Impact of neoadjuvant chemoradiotherapy (NACRT) vs neoadjuvant chemotherapy (NACT) on anastomotic complications in gastric carcinoma.

Impact of neoadjuvant chemoradiotherapy (NACRT) vs neoadjuvant chemotherapy (NACT) on anastomotic complications in gastric carcinoma. | 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 Impact of neoadjuvant chemoradiotherapy (NACRT) vs neoadjuvant chemotherapy (NACT) on anastomotic complications in gastric carcinoma. Shagun Misra, Rakesh Shaghanti, Sreenivas Reddy Beeravelly, Rajneesh Kumar Singh, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6596808/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: Our institution conducted a pilot study of neoadjuvant chemoradiotherapy (NACRT) in carcinoma stomach. The surgical complications were compared with a contemporary cohort of patients receiving neoadjuvant chemotherapy (NACT) in carcinoma stomach. Materials and Methods: Patients who underwent neoadjuvant therapy followed by curative gastrectomy between 2015-2022 were included in this ambispective analysis. These patients were divided into groups: Group 1: NACT and Group 2: NACRT. NACT was given as 3 cycles of ECX/ECF, while NACRT was given as 2 cycles of CX chemotherapy (CT) followed by concurrent radiotherapy (RT) to a dose of 45 Gy/25 # with Intensity-modulated radiation therapy (IMRT) technique and concurrent Capecitabine(X). The primary outcome measure was anastomotic complications, which were compared between groups. Crude percentages, median, and means are reported and compared using the chi-square test and t-test. Univariable and multivariable analyses were performed to identify predictors of complications. Results: During this period, 42 patients who underwent curative resections were identified. The median age was 51 years (IQR 42-65). The majority (50%) had an antropyloric location, 32 (76%) patients had T3/4 disease, and 27 (64%) patients had node-positive disease. Of them, 27 (64%) patients received NACT, and the remaining 15 (36%) received NACRT. Most had distal/subtotal gastrectomy (48%) and Billroth II reconstruction (36%). At a median follow-up of 28 months, overall anastomotic complications were seen in 6 (14%) patients, anastomotic leak in 4 (9%) and anastomotic stenosis in 6 (14%) patients. The incidence of anastomotic leak was 7% vs 13% (p=0.53), and anastomotic stenosis was 7% vs 27% (p=0.08) in Grp 1 vs 2. Overall, anastomotic complications were 7% vs 27% (p=0.08), pulmonary (29.6 %vs 26.7%, p=0.839) and cardiac complications (0 vs 6.7%, p=0.174) in groups 1 vs 2. The median duration of hospital stay was 12 vs. 14 days (p=0.84), and the 90-day mortality rate was 3.7% vs 0%, p=0.45 in groups 1 vs 2. On multivariable regression analysis, increasing age (p=0.04, OR=0.91), NACRT (p=0.04, OR=14.6), and adjuvant therapy (p=0.03, OR=24.7) were predictors of overall anastomotic complications. Conclusion: NACRT increases anastomotic complications as compared to NACT and should be used cautiously in patients with GC. Neoadjuvant chemoradiotherapy gastric cancer anastomotic complications Highlights Gastric carcinoma often requires multimodal therapy to improve resectability and survival. Neoadjuvant therapy is used to downstage tumors, but may influence postoperative complications, particularly anastomotic outcomes. NACRT may be associated with a higher risk of anastomotic stenosis , even if leak rates are not significantly elevated. NACT remains standard for many resectable gastric cancers due to a favorable balance of efficacy and safety. Careful patient selection is crucial when considering NACRT, particularly when tumors are located near the gastroesophageal junction. Introduction Gastric cancer (GC) is the fourth most common malignancy and the second leading cause of cancer deaths worldwide [ 1 , 2 ]. Surgery is the only curative treatment for gastric cancer, but the prognosis of patients with locally advanced GC is still poor even after curative resection. A multimodal strategy is desirable for improving the prognosis of patients with advanced GC. Perioperative (neoadjuvant and adjuvant) chemotherapy is recommended for patients with resectable stage ≥ IB GC, leading to improved progression-free survival and overall survival compared with surgery alone [ 3 , 4 , 5 ]. Postoperative chemoradiotherapy has shown an advantage in older trials [ 6 ], but recent studies have failed to demonstrate the benefit of postoperative chemoradiotherapy over chemotherapy alone in patients with radically resected gastric cancer (GC) undergoing D2 dissection [ 7 ]. Given the advantages of preoperative therapy, including tumour downstaging and a better side-effect profile than postoperative therapy, especially in esophageal cancers, interest in the use of neoadjuvant chemoradiotherapy (NACRT) for gastric cancer has been high. Conversely, the potential benefit of NACRT in gastric cancer remains unknown. The TOPGEAR trial (Trial of Preoperative Therapy for Gastric and Esophagogastric Junction Adenocarcinoma) was designed to address the question of whether the addition of preoperative CRT to perioperative chemotherapy would improve survival in patients with resectable gastric cancer [ 8 ]. The initial results demonstrated that NACRT in gastric cancer can be safely delivered without a significant increase in toxicity or surgical morbidity [ 9 ]. A pilot study reported on the early outcomes and overall surgical morbidity after NACRT in gastric cancer with no overt increase in surgical mortality and encouraging R0 resection rates [ 10 ]. The survival outcomes of TOPGEAR were recently published and did not demonstrate an overall or progression-free survival advantage of NACRT as compared to perioperative chemotherapy[ 8 ]. An essential premise of preoperative treatments is that they should not be overtly toxic to cause an increase in surgical morbidity. Gastrectomy for cancer requires expertise, and anastomotic leak and stenosis are expected, with an incidence of about 0–17% and 0–21%, respectively, after total gastrectomy [ 11 ]. These complications are problematic due to their effect on further treatment plans, quality of life, and mortality rates [ 12 ]. In this study, we examined the impact of NACRT on long-term surgical morbidity, explicitly focusing on anastomotic complications and compared to a contemporary cohort receiving perioperative chemotherapy alone. Materials and Methods This was an ambispective observational study done at a tertiary centre, duly approved by the ethics committee (2023-93-MCh-EXP-52/PGI/BE/224/2023). Consecutive patients with biopsy-proven gastric adenocarcinoma (including Siewert type 3 GEJ adenocarcinoma) who received neoadjuvant therapy followed by curative gastrectomy between 2015 to 2022 were included. During the study period, patients who received neoadjuvant treatment but were subsequently found to have metastatic disease and underwent palliative gastrectomy, as well as those who could not undergo curative resection for other reasons, were excluded. All included patients had clinically suspected gastric cancer, confirmed by endoscopy with biopsy, and were staged using contrast-enhanced computed tomography (CECT) of the abdomen and pelvis. Staging laparoscopy was not mandatory before initiating neoadjuvant treatment. Following evaluation by a multidisciplinary tumor board, patients were selected for neoadjuvant therapy based on the presence of T3/T4 disease and/or significant lymphadenopathy on imaging. These patients were divided into Group 1: neoadjuvant chemotherapy (NACT group) and Group 2: neoadjuvant chemoradiotherapy (NACRT group). NACT was given as 3 cycles of ECX; Epirubicin 50mg/m 2 iv day 1, Cisplatin 60 mg/m 2 iv day 1, Capecitabine (Xeloda) 625 mg/m 2 peroral twice daily, days 1–21. Neoadjuvant chemoradiotherapy (NACRT) was given as two cycles of cisplatin capecitabine (CX) (cisplatin 60 mg/m 2 D1 + capecitabine 1250 mg/m 2 D1 to 21), at 3-weekly intervals with a 2-week to 4-week gap to receive 45 Gy in 25 fractions over 5 weeks along with concurrent capecitabine 825 mg/m 2 bid on all RT treatment days. Intensity-modulated radiotherapy (IMRT) was planned with 6 MV photons (Varian 2100CD with onboard cone-beam imaging) with appropriate quality assurance and portal imaging protocols in place. Details of the radiotherapy protocol are reported in the prior publication [ 10 ]. Depending on the anatomical location of the tumour, patients underwent either distal/subtotal or proximal/total gastrectomy with D2 lymphadenectomy, with Billroth II/Roux-en-Y gastrojejunostomy or esophagogastric anastomosis/Roux-en-Y-esophagojejunostomy within 6–8 weeks after completion of neoadjuvant therapy. Surgery was done either open or laparoscopically; reconstruction was either handsewn or stapled. Demographic, clinicopathological, operative, and post-operative recovery-related data was retrieved from the electronic hospital information system and case files. The definition of anastomotic leak and anastomotic stenosis was taken from our previous study [ 12 ]. Anastomotic leak was defined as the leakage of luminal contents from the anastomotic line at the Roux-en-Y esophago-jejunal (RYEJ)/esophagogastric (EG) or gastrojejunal (GJ) anastomotic site, accompanied by clinical manifestations. They presented clinically as luminal contents through a wound or drain, or with a collection near the anastomosis, associated with fever, inflammatory response, metabolic disturbance, and/or multiple-organ failure, confirmed by oral contrast CT or at reoperation. Anastomotic stenosis was defined as anastomotic site narrowing post-gastrectomy who presented with features of gastric outlet obstruction at least after one month of surgery confirmed by endoscopy or contrast study and those requiring endoscopic intervention or revision surgery [ 12 ]. Tumour staging was done according to the American Joint Committee on Cancer (AJCC) 8th manual tumour, node, and metastasis (TNM) classification[ 13 ]. The primary outcome measure was anastomotic complications, which was compared between groups. Variables were expressed as frequencies, crude percentages for categorical variables, and median range for continuous variables. Categorical variables were compared using the chi-square test, and continuous variables were compared using an independent-sample t-test. Univariate and multivariable logistic regression analysis was done to determine the association between variables and risk of anastomotic complications. For multivariable logistic regression analysis, we included variables with p-value < 0.10 in univariate analysis and p-value ≤ 0.05 was considered significant in multivariable regression analysis. Statistical analysis was performed using SPSS version 26.0 (SPSS Inc., Chicago, IL, USA). This research received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Results During the study period, 112 patients underwent