Evaluation of liver segmental dose threshold for hepatocyte regeneration following liver stereotactic body radiation therapy.

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.

Differential impact of incrementally elevated CA 19-9 levels on prognosis of resected pancreatic ductal adenocarcinoma.

BACKGROUND: CA 19-9 is an extremely useful biomarker for pancreatic ductal adenocarcinomas (PDACs). However, the optimal cut-off and prognostic significance at higher cut-offs are yet to be determined. METHODS: Retrospective analysis included patients with PDAC who underwent curative resection from January 2010 to May 2020 at Tata Memorial Centre, Mumbai. The pretherapy CA 19-9 was dichotomized using various cut-off levels and analysed. RESULTS: In 244 included patients, the median overall survival (OS) for those with CA19-9 level (IU/ml) < or >78, 200, 500, 1000, and 2000 was 27, 24, 23, 22, 21 months versus 18, 16, 15, 14, 13 months; respectively, and was statistically significant (p-value- 0.002, 0.001, 0.002, 0.002 and 0.004, respectively). The number of recurrences and mortality had significant correlation with CA 19-9 cut-offs. On multivariate analysis, adjuvant treatment completion (p-0.004) and decreasing or stable CA19-9 after Neoadjuvant therapy (NAT) (p- 0.031) were associated with improved OS. CONCLUSION: The prognostic significance of CA 19-9 was observed at all the cut-off levels examined, beyond mere elevated value as per the standard cut-off level. In patients with high CA19-9 level, surgery should be offered if technically and conditionally feasible, only when a response in CA19-9 level to NAT is achieved.

Pathological N3 Stage (pN3/ypN3) Gastric Cancer: Outcomes, Prognostic Factors and Pattern of Recurrences After Curative Treatment.

BACKGROUND: pN3 or ypN3 stage gastric cancers (GCs) are known to have aggressive clinical behaviour. This study aimed to investigate factors affecting survival and pattern of recurrences of N3 stage GCs, treated with curative intent. METHODS: A total of 196 GC patients, operated on at the Tata Memorial Centre from 2003 to 2017 and reported as pN3 or ypN3 status on histopathology after D2 gastrectomy were included in this retrospective analysis. RESULTS: On multivariate analysis, use of NACT (neoadjuvant chemotherapy) and LN ratio (≤ 0.5/> 0.5) emerged as significant predictors for long-term survival. Patients who received NACT but were still harbouring N3 nodes (ypN3; n = 102) had a worse prognosis than those operated on upfront (pN3; n = 94), with a median survival of 19 months versus 24 months respectively (p = 0.003). The 5-year overall survival of the entire cohort was 16.3% (95% CI 12.8-19.8%), while 5-year disease-free survival (DFS) was 14.6% (95% CI 12.6-20%). Adjuvant chemoradiotherapy, though offered in a small number of patients (n = 38) resulted in improvement in DFS. Median DFS of adjuvant CT versus adjuvant CRT was 13 months versus 23 months (p = 0.020). The commonest site of relapse was the peritoneum (49.18%) and incidence of isolated loco-regional failure was 10.7%. CONCLUSION: In GCs with N3 stage determined after radical D2 gastrectomy, LN ratio of > 0.5 and ypN3 status are predictors of poor prognosis. Considering the high incidence of peritoneal and loco-regional relapse in these patients, the role of more radical surgery, adjuvant chemoradiotherapy after upfront resection and intraperitoneal chemotherapy should be evaluated in prospective randomized clinical trials.

Laparoscopic ovarian transposition in teenage and young women with locally advanced rectal cancer: Respite amidst cancer chaos.

