Background: Achieving competency is crucial to ensure optimal outcomes in minimally invasive Intersphincteric resection. This study documents the learning curves for minimally invasive Intersphincteric resection using risk-adjusted cumulative sum curves with the surgical failure as a composite endpoint, providing a dynamic assessment of performance and competency attainment. Methods: All consecutive minimally invasive Intersphincteric resections performed by a single team of surgeons at a tertiary referral colorectal cancer unit were audited. Surgical failure was defined as any of the following: positive resection margin, local recurrence, or unreversed ostomy at one year. Risk-adjusted cumulative sum and Bernoulli cumulative sum curves were used for sequential assessment of performance. Results: Amongst 310 Intersphincteric resections, surgical failure was observed in 66 patients (21%). A positive margin was seen in 11 patients (3.5%), unreversed stoma at one year in 53 (17%), and local recurrence in 18 patients (5.8%). The risk-adjusted cumulative sum identified the first inflexion point corresponding to the achievement of competency after the 40th case. Further, other instances of higher-than-predicted surgical failures were observed and explained. While laparoscopic Intersphincteric resection risk-adjusted cumulative sum curves mirrored the curves for entire cohort, the robotic curves could not identify any discernable inflexion. Conclusions: The learning curve for Intersphincteric resection by minimally invasive technique was achieved after the 40th case for a team that was trained in minimally invasive colorectal surgery. The broader applicability of cumulative sum curves for early detection of deterioration in outcomes highlights the need for their wider use in procedural monitoring.

ABSTRACT Background Patients with locally advanced rectal cancer show variable responses to neoadjuvant chemoradiotherapy (NACTRT), making early prediction of treatment response clinically important. Radiomics and machine learning may offer a potential non‐invasive imaging biomarker to identify patients who are more likely to respond to treatment. Aim We investigated a machine learning‐based radiomic approach to predict tumor response (TR) to NACTRT in patients with adenocarcinoma of the rectum from baseline and post‐NACTRT magnetic resonance imaging (MRI). Methods One hundred patients with locally advanced rectal cancer, who underwent pre‐ and post‐treatment MRI after NACTRT were included in the study after approval from the institutional ethics committee. One hundred twenty‐four radiomic features were extracted using the TexRad softwareTm, from pre‐ and post‐treatment T2W MRI, which included first‐order, GLCM, and shape features. Features were selected by the recursive feature elimination (RFE) algorithm. Five machine learning classifiers—support vector machine (SVM), random forest (RF), gradient boost (GB), Naive Bayes (NB) and AdaBoost (AB) classifiers were used to develop a prediction model for predicting TR. Results Five radiomic features were selected using for TR using RFE using RF algorithm. The RF model with 10‐fold internal cross‐validation performed the best for predicting TR. The predictive performance of the RF model for TR was found to be AUC: 0.79 ± 0.15, accuracy: 0.72 ± 0.12, and precision: 0.77 ± 0.10 for the test cohort respectively. Conclusion RF classifier based radiomic model provided a non‐invasive method to predict TR in patients of carcinoma rectum undergoing NACTRT treatment. The predictive potential of the radiomic features further requires validation in a larger cohort of patients in a multicentric study for clinical translation.

BACKGROUND AND PURPOSE:Gastrointestinal (GI) side effects are common after radiotherapy for gynecological cancers. Normal tissue complication probability (NTCP) models providing individual risk estimates for GI adverse events in gynecological cancers are not yet available. The aim of this study was to develop NTCP models for GI toxicity after postoperative (chemo)radiotherapy for cervical cancer. MATERIALS AND METHODS:Data from the phase-III PARCER trial (NCT01279135) was used. Tested variables included patient- and treatment-related characteristics and dosimetric parameters of small, large, and total individual bowel loops, and bowel bag as peritoneal space. NTCP endpoints included acute and late ≥G2 diarrhea and GI toxicity (CTCAEv3.0) and late persistent GI toxicity defined with the Cumulative-Month and Severity Score (C-MOSES). Logistic or Cox regression were used for multivariable models, selecting variables with Least Absolute Shrinkage and Selection Operator. Internal model performance was evaluated with area-under-the-curve (AUC) or C-index. RESULTS:The median follow-up of the 283 included patients was 43 months. Volumes of the bowel receiving 30 Gy (V30Gy) and 40 Gy (V40Gy) were associated with acute and late ≥G2 diarrhea and persistent GI toxicity. IMRT reduced risk of late ≥G2 and persistent GI toxicity, whereas radical hysterectomy with bilateral lymphadenectomy increased it. AUC/C-indices ranged from 0.588 (persistent GI toxicity) to 0.761 (late ≥ G2 diarrhea). CONCLUSION:NTCP models for acute and late diarrhea and persistent GI toxicity after postoperative radiotherapy for cervical cancer included bowel V30Gy and V40Gy. Furthermore, 3DCRT and more extensive surgery increased risks. Further studies should explore additional variables to improve model performance, reach consensus on bowel delineation methods, and validate models externally.