curative gastrectomy for gastric adenocarcinoma; 70 patients underwent upfront curative gastrectomy and were excluded from the study. The remaining 42 patients who received neoadjuvant therapy before curative gastrectomy were included in the study. The median follow-up of the entire cohort was 28 months. The median age of the entire cohort was 51 years. Most were male (76%), and the most common tumour location was in the antropyloric region (50%). Most patients had T3/4 disease (32, 76%), and 27 (64%) had node-positive disease. Among the study population, 27 (64%) patients received NACT (Grp 1), and the remaining 15 (36%) received NACRT (Grp 2). Patient demographics and clinicopathological characteristics are shown in Table 1 . Most of the parameters were well balanced between both the groups except for technique of anastomosis with stapled anastomosis being more common in NACRT group (Grp1 vs 2: 19% vs 73%,p = 0.001) Table 1: Patient demographic and treatment characteristics. Characteristic Overall N=42 (%) Group 1 (NACT) n=27 (64%) Group 2 (NACRT) n=15 (36%) p-value Age (Median, IQR) 51(42-65) 47 (42-70) 53 (42-62) 0.94 Gender n(%) Male Female 32 (76) 10 (24) 19 (70) 8 (30) 13 (87) 2 (13.3) 0.23 Comorbidities n(%) Present Absent 11 (26) 31 (74) 8 (30) 19 (70) 3 (20) 12 (80) 0.49 Smoking n(%) Smoker Non-smoker 12 (29) 30 (71) 9 (33) 18 (67) 3 (20) 12 (80) 0.35 Anaemia n(%) Present Absent 18 (43) 24 (57) 14 (52) 13 (48) 4 (27) 11 (73) 0.11 Hypoalbuminemia n(%) Present Absent 4 (9.5) 38 (90.5) 3 (11) 24 (89) 1 (7) 14 (93) 0.64 Tumour location n(%) GEJ (Siewert type 3) Antro-pyloric region Diffuse or Body 13 (31) 21 (50) 8 (19) 6 (22) 16 (59) 5 (19) 7 (47) 5 (33) 3 (20) 0.21 Surgical procedure n(%) Proximal gastrectomy Distal/subtotal gastrectomy Total gastrectomy 10 (24) 20 (48) 12 (28) 6 (22) 15 (56) 6 (22) 4 (27) 5 (33) 6 (40) 0.35 Type of reconstruction n(%) Esophagogastric anastomosis Roux-en-Y-esophagojejunostomy Roux-en-Y-Gastrojejunostomy Billroth II anastomosis 9 (21) 8 (19) 10 (24) 15 (36) 5 (18) 6 (22) 7 (26) 9 (34) 4 (27) 2 (13) 3 (20) 6 (40) 0.81 Technique of anastomosis n(%) Handsewn Stapled 27 (64) 15 (36) 22 (81) 5 (19) 4 (27) 11 (73) 0.001 Histopathology n(%) Adenocarcinoma Signet ring cell morphology 34 (81) 8 (19) 21 (78) 6 (22) 13 (87) 2 (13) 0.48 Pathological T-stage n(%) T1/T2 T3/T4 10 (24) 32 (76) 6 (22) 21 (78) 4 (27) 11 (73) 0.74 Pathological N-stage n(%) N0 N+ 15 (36) 27 (64) 9 (33.3) 18 (67.7) 6 (40) 9 (60) 0.66 Margin status n(%) Negative margin Microscopic margin positive Macroscopic margin positive 38 (90.5) 4 (9.5) 0 24 (89) 3 (11) 0 14 (93) 1 (7) 0 0.64 Adjuvant therapy received n(%); Yes 37 (88) 23 (85) 14 (93) 0.43 N=Number of patients; NACT=neoadjuvant chemotherapy; NACRT=Neoadjuvant chemoradiotherapy; GEJ = Gastroesophageal junction; T= Tumour stage; N0= Node negative; N+ = Node positive. Incidence of anastomotic complications and duration of hospital stay At a median follow-up of 28 months, overall anastomotic complications were seen in 6 (14%) patients. This comprised anastomotic leak seen in 4 (9%) and anastomotic stenosis in 6 (14%) patients. One patient with anastomotic leak developed stenosis in the long term. Among patients with an anastomotic leak, 2 required re-exploration, and the remaining two were managed conservatively with a percutaneous drain and antibiotics. The crude incidence of anastomotic leak was 7% (2/27) in group 1 and 13% (2/15) in group 2 (p = 0.53). The incidence of anastomotic stenosis was 7% (2/27) in group 1 and 27% (4/15) in group 2 (p = 0.08). Overall, anastomotic complications were 7% vs 27% in Group 1 vs 2 (p = 0.08). The median duration of hospital stay was 12 and 14 days (p = 0.84), and the 90-day mortality rate was 3.7% vs 0%, p = 0.45 in groups 1 vs 2. Pulmonary and cardiac complications were similar in both groups. (Table 2 ). Table 2 Perioperative and Postoperative surgical morbidity. Characteristic Overall N = 42 (%) Group 1 (NACT) n = 27 (64%) Group 2 (NACRT) n = 15 (36%) p-value Duration of hospital stay (median, range in days) 12 (7–64) 12 (7–64) 14 (8–44) 0.84 Anastomotic leak n(%) 4 (9.5) 2 (7.4) 2 (13) 0.53 Anastomotic stenosis n(%) 6 (14.3) 2 (7.4) 4 (27) 0.08 Pulmonary Complications n(%) 12(28.6) 8(29.6) 4(26.7) 0.83 Cardiac Complications n(%) 1(2.4) 0 1(6.7) 0.174 Overall Morbidity n(%) 15 (35.7) 10 (37) 5 (33.3) 0.83 CD Grade 3–5 n(%) 6(14.3) 5(18) 1(6.7) 0.75 90-day mortality n(%) 1 (2.4) 1 (3.7) 0 0.45 N = Number of patients; NACT = neoadjuvant chemotherapy; NACRT = Neoadjuvant chemoradiotherapy; CD = Clavien-Dindo grade Risk factors for anastomotic complications On univariate analysis, none of the factors predicted for anastomotic complications except for increasing age, which had borderline significance (Suppl. Table 1) for the development of anastomotic complications. On multivariable logistic regression analysis, increasing age (OR: 0.91, p = 0.04), NACRT (OR: 14.67, p = 0.04), and use of adjuvant treatment (OR: 24.75, p = 0.03) were independently associated with the risk of anastomotic complications (Table 3 ). Table 3 Multivariable analysis of predictors of overall anastomotic complications. Characteristic Odd’s ratio (95% CI) p-value Age 0.91 (0.83–0.99) 0.04 Type of neoadjuvant therapy (NACRT vs NACT) 14.67(1.06–206) 0.04 Adjuvant therapy (Yes vs No) 24.75 (1.3–465) 0.03 NACRT-Neoadjuvant chemoradiotherapy; NACT-neoadjuvant chemotherapy. Discussion For patients with localised GC, surgery is the mainstay of curative treatment; however, despite resection, GC has a relatively dismal prognosis. Hence, perioperative therapy has been practiced as a standard modality, as shown in the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) Trial [ 4 ] and Intergroup Study 0116 [ 6 ] that supported using perioperative chemotherapy and adjuvant chemoradiotherapy, respectively. These strategies showed improvement in survival in localised gastric carcinomas. However, these improvements didn’t prevent recurrence due to locoregional regrowth following surgery [ 4 , 14 , 15 ]. Neoadjuvant CRT is mainly used to reduce local tumour burden in patients with advanced gastric cancer, in turn making patients operable, while the pathological response after NACRT can provide prognostic information [ 16 , 17 ]. NACRT was established as a treatment strategy in the oesophagus and GEJ cancers [ 18 ], but limited studies showed conflicting results in GC [ 9 , 10 , 15 , 19 – 26 ]. As with other gastrointestinal tumour sites, there was an increasing interest in using preoperative chemoradiotherapy for GC, which has several distinct advantages compared to postoperative treatment. One of the main advantages is the potential for tumour downstaging with an increase in the complete R0 resection rate. Preoperative therapy is much better tolerated than postoperative therapy, ensuring that all patients receive the intended treatment. Both of these advantages were clearly demonstrated in the MAGIC study [ 4 ]. We previously embarked on a pilot study of NACRT in gastric cancer, which demonstrated encouraging R0 resection of 92% while significant surgical morbidity was seen in 31% of patients (4/13) with no surgical mortality. This approach was considered to be feasible and effective. As expected, post-surgery completion of 3 cycles of chemotherapy was in 25% intention to treat population [ 10 ]. Preoperative radiotherapy alone has been investigated in a phase III trial from Beijing in which 370 patients with gastric cancer were randomized to radiotherapy (40 Gy in 20 fractions) and surgery, or surgery alone. The operative mortality rates were 0.6% and 2.5%; intrathoracic leak rates were 1.8% and 4.0% respectively in upfront surgery versus preoperative RT [ 19 ]. Many prospective and retrospective observational studies confirmed the safety and usefulness of neoadjuvant RT in advanced gastric cancer patients [ 20 – 26 ]. The TOPGEAR trial was designed to answer the utility of NACRT in gastric cancer [ 8 ] and recently reported that although the addition of NACRT doubled the pathological complete response and led to a higher rate of patients with tumour downstaging than NACT alone, these improvements did not translate into improvements in overall or progression-free survival [ 8 ]. While there is a concern that preoperative radiotherapy may lead to an increased risk of anastomotic complications, there were not many studies comparing NACT with NACRT in gastric cancer concerning their surgical morbidity. In 2015, a retrospective analysis of 2764 gastric cancer patients with 2% receiving preoperative RT showed that there was no difference in surgical morbidity in patients receiving preoperative RT [ 15 ]. In a study by Haskins et al, a total of 1135 patients with 4.6% receiving preoperative RT showed that neither preoperative chemotherapy nor radiotherapy was associated with an increased risk of anastomotic leak compared with the upfront surgery group [ 27 ]. Another retrospective analysis of 346 patients, with 44% of patients receiving NACRT, showed that there was no significant increase in anastomotic leaks in patients receiving NACRT compared to NACT or the upfront surgery group [ 28 ]. The TOPGEAR trial reported no meaningful difference between groups in operative mortality or grade 3 surgical complications. Anastomotic leak was 7% in NACRT vs 5% in the NACT group, which was not different [ 8 ]. All these studies analysed short-term anastomotic complications. In our study, we examined both short-term and long-term anastomotic complications. Our study reports these complications on a consecutive and contemporary patient population of gastric cancer treated with neoadjuvant approaches, with 64% in the NACT group and 36% in the NACRT group. We found that NACRT was significantly associated with an increased risk of overall anastomotic complications (OR = 14.6, p = 0.04). The increased risk was primarily driven by the long-term side effects of anastomotic stenosis with a four times higher rate in NACRT compared to NACT (27% vs 7%, p = 0.08). The anastomotic leak rates were numerically higher in the NACRT group than in the NACT group (13% vs 7%, p = 053). The rates were doubled with use of NACRT but did not reach a statistical significance due to small numbers. The stapled anastomosis was much more common in the NACRT group (73% vs 19%, P = 0.001), however logistic regression analysis to evaluate the risk factors for anastomotic complications revealed no significant association with anastomotic complications. Multivariate logistic regression analysis of risk factors for overall anastomotic complications revealed the type of preoperative therapy, i.e. NACRT (OR = 14, p = 0.04), age (OR = 0.9, p = 0.04), and the use of adjuvant chemotherapy (OR = 24, p = 0.03) as significant predictors of anastomotic complications. The overall morbidity (35.4%) and mortality (2.4%) in the study population were similar