciplinary team discussions on lower gastrointestinal tract cancers. Korean J Radiol. 2022;23(7):732. Neumann P-A, Berlet MW, Friess H. Surgical oncology in the age of multimodality therapy for cancer of the upper and lower gastrointestinal tract. Expert Rev Anticancer Ther. 2021;21(5):511–22. Yang J, et al. Effects of Neoadjuvant Radiotherapy on Postoperative Complications in Rectal Cancer: A Meta-Analysis. J Oncol. 2022;2022(1):8197701. Qin Q, et al. Radiation-induced injury on surgical margins: a clue to anastomotic leakage after rectal-cancer resection with neoadjuvant chemoradiotherapy? Gastroenterol Rep. 2019;7(2):98–106. Ólafsdóttir HS, et al. Postoperative complications after esophagectomy for cancer, neoadjuvant chemoradiotherapy compared to neoadjuvant chemotherapy: A single institutional cohort study. Clin Translational Radiation Oncol. 2023;40:100610. Cellini F, et al. Modern management of esophageal cancer: Radio-oncology in neoadjuvancy, adjuvancy and palliation. Cancers. 2022;14(2):431. Sprenger T, et al. The long-term influence of hospital and surgeon volume on local control and survival in the randomized German Rectal Cancer Trial CAO/ARO/AIO-94. Surg Oncol. 2020;35:200–5. Kapiteijn E, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345(9):638–46. Temmink SJ, et al. Surgical Outcomes after Radiotherapy in Rectal Cancer. Cancers. 2024;16(8):1539. Tokunaga M, et al. Perioperative chemotherapy for locally advanced gastric cancer in Japan: current and future perspectives. Surg Today. 2020;50:30–7. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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-5360326","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":374715421,"identity":"a2173b70-9c9d-40e7-ad28-cd7b636c913c","order_by":0,"name":"Xuxing Ye","email":"","orcid":"","institution":"Affiliated Jinhua Hospital, Jinhua Municipal Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xuxing","middleName":"","lastName":"Ye","suffix":""},{"id":374715422,"identity":"3d1e6379-e0b1-4cff-9a8e-eb86373055ad","order_by":1,"name":"Zhangqiang Wu","email":"","orcid":"","institution":"Guang Fu Oncology Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zhangqiang","middleName":"","lastName":"Wu","suffix":""},{"id":374715423,"identity":"556146a5-28f3-4811-8958-361b81347e74","order_by":2,"name":"Weijun Teng","email":"","orcid":"","institution":"Jinhua Municipal Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Weijun","middleName":"","lastName":"Teng","suffix":""},{"id":374715424,"identity":"117c8cf9-6219-4621-9749-b803b9333768","order_by":3,"name":"Yili Zhang","email":"","orcid":"","institution":"Affiliated Jinhua Hospital, Jinhua Municipal Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yili","middleName":"","lastName":"Zhang","suffix":""},{"id":374715425,"identity":"b916cc78-ce3c-46de-adae-aba73a868e0b","order_by":4,"name":"Yanping Chen","email":"","orcid":"","institution":"Jinhua Municipal Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yanping","middleName":"","lastName":"Chen","suffix":""},{"id":374715426,"identity":"d345d1d8-d581-44d4-a736-31bbce9b6602","order_by":5,"name":"Lin Sheng","email":"","orcid":"","institution":"Jinhua Municipal Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Lin","middleName":"","lastName":"Sheng","suffix":""},{"id":374715427,"identity":"c4fe70ae-0989-4122-acf4-06c025474c55","order_by":6,"name":"Junmei Lin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5ElEQVRIie3PsarCMBiG4b8E6pIaxxSk11AQnLyYBsFNcMzgUFDaQXTWwXsouDgmBOpgiquDgy5uQt2cDkfcXExGwbxb4H/4CIDL9YU1QYCo+R8mqCHPCR+biQ/Ck0stojDH/fisSxsCSAVT0YkP0A0vU2RBvH2igvTECgUDzlIfSD5LDCtVIdfbK1sprzyybRuorgojETeN2OK5cmTah5gOLUiQIZYq6I5YhuyIDDLVaT0J2JOlHkThBPdpokts/Auh1aaueQ8TspP3Bx9HJJ9/JkDF+xt/Pn/NpOYbl8vl+vH+AVHvVXOJZ8BIAAAAAElFTkSuQmCC","orcid":"","institution":"Jinhua Municipal Central Hospital","correspondingAuthor":true,"prefix":"","firstName":"Junmei","middleName":"","lastName":"Lin","suffix":""},{"id":374715428,"identity":"76d49551-7935-42d1-8bfe-547766e462ae","order_by":7,"name":"Xiaobo Wang","email":"","orcid":"","institution":"Zhejiang Chinese Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xiaobo","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2024-10-30 09:53:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5360326/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5360326/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":76888328,"identity":"c0d64296-3779-4024-8813-bb1f9034b419","added_by":"auto","created_at":"2025-02-21 19:38:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":923958,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5360326/v1/90bdbf77-7648-46fb-953d-acb079a7cf61.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Surgery versus Carboplatin and Cisplatin followed by Radiotherapies and Surgery in Locally advanced Gastrointestinal tract Cancer","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGastrointestinal (GI) tract cancers are a major health issue affecting millions of patients worldwide including a wide spectrum of neoplasms originating in organs of the digestive tract [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. These cancers are; esophageal cancer, gastric cancer, colorectal, and anal cancer; they contribute significantly to morbidity and mortality from cancers around the world [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The therapy of locally advanced GI tract cancer has undergone dramatic changes in the last decades where emphasis has been given to the combination of surgery, chemotherapy, and radiotherapy [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In the past, the operation has remained the mainstay of therapy for locally advanced GI tract cancers [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. But even assuming improvements in the surgical procedures and the management of the patients during the operation, the results of the patients who underwent surgery alone have been far from satisfactory, especially for those patients who have undergone surgery at an early stage of their diseases. Local recurrence and distant metastases continue to be major challenges in the management of colorectal cancer and the application of combined modality treatment that implies the integration of locoregional and systemic treatments for the comprehensive management of the disease [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNeoadjuvant therapy or pre-operative treatment aimed at performing chemotherapy and radiotherapy before resection of malignant tumors has been widely researched in GI tract cancers. This approach has several theoretical benefits on which it is based. First, neoadjuvant therapy can influence the tumour stage and size that can be removed by surgery fully. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Second, it involves the possibility for the treatment of even tiny metastases, and thereby a chance to minimize the probability of the distant recurrence. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Carboplatin and cisplatin platinum-containing regimens have become an important component of combined-modality treatment for GI tract cancers in the course of neoadjuvant therapy. [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. These agents have shown effectiveness in many solid tumour types and there is evidence from many studies about synergy with other anticancer drugs as well as radiation. [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Carboplatin and cisplatin are the two main platinum-containing drugs used in chemotherapy. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]; however, the choice between carboplatin and cisplatin can be influenced by tumour type, patient\u0026rsquo;s characteristics, side effects or toxicity profiles.\u003c/p\u003e \u003cp\u003eThe incorporation of radiotherapy in neoadjuvant modalities has additionally illuminated other prospects of local tumor control [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Improvements in radiation technology like IMRT and VMAT led to minimizing the dose to the healthy tissue and maximizing the dose to tumors [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. This has made it possible to establish new approaches in dose escalation and find other ways of increasing the efficiency of combined modality treatments. There are several reasons why chemotherapy and radiotherapy may be given concurrently in a neoadjuvant strategy. Radiosensitivity can also be seen in chemotherapy treatment where it functions as an enhancer of radiation therapy [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Furthermore, the nonspecific cure of chemotherapy may also assist in eradicating micro metastases that may be out of the reach of localized radiotherapy [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The use of these modalities in combination might enhance local and distant disease control. Despite the possible advantages of neoadjuvant chemoradiotherapy, its application in the treatment of locally advanced GI tract cancer has undergone a lot of research and controversy [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe effects that neoadjuvant therapy has on the surgery is another subject that has to be studied. While neoadjuvant therapy may enhance the chance of negative surgical margin [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], these techniques may also change the tissue planes and may thus be much more technique-demanding intra-operatively [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. To avoid postoperative complications and enhance the postoperative outcome it is significant to recognize and manage any possible negative consequences on it. However, the evaluation of the treatment response after providing neoadjuvant therapy has its strengths and weaknesses. Nevertheless, it remains difficult to predict and assess response to neoadjuvant therapy and ongoing efforts are being made to find better imaging modalities and molecular biomarkers. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Other changes in GI tract cancer management are also applying the shift in oncology in general, including immunotherapy and target therapy. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. These techniques are not established in neoadjuvant protocols for GI tract cancers, although they have been utilized in several types of cancer [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Current research is underway trying to add new agents to the established chemoradiotherapy regimens to enhance survival rates. The perceptual aspects or \u0026lsquo;\u0026lsquo;quality of life\u0026rsquo;\u0026rsquo; issues are today considered important determinants in the management of cancer. This is very crucial in tract malignancies, as the treatments we offer impact features of life such as peristalsis, ingestion, and defecation.\u003c/p\u003e \u003cp\u003eTherefore, the management of locally advanced GI tract cancers is dependent on several factors that call for a team effort from both medical professionals and patients. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Multidisciplinary tumor boards containing surgeons, medical oncologists, radiation oncologists, radiologists, pathologists, and others are important in personalized medicine for cancer. Here some of the considerations are tumor location, stage, molecular characteristics, age, presence of the comorbidities, and, most importantly, preferences [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhile advanced research progresses in revealing fundamental ideas as to the progression, detailing cell reactions to therapies, and identification of individual patient attributes that define the likelihood of progression and responses, the ultimate aim is to enhance approaches to managing these intricate cancers. This study aims to provide useful information about these endeavours to try and achieve better survival and quality of life for those with locally advanced cancer of the GI tract.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy Design and Population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was a retrospective analysis conducted at Zhejiang Jinhua Guangfu Cancer Hospital. We reviewed the medical records of patients diagnosed with locally advanced gastrointestinal tract cancer who underwent treatment between January 2021, and December 2023. The study protocol was approved by the Institutional Review Board of Zhejiang Jinhua Guangfu Cancer Hospital, and the requirement for informed consent was waived due to the retrospective nature of the study.\u003c/p\u003e\n\u003cp\u003eA total of 245 patients met the inclusion criteria and were included in the analysis. The inclusion criteria were as follows: Age ≥ 18 years, histologically confirmed locally advanced gastrointestinal tract cancer (including esophageal, gastric, colorectal, and anal cancers), Clinical stage II-III according to the 8\u003csup\u003eth\u003c/sup\u003e edition of the American Joint Committee on Cancer (AJCC) TNM staging system, Adequate organ function. Exclusion criteria included: Distant metastases at the time of diagnosis, Previous history of malignancy within the past 5 years, Contraindications to surgery or chemotherapy, and Incomplete medical records.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTreatment Groups\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients were divided into two cohorts based on their treatment approach:\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003eDirect Surgery (DS) cohort (n = 107): Patients who underwent upfront surgery without neoadjuvant therapy.\u003c/li\u003e\n \u003cli\u003eChemoradiotherapy followed by Surgery (CRS) cohort (n = 138): Patients who received neoadjuvant platinum-based chemotherapy followed by radiotherapy and then surgery.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003eTreatment Protocols\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDirect Surgery (DS) Cohort:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatients in this group underwent standard surgical procedures appropriate for their specific gastrointestinal cancer type and location. The surgical approaches included: Esophagectomy for esophageal cancer, Gastrectomy (total or subtotal) for gastric cancer, Colectomy or low anterior resection for colorectal cancer, and\u0026nbsp;Abdominoperineal resection for anal cancer. The extent of lymph node dissection was determined based on the tumor location and stage. All surgeries were performed by experienced surgical oncologists following standardized protocols.