The primary curative therapies for hepatocellular carcinoma are resection or liver transplantation. For patients requiring downstaging or who are unresectable at presentation, the landscape of local treatment options has vastly changed over the past decades. This change is partly due to the paucity of high-level evidence to guide the selection of liver-directed therapies, where physician preference and treatment patterns have historically resulted in relegating external-beam radiation therapy (EBRT) to a secondary option in the treatment of hepatocellular carcinoma in cases where arterially directed therapies or thermal ablations were not possible. However, technology advancements have substantially improved the ability to treat liver malignancies with high doses of radiation therapy and to minimise doses to uninvolved hepatic parenchyma and other nearby organs. These advancements have enabled safe treatment of hepatocellular carcinoma with EBRT, with low risk of toxicity. Recent randomised trials support the role of EBRT in the treatment of hepatocellular carcinoma from early to advanced stages. These trials identified that EBRT improved several key patient-centred outcomes, including overall survival when using stereotactic body radiotherapy and sorafenib compared with sorafenib alone in unresectable hepatocellular carcinoma, recurrence-free survival with the use of adjuvant EBRT in select patients after hepatocellular carcinoma resection, and quality of life for patients with painful hepatocellular carcinoma masses treated with palliative EBRT. With emerging high-quality evidence, hepatocellular carcinoma therapeutic guidelines should include the growing role of EBRT in improving the quality and quantity of life for patients with liver cancer.

AimStatins have been shown to improve the possibility of a pathological complete response (pCR) in patients with locally advanced rectal cancer when given in combination with neo-adjuvant chemo-radiation (NACTRT) in observational studies. The primary objective of this phase II randomized controlled trial (RCT) is to determine the impact of rosuvastatin in improving pCR rates in patients with locally advanced rectal cancer who are undergoing NACTRT. The secondary objectives are to compare adverse events, postoperative morbidity and mortality, disease-free survival (DFS), and overall survival in the two arms and to identify potential prognostic and predictive factors determining outcomes. If the study is positive, we plan to proceed to a phase III RCT with 3-year DFS as the primary endpoint.MethodsThis is a prospective, randomized, open-label phase II/III study. The phase II study has a sample size of 316 patients (158 in each arm) to be accrued over 3 years to have 288 evaluable patients. The standard arm will receive NACTRT while the intervention group will receive 20 mg rosuvastatin orally once daily along with NACTRT for 6 weeks followed by rosuvastatin alone for 6–10 weeks until surgery. All patients will be reviewed after repeat imaging by a multidisciplinary tumor board at 12–16 weeks after starting NACTRT and operable patients will be planned for surgery. The pathological response rate, tumor regression grade (TRG), and post-surgical complications will be recorded.ConclusionThe addition of rosuvastatin to NACTRT may improve the oncological outcomes by increasing the likelihood of pCR in patients with locally advanced rectal cancer undergoing NACTRT. This would be a low-cost, low-risk intervention that could potentially lead to the refinement of strategies, such as “watch and wait”, in a select subgroup of patients.Clinical trial registrationClinical Trials Registry of India, identifier CTRI/2018/11/016459.