AIM: Ovarian transposition is an established surgical technique to salvage ovaries in premenopausal women requiring pelvic radiation. The success rate of ovarian transposition varies widely depending on the route, technique of surgery, type of cancer and treatment. Here, we aimed to analyse the effectiveness of laparoscopic ovarian transposition (LOT) in teenage and young women prior to pelvic radiation in locally advanced rectal cancers (LARC). METHODS: Patients who underwent LOT for rectal cancers were retrieved from a prospectively maintained database from June 2013-September 2019. Disease characteristics, return of menstrual function and oncological outcomes were analysed. RESULTS: A total of 46 women with a mean age of 25.2 years who underwent LOT at the cancer centre were included in the study. Seventy percent were nulliparous. All patients were fit for discharge by 24 h. Mean time to start radiation was 19.6 days (range 3-47 days). Median follow-up of patients was 42 months. A total of 41 patients were assessable for ovarian function, 65.5% had resumption of menses. Median ovarian survival was 79 months and 5-year ovarian survival was 54%. Median overall survival from rectal cancer was 51 months. CONCLUSION: Laparoscopic ovarian transposition is a safe and effective technique of ovarian protection from the gonadotoxic effects of pelvic radiation in LARC. It does not delay primary treatment and does not compromise oncological outcomes. Long-term follow-up is required to evaluate fertility and quality of life.

Long-term oncological outcomes of the sphincter preserving total mesorectal excision with varying distal resection margins.

INTRODUCTION: A subcentimeter distal resection margin (DRM) appears to be acceptable for most patients, however, long-term follow up and specific subsets where DRM would influence recurrences have not been adequately investigated. METHODS: A retrospective analysis of all sphincter-preserving resections for mid and low rectal cancers between July 2011 and May 2015 was performed. Extended total mesorectal excisions (TME) and patients with positive pathologic circumferential margins (CRM) were excluded. RESULTS: Two hundred and thirty-six patients fit the inclusion criteria. DRM > 20 mm was obtained in 117 patients (49.6%), between 10 and 20 mm in 78 (33%) and <10 mm in 41 (17.4%) patients. Pathological DRM was positive in 4 patients (1.7%). Sixty-five recurrences occurred at a median follow up of 78.5 months. DRM did not influence any of the oncological outcomes. In a subset analysis of patients with poor pathological response to neoadjuvant radiation, that is, tumor regression grade > 3, DRM influenced disease-free survival (DFS) but not overall survival with a hazard ratio of 4.4 (p = 0.02). This was confirmed on multivariate regression analysis in this subgroup as well where pathological nodal status and DRM < 10 mm were independent predictors of DFS. CONCLUSIONS: A subcentimeter DRM may be acceptable in most patients except those who have an inadequate response to neoadjuvant radiation.

Towards standardization of management of gallbladder carcinoma with obstructive jaundice: Analysis of 113 cases over 10 years at a single institution.

BACKGROUND: Presence of jaundice in gallbladder carcinoma (GBC) is considered a sign of inoperability with no defined treatment pathways. METHODS: Retrospective analysis of all surgically treated GBC patients from January 2010 to December 2019 was performed for evaluating etiology of obstructive jaundice, resectability, postoperative morbidity, mortality, disease-free survival (DFS) and overall survival (OS). RESULTS: Out of 954 patients, 521 patients (54.61%) were locally advanced gallbladder carcinoma (LAGBC: Stage III and IV) and 113 patients (11.84%) had jaundice at presentation. Thirty-four (30%) patients had benign cause of obstructive jaundice. Median OS of the whole cohort (n=113) was 22 months (16.5-27.49 months) with resectability rate of 62% (70/113). Median OS of curative resection group (n=70) was 32 months and DFS was 25 months. Treatment completion was achieved in 30% (n= 21/70) patients with median OS of 46 months and median DFS of 27 months. Isolated bile duct infiltration subgroup fared the best with median OS of 74 months with a 5-year survival of 66.7%. CONCLUSION: Surgical resection as a part of multimodality treatment improves survival in carefully selected locally advanced gallbladder cancer patients with jaundice. Early introduction of systemic therapy is the key in the management of this disease with aggressive tumor biology.

Laparoscopic versus open resection in locally advanced rectal cancers: a propensity matched analysis of oncological and short-term outcomes.