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eChemoradiotherapy followed by Surgery (CRS) Cohort:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatients in this group received a multimodal treatment approach consisting of:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNeoadjuvant Chemotherapy:\u003c/strong\u003e Patients received either carboplatin or cisplatin-based chemotherapy regimens. The choice between carboplatin and cisplatin was made by the treating oncologist based on individual patient factors such as renal function, comorbidities, and potential toxicity profiles. Each patient received only one platinum drug throughout their treatment course. Common regimens included, For upper gastrointestinal cancers: a) Carboplatin (AUC 5) on day 1 + 5-fluorouracil (5-FU) 1000 mg/m2/day continuous infusion on days 1-4, every 3 weeks for 2-3 cycles OR b) Cisplatin 75 mg/m2 on day 1 + 5-FU 1000 mg/m2/day continuous infusion on days 1-4, every 3 weeks for 2-3 cycles. For colorectal and anal cancers: a) Carboplatin (AUC 5) on day 1 + capecitabine 1000 mg/m2 twice daily on days 1-14, every 3 weeks for 2-3 cycles OR b) Cisplatin 75 mg/m2 on day 1 + capecitabine 1000 mg/m2 twice daily on days 1-14, every 3 weeks for 2-3 cycles.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRadiotherapy:\u003c/strong\u003e Following neoadjuvant chemotherapy, patients underwent radiotherapy. The radiation dose and fractionation were tailored to the specific cancer type and location. For example, for Esophageal cancer it was 41.4-50.4 Gy in 23-28 fractions, for Gastric cancer it was 45 Gy in 25 fractions, for Rectal cancer it was 45-50.4 Gy in 25-28 fractions, and for Anal cancer, it was 50.4-54 Gy in 28-30 fractions.\u003c/p\u003e\n\u003cp\u003eIntensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) techniques were used to deliver the prescribed dose while minimizing exposure to surrounding healthy tissues.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSurgery\u003c/strong\u003e: Approximately 6-8 weeks after completing chemoradiotherapy, patients underwent surgical resection following the same principles as the DS cohort. The timing of surgery was determined based on the patient's recovery from neoadjuvant therapy and restaging results.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcome Measures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome measure was Disease-Free Survival (DFS), defined as the time from the date of surgery (for both cohorts) to the date of first recurrence, death from any cause, or last follow-up, whichever occurred first.\u003c/p\u003e\n\u003cp\u003eSecondary outcome measures included:\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003eOverall Survival (OS): Time from the date of diagnosis to the date of death from any cause or last follow-up\u003c/li\u003e\n \u003cli\u003ePathological complete response rate in the CRS cohort\u003c/li\u003e\n \u003cli\u003ePostoperative complication rates\u003c/li\u003e\n \u003cli\u003eR0 resection rates (negative surgical margins)\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll statistical analyses were performed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± standard deviation or median (interquartile range) depending on the distribution of data. Categorical variables were presented as frequencies and percentages. A two-sided p-value \u0026lt; 0.05 was considered statistically significant for all analyses.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSample Size\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe sample size was determined based on the available patient population treated at Zhejiang Jinhua Guangfu Cancer Hospital during the specified period (2021-2023). With 245 patients (107 in the DS cohort and 138 in the CRS cohort).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Considerations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted by the Declaration of Helsinki and Good Clinical Practice guidelines. The study protocol was approved by the Institutional Review Board of Zhejiang Jinhua Guangfu Cancer Hospital (approval number: ZJHGFCH-2024-001). Due to the retrospective nature of the study, the requirement for informed consent was waived. All patient data were de-identified and stored securely to ensure confidentiality.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003ePatient Characteristics\u003c/h2\u003e \u003cp\u003eThis retrospective analysis included 245 patients with locally advanced gastrointestinal tract cancer. The Direct Surgery (DS) cohort comprised 107 patients, while the Chemoradiotherapy followed by Surgery (CRS) cohort included 138 patients. There were no significant differences between the two groups in terms of age, sex, BMI, ECOG performance status, or cancer type distribution (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient and treatment characteristics and comparison of demographic and tumor-related parameters of the patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDirect Surgery (DS) Cohort (n\u0026thinsp;=\u0026thinsp;107)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eChemoradiotherapy followed by Surgery (CRS) Cohort (n\u0026thinsp;=\u0026thinsp;138)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62.5\u0026thinsp;\u0026plusmn;\u0026thinsp;11.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60.8\u0026thinsp;\u0026plusmn;\u0026thinsp;10.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.230\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.506\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Male\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65 (60.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78 (56.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Female\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42 (39.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60 (43.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI, kg/m\u0026sup2; (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.435\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECOG Performance Status, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.777\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45 (42.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62 (44.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e-1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52 (48.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61 (44.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e-2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (9.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (10.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCancer Type, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.866\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Esophageal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (26.