Purpose Treatment intensification using either contact X-ray brachytherapy boost (CXB) or chemotherapy (TNT) has become the standard option for rectal preservation. Besides CXB, CT and MRI-based HDR brachytherapy (MR-BCT) are other options to escalate radiation doses. With long-course chemoradiation, MR-BCT is usually added after a gap of 2-6 weeks. Similar information on adding BCT with a TNT setting is not known. We report here the feasibility of MR-BCT in locally advanced rectal cancer patients (>5 cm) being treated with intent for non-operative management (NOM) using short-course radiotherapy (SCRT) followed by 18 weeks of adjuvant chemotherapy (TNT) in a prospective phase II study (SCOTCH study; NCT05856305). Materials and Methods Seventy-six patients were accrued in the study, randomized (1:1) to receive either the NrF-2 activator (Chlorophyllin) or placebo (double-blinded), along with SCRT-based TNT. As per the protocol, all patients, irrespective of the study arm, were planned to be assessed at 8-12 (±4) weeks post-SCRT for suitability to undergo MR-BCT. Two independent radiation oncologists assessed this by doing a digital rectal examination. Patients were offered MR-BCT if they had a significant local response with residual disease/scar craniocaudal length of <3 cm and <75% circumference (ideally <50%), rectal lumen at least 2 cm in diameter (corresponding applicator diameter), and distance from the anal verge within 10 cm. The patients identified thus underwent MR-BCT of 5-7 Gy x 3 fractions prescribed to the outer surface of the tumor, with tumor-mucosa restricted to 200% dose. The opposite rectal mucosal dose was limited to <50% using two inflatable balloons over an indigenously designed 3D-printed six-channel applicator. The data presented shows when patients may be suitable for MR-BCT when assessed 8 -12 weeks post SCRT on TNT and reasons for non-suitability. This study is ongoing. Results Of the 76 randomized patients, 73 were assessed for MR-BCT. Sixty-three (86.3%) were found suitable at a median of 10 weeks (IQR: 9.1-11.1) post-SCRT. Of these, 61 (96.8%) completed MR-BCT, while two refused MR-BCT and continued TNT. Suitable patients received MR-BCT at a median of 12 weeks (IQR: 10.1-13.2) from SCRT. Ten percent of patients were suitable as early as the 8-9th week, while another 10% were as late as the 15th-16th week. The median CCL of tumors at presentation was 5.8 cm (IQR: 5.07-6.4) on MRI at diagnosis. Overall, there was a median 65.3% shrinkage in CCL and 91.97% shrinkage in volume at MR-BCT. Of the 10 patients (13.7%) who were ineligible for brachytherapy, nine were due to technical reasons (seven: fibrotic lumen <2 cm; two: residual >10 cm from the anal verge) and one clinical (a suspicious local ulcer involving the dentate region with severe pain affecting ADL). This patient underwent surgery and was found to have a pCR. Conclusions MR-BCT is feasible in the majority of patients between 9-11 weeks during TNT, with about 10% being eligible as late as 16 weeks.

AIM:Consensus is lacking regarding the management of extramesorectal lymph nodes (EMLN) in rectal cancer. Using simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT), we targeted involved EMLN and reserved lateral pelvic lymph nodal dissection (LPLND) for nonresponders. The primary aim of this work was to determine the proportion of patients who avoided LPLND and to establish the pathological EMLN positivity rate. METHOD:Consecutive patients with rectal cancer with suspicious EMLN [short axis dimension (SAD) ≥ 7 mm], receiving SIB-IMRT as part of neoadjuvant chemoradiotherapy and subsequently undergoing total mesorectal excision (TME) or watch-and-wait, were included. Our primary objective was to determine the proportion of patients with a good nodal response (EMLN SAD < 5 mm) who were spared LPLND. The 3-year locoregional relapse rate, distant metastasis-free survival (DMFS) and overall survival (OS) were also assessed. RESULTS:Of the 61 patients studied, 38 (62.3%) responded well to SIB-IMRT. In this group, 32 patients underwent TME alone and six were observed as per watch-and-wait. The remaining 23 (37.7%) patients with persistent EMLN received TME with LPLND. On pathological evaluation, 7 (30.4%) patients had positive nodes while 16 (69.6%) were negative. At a median follow-up of 32 months (95% CI 23.3-40.7 months), 10 (16.4%) patients developed distant metastases while none had local or pelvic relapse. The resultant 3-year DMFS and OS for the whole cohort were 84.4% and 95.1%, respectively. Overall, 5/61 (8.2%) patients encountered radiation-induced toxicity of grade 3 or above and 8/55 (14.5%) patients had severe postoperative complications. CONCLUSION:SIB-IMRT targeting EMLN followed by selective LPLND exhibits excellent oncological outcomes. While patients responding to SIB-IMRT safely avoid LPLND, the potential for increased morbidity in nonresponders must be considered.