AIM: The aim was to compare oncological and short-term outcomes between open and laparoscopic surgery in locally advanced rectal cancers. METHODS: It is a retrospective analysis conducted in a high volume tertiary centre. Matching was carried out for nine variables, including preoperative factors, neoadjuvant treatment and sphincter preservation. RESULTS: Both the open and laparoscopic surgery arms had 239 patients each. The distributions of pretreatment MRI T3, T4, circumferential resection margin (CRM) positive tumours, neoadjuvant long-course chemoradiation and sphincter preservation were 80.3%, 13.6%, 50%, 89% and 56.4% respectively. The mean number of nodes harvested (12.9 vs. 12.7, P = 0.716), pathological CRM positivity (6.3% in open vs. 5.4% in laparoscopic, P = 0.697) and distal resection margins were similar. The mean blood loss was higher in open surgeries (910 ml vs. 349 ml, P < 0.001). Anastomotic leaks and Clavien-Dindo Grade 3-4 complications were higher in the open arm than in the laparoscopy arm (5.9% vs. 1.7%, P = 0.024, and 12.5% vs. 6.7%, P = 0.015 respectively). The median postoperative hospital stay was significantly shorter in the laparoscopy arm (7 vs. 6, P = 0.015). In CRM positive and threatened cases, the measured outcomes were similar between the two groups except for blood loss which was significantly higher in the open surgery (872 vs. 379, P = 0.000). CONCLUSIONS: In high volume centres, in the hands of experienced colorectal surgeons, laparoscopic rectal surgery is oncologically safe in locally advanced rectal cancers and has lesser morbidity and shorter hospital stay than open surgery. In CRM positive and threatened cases the laparoscopic surgery showed less blood loss compared to open surgery, while other outcome measures were similar to open surgery.

Outcomes of radical surgical resections for nonmetastatic anorectal melanomas: Experience from a tertiary care centre.

AIM: The outcome of radical surgery in nonmetastatic anorectal melanoma (AM) patients is studied infrequently. Here, we aimed to explore the stage-wise outcomes and the impact of radical resections in these patients. METHODS: In this single-centre retrospective study, data of 154 eligible patients were recorded and analysed. Data were obtained from November 2010 to September 2019 with follow-up until November 2020. Overall survival (OS) and disease-free survival (DFS) was calculated by Kaplan Meir method and univariate analysis of prognostic factors by Cox regression. RESULTS: Of 154 patients, 110 were metastatic (stage III) and 44 were nonmetastatic (stage I:22, stage II:22) and underwent curative resections. Median follow-up was 48 months (14-119 months). A total of 39 patients underwent total mesorectal excisions (TME) and five transanal excision (TAE) were performed. Seven patients underwent extended resections. Stage I and II patients had 3- and 5-year OS of 40% and 36%; and DFS of 45% and 33.2%, respectively. Median OS and DFS were 31 and 24 months, respectively. Stage II (node-positive) patients had better median OS compared to stage III (21 vs. 4 months; p = 0.000), and 54.5% patients had recurrences, most commonly both systemic and nodal (45.83%). Median OS of patients without recurrence was 34 months. CONCLUSION: In this large surgical series of AMs, outcome in stage I and II patients was significantly better than stage III and patients with stage II disease can have acceptable oncological outcomes. Radical surgical resections with or without lymphadenectomy could be considered in these patients. The role of adjuvant systemic therapy and radiation needs to be explored as part of multimodality treatment.

Urinary reconstruction following total pelvic exenteration for locally advanced rectal cancer: complications and factors affecting outcomes.

INTRODUCTION: Total pelvic exenteration (TPE) for rectal cancers is associated with significant morbidity. We evaluated the complications related to urinary reconstruction following TPE and factors predicting urologic morbidity. METHODS: Retrospective analysis of TPE patients with incontinent urinary diversions between August 2013 and January 2020. RESULTS: One hundred TPE were performed with 96 ileal conduits (IC). Early complications occurred in 10 patients that included uretero-ileal leaks (5%), conduit-related complications (3%), and acute pyelonephritis (3%). Late complications were seen in 26% of patients with uretero-intestinal strictures in 11%. Mortality attributable to urinary complications was seen in 2%. No single factor, including prior radiation, recurrent disease, type of anastomosis, or blood loss, predicted development of urinary morbidity. CONCLUSION: Conduit urinary diversion following TPE is associated with high urinary morbidity rate but low mortality. It can be safely performed even after previous surgeries and radiation by a dedicated colorectal team.

Outcomes of exenteration in cT4 and fixed cT3 stage primary rectal adenocarcinoma: a subgroup analysis of consolidation chemotherapy following neoadjuvant concurrent chemoradiotherapy.