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 (29.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Gastric\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (32.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (34.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Colorectal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (35.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42 (30.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Anal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (5.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (5.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical Stage, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.035*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (45.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (32.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58 (54.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93 (67.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of Surgery, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.866\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e-Esophagectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (26.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 (29.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e-Gastrectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (32.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (34.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e-Colectomy/Low anterior resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (35.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42 (30.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e-Abdominoperineal resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (5.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (5.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOperative time, minutes (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e245\u0026thinsp;\u0026plusmn;\u0026thinsp;62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e278\u0026thinsp;\u0026plusmn;\u0026thinsp;71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood loss, mL (median [IQR])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e280 [150\u0026ndash;450]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e320 [180\u0026ndash;520]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.038*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR0 resection rate\u003c/p\u003e \u003cp\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92 (86.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e128 (92.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.082\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative complications, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (26.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42 (30.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.463\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e*Statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) SD: Standard Deviation; IQR: Interquartile Range\u003c/p\u003e \u003cp\u003eHowever, the CRS cohort had a significantly higher proportion of patients with clinical stage III disease compared to the DS cohort (67.4% vs. 54.2%, p\u0026thinsp;=\u0026thinsp;0.035). This difference in staging distribution should be considered when interpreting the outcomes.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eTreatment Outcomes:\u003c/h2\u003e \u003cp\u003eSurgical Outcomes: The CRS cohort had longer operative times (278\u0026thinsp;\u0026plusmn;\u0026thinsp;71 min vs. 245\u0026thinsp;\u0026plusmn;\u0026thinsp;62 min, p\u0026thinsp;=\u0026thinsp;0.001) and higher intraoperative blood loss (median 320 mL vs. 280 mL, p\u0026thinsp;=\u0026thinsp;0.038) compared to the DS cohort. Despite these differences, there was no significant difference in postoperative complication rates between the two groups (30.4% for CRS vs. 26.2% for DS, p\u0026thinsp;=\u0026thinsp;0.463). The R0 resection rate was higher in the CRS group, although this difference did not reach statistical significance (92.8% vs. 86.0%, p\u0026thinsp;=\u0026thinsp;0.082).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eSurvival Outcomes:\u003c/h2\u003e \u003cp\u003eWith a median follow-up of 28 months (range 12\u0026ndash;48) in the DS cohort and 30 months (range 12\u0026ndash;48) in the CRS cohort, the CRS group demonstrated improved survival outcomes (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e):\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eDisease-Free Survival (DFS): The CRS cohort had a significantly higher 2-year DFS rate compared to the DS cohort (76.81% vs. 65.42%, p\u0026thinsp;=\u0026thinsp;0.049). The median DFS was also significantly longer in the CRS group (34.7 months vs. 28.3 months, p\u0026thinsp;=\u0026thinsp;0.023).\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eOverall Survival (OS): Although not statistically significant, there was a trend towards improved OS in the CRS cohort. The 2-year OS rate was 81.16% in the CRS group compared to 72.90 in the DS group (p\u0026thinsp;=\u0026thinsp;0.124). The median OS was 41.2 months in the CRS group versus 36.5 months in the DS group (p\u0026thinsp;=\u0026thinsp;0.062).\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eRecurrence Patterns:\u003c/h2\u003e \u003cp\u003eThe CRS cohort showed lower rates of both local recurrence (10.1% vs. 16.8%, p\u0026thinsp;=\u0026thinsp;0.124) and distant metastases (15.9% vs. 23.4%, p\u0026thinsp;=\u0026thinsp;0.143) compared to the DS cohort, although these differences did not reach statistical significance.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eToxicity:\u003c/h2\u003e \u003cp\u003eTables\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e detail the acute toxicities observed during chemoradiotherapy and adjuvant chemotherapy in the CRS cohort. The most common grade 3\u0026ndash;4 toxicities during chemoradiotherapy were neutropenia (5.8%), fatigue (5.8%), and nausea (5.1%). During adjuvant chemotherapy, the most frequent grade 3\u0026ndash;4 toxicities were neutropenia (5.1%), fatigue (4.3%), and anemia (2.9%). No grade 4 toxicities were observed for most adverse events, indicating that the treatment was generally well-tolerated.\u003c/p\u003e \u003cp\u003e This retrospective analysis suggests that a multimodal approach of neoadjuvant chemoradiotherapy followed by surgery may offer improved disease-free survival compared to upfront surgery in patients with locally advanced gastrointestinal tract cancer. While there was a trend towards improved overall survival with the multimodal approach, this difference did not reach statistical significance. The neoadjuvant approach was associated with acceptable toxicity profiles and did not significantly increase postoperative complications.