to previous studies [ 12 , 15 , 27 , 28 ]. The anastomotic leak rate in our study (9.5%) was similar to previous studies ranging between 1.5–14.4% [ 11 , 15 , 27 , 28 ]. The anastomotic stenosis rate in our study (14%) was comparable with other studies (3.4%-18%) [ 11 , 29 , 30 , 31 ]. The long-term results of anastomotic complications from the randomised trial are awaited [ 8 ]. A recent meta-analysis found that NACRT improved pathological complete response and 3-year overall survival compared to NACT without a significant increase in postoperative complications, including anastomotic complications [ 32 ]. Another phase II study documented a lower incidence of postoperative complications in the NACRT group (23.1%) than in the adjuvant chemotherapy group (30.0%). However, this study did not comment on the anastomotic complications[ 33 ]. The median duration of hospital stay in the current study was 12 and 14 days (p = 0.84) for groups 1 and 2, respectively, with no statistically significant difference in duration. This study did not document an increased perioperative pulmonary or cardiac complication risk. The study's limitations include the smaller size of the study population with a low incidence of anastomotic complications, leading to wide confidence intervals, limited power, the retrospective nature of the study, and the fact that the definition of anastomotic complications or anastomotic leak has not been standardised in the literature, which makes comparisons with other studies difficult. Few patients who presented with stenosis on follow-up had associated local recurrence, which was biopsy-proven and excluded from the risk estimates of anastomotic complications. It's important to note that this analysis was conducted in a real-world setting, specifically at a tertiary care centre with extensive experience managing these patients. This study had a reasonable follow-up of 28 months, which allowed us to present the long-term surgical morbidity, which includes anastomotic stenosis. This study demonstrates that neoadjuvant chemoradiotherapy (NACRT) increases the risk of overall anastomotic complications as compared to NACT. Patients receiving NACRT had a numerically higher incidence of anastomotic leak and anastomotic stenosis compared to those treated with neoadjuvant chemotherapy (NACT) alone. Conclusion Neoadjuvant chemoradiotherapy (NACRT) in gastric carcinoma is associated with an increased risk of anastomotic complications arising in the short or long term. While NACRT may offer oncologic benefits in select cases, its role in resectable gastric cancer remains limited. Clinicians should exercise caution when incorporating radiation into neoadjuvant protocols, prioritising individualized risk assessment and multidisciplinary decision-making to optimise surgical morbidity and outcomes. Declarations Funding: “The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.” Competing Interests: “The authors have no relevant financial or non-financial interests to disclose.” Author Contributions: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Rakesh Shaganthi, Sreenivas Reddy Beeravelly and Shagun Misra. The first draft of the manuscript was written by Rakesh Shaganthi, Shagun Misra and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Data Availability: “The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.” Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the Institute. References Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. Gastric cancer. Lancet. 2020 Aug 29;396(10251):635-648. doi: 10.1016/S0140-6736(20)31288-5. PMID: 32861308. Lordick F, Carneiro F, Cascinu S, Fleitas T, Haustermans K, Piessen G, Vogel A, Smyth EC; ESMO Guidelines Committee. Electronic address: [email protected] . Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022 Oct;33(10):1005-1020. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M et al, MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. doi: 10.1056/NEJMoa055531. PMID: 16822992. Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S et al. FLOT4-AIO Investigators. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet. 2019 May 11;393(10184):1948-1957. doi: 10.1016/S0140-6736(18)32557-1. Epub 2019 Apr 11. PMID: 30982686. Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001 Sep 6;345(10):725-30. doi: 10.1056/NEJMoa010187. PMID: 11547741. Cats A et al. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. doi: 10.1016/S1470-2045(18)30132-3. Epub 2018 Apr 9. PMID: 29650363. Leong T, Smithers BM, Michael M, Haustermans K, Wong R, Gebski V, O'Connell RL, Zalcberg J, Boussioutas A, Findlay M, Willis D, Moore A, Murray WK, Lordick F, O'Callaghan C, Swallow C, Darling G, Miller D, Strickland A, Liberman M, Mineur L, Simes J; Australasian Gastro-Intestinal Trials Group, National Health and Medical Research Council Clinical Trials Centre, Trans-Tasman Radiation Oncology Group, European Organisation for Research and Treatment of Cancer, and Canadian Cancer Trials Group. Preoperative Chemoradiotherapy for Resectable Gastric Cancer. N Engl J Med. 2024 Nov 14;391(19):1810-1821. doi: 10.1056/NEJMoa2405195. Epub 2024 Sep 14. PMID: 39282905. Leong T, Smithers BM, Haustermans K, Michael M, Gebski V, Miller D, Zalcberg J et al. TOPGEAR: A Randomized, Phase III Trial of Perioperative ECF Chemotherapy with or Without Preoperative Chemoradiation for Resectable Gastric Cancer: Interim Results from an International, Intergroup Trial of the AGITG, TROG, EORTC and CCTG. Ann Surg Oncol. 2017 Aug;24(8):2252-2258. doi: 10.1245/s10434-017-5830-6. Epub 2017 Mar 23. PMID: 28337660. Misra S, Yeshala SK, Singh S, Singh RK, Maria Das KJ, Kumar S, Kumar S. A Pilot Study of Perioperative Cisplatin-Capecitabine Chemotherapy With Preoperative Chemoradiation for Resectable Gastric Cancers. Am J Clin Oncol. 2021 Sep 1;44(9):475-481. doi: 10.1097/COC.0000000000000844. PMID: 34183522. Inokuchi M, Otsuki S, Fujimori Y, Sato Y, Nakagawa M, Kojima K. Systematic review of anastomotic complications of esophagojejunostomy after laparoscopic total gastrectomy. World J Gastroenterol. 2015 Aug 28;21(32):9656-65. doi: 10.3748/wjg.v21.i32.9656. PMID: 26327774; PMCID: PMC4548127. Shaganti R, Kumar Godara S, Kumar Singh R, R R, Misra S, Kumar S. Factors associated with anastomotic leak following gastrectomy for gastric adenocarcinoma and its effect on long-term outcomes. Turk J Surg. 2024 Jun 28;40(2):111-118. doi: 10.47717/turkjsurg.2024.6351. PMID: 39628503; PMCID: PMC11610612. Amin MB et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA Cancer J Clin. 2017 Mar;67(2):93-99. doi: 10.3322/caac.21388. Epub 2017 Jan 17. PMID: 28094848. Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, Gunderson LL, Goldman B, Martenson JA, Jessup JM, Stemmermann GN, Blanke CD, Macdonald JS. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012 Jul 1;30(19):2327-33. doi: 10.1200/JCO.2011.36.7136. Epub 2012 May 14. PMID: 22585691; PMCID: PMC4517071. Sun Z, Nussbaum DP, Speicher PJ, Czito BG, Tyler DS, Blazer DG 3rd. Neoadjuvant radiation therapy does not increase perioperative morbidity among patients undergoing gastrectomy for gastric cancer. J Surg Oncol. 2015 Jul;112(1):46-50. doi: 10.1002/jso.23957. Epub 2015 Jul 14. PMID: 26179329. Tormo Ferrero V, Andreu Martínez FJ, Cardenal Macía R, Pomares Arias A. Evaluation of the toxicity of the combined treatment of chemoradiotherapy, according to the scheme of Macdonald, after radical surgery in patients diagnosed of gastric cancer. Clin Transl Oncol. 2006 Aug;8(8):611-5. doi: 10.1007/s12094-006-0068-y. PMID: 16952851. Yao JC, Mansfield PF, Pisters PW, Feig BW, Janjan NA, Crane C, Ajani JA. Combined-modality therapy for gastric cancer. Semin Surg Oncol. 2003;21(4):223-7. doi: 10.1002/ssu.10040. PMID: 14648779. van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, van der Gaast A; CROSS Group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012 May 31;366(22):2074-84. doi: 10.1056/NEJMoa1112088. PMID: 22646630. Zhang ZX, Gu XZ, Yin WB, Huang GJ, Zhang DW, Zhang RG. Randomized clinical trial on the combination of preoperative irradiation and surgery in the treatment of adenocarcinoma of gastric cardia (AGC)--report on 370 patients. Int J Radiat Oncol Biol Phys. 1998 Dec 1;42(5):929-34. doi: 10.1016/s0360-3016(98)00280-6. PMID: 9869212. Ajani JA, Mansfield PF, Janjan N, Morris J, Pisters PW, Lynch PM, Feig B, Myerson R, Nivers R, Cohen DS, Gunderson LL. Multi-institutional trial of preoperative chemoradiotherapy in patients with potentially resectable gastric carcinoma. J Clin Oncol. 2004 Jul 15;22(14):2774-80. doi: 10.1200/JCO.2004.01.015. Erratum in: J Clin Oncol. 2004 Nov 1;22(21):4435. Erratum in: J Clin Oncol. 2005 Jan 20;23(3):656. PMID: 15254045. Ajani JA, Mansfield PF, Crane CH, Wu TT, Lunagomez S, Lynch PM, Janjan N, Feig B, Faust J, Yao JC, Nivers R, Morris J, Pisters PW. Paclitaxel-based chemoradiotherapy in localized gastric carcinoma: degree of pathologic response and not clinical parameters dictated patient outcome. J Clin Oncol. 2005 Feb 20;23(6):1237-44. doi: 10.1200/JCO.2005.01.305. PMID: 15718321. Balandraud P, Moutardier V, Giovannini M, Giovannini MH, Lelong B, Guiramand J, Magnin V, Houvenaeghel G, Delpero JR. Locally advanced adenocarcinomas of the gastric cardia: results of pre-operative chemoradiotherapy. Gastroenterol Clin Biol. 2004 Aug-Sep;28(8-9):651-7. doi: 10.1016/s0399-8320(04)95043-9. PMID: 15646531. Klautke G, Foitzik T, Ludwig K, Ketterer P, Klar E, Fietkau R. Neoadjuvant radiochemotherapy in locally advanced gastric carcinoma. Strahlenther Onkol. 2004 Nov;180(11):695-700. doi: 10.1007/s00066-004-9194-z. PMID: 15549187. Lowy AM, Feig BW, Janjan N, Rich TA, Pisters PW, Ajani JA, Mansfield PF. A pilot study of preoperative chemoradiotherapy for resectable gastric cancer. Ann Surg Oncol. 2001 Jul;8(6):519-24. doi: 10.1007/s10434-001-0519-1. PMID: 11456051. Kumagai K, Rouvelas I, Tsai JA, Mariosa D, Lind PA, Lindblad M, Ye W, Lundell L, Schuhmacher C, Mauer M, Burmeister BH, Thomas JM, Stahl M, Nilsson M. Survival benefit and additional value of preoperative chemoradiotherapy in resectable gastric and gastro-oesophageal junction cancer: a direct and adjusted indirect comparison meta-analysis. Eur J Surg Oncol. 