Purpose:Long-course chemoradiation followed by a brachytherapy boost is one of the acceptable treatment options for watch-and-wait (W&W) eligible rectal cancer patients. However, MRI acquisition, planning, and treatment delivery delays can affect patient satisfaction and treatment success. This study used the classical quality improvement methodology to optimise the MRI-based rectal brachytherapy process. Material and methods:A multidisciplinary core team was formed, including a radiation oncologist, radiologist, medical physicist, specialist technologist and nurse. Data on wait times from MRI to brachytherapy treatment were collected for patients receiving rectal brachytherapy between August and November 2022. We aimed to reduce the number of days of the gap between the planning MRI day and the treatment delivery day from a median (Dmedian) and mean (Dmean) of 14 and 15 days, respectively, to < 1 day each (primary goal) and to increase the number of same-day treatments (D0%) from currently 0% to at least 70% (secondary goal) by 31st January 2023. The balancing measure was treatment errors or delays. Quality improvement measures were implemented using the Plan-Do-Study-Act (PDSA) cycles. Results:The post-implementation data at PDSA 1 and 2 from 14 patients each were analysed. The post-change Dmedian, Dmean and D0% improved to 3, 3 days and 35.7% for PDSA 1. This further improved to zero, 0.2 days and 78.9%, respectively, for PDSA 2. A sustained shift in the process was apparent on a control run chart, suggesting sustainability. Further in the sustenance phase, the Dmedian, Dmean and D0% were maintained at 0.3, 0 days and 74%, respectively, for over 42 patients. Conclusions:Using the classical quality improvement methodology, we sustainably reduced the delay between the planning MRI day and the treatment delivery day. These strategies may serve as a model for other institutions implementing MRI-based brachytherapy programmes for the W&W approach in suitable rectal cancer patients.

4007 Background: Locally advanced Gallbladder cancers (LAGBC)initially deemed not suitable for R0 resection receive either neoadjuvant chemotherapy (NACT)or neoadjuvant chemoradiation (NACRT)downstaging for resection and to improve outcomes. Methods: This is a randomized phase 3 trial (NCT02867865) that included fit patients with LAGBC adenocarcinoma,. T3/T4 with liver infiltration ( > 2cm, < 5cm); N1 nodal status; obstructive jaundice (type I/II biliary obstruction) ;duodenal or colonic abutment with no mucosal infiltration , < 180°vascular involvement. The patients were randomized (1:1) to NACT arm (Gemcitabine + platinum for four cycles) versus NACRT arm (55 -57Gy with concurrent gemcitabine followed by two cycles of chemotherapy) and were then evaluated for surgery. A sample size of 314 patients was required to detect a 5.5 months difference (11 mo.to 16.5 mo in the test arm) with median overall survival (OS) as the primary endpoint (hazard ratio, 0.7; 2-sided α = 0.05; β = 0.2). Secondary endpoints were event free survival (EFS),R0 resection rates and post-operative complication rates. Due to slow accrual Institutional Ethics committee requested the investigators for interim analysis and approval was obtained for the same. Results: From Oct 2016 to Sept 2024 , 124 patients (64 NACT, 60 NACTRT)were enrolled at 2 centers. At the time of analysis 93 OS events were observed in 124 patients. Median follow-up was 62 (range 6.9-94) months. More number of patients underwent R0 resection in NACRT than NACT arm 51.6 vs 29.7% (p = 0.01) In the intention to treat analysis, the NACTRT arm showed improved OS compared to the NACT arm [21.8 mo.vs.10.1 mo. p = 0.006]. EFS was 10.6 mo. vs 4.9 months, p = 0.006]. Similar results were noted in the per protocol analysis(n = 110). Clavien Dindo postoperative morbidity of grade 3 and above was 4/22 (18.18%) in NACT arm vs 9/32(28.12%) in NACRT arm (p = 0.30). The interim analysis demonstrated a significant improvement in efficacy in the NACRT arm. Based on the current data, the conditional power was calculated to be 99.96%. Conclusions: This trial demonstrates that the addition of concurrent chemoradiation to chemotherapy improves overall survival and resection rates in patients with locally advanced gallbladder cancers. These results provide important evidence to guide treatment decisions in this traditionally difficult to treat set of gallbladder cancers. Clinical trial information: NCT02867865 . Treatment outcomes. Outcome measures NACTRTN=60 NACTN=64 HR p Patients surgically explored 39(65%) 29(45.3%) 0.03 Patients undergoing R0 resection 31 (51.6%) 19 (29.7%) 0.01 Median OS (months) (95% CI) 21.8 (14.6-29.14) 10.1 (8.5-11.7) HR- 0.5695%CI- 0.37-0.84 0.006 5 Year survival (95% CI) 27 (17.7-43)% 18 (10-31) % EFS (months) (95% CI) 10.6 (6.07-15.5-15) 4.89 (3.06-6.73) HR-0.5895%CI- 0.39-0.85 0.006 5 Yr EFS (%) 21 (12-35.7)% 12.7 (6-24.6)%