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLocal recurrence, distant metastases, overall survival, and disease-free survival rates of the patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDirect Surgery (DS) Cohort (n\u0026thinsp;=\u0026thinsp;107)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eChemoradiotherapy followed by Surgery (CRS) Cohort (n\u0026thinsp;=\u0026thinsp;138)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian follow-up, months (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (12\u0026ndash;48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (12\u0026ndash;48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.624\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLocal recurrence, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (16.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (10.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.124\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDistant metastases, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (23.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (15.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.143\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2-year Overall Survival rate (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72.90%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81.16%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.124\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2-year Disease-Free Survival rate (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65.42%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76.81%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.049*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian Overall Survival, months (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36.5 (32.8\u0026ndash;40.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41.2 (37.9\u0026ndash;44.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.062\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian Disease-Free Survival, months (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.3 (24.6\u0026ndash;32.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34.7 (31.2\u0026ndash;38.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.023*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e*Statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) CI: Confidence Interval\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe acute toxicity encountered during the chemoradiotherapy period for all patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eToxicity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGrade 1 n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGrade 2 n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGrade 3 n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGrade 4 n (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHematological\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Anemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e28 (20.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15 (10.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5 (3.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Neutropenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e35 (25.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22 (15.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8 (5.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (1.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Thrombocytopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20 (14.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (7.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3 (2.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Nausea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e45 (32.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25 (18.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7 (5.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Vomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30 (21.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18 (13.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5 (3.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Diarrhea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e25 (18.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15 (10.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4 (2.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Mucositis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22 (15.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (8.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3 (2.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Fatigue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e50 (36.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30 (21.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8 (5.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Dermatitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e35 (25.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20 (14.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5 (3.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Nephrotoxicity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15 (10.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (5.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2 (1.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe acute toxicity related to the adjuvant chemotherapy period for the patients in the chemoradiotherapy\u0026thinsp;+\u0026thinsp;chemotherapy (CRT\u0026thinsp;+\u0026thinsp;CT) group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eToxicity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGrade 1 n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGrade 2 n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGrade 3 n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGrade 4 n (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHematological\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Anemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20 (14.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (8.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4 (2.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Neutropenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e25 (18.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18 (13.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7 (5.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (0.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Thrombocytopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15 (10.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (5.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2 (1.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Nausea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30 (21.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20 (14.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5 (3.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Vomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22 (15.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15 (10.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3 (2.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Diarrhea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18 (13.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (7.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2 (1.