2015 Mar;41(3):282-94. doi: 10.1016/j.ejso.2014.11.039. Epub 2014 Nov 27. PMID: 25491892. Fiorica F, Cartei F, Enea M, Licata A, Cabibbo G, Carau B, Liboni A, Ursino S, Cammà C. The impact of radiotherapy on survival in resectable gastric carcinoma: a meta-analysis of literature data. Cancer Treat Rev. 2007 Dec;33(8):729-40. doi: 10.1016/j.ctrv.2007.08.005. Epub 2007 Nov 1. PMID: 17935888. Haskins IN, Kroh MD, Amdur RL, Ponksy JL, Rodriguez JH, Vaziri K. The Effect of Neoadjuvant Chemoradiation on Anastomotic Leak and Additional 30-Day Morbidity and Mortality in Patients Undergoing Total Gastrectomy for Gastric Cancer. J Gastrointest Surg. 2017 Oct;21(10):1577-1583. doi: 10.1007/s11605-017-3496-9. Epub 2017 Jul 25. PMID: 28744744. Ikoma N, Das P, Blum M, Estrella JS, Devine CE, Wang X, Fournier K, Mansfield P, Minsky BD, Ajani J, Badgwell BD. Preoperative Chemoradiation Therapy Does Not Increase Risk of Anastomotic Leak in Patients With Gastric Cancer. Int J Radiat Oncol Biol Phys. 2017 Nov 1;99(3):660-666. doi: 10.1016/j.ijrobp.2017.07.018. Epub 2017 Jul 20. PMID: 29280460. Fukagawa T, Gotoda T, Oda I, Deguchi Y, Saka M, Morita S, Katai H. Stenosis of esophago-jejuno anastomosis after gastric surgery. World J Surg. 2010 Aug;34(8):1859-63. doi: 10.1007/s00268-010-0609-y. PMID: 20458580. Peifer KJ, Shiels AJ, Azar R, Rivera RE, Eagon JC, Jonnalagadda S. Successful endoscopic management of gastrojejunal anastomotic strictures after Roux-en-Y gastric bypass. Gastrointest Endosc. 2007 Aug;66(2):248-52. doi: 10.1016/j.gie.2006.10.012. Epub 2007 Apr 23. PMID: 17451700. Csendes A, Burgos AM, Burdiles P. Incidence of anastomotic strictures after gastric bypass: a prospective consecutive routine endoscopic study 1 month and 17 months after surgery in 441 patients with morbid obesity. Obes Surg. 2009 Mar;19(3):269-73. doi: 10.1007/s11695-008-9625-5. Epub 2008 Aug 12. PMID: 18696171. Zhu Y, Chen J, Sun X, Lou Y, Fang M, Zhou F, Zhang L, Xin Y. Survival and complications after neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for locally advanced gastric cancer: a systematic review and meta-analysis. Front Oncol. 2023 May 9;13:1177557. doi: 10.3389/fonc.2023.1177557. PMID: 37228495; PMCID: PMC10203550. Wang F, Qu A, Sun Y, Zhang J, Wei B, Cui Y, Liu X, Tian W, Li Y. Neoadjuvant chemoradiotherapy plus postoperative adjuvant XELOX chemotherapy versus postoperative adjuvant chemotherapy with XELOX regimen for local advanced gastric cancer-A randomized, controlled study. Br J Radiol. 2021 Aug 1;94(1124):20201088. doi: 10.1259/bjr.20201088. Epub 2021 Jul 14. PMID: 34260297; PMCID: PMC8764914. Additional Declarations No competing interests reported. Supplementary Files 20250423SupplTable.docx 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-6596808","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":454433378,"identity":"1b4fdc22-1da1-437e-8cfd-8b761e83e207","order_by":0,"name":"Shagun Misra","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4ElEQVRIiWNgGAWjYDACZjB5AEQwPoAyiNfCbECcFgaEFjYJorTotrM/+/Djzx15+YjcY9U8NXfk+BmYHz66gUeL2WEe45m9bc8MN97IS7vNc+yZsWQDm7FxDn4tzAy8DYcZN87IMbvNw3Y4ccMBHjZp/FrYHzP++XPYHqSlmOcfUVoYjJlBhs+XyDFj5m0jSguPMbNs2+HkDTxvjCXn9h02lmwm5Jfzxx8zvvlz2HZ+e47hhzffDsvxszc/fIxPCxwYHGBgYOIBsZiJUQ4C8g3AFPODWNWjYBSMglEwogAA2A1Qa8aPGQ4AAAAASUVORK5CYII=","orcid":"","institution":"Sanjay Gandhi Post Graduate Institute of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Shagun","middleName":"","lastName":"Misra","suffix":""},{"id":454433379,"identity":"c6473dfb-58e1-4c8c-8b23-ce74d566bf1c","order_by":1,"name":"Rakesh Shaghanti","email":"","orcid":"","institution":"Sanjay Gandhi Post Graduate Institute of Medical 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Sciences","correspondingAuthor":false,"prefix":"","firstName":"Shaleen","middleName":"","lastName":"Kumar","suffix":""}],"badges":[],"createdAt":"2025-05-05 18:53:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6596808/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6596808/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":84127201,"identity":"aa2c7c55-e619-4ea3-8b58-22b1b336d3b4","added_by":"auto","created_at":"2025-06-07 12:38:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1078489,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6596808/v1/d43f4990-3efb-41df-9fec-46bec06cb6ac.pdf"},{"id":82647227,"identity":"0ea89ccc-7a63-4895-96af-3bf6c8d00a5f","added_by":"auto","created_at":"2025-05-13 16:21:39","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":18249,"visible":true,"origin":"","legend":"","description":"","filename":"20250423SupplTable.docx","url":"https://assets-eu.researchsquare.com/files/rs-6596808/v1/a913350c16b10173ca1a0c33.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of neoadjuvant chemoradiotherapy (NACRT) vs neoadjuvant chemotherapy (NACT) on anastomotic complications in gastric carcinoma.","fulltext":[{"header":"Highlights","content":"\u003cp\u003e\u003cstrong\u003eGastric carcinoma often requires multimodal therapy to improve resectability and survival.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNeoadjuvant therapy is used to downstage tumors, but may influence postoperative complications, particularly anastomotic outcomes.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNACRT\u003c/strong\u003e may be associated with a \u003cstrong\u003ehigher risk of anastomotic stenosis\u003c/strong\u003e, even if leak rates are not significantly elevated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNACT\u003c/strong\u003e remains standard for many resectable gastric cancers due to a favorable balance of efficacy and safety.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCareful patient selection\u003c/strong\u003e is crucial when considering NACRT, particularly when tumors are located near the gastroesophageal junction.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eGastric cancer (GC) is the fourth most common malignancy and the second leading cause of cancer deaths worldwide [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Surgery is the only curative treatment for gastric cancer, but the prognosis of patients with locally advanced GC is still poor even after curative resection. A multimodal strategy is desirable for improving the prognosis of patients with advanced GC. Perioperative (neoadjuvant and adjuvant) chemotherapy is recommended for patients with resectable stage\u0026thinsp;\u0026ge;\u0026thinsp;IB GC, leading to improved progression-free survival and overall survival compared with surgery alone [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Postoperative chemoradiotherapy has shown an advantage in older trials [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], but recent studies have failed to demonstrate the benefit of postoperative chemoradiotherapy over chemotherapy alone in patients with radically resected gastric cancer (GC) undergoing D2 dissection [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Given the advantages of preoperative therapy, including tumour downstaging and a better side-effect profile than postoperative therapy, especially in esophageal cancers, interest in the use of neoadjuvant chemoradiotherapy (NACRT) for gastric cancer has been high. Conversely, the potential benefit of NACRT in gastric cancer remains unknown. The TOPGEAR trial (Trial of Preoperative Therapy for Gastric and Esophagogastric Junction Adenocarcinoma) was designed to address the question of whether the addition of preoperative CRT to perioperative chemotherapy would improve survival in patients with resectable gastric cancer [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The initial results demonstrated that NACRT in gastric cancer can be safely delivered without a significant increase in toxicity or surgical morbidity [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. A pilot study reported on the early outcomes and overall surgical morbidity after NACRT in gastric cancer with no overt increase in surgical mortality and encouraging R0 resection rates [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The survival outcomes of TOPGEAR were recently published and did not demonstrate an overall or progression-free survival advantage of NACRT as compared to perioperative chemotherapy[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAn essential premise of preoperative treatments is that they should not be overtly toxic to cause an increase in surgical morbidity. Gastrectomy for cancer requires expertise, and anastomotic leak and stenosis are expected, with an incidence of about 0\u0026ndash;17% and 0\u0026ndash;21%, respectively, after total gastrectomy [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. These complications are problematic due to their effect on further treatment plans, quality of life, and mortality rates [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In this study, we examined the impact of NACRT on long-term surgical morbidity, explicitly focusing on anastomotic complications and compared to a contemporary cohort receiving perioperative chemotherapy alone.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e This was an ambispective observational study done at a tertiary centre, duly approved by the ethics committee (2023-93-MCh-EXP-52/PGI/BE/224/2023). Consecutive patients with biopsy-proven gastric adenocarcinoma (including Siewert type 3 GEJ adenocarcinoma) who received neoadjuvant therapy followed by curative gastrectomy between 2015 to 2022 were included. During the study period, patients who received neoadjuvant treatment but were subsequently found to have metastatic disease and underwent palliative gastrectomy, as well as those who could not undergo curative resection for other reasons, were excluded. All included patients had clinically suspected gastric cancer, confirmed by endoscopy with biopsy, and were staged using contrast-enhanced computed tomography (CECT) of the abdomen and pelvis. Staging laparoscopy was not mandatory before initiating neoadjuvant treatment. Following evaluation by a multidisciplinary tumor board, patients were selected for neoadjuvant therapy based on the presence of T3/T4 disease and/or significant lymphadenopathy on imaging. These patients were divided into Group 1: neoadjuvant chemotherapy (NACT group) and Group 2: neoadjuvant chemoradiotherapy (NACRT group).