PURPOSE: The aim was to evaluate the oncological outcomes and the prognostic factors following pelvic exenteration (PE) in cT4 and fixed cT3 stage primary rectal adenocarcinoma and to study the impact of consolidation chemotherapy following neoadjuvant concurrent chemoradiotherapy (NACRT). METHODS: A retrospective analysis of a prospectively maintained database of PE from 2013 to 2018. RESULTS: Out of 2900 colorectal resections, there were 131 pelvic exenterations that were performed, and 100 of these patients had undergone exenteration for primary rectal adenocarcinoma. Of these 100 patients, there were 81 patients who had received NACRT followed by surgery, 50 of whom who had received consolidation chemotherapy and 31 who had undergone surgery without consolidation chemotherapy. R0 resection was achieved in 90% cases. At a median follow-up of 32 months, 2-year disease free survival was 61.8% and estimated 5-year overall survival was 62%. The incidence of distant metastases was 44% vs. 19% (p = 0.023), and the 2-year distant recurrence-free survival was 58% vs. 89% (p = 0.025), respectively, in the 'consolidation chemotherapy group' and the 'no chemotherapy group'. The poorly differentiated grade of tumours, presence of lympho-vascular-invasion, consolidation chemotherapy, and disease recurrence were all found to affect the survival. CONCLUSION: PE with R0 resection achieves excellent survival rates in cT4 and fixed cT3 stage primary rectal adenocarcinoma. The distant recurrence rate may not be altered by consolidation chemotherapy in the subset of high-risk patients. However, further research on consolidation chemotherapy following NACRT in cT4 and fixed cT3 stage primary rectal adenocarcinoma will give a definite answer in the future.

Temporal course of late rectal toxicity & impact of intervention in patients undergoing radiation for cervical cancer.

BACKGROUND & OBJECTIVES: : There is limited information available on the temporal course of late stage radiotherapy adverse effects. The present study reports on the temporal course of late toxicities after chemoradiation and brachytherapy. METHODS: : Women with cervical cancer who presented with late toxicity after (chemo) radiation were included in the study. Grade of toxicity (Clinical Toxicity Criteria for Adverse Events version 4.03) and type of intervention were recorded at three-monthly interval for the first year and then six monthly until 24 months. Direct cost for the management of toxicity was calculated. Univariate analysis was performed to understand the impact of various factors on persistence of toxicity. RESULTS: : Ninety two patients were included in this study. Grades I, II, III and IV toxicities were observed in 50 (54%), 33 (36%), 7 (8%) and 2 (2%) patients, respectively, at first reporting. Patients spent a median of 12 (3-27) months with toxicity. At 12 months, 48/92 (52.2%) patients had a complete resolution of toxicity, whereas 27/92 (29.3%) patients had low grade (I-II) persistent toxicity. Only 6/92 (6.5%) patients who had grade III-IV toxicity had resolution to a lower grade. Four (4.3%) patients died due to toxicity. At 24 months, 9 (10%) patients continued to have grade ≥ III toxicity. On an average, 7 (2-24) interventions were required for the clinical management of late toxicity and median direct cost incurred was ₹ 50,625 (1,125-303,750). INTERPRETATION & CONCLUSIONS: : In this study late radiation toxicity resolved within 12 months in more than half of patients. However, others are likely to have had persistent lower grade toxicity or progression to higher grade. Structured strategies are hence needed for the effective management of late toxicities.

Impact of HPV 16/18 infection on clinical outcomes in locally advanced cervical cancers treated with radical radio (chemo) therapy - A prospective observational study.

OBJECTIVE: With an aim to investigate the impact of Human Papilloma Virus (HPV) 16/18 infection on clinical outcomes in locally advanced cervical cancers treated with radical radio (chemo) therapy, we undertook this prospective study. METHODS: Between May 2010 and April 2012, 150 histologically proven cervical cancer patients treated with radio (chemo) therapy were accrued. Cervical biopsies/brushings were collected at pre-treatment, end of treatment and at 3 monthly intervals up to 24months. Quantitative estimation of HPV 16/18 was done using real-time polymerase chain reaction (RT-PCR) and correlated with various clinical end-points. RESULTS: Out of 150 patients accrued, 135 patients were considered for final analysis. Pre-treatment HPV16/18 DNA was detected in 126 (93%) patients, with HPV-16 present in 91%. The mean log (±SD) HPV-16 and HPV-18 viral load at pre-treatment was 4.76 (±2.5) and 0.14 (±2.1) copies/10ng of DNA, respectively. Though significant decline in viral load was observed on follow-ups (p<0.0001); by 9-month follow-up, 89 (66%) patients had persistence of HPV infection. Patients with persistent HPV 16/18 infection had a significantly higher overall and loco-regional relapses [44/89 (49%) and 29/89 (32%)] as compared to HPV clearance by 9months [12/43 (28%) and 5/43 (11%)] with p=0.024 and p=0.02, respectively. Also, persistent HPV infection by 24-month showed a significant impact on loco-regional control (LRC) and recurrence-free survival (RFS). CONCLUSION: In locally advanced cervical cancers treated with radical radio (chemo) therapy, persistent HPV 16/18 infection is significantly high in immediate post-treatment period and correlated with higher loco-regional, overall relapses and was also associated with early relapses.