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Mucositis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15 (10.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (5.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1 (0.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Fatigue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e35 (25.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22 (15.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Neuropathy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20 (14.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (8.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3 (2.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Nephrotoxicity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10 (7.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (3.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1 (0.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis retrospective study showed the respective survivals between the use of DS and neo-chemoradiotherapy with subsequent CRS in treating localized gastrointestinal tract malignancies. The examination of 245 patients (107 in the DS cohort and 138 in the CRS cohort) who received Zhejiang Jinhua Guangfu Cancer Hospital treatment from 2021 and 2023. The target patient population consisted of patients diagnosed with different types of GI Cancer, such as esophageal, gastric, colon, and anal cancer. There was no significant difference in the cancer distribution for the two groups such that each comparison was balanced. However, there is a noteworthy difference between the CRS and DS cohort regarding clinical stage: a higher proportion of patients in the CRS cohort were diagnosed with clinical stage III (67. 4% vs. 54. 2%, p\u0026thinsp;=\u0026thinsp;0. 035). The importance of the understanding of the results is the difference in staging distribution, which indicates the fact that patients with more developed diseases were treated with neoadjuvant therapy. This approach is consistent with treatment plans in which there is a combination of therapy and medication for higher stages of GI cancers. The CRS group needed longer operative time than the DS group (278\u0026thinsp;\u0026plusmn;\u0026thinsp;71 min vs 245\u0026thinsp;\u0026plusmn;\u0026thinsp;62 min, p\u0026thinsp;=\u0026thinsp;0.001) together with higher intraoperative blood loss; (Median, 320 mL vs 280 mL, p\u0026thinsp;=\u0026thinsp;0.038). These results are comparable with the studies that have established that there is enhanced surgical invasiveness after neoadjuvant treatment. For example, [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] Discussed neoadjuvant chemoradiotherapy in rectal cancer where patients had similar prolongation of their operative time and a similar increase in blood loss as patients not treated with preoperative chemoradiotherapy.\u003c/p\u003e \u003cp\u003eHowever, it has to be noted that there was no substantial difference in intraoperative parameters between the two groups, except for the duration of operation, which was shorter in the case of DS (278\u0026thinsp;\u0026plusmn;\u0026thinsp;71 min vs. 245\u0026thinsp;\u0026plusmn;\u0026thinsp;62 min, p\u0026thinsp;\u0026lt;\u0026thinsp;0. 001). This leaves an impression that neoadjuvant therapy did not up the ante in terms of surgical morbidity thus it is significant in the safety compliance of the patients as well as their quality of life. This finding agrees with a large retrospective study by [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] on esophageal cancer where they also did not report a significant increase in postoperative complications following neoadjuvant chemoradiotherapy. Although this did not reach statistical significance, the clinically relevant increase of the R0 resection rate in the CRS group (92. 8% vs. 86. 0%, p\u0026thinsp;=\u0026thinsp;0. 082). Furthermore, the percentage of T3/4 tumors did not differ significantly between both groups. Surgical margin status is one of the important predictors of long-term oncological results. The increased R0 resection rate observed in the CRS cohort fully corresponds with the results of other investigations of various GICTs. For instance, a study of esophageal cancer done by [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] that involved a randomized controlled trial showed that a combination of neoadjuvant chemoradiotherapy and surgery enhanced R0 resection as compared to surgery alone registering 92% as opposed to 69% p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 Another study that gave short-term adjuvant chemotherapy after CRS was able to demonstrate improved DFS in their CRS population. DFS, with a 2-year DFS rate of 76. 81% in the CRS group vs 65. 42% in the surgery group, p\u0026thinsp;=\u0026thinsp;0. 049, median DFS of 34. 7 months in the CRS group vs 28. 3 months in the surgery group, p\u0026thinsp;=\u0026thinsp;0.023. These results strengthen the argument that neoadjuvant chemoradiotherapy should be more frequently applied in locally advanced gastrointestinal cancers. The increase in DFS noted in this study has been registered in several major randomized controlled trials as well as meta-analyses in various kinds of gastrointestinal cancers. For example, in a CROSS trial randomized patients with esophageal cancer [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] observed a statistically significant increase in DFS with neoadjuvant chemoradiotherapy. Likewise, in rectal cancer, the German CAO/ARO/AIO-94 trial [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] confirmed significantly better DFS in patients with preoperative chemoradiation than in those with postoperative treatment.\u003c/p\u003e \u003cp\u003eIn the present study, a trend toward a better overall survival was observed in the CRS group with a 2-year overall survival of 81.16% compared to 72. 90% in the DS group, the difference was nevertheless not statistically significant (p\u0026thinsp;=\u0026thinsp;0. 124). Similar trends were noted where the median overall survival (OS) was also numerically better in the CRS group (41. Even though we found a statistically significant improvement in DFS, we did not find a statistically significant improvement in OS, a situation that is not strange when analyzing the results of neoadjuvant treatment in gastrointestinal cancers. This pattern has been established in multiple trials among others being the CROSS trial in esophageal cancer whereby the up. The study also reported reduced rates of local recurrence in the CRS group (10. 1% vs 16. 8%; P\u0026thinsp;=\u0026thinsp;0.124) and distant metastases (15. 9% vs 23. 4%; P\u0026thinsp;=\u0026thinsp;0.143) as compared to the DS group but these were not statistically significant. Such findings indicate that neoadjuvant chemoradiotherapy may assist in the management of locoregional and systemic diseases hence improved DFS noted in the CRS group.