BACKGROUND:To evaluate outcomes of postneoadjuvant chemoradiotherapy (NACTRT) wait and watch strategy (WWS) in distal rectal cancers. METHODS:All consecutive patients from December 2012 to 2019 diagnosed with distal rectal tumors (T2-T4 N0-N+) having a complete or near-complete response (cCR or nCR respectively) post-NACTRT and wished for nonsurgical treatment option of WWS were included in this study. Patients were observed with 3 monthly MRI, sigmoidoscopy, and digital rectal examination (DRE) for 2 years and 6 monthly thereafter. Organ preservation rate (OPR), local regrowth rate (LRR), nonregrowth recurrence-free survival, and overall survival (OS) were estimated using the Kaplan-Meier method, and factors associated with LRR were identified on univariate and multivariate analysis using the log-rank test (P < 0.05 significant). RESULTS:Sixty-one consecutive patients post-NACTRT, achieving cCR [44 (72%)] and nCR [17 (28%)], respectively, were identified. All patients received pelvic radiotherapy to a dose of 45-50Gy conventional fractionation with concurrent Capecitabine. Additional boost dose with either external beam or brachytherapy was given to 39 patients. At a median follow-up of 39 months, 11 (18%) patients had local regrowth, of which seven were salvaged with surgery and the rest are alive with disease, as they refused surgery. The overall OPR, nonregrowth recurrence-free survival, OS was 83%, 95%, and 98%, respectively. Seven (11%) patients developed distant metastasis, of which six underwent metastasectomy and are alive and well. LRR was higher in patients with nCR versus cCR (P = 0.05). CONCLUSION:The wait-and-watch strategy is a safe nonoperative alternative management for selected patients attaining cCR/nCR after NACTRT with excellent outcomes.