\u003c/p\u003e \u003cp\u003eNACT was given as 3 cycles of ECX; Epirubicin 50mg/m\u003csup\u003e2\u003c/sup\u003e iv day 1, Cisplatin 60 mg/m\u003csup\u003e2\u003c/sup\u003e iv day 1, Capecitabine (Xeloda) 625 mg/m\u003csup\u003e2\u003c/sup\u003e peroral twice daily, days 1\u0026ndash;21. Neoadjuvant chemoradiotherapy (NACRT) was given as two cycles of cisplatin capecitabine (CX) (cisplatin 60 mg/m\u003csup\u003e2\u003c/sup\u003e D1\u0026thinsp;+\u0026thinsp;capecitabine 1250 mg/m\u003csup\u003e2\u003c/sup\u003e D1 to 21), at 3-weekly intervals with a 2-week to 4-week gap to receive 45 Gy in 25 fractions over 5 weeks along with concurrent capecitabine 825 mg/m\u003csup\u003e2\u003c/sup\u003e bid on all RT treatment days. Intensity-modulated radiotherapy (IMRT) was planned with 6 MV photons (Varian 2100CD with onboard cone-beam imaging) with appropriate quality assurance and portal imaging protocols in place. Details of the radiotherapy protocol are reported in the prior publication [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDepending on the anatomical location of the tumour, patients underwent either distal/subtotal or proximal/total gastrectomy with D2 lymphadenectomy, with Billroth II/Roux-en-Y gastrojejunostomy or esophagogastric anastomosis/Roux-en-Y-esophagojejunostomy within 6\u0026ndash;8 weeks after completion of neoadjuvant therapy. Surgery was done either open or laparoscopically; reconstruction was either handsewn or stapled. Demographic, clinicopathological, operative, and post-operative recovery-related data was retrieved from the electronic hospital information system and case files. The definition of anastomotic leak and anastomotic stenosis was taken from our previous study [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Anastomotic leak was defined as the leakage of luminal contents from the anastomotic line at the Roux-en-Y esophago-jejunal (RYEJ)/esophagogastric (EG) or gastrojejunal (GJ) anastomotic site, accompanied by clinical manifestations. They presented clinically as luminal contents through a wound or drain, or with a collection near the anastomosis, associated with fever, inflammatory response, metabolic disturbance, and/or multiple-organ failure, confirmed by oral contrast CT or at reoperation. Anastomotic stenosis was defined as anastomotic site narrowing post-gastrectomy who presented with features of gastric outlet obstruction at least after one month of surgery confirmed by endoscopy or contrast study and those requiring endoscopic intervention or revision surgery [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Tumour staging was done according to the American Joint Committee on Cancer (AJCC) 8th manual tumour, node, and metastasis (TNM) classification[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The primary outcome measure was anastomotic complications, which was compared between groups.\u003c/p\u003e \u003cp\u003eVariables were expressed as frequencies, crude percentages for categorical variables, and median range for continuous variables. Categorical variables were compared using the chi-square test, and continuous variables were compared using an independent-sample t-test. Univariate and multivariable logistic regression analysis was done to determine the association between variables and risk of anastomotic complications. For multivariable logistic regression analysis, we included variables with p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.10 in univariate analysis and p-value\u0026thinsp;\u0026le;\u0026thinsp;0.05 was considered significant in multivariable regression analysis. Statistical analysis was performed using SPSS version 26.0 (SPSS Inc., Chicago, IL, USA). This research received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eDuring the study period, 112 patients underwent curative gastrectomy for gastric adenocarcinoma; 70 patients underwent upfront curative gastrectomy and were excluded from the study. The remaining 42 patients who received neoadjuvant therapy before curative gastrectomy were included in the study. The median follow-up of the entire cohort was 28 months.\u003c/p\u003e \u003cp\u003eThe median age of the entire cohort was 51 years. Most were male (76%), and the most common tumour location was in the antropyloric region (50%). Most patients had T3/4 disease (32, 76%), and 27 (64%) had node-positive disease. Among the study population, 27 (64%) patients received NACT (Grp 1), and the remaining 15 (36%) received NACRT (Grp 2). Patient demographics and clinicopathological characteristics are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Most of the parameters were well balanced between both the groups except for technique of anastomosis with stapled anastomosis being more common in NACRT group (Grp1 vs 2: 19% vs 73%,p\u0026thinsp;=\u0026thinsp;0.001)\u003c/p\u003e \u003cp\u003e\u003cstrong\u003eTable 1: Patient demographic and treatment characteristics.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 233px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eN=42 (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup 1 (NACT)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=27 (64%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup 2 (NACRT)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=15 (36%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 233px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u0026nbsp;\u003c/strong\u003e(Median, IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e51(42-65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e47 (42-70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e53 (42-62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.94\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 233px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e32 (76)\u003c/p\u003e\n \u003cp\u003e10 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e19 (70)\u003c/p\u003e\n \u003cp\u003e8 (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13 (87)\u003c/p\u003e\n \u003cp\u003e2 (13.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.23\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 233px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eComorbidities n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003cp\u003eAbsent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e11 (26)\u003c/p\u003e\n \u003cp\u003e31 (74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8 (30)\u003c/p\u003e\n \u003cp\u003e19 (70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (20)\u003c/p\u003e\n \u003cp\u003e12 (80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.49\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 233px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSmoking\u003c/strong\u003e \u003cstrong\u003en(%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eSmoker\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNon-smoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12 (29)\u003c/p\u003e\n \u003cp\u003e30 (71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9 (33)\u003c/p\u003e\n \u003cp\u003e18 (67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (20)\u003c/p\u003e\n \u003cp\u003e12 (80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.35\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 233px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnaemia n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003cp\u003eAbsent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e18 (43)\u003c/p\u003e\n \u003cp\u003e24 (57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14 (52)\u003c/p\u003e\n \u003cp\u003e13 (48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (27)\u003c/p\u003e\n \u003cp\u003e11 (73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.11\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 233px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHypoalbuminemia n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003cp\u003eAbsent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (9.5)\u003c/p\u003e\n \u003cp\u003e38 (90.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (11)\u003c/p\u003e\n \u003cp\u003e24 (89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (7)\u003c/p\u003e\n \u003cp\u003e14 (93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 233px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTumour location n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eGEJ (Siewert type 3)\u003c/p\u003e\n \u003cp\u003eAntro-pyloric region\u003c/p\u003e\n \u003cp\u003eDiffuse or Body\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13 (31)\u003c/p\u003e\n \u003cp\u003e21 (50)\u003c/p\u003e\n \u003cp\u003e8 (19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (22)\u003c/p\u003e\n \u003cp\u003e16 (59)\u003c/p\u003e\n \u003cp\u003e5 (19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7 (47)\u003c/p\u003e\n \u003cp\u003e5 (33)\u003c/p\u003e\n \u003cp\u003e3 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 233px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgical procedure n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eProximal gastrectomy\u003c/p\u003e\n \u003cp\u003eDistal/subtotal gastrectomy\u003c/p\u003e\n \u003cp\u003eTotal gastrectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10 (24)\u003c/p\u003e\n \u003cp\u003e20 (48)\u003c/p\u003e\n \u003cp\u003e12 (28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (22)\u003c/p\u003e\n \u003cp\u003e15 (56)\u003c/p\u003e\n \u003cp\u003e6 (22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (27)\u003c/p\u003e\n \u003cp\u003e5 (33)\u003c/p\u003e\n \u003cp\u003e6 (40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 233px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of reconstruction n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eEsophagogastric anastomosis\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRoux-en-Y-esophagojejunostomy\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRoux-en-Y-Gastrojejunostomy\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eBillroth II anastomosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9 (21)\u003c/p\u003e\n \u003cp\u003e8 (19)\u003c/p\u003e\n \u003cp\u003e10 (24)\u003c/p\u003e\n \u003cp\u003e15 (36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 (18)\u003c/p\u003e\n \u003cp\u003e6 (22)\u003c/p\u003e\n \u003cp\u003e7 (26)\u003c/p\u003e\n \u003cp\u003e9 (34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (27)\u003c/p\u003e\n \u003cp\u003e2 (13)\u003c/p\u003e\n \u003cp\u003e3 (20)\u003c/p\u003e\n \u003cp\u003e6 (40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.81\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 233px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTechnique of anastomosis n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eHandsewn\u003c/p\u003e\n \u003cp\u003eStapled\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e27 (64)\u003c/p\u003e\n \u003cp\u003e15 (36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e22 (81)\u003c/p\u003e\n \u003cp\u003e5 (19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (27)\u003c/p\u003e\n \u003cp\u003e11 (73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 233px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistopathology n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eAdenocarcinoma\u003c/p\u003e\n \u003cp\u003eSignet ring cell morphology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e34 (81)\u003c/p\u003e\n \u003cp\u003e8 (19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21 (78)\u003c/p\u003e\n \u003cp\u003e6 (22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13 (87)\u003c/p\u003e\n \u003cp\u003e2 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.48\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 233px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePathological T-stage n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eT1/T2\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eT3/T4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10 (24)\u003c/p\u003e\n \u003cp\u003e32 (76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (22)\u003c/p\u003e\n \u003cp\u003e21 (78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (27)\u003c/p\u003e\n \u003cp\u003e11 (73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 233px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePathological N-stage n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eN0\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eN+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15 (36)\u003c/p\u003e\n \u003cp\u003e27 (64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9 (33.3)\u003c/p\u003e\n \u003cp\u003e18 (67.