\u003c/p\u003e \u003cp\u003eThe trend of less local recurrence in the CRS group is complemented by several works dedicated to various types of gastrointestinal cancers. For instance in rectal cancer, a Dutch TME trial [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] established a considerable decrease in local relapse in patients who received preoperative radiotherapy. Likewise in Gastric cancer, [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] reported better local control with perioperative chemotherapy. There are some potential decreases in distant metastases in this work; it seems that neoadjuvant therapy has not only the local effect on tumor bulk but also the systemic effect. Neoadjuvant therapy is thought to be advantageous for reasons, including control of micrometastases and enhanced drug delivery to the primary tumor site owing to vascular permeability, which gains support from this study.\u003c/p\u003e \u003cp\u003eThe study also offered the investigators explicit findings of acute toxicities during chemoradiotherapy and adjuvant chemotherapy in the CRS group. The incidence of grade 3\u0026ndash;4 toxicities during chemoradiotherapy was neutropenia at 5.8%, and fatigue at 5. 8%, and nausea 5. 1%. When receiving adjuvant chemotherapy, the most common serious toxicity that occurred in the first cycle was neutropenia at 5.1%, fatigue 4. At 3%, and anemia 2.9%. The above-mentioned toxicity profiles are quite in tandem with other published reports of neoadjuvant chemoradiotherapy in gastrointestinal cancers. For example, the CROSS trial of chemoradiotherapy for esophageal cancer revealed similar toxicities of hematologic and gastrointestinal origins. The lack of grade 4 toxicities for most AEs in this study raises the idea that the neoadjuvant approach to the presented treatment regimen was spared from critical side effects. The study has however a few important limitations that merit consideration, among them is the fact that the long-term toxicities as well as the quality-of-life issues were not assessed within the study. Such factors are important factors to pronounce the overall advantage of neoadjuvant therapy and seem to be driven into prospective trial. This study possesses several advantages: a rather large patient cohort, multiple types of gastrointestinal cancer, a clear description of surgical results, and toxic effects. Performing the surgeries with standardized treatment plans and qualified surgical teams contributes to the credibility of the results. However, there are also important limitations that should be mentioned: selective inclusion of patients that created the risk of selection bias and confounding factors. The findings may not extend to other hospitals or clients. Although including multiple gastrointestinal cancers gives a wide view of the results, it may obscure the effects of cancer-specific treatment. The median follow-up of 28\u0026ndash;30 months might have been insufficient to assess the survival rate, especially in patients with better prognosis about their cancer type. In this work, a posteriori, there is argumentation towards the use of neoadjuvant chemoradiotherapy and then surgery for locally advanced gastrointestinal tract cancers. The significant improvement in disease-free survival, the trend towards better overall survival, and the acceptable toxicity profile suggest that this multimodal approach may offer benefits over upfront surgery alone.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe results of this study show the use of neoadjuvant chemoradiotherapy and then surgery as a viable approach to the management of locally advanced GI tract cancer. This approach seems to provide better disease control and yet results in little or no increase in the morbidity from the treatment. However, long-term prospective, randomized studies with better selection criteria, extended follow-up, and better definition of disease and quality of life parameters outcome need to be performed. Also, further study should involve the evaluation of patient populations that are most likely to benefit from this multimodal system and analysis of improvements to the neoadjuvant regime that can be made, including target therapies or immunotherapy.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere is no source of funding for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approved number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by the Institutional Review Board of Zhejiang Jinhua Guangfu Cancer Hospital (approval number: ZJHGFCH-2024-001).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict Of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere is no conflict of Interest in this paper\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eXuxing Y and Zhangqiang Wu have contributed equally to this work and share the first authorship. Junmei Lin and Xiaobo Wang have contributed equally to this work and share the Correspondence author.\u0026nbsp;\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eN/A\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eVaes N, et al. Nerves in gastrointestinal cancer: from mechanism to modulations. Nat Reviews Gastroenterol Hepatol. 2022;19(12):768\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSingh A. Global burden of five major types of gastrointestinal cancer. Gastroenterol Review/Przegląd Gastroenterologiczny, 2024. 19(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiang X, et al. Treatment strategies for metastatic gastric cancer: chemotherapy, palliative surgery or radiotherapy? Future Oncol. 2020;16(5):91\u0026ndash;102.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRosenbaum MW, Gonzalez RS. Targeted therapy for upper gastrointestinal tract cancer: current and future prospects. Histopathology. 2021;78(1):148\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMartin J, et al. Colorectal liver metastases: Current management and future perspectives. World J Clin Oncol. 2020;11(10):761.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eByrd DR, et al. Current and future cancer staging after neoadjuvant treatment for solid tumors. Cancer J Clin. 2021;71(2):140\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBody A, et al. Neoadjuvant therapy for locally advanced rectal cancer: recent advances and ongoing challenges. Clin Colorectal Cancer. 2021;20(1):29\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTsvetkova D, Ivanova S. Application of approved cisplatin derivatives in combination therapy against different cancer diseases. Molecules. 2022;27(8):2466.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCiarimboli G. \u003cem\u003eAnticancer platinum drugs update\u003c/em\u003e. 2021, MDPI. p. 1637.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAkakuru OU, et al. Chemotherapeutic nanomaterials in tumor boundary delineation: Prospects for effective tumor treatment. Acta Pharm Sinica B. 2022;12(6):2640\u0026ndash;57.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEl-Sayed SM, et al. Stereotactic body radiation therapy for prostate cancer: a dosimetric comparison of IMRT and VMAT using flattening filter and flattening filter-free beams. Radiation and Environmental Biophysics; 2024. pp. 1\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTo NH, et al. Radiation therapy for triple-negative breast cancer: emerging role of microRNAs as biomarkers and radiosensitivity modifiers. A systematic review. Breast Cancer Res Treat. 