Chemoradiation with capecitabine radiotherapy (Cape–RT) has been the standard of care as neoadjuvant treatment in locally advanced rectal cancer (LARC) for more than a decade. However, total neoadjuvant therapy has recently emerged as an alternative with the potential to impact survival outcomes; baseline outcomes with Cape–RT in real-world practice in the Indian context are not well known. Treatment-naive patients with adenocarcinoma on histology and clinical-radiologically diagnosed LARC who received Cape–RT from June 2014 to December 2021 after multidisciplinary discussion were included. Patients received a long course of conventionally fractionated external beam RT (45–50 Gy in 25#) with concurrent oral capecitabine at a dose of 1650 mg/m2/day. Post approximately 6 to 8 weeks of completion of Cape–RT, patients were evaluated clinically and by magnetic resonance imaging pelvis for total mesorectal excision (TME) in the multidisciplinary team meetings. The primary endpoint of the study was event-free survival (EFS), and the secondary endpoint was overall survival (OS) and pathological complete response (PCR) rates. EFS and OS were calculated using the Kaplan–Meier method. A total of 1,189 patients with a median age of 49 years (range: 15–95) were identified and included. A significant proportion of patients had high-risk characteristics, such as T3/T4 disease (94%) and node positivity (90%), and they involved circumferential resection margin (CRM) (51%) at baseline. Signet ring and mucinous histology were seen in 13 and 11% of patients. Two hundred and seventy-six patients (23%) required further consolidation chemotherapy (commonly CAPOX [capecitabine-oxaliplatin] or modified FOLFIRINOX [5-fluorouracil-leucovorin-irinotecan-oxaliplatin]) post-Cape–RT prior to attempting surgery due to either persistent CRM positivity, clinical T4 disease, prostate abutment, sphincter involvement (248 patients, 21%), or extensive bulky disease with poor response (12 patients, 1%). Overall, 14 patients (6%) had an interruption in RT and 22 (8%) in chemotherapy. Post-Cape–RT, with or without chemotherapy, 945 patients (79%) underwent TME. Chemotherapy post-TME was administered in 808 patients (78%). With a median follow-up of 54 months (range: 51.2–57.2), the 3- and 5-year EFS for the entire cohort was 73.2% (95% confidence interval [CI]: 70.6–75.8) and 64.3% (95% CI: 61.1–67.5), respectively, while the estimated 3- and 5-year OS was 81.3% (95% CI: 78.9–83.7) and 73% (95% CI: 70–76), respectively. On multivariate analysis, the presence of higher T stage (p < 0.001) and signet ring histology (p = 0.004) predicted inferior OS. Real-world data in a less-resourced setting concurs with published prospective and Western real-world data. This provides confidence in implementing consolidation chemotherapy in total neoadjuvant settings in countries with fewer resources.

Background: The European Organization for the Research and Treatment of Cancer (EORTC) has developed a commonly used validated questionnaire specific to anal cancer (EORTC QLQ-ANL27). It is used as an adjunct to the core EORTC quality-of-life (QoL) questionnaire QLQ-C30. This validated questionnaire was not available in any Indian language, and therefore, Indian patients not familiar with English could not fill it. Objective: We aimed to translate and validate the EORTC QLQ-ANL27 module in Hindi, Marathi, and Bangla languages. Materials and Methods: This study was conducted in the Department of Radiation Oncology at the Tata Memorial Hospital, a tertiary cancer center in Mumbai, India, from September 01, 2022, to March 31, 2023. The QLQ-ANL27 questionnaire was translated into Hindi, Marathi, and Bangla languages using the standard EORTC guidelines. The overall process comprised two independent forward translations of the original English questionnaire into the target languages, followed by reconciliation between the two forward translations. The reconciled version was then back translated to English. The report generated was sent to the EORTC translation unit (TU) for review. Once approved by the EORTC TU, these translated versions were pilot tested on 30 patients (10 for each language) with cancer of the rectum or anal canal. After responding to the questionnaires, each patient was individually interviewed to explore any difficulty encountered while answering the QoL questionnaire. The interviewer specifically asked whether the patients found any words or sentences difficult to answer, confusing, or upsetting, and for suggestions on better phrasing. Results: The EORTC QLQ-ANL27 was translated to Hindi, Marathi, and Bangla, followed by back translation into English within a period of 2 months between September 2022 and October 2022. The translated versions were approved by the EORTC TU in October 2022. Validation of the translated versions was conducted between December 2022 and March 2023 in 30 patients diagnosed with anorectal cancer. The median age of the patients was 55 (interquartile range, 29–77); the male-to-female ratio was 2:1. There were no suggestions or doubts in the Hindi, Marathi, and Bangla questionnaires during the pilot testing. After reviewing the pilot testing reports, the EORTC TU approved the translated versions of QLQ-ANL27. The reliability of the translated questionnaires was confirmed using Cronbach’s alpha, which were 0.838, 0.743, and 0.808 for the Hindi, Marathi, and Bangla versions, respectively. Conclusions: The Hindi, Marathi, and Bangla translations of the QLQ-ANL27 module have been validated and approved by the EORTC and are now available for use (Clinical Trials Registry-India, CTRI/2022/12/047970).