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (40)\u003c/p\u003e\n \u003cp\u003e9 (60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.66\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 233px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMargin status n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNegative margin\u003c/p\u003e\n \u003cp\u003eMicroscopic margin positive\u003c/p\u003e\n \u003cp\u003eMacroscopic margin positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e38 (90.5)\u003c/p\u003e\n \u003cp\u003e4 (9.5)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e24 (89)\u003c/p\u003e\n \u003cp\u003e3 (11)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14 (93)\u003c/p\u003e\n \u003cp\u003e1 (7)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 233px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjuvant therapy received n(%); Yes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e37 (88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e23 (85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e14 (93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.43\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eN=Number of patients; NACT=neoadjuvant chemotherapy; NACRT=Neoadjuvant chemoradiotherapy; GEJ = Gastroesophageal junction; T= Tumour stage; N0= Node negative; N+ = Node positive.\u003c/p\u003e\n\u003ch3\u003eIncidence of anastomotic complications and duration of hospital stay\u003c/h3\u003e\n\u003cp\u003eAt a median follow-up of 28 months, overall anastomotic complications were seen in 6 (14%) patients. This comprised anastomotic leak seen in 4 (9%) and anastomotic stenosis in 6 (14%) patients. One patient with anastomotic leak developed stenosis in the long term. Among patients with an anastomotic leak, 2 required re-exploration, and the remaining two were managed conservatively with a percutaneous drain and antibiotics.\u003c/p\u003e \u003cp\u003eThe crude incidence of anastomotic leak was 7% (2/27) in group 1 and 13% (2/15) in group 2 (p\u0026thinsp;=\u0026thinsp;0.53). The incidence of anastomotic stenosis was 7% (2/27) in group 1 and 27% (4/15) in group 2 (p\u0026thinsp;=\u0026thinsp;0.08). Overall, anastomotic complications were 7% vs 27% in Group 1 vs 2 (p\u0026thinsp;=\u0026thinsp;0.08). The median duration of hospital stay was 12 and 14 days (p\u0026thinsp;=\u0026thinsp;0.84), and the 90-day mortality rate was 3.7% vs 0%, p\u0026thinsp;=\u0026thinsp;0.45 in groups 1 vs 2. Pulmonary and cardiac complications were similar in both groups. (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\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\u003ePerioperative and Postoperative surgical morbidity.\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=\"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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\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\u003eOverall\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;42 (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGroup 1 (NACT)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;27 (64%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGroup 2 (NACRT)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;15 (36%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\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\u003e\u003cb\u003eDuration of hospital stay\u003c/b\u003e (median, range in days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (7\u0026ndash;64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (7\u0026ndash;64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (8\u0026ndash;44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.84\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnastomotic leak n(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (9.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (7.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.53\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnastomotic stenosis n(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (7.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePulmonary Complications n(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12(28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8(29.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4(26.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.83\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCardiac Complications n(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.174\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOverall Morbidity n(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (35.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.83\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCD Grade 3\u0026ndash;5 n(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.75\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e90-day mortality n(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (3.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.45\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eN\u0026thinsp;=\u0026thinsp;Number of patients; NACT\u0026thinsp;=\u0026thinsp;neoadjuvant chemotherapy; NACRT\u0026thinsp;=\u0026thinsp;Neoadjuvant chemoradiotherapy; CD\u0026thinsp;=\u0026thinsp;Clavien-Dindo grade\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eRisk factors for anastomotic complications\u003c/h3\u003e\n\u003cp\u003eOn univariate analysis, none of the factors predicted for anastomotic complications except for increasing age, which had borderline significance (Suppl. Table\u0026nbsp;1) for the development of anastomotic complications. On multivariable logistic regression analysis, increasing age (OR: 0.91, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04), NACRT (OR: 14.67, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04), and use of adjuvant treatment (OR: 24.75, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.03) were independently associated with the risk of anastomotic complications (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\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\u003eMultivariable analysis of predictors of overall anastomotic complications.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\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 \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\u003eOdd\u0026rsquo;s ratio (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\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\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.91 (0.83\u0026ndash;0.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eType of neoadjuvant therapy\u003c/b\u003e (NACRT vs NACT)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14.67(1.06\u0026ndash;206)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAdjuvant therapy\u003c/b\u003e (Yes vs No)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e24.75 (1.3\u0026ndash;465)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eNACRT-Neoadjuvant chemoradiotherapy; NACT-neoadjuvant chemotherapy.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eFor patients with localised GC, surgery is the mainstay of curative treatment; however, despite resection, GC has a relatively dismal prognosis. Hence, perioperative therapy has been practiced as a standard modality, as shown in the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) Trial [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] and Intergroup Study 0116 [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] that supported using perioperative chemotherapy and adjuvant chemoradiotherapy, respectively. These strategies showed improvement in survival in localised gastric carcinomas. However, these improvements didn\u0026rsquo;t prevent recurrence due to locoregional regrowth following surgery [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Neoadjuvant CRT is mainly used to reduce local tumour burden in patients with advanced gastric cancer, in turn making patients operable, while the pathological response after NACRT can provide prognostic information [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. NACRT was established as a treatment strategy in the oesophagus and GEJ cancers [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], but limited studies showed conflicting results in GC [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan additionalcitationids=\"CR20 CR21 CR22 CR23 CR24 CR25\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. As with other gastrointestinal tumour sites, there was an increasing interest in using preoperative chemoradiotherapy for GC, which has several distinct advantages compared to postoperative treatment. One of the main advantages is the potential for tumour downstaging with an increase in the complete R0 resection rate. Preoperative therapy is much better tolerated than postoperative therapy, ensuring that all patients receive the intended treatment. Both of these advantages were clearly demonstrated in the MAGIC study [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. We previously embarked on a pilot study of NACRT in gastric cancer, which demonstrated encouraging R0 resection of 92% while significant surgical morbidity was seen in 31% of patients (4/13) with no surgical mortality. This approach was considered to be feasible and effective. As expected, post-surgery completion of 3 cycles of chemotherapy was in 25% intention to treat population [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePreoperative radiotherapy alone has been investigated in a phase III trial from Beijing in which 370 patients with gastric cancer were randomized to radiotherapy (40 Gy in 20 fractions) and surgery, or surgery alone. The operative mortality rates were 0.6% and 2.5%; intrathoracic leak rates were 1.8% and 4.0% respectively in upfront surgery versus preoperative RT [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Many prospective and retrospective observational studies confirmed the safety and usefulness of neoadjuvant RT in advanced gastric cancer patients [\u003cspan additionalcitationids=\"CR21 CR22 CR23 CR24 CR25\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The TOPGEAR trial was designed to answer the utility of NACRT in gastric cancer [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] and recently reported that although the addition of NACRT doubled the pathological complete response and led to a higher rate of patients with tumour downstaging than NACT alone, these improvements did not translate into improvements in overall or progression-free survival [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhile there is a concern that preoperative radiotherapy may lead to an increased risk of anastomotic complications, there were not many studies comparing NACT with NACRT in gastric cancer concerning their surgical morbidity. In 2015, a retrospective analysis of 2764 gastric cancer patients with 2% receiving preoperative RT showed that there was no difference in surgical morbidity in patients receiving preoperative RT [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In a study by Haskins et al, a total of 1135 patients with 4.6% receiving preoperative RT showed that neither preoperative chemotherapy nor radiotherapy was associated with an increased risk of anastomotic leak compared with the upfront surgery group [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Another retrospective analysis of 346 patients, with 44% of patients receiving NACRT, showed that there was no significant increase in anastomotic leaks in patients receiving NACRT compared to NACT or the upfront surgery group [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The TOPGEAR trial reported no meaningful difference between groups in operative mortality or grade 3 surgical complications. Anastomotic leak was 7% in NACRT vs 5% in the NACT group, which was not different [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAll these studies analysed short-term anastomotic complications. In our study, we examined both short-term and long-term anastomotic complications. Our study reports these complications on a consecutive and contemporary patient population of gastric cancer treated with neoadjuvant approaches, with 64% in the NACT group and 36% in the NACRT group. We found that NACRT was significantly associated with an increased risk of overall anastomotic complications (OR\u0026thinsp;=\u0026thinsp;14.6, p\u0026thinsp;=\u0026thinsp;0.04). The increased risk was primarily driven by the long-term side effects of anastomotic stenosis with a four times higher rate in NACRT compared to NACT (27% vs 7%, p\u0026thinsp;=\u0026thinsp;0.08). The anastomotic leak rates were numerically higher in the NACRT group than in the NACT group (13% vs 7%, p\u0026thinsp;=\u0026thinsp;053). The rates were doubled with use of NACRT but did not reach a statistical significance due to small numbers.\u003c/p\u003e \u003cp\u003eThe stapled anastomosis was much more common in the NACRT group (73% vs 19%, P\u0026thinsp;=\u0026thinsp;0.001), however logistic regression analysis to evaluate the risk factors for anastomotic complications revealed no significant association with anastomotic complications. Multivariate logistic regression analysis of risk factors for overall anastomotic complications revealed the type of preoperative therapy, i.e. NACRT (OR\u0026thinsp;=\u0026thinsp;14, p\u0026thinsp;=\u0026thinsp;0.04), age (OR\u0026thinsp;=\u0026thinsp;0.9, p\u0026thinsp;=\u0026thinsp;0.04), and the use of adjuvant chemotherapy (OR\u0026thinsp;=\u0026thinsp;24, p\u0026thinsp;=\u0026thinsp;0.03) as significant predictors of anastomotic complications. The overall morbidity (35.4%) and mortality (2.4%) in the study population were similar to previous studies [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The anastomotic leak rate in our study (9.5%) was similar to previous studies ranging between 1.5\u0026ndash;14.4% [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The anastomotic stenosis rate in our study (14%) was comparable with other studies (3.4%-18%) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. The long-term results of anastomotic complications from the randomised trial are awaited [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. A recent meta-analysis found that NACRT improved pathological complete response and 3-year overall survival compared to NACT without a significant increase in postoperative complications, including anastomotic complications [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Another phase II study documented a lower incidence of postoperative complications in the NACRT group (23.1%) than in the adjuvant chemotherapy group (30.0%). However, this study did not comment on the anastomotic complications[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. The median duration of hospital stay in the current study was 12 and 14 days (p\u0026thinsp;=\u0026thinsp;0.84) for groups 1 and 2, respectively, with no statistically significant difference in duration. This study did not document an increased perioperative pulmonary or cardiac complication risk.\u003c/p\u003e \u003cp\u003eThe study's limitations include the smaller size of the study population with a low incidence of anastomotic complications, leading to wide confidence intervals, limited power, the retrospective nature of the study, and the fact that the definition of anastomotic complications or anastomotic leak has not been standardised in the literature, which makes comparisons with other studies difficult. Few patients who presented with stenosis on follow-up had associated local recurrence, which was biopsy-proven and excluded from the risk estimates of anastomotic complications. It's important to note that this analysis was conducted in a real-world setting, specifically at a tertiary care centre with extensive experience managing these patients. This study had a reasonable follow-up of 28 months, which allowed us to present the long-term surgical morbidity, which includes anastomotic stenosis.\u003c/p\u003e \u003cp\u003eThis study demonstrates that neoadjuvant chemoradiotherapy (NACRT) increases the risk of overall anastomotic complications as compared to NACT. Patients receiving NACRT had a numerically higher incidence of anastomotic leak and anastomotic stenosis compared to those treated with neoadjuvant chemotherapy (NACT) alone.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eNeoadjuvant chemoradiotherapy (NACRT) in gastric carcinoma is associated with an increased risk of anastomotic complications arising in the short or long term. While NACRT may offer oncologic benefits in select cases, its role in resectable gastric cancer remains limited. Clinicians should exercise caution when incorporating radiation into neoadjuvant protocols, prioritising individualized risk assessment and multidisciplinary decision-making to optimise surgical morbidity and outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eFunding: \u003cem\u003e\u0026ldquo;The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u0026rdquo;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eCompeting Interests:\u003cem\u003e\u0026ldquo;The authors have no relevant financial or non-financial interests to disclose.\u0026rdquo;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAuthor Contributions: \u003cem\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Rakesh Shaganthi, Sreenivas Reddy Beeravelly and Shagun Misra. The first draft of the manuscript was written by Rakesh Shaganthi, Shagun Misra and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eData Availability:\u003cem\u003e\u0026ldquo;The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.\u0026rdquo;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eEthics approval:\u003cem\u003eThis study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the Institute.\u003c/em\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eSung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSmyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. Gastric cancer. Lancet. 2020 Aug 29;396(10251):635-648. doi: 10.1016/S0140-6736(20)31288-5. PMID: 32861308.\u003c/li\u003e\n \u003cli\u003eLordick F, Carneiro F, Cascinu S, Fleitas T, Haustermans K, Piessen G, Vogel A, Smyth EC; ESMO Guidelines Committee. Electronic address: [email protected]. Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022 Oct;33(10):1005-1020.\u003c/li\u003e\n \u003cli\u003eCunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M et al, MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. doi: 10.1056/NEJMoa055531. PMID: 16822992.\u003c/li\u003e\n \u003cli\u003eAl-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S et al. FLOT4-AIO Investigators. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet. 2019 May 11;393(10184):1948-1957. doi: 10.1016/S0140-6736(18)32557-1. Epub 2019 Apr 11. PMID: 30982686.\u003c/li\u003e\n \u003cli\u003eMacdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001 Sep 6;345(10):725-30. doi: 10.1056/NEJMoa010187. PMID: 11547741.\u003c/li\u003e\n \u003cli\u003eCats A et al. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. doi: 10.1016/S1470-2045(18)30132-3. Epub 2018 Apr 9. PMID: 29650363.\u003c/li\u003e\n \u003cli\u003eLeong T, Smithers BM, Michael M, Haustermans K, Wong R, Gebski V, O\u0026apos;Connell RL, Zalcberg J, Boussioutas A, Findlay M, Willis D, Moore A, Murray WK, Lordick F, O\u0026apos;Callaghan C, Swallow C, Darling G, Miller D, Strickland A, Liberman M, Mineur L, Simes J; Australasian Gastro-Intestinal Trials Group, National Health and Medical Research Council Clinical Trials Centre, Trans-Tasman Radiation Oncology Group, European Organisation for Research and Treatment of Cancer, and Canadian Cancer Trials Group. Preoperative Chemoradiotherapy for Resectable Gastric Cancer. N Engl J Med. 2024 Nov 14;391(19):1810-1821. doi: 10.1056/NEJMoa2405195. Epub 2024 Sep 14. PMID: 39282905.\u003c/li\u003e\n \u003cli\u003eLeong T, Smithers BM, Haustermans K, Michael M, Gebski V, Miller D, Zalcberg J et al. TOPGEAR: A Randomized, Phase III Trial of Perioperative ECF Chemotherapy with or Without Preoperative Chemoradiation for Resectable Gastric Cancer: Interim Results from an International, Intergroup Trial of the AGITG, TROG, EORTC and CCTG. Ann Surg Oncol. 2017 Aug;24(8):2252-2258. doi: 10.1245/s10434-017-5830-6. Epub 2017 Mar 23. PMID: 28337660.\u003c/li\u003e\n \u003cli\u003eMisra S, Yeshala SK, Singh S, Singh RK, Maria Das KJ, Kumar S, Kumar S. A Pilot Study of Perioperative Cisplatin-Capecitabine Chemotherapy With Preoperative Chemoradiation for Resectable Gastric Cancers. Am J Clin Oncol. 2021 Sep 1;44(9):475-481. doi: 10.1097/COC.0000000000000844. PMID: 34183522.\u003c/li\u003e\n \u003cli\u003eInokuchi M, Otsuki S, Fujimori Y, Sato Y, Nakagawa M, Kojima K. Systematic review of anastomotic complications of esophagojejunostomy after laparoscopic total gastrectomy. World J Gastroenterol. 2015 Aug 28;21(32):9656-65. doi: 10.3748/wjg.v21.i32.9656. PMID: 26327774; PMCID: PMC4548127.