2022;193(2):265\u0026ndash;79.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKong X, et al. Nanomedicines inhibiting tumor metastasis and recurrence and their clinical applications. Nano Today. 2021;36:101004.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePapaccio F, et al. Neoadjuvant chemotherapy in locally advanced rectal cancer. Cancers. 2020;12(12):3611.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDevane LA, et al. The impact of neoadjuvant chemotherapy on margin re-excision in breast-conserving surgery. World J Surg. 2020;44:1547\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBray J, Eward W, Breen M. Defining the relevance of surgical margins. Part two: Strategies to improve prediction of recurrence risk. Vet Comp Oncol. 2023;21(2):145\u0026ndash;58.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePalumbo D, et al. Imaging in evaluation of response to neo-adjuvant treatment. Annals of Esophagus; 2020. p. 3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKelly RJ et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of gastrointestinal cancer. J Immunother Cancer, 2023. 11(6).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePetricevic B, et al. Neoadjuvant immunotherapy in gastrointestinal cancers\u0026ndash;The new standard of care? Seminars in cancer biology. Elsevier; 2022.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShah MA, et al. Treatment of locally advanced esophageal carcinoma: ASCO guideline. J Clin Oncol. 2020;38(23):2677\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJeon SK, et al. Role of dedicated subspecialized radiologists in multidisciplinary team discussions on lower gastrointestinal tract cancers. Korean J Radiol. 2022;23(7):732.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNeumann P-A, Berlet MW, Friess H. Surgical oncology in the age of multimodality therapy for cancer of the upper and lower gastrointestinal tract. Expert Rev Anticancer Ther. 2021;21(5):511\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang J, et al. Effects of Neoadjuvant Radiotherapy on Postoperative Complications in Rectal Cancer: A Meta-Analysis. J Oncol. 2022;2022(1):8197701.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQin Q, et al. Radiation-induced injury on surgical margins: a clue to anastomotic leakage after rectal-cancer resection with neoadjuvant chemoradiotherapy? Gastroenterol Rep. 2019;7(2):98\u0026ndash;106.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u0026Oacute;lafsd\u0026oacute;ttir HS, et al. Postoperative complications after esophagectomy for cancer, neoadjuvant chemoradiotherapy compared to neoadjuvant chemotherapy: A single institutional cohort study. Clin Translational Radiation Oncol. 2023;40:100610.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCellini F, et al. Modern management of esophageal cancer: Radio-oncology in neoadjuvancy, adjuvancy and palliation. Cancers. 2022;14(2):431.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSprenger T, et al. The long-term influence of hospital and surgeon volume on local control and survival in the randomized German Rectal Cancer Trial CAO/ARO/AIO-94. Surg Oncol. 2020;35:200\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKapiteijn E, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345(9):638\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTemmink SJ, et al. Surgical Outcomes after Radiotherapy in Rectal Cancer. Cancers. 2024;16(8):1539.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTokunaga M, et al. Perioperative chemotherapy for locally advanced gastric cancer in Japan: current and future perspectives. Surg Today. 2020;50:30\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"neoadjuvant-applied chemoradiotherapy, postoperative complications, Gastrointestinal tract cancer, GI cancer treatment, multimodal technique","lastPublishedDoi":"10.21203/rs.3.rs-5360326/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5360326/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Gastrointestinal tract cancer is still prevalent in the world. Localized GI cancer treatment has greatly relied on surgery, even for locally advanced diseases. Aim and objectives: The goal of this study was to assess the prognosis of direct surgery and neoadjuvant chemoradiotherapy and surgery in patients with locally advanced GI tract cancers.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and Methods:\u003c/strong\u003e A cross-sectional study was done on patients diagnosed with locally advanced GI cancers who were treated at Zhejiang Jinhua Guangfu Cancer Hospital between the period Jan 2021 to December 2023, total number of patients was 245. Patients were divided into two cohorts: DS of 107 and CRS of 138. Disease-free survival was the main predictor, while the others were considered secondary endpoints; these were overall survival, pathological complete response rate, postoperative complications, and R0 resection rate.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Disease-specific survival benefitted the CRS cohort relative to the DS cohort with a 2-year DFS of 76.81% compared to 65.42% (p= 0. 049). Median DFS also favored the CRS group (34. 7 months vs 28. 3 months, p = 0. 023). While not statistically significant, there was a trend towards improved OS in the CRS cohort (2-year OS rate: The results are as follows: 81. 16% versus 72. 90%, p=0.124. The CRS group had higher resection of R0 (92.8% vs 86.0%, p=0.082), and similarly, the local recurrence and distant metastases, although non-significant, were lower in this group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Locally advanced GI tract cancer appears to be improved from neoadjuvant-applied chemoradiotherapy followed by surgery rather than upfront surgery. Whereas, the trend about OS was in favor of the CRS approach, perhaps more time is required to observe these differences. The multimodal technique had reasonable presurgical toxicities and did not worsen the rate of postoperative complications. These findings support the consideration of neoadjuvant chemoradiotherapy can be recommended as a viable treatment approach for locally advanced GI tract cancers but future comparative prospective trials must be conducted to determine long-term survivals and quality of life patterns.\u003c/p\u003e","manuscriptTitle":"Surgery versus Carboplatin and Cisplatin followed by Radiotherapies and Surgery in Locally advanced Gastrointestinal tract Cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-12 15:16:19","doi":"10.21203/rs.3.rs-5360326/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dbdabdbd-0aae-4df2-9b8f-07cb1fdce2f2","owner":[],"postedDate":"November 12th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-02-21T19:38:11+00:00","versionOfRecord":[],"versionCreatedAt":"2024-11-12 15:16:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5360326","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5360326","identity":"rs-5360326","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}