Background: The evolution and outcomes of extended pancreatectomies at a single institute over 15 years are presented in this study. Methods: A retrospective analysis of the institutional database was performed from 2015 to 2022 (period B). Patients undergoing extended pancreatic resections, as defined by the International Study Group for Pancreatic Surgery, were included. Perioperative and survival outcomes were compared with data from 2007-2015 (period A). Regression analyses were used to identify factors affecting postoperative and long-term survival outcomes. Results: A total of 197 (16.1%) patients underwent an extended resection in period B compared to 63 (9.2%) in period A. Higher proportions of borderline resectable (5 (18.5%) versus 51 (47.7%), P = 0.011) and locally advanced tumours (1 (3.7%) versus 24 (22.4%), P < 0.001) were resected in period B with more frequent use of neoadjuvant therapy (6 (22.2%) versus 79 (73.8%), P < 0.001). Perioperative mortality (4 (6.0%) versus 12 (6.1%), P = 0.81) and morbidity (23 (36.5%) versus 83 (42.1%), P = 0.57) rates were comparable. The overall survival for patients with pancreatic adenocarcinoma was similar in both periods (17.5 (95% c.i. 6.77 to 28.22) versus 18.3 (95% c.i. 7.91 to 28.68) months, P = 0.958). Resectable, node-positive tumours had a longer disease-free survival (DFS) in period B (5.81 (95% c.i. 1.73 to 9.89) versus 14.03 (95% c.i. 5.7 to 22.35) months, P = 0.018). Conclusion: Increasingly complex pancreatic resections were performed with consistent perioperative outcomes and improved DFS compared to the earlier period. A graduated approach to escalating surgical complexity, multimodality treatment, and judicious patient selection enables the resection of advanced pancreatic tumours.

30 Background: Optimal management for lateral pelvic lymph nodes (LPLN) in Ugly locally advanced rectal cancer (LARC) is unknown & is associated with worse outcomes. We hypothesise that total neo-adjuvant (TNT) using Short-course radiotherapy (SCRT) with SIB to lateral pelvic lymph nodes would improve outcomes. Methods: All consecutive patients of LARC with LPLN treated with SCRT-based TNT from Jan 2021 – Dec 2022 were reviewed (IEC No: 4116). The LPLN (external, internal, common iliac or obturator) was considered radiologically significant based on joint clinic review with classical criteria. They were divided into two groups (SIB-IMRT: up to 30Gy/5#; or not). The chemotherapy schedule was similar to RAPIDO study, followed by TME +/- LPLN dissection based on radiological response assessed in joint clinic. Two groups were compared for baseline features using Fisher’s exact/Chi-Square tests as appropriate. Outcomes were reviewed for overall response in LPLN (radiological or pathological), disease outcomes & toxicity (acute radiotherapy CTCAE v5, 30-day Clavien Dindo post-surgical, & HRQL EOTRC QLQ-C30). Results: From 398 patients, 83 (20.8%) were identified with LPLN receiving SCRT with TNT, of which 44 (53.01%) received a SIB boost. Overall, 40% were aged ≤ 45 years, 50% had poor histology (signet, PDAC, Mucinous), 35% had EMVI, and 83% were N2+. The two groups had a similar distribution of baseline features (p>0.05) & were matched for poor prognostic factors. The patients who received a boost were 20% more likely to complete TNT and undergo TME than patients who did not (81.8% vs 61.5%; p=0.0099), mainly due to a significantly lesser event of disease progression before surgery, rendering them inoperable (25% vs 33.3%; p=0.024). Boost was associated with an increased overall response at LPLN by 20% (84.1% vs 64.1%; p=0.011) & decreased need for PLND by 15% in patients considered for surgery (15.9% vs 30.56%; p=0.072). At a median follow-up of 18 months, 26 patients (31.33%) identified with disease progression were similarly distributed in two groups with similar patterns (all but one had distant metastasis, of which 6 had loco-regional failures). A total of 17 deaths with a non-significant trend of higher 18-month OS observed (boost: 83.4+6.3 vs 75.6+7.8%; HR:2.29(CI:0.85 - 6.19; p=0.09). None of the patients had acute > grade 3 CTCAE v5 toxicity within 4 weeks of radiotherapy completion. Four (4.8%) deaths were chemotherapy-related, & one post-surgery toxicity with similar > grade 3 Clavien Dindo complications in two arms. EORTC QLQ C-30 PROM scores were similar in two groups. Conclusions: In ugly, poor biology LARC, TNT with SCRT-SIB to LPLN seem safe & feasible with improved response, treatment completion & operability without significantly increase in toxicity rates. Long-term prospective studies are warranted to identify significant survival impact.