\u003c/li\u003e\n \u003cli\u003eShaganti R, Kumar Godara S, Kumar Singh R, R R, Misra S, Kumar S. Factors associated with anastomotic leak following gastrectomy for gastric adenocarcinoma and its effect on long-term outcomes. Turk J Surg. 2024 Jun 28;40(2):111-118. doi: 10.47717/turkjsurg.2024.6351. PMID: 39628503; PMCID: PMC11610612.\u003c/li\u003e\n \u003cli\u003eAmin MB et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more \u0026quot;personalized\u0026quot; approach to cancer staging. CA Cancer J Clin. 2017 Mar;67(2):93-99. doi: 10.3322/caac.21388. Epub 2017 Jan 17. PMID: 28094848.\u003c/li\u003e\n \u003cli\u003eSmalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, Gunderson LL, Goldman B, Martenson JA, Jessup JM, Stemmermann GN, Blanke CD, Macdonald JS. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012 Jul 1;30(19):2327-33. doi: 10.1200/JCO.2011.36.7136. Epub 2012 May 14. PMID: 22585691; PMCID: PMC4517071.\u003c/li\u003e\n \u003cli\u003eSun Z, Nussbaum DP, Speicher PJ, Czito BG, Tyler DS, Blazer DG 3rd. Neoadjuvant radiation therapy does not increase perioperative morbidity among patients undergoing gastrectomy for gastric cancer. J Surg Oncol. 2015 Jul;112(1):46-50. doi: 10.1002/jso.23957. Epub 2015 Jul 14. PMID: 26179329.\u003c/li\u003e\n \u003cli\u003eTormo Ferrero V, Andreu Mart\u0026iacute;nez FJ, Cardenal Mac\u0026iacute;a R, Pomares Arias A. Evaluation of the toxicity of the combined treatment of chemoradiotherapy, according to the scheme of Macdonald, after radical surgery in patients diagnosed of gastric cancer. Clin Transl Oncol. 2006 Aug;8(8):611-5. doi: 10.1007/s12094-006-0068-y. PMID: 16952851.\u003c/li\u003e\n \u003cli\u003eYao JC, Mansfield PF, Pisters PW, Feig BW, Janjan NA, Crane C, Ajani JA. Combined-modality therapy for gastric cancer. Semin Surg Oncol. 2003;21(4):223-7. doi: 10.1002/ssu.10040. PMID: 14648779.\u003c/li\u003e\n \u003cli\u003evan Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, van der Gaast A; CROSS Group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012 May 31;366(22):2074-84. doi: 10.1056/NEJMoa1112088. PMID: 22646630.\u003c/li\u003e\n \u003cli\u003eZhang ZX, Gu XZ, Yin WB, Huang GJ, Zhang DW, Zhang RG. Randomized clinical trial on the combination of preoperative irradiation and surgery in the treatment of adenocarcinoma of gastric cardia (AGC)--report on 370 patients. Int J Radiat Oncol Biol Phys. 1998 Dec 1;42(5):929-34. doi: 10.1016/s0360-3016(98)00280-6. PMID: 9869212.\u003c/li\u003e\n \u003cli\u003eAjani JA, Mansfield PF, Janjan N, Morris J, Pisters PW, Lynch PM, Feig B, Myerson R, Nivers R, Cohen DS, Gunderson LL. Multi-institutional trial of preoperative chemoradiotherapy in patients with potentially resectable gastric carcinoma. J Clin Oncol. 2004 Jul 15;22(14):2774-80. doi: 10.1200/JCO.2004.01.015. Erratum in: J Clin Oncol. 2004 Nov 1;22(21):4435. Erratum in: J Clin Oncol. 2005 Jan 20;23(3):656. PMID: 15254045.\u003c/li\u003e\n \u003cli\u003eAjani JA, Mansfield PF, Crane CH, Wu TT, Lunagomez S, Lynch PM, Janjan N, Feig B, Faust J, Yao JC, Nivers R, Morris J, Pisters PW. Paclitaxel-based chemoradiotherapy in localized gastric carcinoma: degree of pathologic response and not clinical parameters dictated patient outcome. J Clin Oncol. 2005 Feb 20;23(6):1237-44. doi: 10.1200/JCO.2005.01.305. PMID: 15718321.\u003c/li\u003e\n \u003cli\u003eBalandraud P, Moutardier V, Giovannini M, Giovannini MH, Lelong B, Guiramand J, Magnin V, Houvenaeghel G, Delpero JR. Locally advanced adenocarcinomas of the gastric cardia: results of pre-operative chemoradiotherapy. Gastroenterol Clin Biol. 2004 Aug-Sep;28(8-9):651-7. doi: 10.1016/s0399-8320(04)95043-9. PMID: 15646531.\u003c/li\u003e\n \u003cli\u003eKlautke G, Foitzik T, Ludwig K, Ketterer P, Klar E, Fietkau R. Neoadjuvant radiochemotherapy in locally advanced gastric carcinoma. Strahlenther Onkol. 2004 Nov;180(11):695-700. doi: 10.1007/s00066-004-9194-z. PMID: 15549187.\u003c/li\u003e\n \u003cli\u003eLowy AM, Feig BW, Janjan N, Rich TA, Pisters PW, Ajani JA, Mansfield PF. A pilot study of preoperative chemoradiotherapy for resectable gastric cancer. Ann Surg Oncol. 2001 Jul;8(6):519-24. doi: 10.1007/s10434-001-0519-1. PMID: 11456051.\u003c/li\u003e\n \u003cli\u003eKumagai K, Rouvelas I, Tsai JA, Mariosa D, Lind PA, Lindblad M, Ye W, Lundell L, Schuhmacher C, Mauer M, Burmeister BH, Thomas JM, Stahl M, Nilsson M. Survival benefit and additional value of preoperative chemoradiotherapy in resectable gastric and gastro-oesophageal junction cancer: a direct and adjusted indirect comparison meta-analysis. Eur J Surg Oncol. 2015 Mar;41(3):282-94. doi: 10.1016/j.ejso.2014.11.039. Epub 2014 Nov 27. PMID: 25491892.\u003c/li\u003e\n \u003cli\u003eFiorica F, Cartei F, Enea M, Licata A, Cabibbo G, Carau B, Liboni A, Ursino S, Camm\u0026agrave; C. The impact of radiotherapy on survival in resectable gastric carcinoma: a meta-analysis of literature data. Cancer Treat Rev. 2007 Dec;33(8):729-40. doi: 10.1016/j.ctrv.2007.08.005. Epub 2007 Nov 1. PMID: 17935888.\u003c/li\u003e\n \u003cli\u003eHaskins IN, Kroh MD, Amdur RL, Ponksy JL, Rodriguez JH, Vaziri K. The Effect of Neoadjuvant Chemoradiation on Anastomotic Leak and Additional 30-Day Morbidity and Mortality in Patients Undergoing Total Gastrectomy for Gastric Cancer. J Gastrointest Surg. 2017 Oct;21(10):1577-1583. doi: 10.1007/s11605-017-3496-9. Epub 2017 Jul 25. PMID: 28744744.\u003c/li\u003e\n \u003cli\u003eIkoma N, Das P, Blum M, Estrella JS, Devine CE, Wang X, Fournier K, Mansfield P, Minsky BD, Ajani J, Badgwell BD. Preoperative Chemoradiation Therapy Does Not Increase Risk of Anastomotic Leak in Patients With Gastric Cancer. Int J Radiat Oncol Biol Phys. 2017 Nov 1;99(3):660-666. doi: 10.1016/j.ijrobp.2017.07.018. Epub 2017 Jul 20. PMID: 29280460.\u003c/li\u003e\n \u003cli\u003eFukagawa T, Gotoda T, Oda I, Deguchi Y, Saka M, Morita S, Katai H. Stenosis of esophago-jejuno anastomosis after gastric surgery. World J Surg. 2010 Aug;34(8):1859-63. doi: 10.1007/s00268-010-0609-y. PMID: 20458580.\u003c/li\u003e\n \u003cli\u003ePeifer KJ, Shiels AJ, Azar R, Rivera RE, Eagon JC, Jonnalagadda S. Successful endoscopic management of gastrojejunal anastomotic strictures after Roux-en-Y gastric bypass. Gastrointest Endosc. 2007 Aug;66(2):248-52. doi: 10.1016/j.gie.2006.10.012. Epub 2007 Apr 23. PMID: 17451700.\u003c/li\u003e\n \u003cli\u003eCsendes A, Burgos AM, Burdiles P. Incidence of anastomotic strictures after gastric bypass: a prospective consecutive routine endoscopic study 1 month and 17 months after surgery in 441 patients with morbid obesity. Obes Surg. 2009 Mar;19(3):269-73. doi: 10.1007/s11695-008-9625-5. Epub 2008 Aug 12. PMID: 18696171.\u003c/li\u003e\n \u003cli\u003eZhu Y, Chen J, Sun X, Lou Y, Fang M, Zhou F, Zhang L, Xin Y. Survival and complications after neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for locally advanced gastric cancer: a systematic review and meta-analysis. Front Oncol. 2023 May 9;13:1177557. doi: 10.3389/fonc.2023.1177557. PMID: 37228495; PMCID: PMC10203550.\u003c/li\u003e\n \u003cli\u003eWang F, Qu A, Sun Y, Zhang J, Wei B, Cui Y, Liu X, Tian W, Li Y. Neoadjuvant chemoradiotherapy plus postoperative adjuvant XELOX chemotherapy versus postoperative adjuvant chemotherapy with XELOX regimen for local advanced gastric cancer-A randomized, controlled study. Br J Radiol. 2021 Aug 1;94(1124):20201088. doi: 10.1259/bjr.20201088. Epub 2021 Jul 14. PMID: 34260297; PMCID: PMC8764914.\u003c/li\u003e\n\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 chemoradiotherapy, gastric cancer, anastomotic complications","lastPublishedDoi":"10.21203/rs.3.rs-6596808/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6596808/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Our institution conducted a pilot study of neoadjuvant chemoradiotherapy (NACRT) in carcinoma stomach. The surgical complications were compared with a contemporary cohort of patients receiving neoadjuvant chemotherapy (NACT) in carcinoma stomach.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and Methods:\u003c/strong\u003e Patients who underwent neoadjuvant therapy followed by curative gastrectomy between 2015-2022 were included in this ambispective analysis. These patients were divided into groups: Group 1: NACT and Group 2: NACRT. NACT was given as 3 cycles of ECX/ECF, while NACRT was given as 2 cycles of CX chemotherapy (CT) followed by concurrent radiotherapy (RT) to a dose of 45 Gy/25 # with Intensity-modulated radiation therapy (IMRT) technique and concurrent Capecitabine(X). The primary outcome measure was anastomotic complications, which were compared between groups. Crude percentages, median, and means are reported and compared using the chi-square test and t-test. Univariable and multivariable analyses were performed to identify predictors of complications.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDuring this period, 42 patients who underwent curative resections were identified. The median age was 51 years (IQR 42-65). The majority (50%) had an antropyloric location, 32 (76%) patients had T3/4 disease, and 27 (64%) patients had node-positive disease. Of them, 27 (64%) patients received NACT, and the remaining 15 (36%) received NACRT. Most had distal/subtotal gastrectomy (48%) and Billroth II reconstruction (36%).\u003c/p\u003e\n\u003cp\u003eAt a median follow-up of 28 months, overall anastomotic complications were seen in 6 (14%) patients, anastomotic leak in 4 (9%) and anastomotic stenosis in 6 (14%) patients. The incidence of anastomotic leak was 7% vs 13% (p=0.53), and anastomotic stenosis was 7% vs 27% (p=0.08) in Grp 1 vs 2. Overall, anastomotic complications were 7% vs 27% (p=0.08), pulmonary (29.6 %vs 26.7%, p=0.839) and cardiac complications (0 vs 6.7%, p=0.174) in groups 1 vs 2. The median duration of hospital stay was 12 vs. 14 days (p=0.84), and the 90-day mortality rate was 3.7% vs 0%, p=0.45 in groups 1 vs 2. On multivariable regression analysis, increasing age (p=0.04, OR=0.91), NACRT (p=0.04, OR=14.6), and adjuvant therapy (p=0.03, OR=24.7) were predictors of overall anastomotic complications.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e NACRT increases anastomotic complications as compared to NACT and should be used cautiously in patients with GC.\u003c/p\u003e","manuscriptTitle":"Impact of neoadjuvant chemoradiotherapy (NACRT) vs neoadjuvant chemotherapy (NACT) on anastomotic complications in gastric carcinoma.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-13 16:21:34","doi":"10.21203/rs.3.rs-6596808/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":"af19a971-ae8a-4c39-a793-a410f169bc36","owner":[],"postedDate":"May 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-07T12:38:19+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-13 16:21:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6596808","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6596808","identity":"rs-6596808","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}