4124 Background: The optimal adjuvant treatment for gallbladder cancer (GBC) after surgery remains unclear. We previously reported 1 year of disease-free survival (DFS) of adjuvant gemcitabine plus cisplatin (GC) or capecitabine with concurrent capecitabine radiotherapy (Cape-RT). Here, we present the secondary endpoint of the 3-year outcomes of the GECCOR-GB study. Methods: We conducted a multicenter, open-label, non-comparative randomized phase II trial of adjuvant GC or Cape-RT in patients with resected GBC. Patients were randomized 1:1 to receive either GC (gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8 of a 21-day cycle for 6 cycles) or Cape-RT arm {Capecitabine 1000 mg/m2 BD on days 1–14, q 3 weeks for 2-4 cycles followed by chemoradiation (RT: 45 Gy over 25 fractions concurrent with capecitabine: 825 mg/m2 BD) followed by 2-4 cycles of capecitabine for a total of 6 cycles}. The primary endpoint was DFS, and the secondary endpoints were overall survival (OS), safety, and treatment completion rates. Results: We enrolled 90 patients at 3 centers in India between May 2019 and February 2022 and randomly assigned 45 patients to each arm. In the GC arm, the median age of patients was 56 (33–72) years, and 23 (51%) patients were in stage II. While in the cape-RT arm, the median age was 55 (26–69) years, with 27 (60%) patients in stage II. The 3-year DFS was 54.3% in the GC arm and 70.7% in the Cape-RT arm, respectively. The 3-year OS was 75% in the GC arm and 73% in the Cape-RT arm, respectively. The 3-year OS in stage II patients (n = 23) in the GC arm was 91.3%, while in the cape-RT arm (n = 27), it was 91.9%. Median OS in stage III patients (n = 22) was 39.1 (95% CI, 33.4–44.6) months in the GC arm, while in the cape-RT (n = 18), it was 23.2 (95% CI, 7.0–39.4) months. Conclusions: Adjuvant GC arm patients, especially those in stage III, had encouraging OS at 3 years, while both GC and adjuvant Cape-RT arms had excellent 3-year OS, reaching more than 90% in patients with stage II-operated GBC. Further studies are needed to compare and validate these findings for GBC patients. GECCOR-GBwas led by Tata Memorial Hospital (TMC), Mumbai. Clinical trial information: CTRI/2019/05/019323.

Background & objectives: There is limited evidence studying the relationship of liver segmental dose and segmental volume changes. The segmental dose thresholds could potentially allow for segmental regeneration after liver stereotactic body radiation therapy (SBRT). Given improved survival in hepatocellular cancer (HCC) and liver metastases and more salvage therapy options, this has become an important clinical question to explore. This study assesses the impact of liver segmental dose on segmental volume changes (gain or loss) after SBRT. Methods: Liver segmental contours were delineated on baseline and serial follow up triphasic computed tomography scans. The volumes of total liver and doses to total liver, uninvolved liver and individual segments were noted. A correlation was evaluated between liver/segmental volume and dose using Pearson's correlation. Furthermore, receiver operator's curve (ROC) analysis was performed to find the segmental dose, i.e. predictive for liver volume loss. Results: A total of 140 non-tumour liver segments were available for analysis in 21 participants. Overall, 13 participants showed loss of overall liver volume and eight showed gain of overall liver volume. The median dose in segments reporting an increase in volume was 9.1 Gy (7-36 Gy). The median dose in segments losing volume was 15.5 Gy (1-49 Gy). On ROC analysis, segmental dose >11 Gy was associated with volume loss. On univariate analysis, only liver segmental dose contributed to a significant segmental volume loss. Interpretation & conclusions: We propose from the findings of this study that in SBRT for large hepatocellular cancer or liver metastases, liver segments should be individually delineated. Furthermore, 3-5 liver segments may be preferentially subjected to <9 Gy to facilitate hepatocyte regeneration. Preferential sparing of uninvolved liver segments may improve outcomes in liver stereotaxyas lower segmental doses were associated with liver regeneration. This may have implications on future liver SBRT planning where segmental doses may be as important as the mean dose.