Emerging role of multimodality treatment in gall bladder cancer: Outcomes following 510 consecutive resections in a tertiary referral center.

BACKGROUND AND OBJECTIVES: Gall bladder cancer (GBC) is a disease with high incidence in India. We analyzed the outcomes of patients with suspected GBC who underwent surgical exploration. METHODS: Analysis of a prospectively maintained database of patients undergoing surgical exploration for clinic-radiologically suspected GBC from January 2010 to August 2015. Outcomes as well as factors influencing survival were analyzed. RESULTS: Five hundred and ten patients underwent surgery for suspected GBC. Of these 400 had histologically proven malignancy. Eighty patients were deemed inoperable. Radical cholecystectomy was performed in 153 patients, revision surgery for incidental GBC in 160 and port site excision in seven patients. A total of 112 received peri-operative chemotherapy or chemoradiation. Majority were stage III (36%, n = 144) and stage II (31.8% n = 127). At a median follow up of 28.4 months, the median overall survival (OS) was not yet reached. Median disease free survival (DFS) was 33.4 months. Lymph node involvement, stage of the disease and resection status were the main factors influencing outcomes (P = 0.0001). CONCLUSION: Surgery alone is curative only for early GBC (Stage I). Combination of surgery and peri-operative systemic therapy results in favorable outcomes even in stage II/III disease. Potentially, multimodality treatment may add meaningful survival for this disease with inherently aggressive tumor biology.

Pulmonary metastasectomy of colorectal cancer origin: Evaluating process and outcomes.

BACKGROUND: This study was undertaken to evaluate the effect of change in policy of computed tomography (CT) scan of the thorax in staging and follow-up of colorectal cancer (CRC). Another objective was to review the outcomes following pulmonary metastasectomies (Pmets) and to determine the prognostic factors affecting outcomes. METHODS: This is a retrospective analysis from a prospective cohort database of patients, who underwent Pmet for CRC origin from August 2004 to February 2016. The outcome measures were number of Pmets per year, overall survival (OS), disease-free survival (DFS), and prognostic factors affecting survival. RESULTS: Of 71 patients, 38% (n = 27) underwent Pmet before 2013 and 62% ( n = 44) had surgery after 2013. The 2-year DFS after Pmet was 49.3% and estimated 5-year OS was 51.4% at a median follow-up of 28 months. There was a significant increase in number of Pmets/year ( P = 0.0015), increased detection of synchronous pulmonary metastasis (PM) ( P = 0.005), increased diagnosis of extra-pulmonary metastases (EPM) ( P = 0.005), and improved OS ( P = 0.026) after introduction of CT scan as staging tool. Site of primary tumor (colon) ( P = 0.045), primary nodal stage ( P = 0.009), and the presence of EPM ( P = 0.01) were independent important prognostic factors affecting survival. CONCLUSION: The CT scan of thorax as a baseline tool for staging and follow-up in CRC increases referral for pulmonary metastasectomy. Surgery achieves excellent prognosis and long-term survival outcomes in CRC with isolated PM and carefully selected patients with solitary liver metastasis.

Neoadjuvant Chemoradiation Followed by Surgery for Locally Advanced Gallbladder Cancers: A New Paradigm.

PURPOSE: Locally advanced (T3/T4) gallbladder cancers with large fixed portal nodes have a dismal prognosis. If undertaken, surgery entails extensive resections with high morbidity; therefore, in many centers, patients are offered palliative chemotherapy. In this prospective study, we used neoadjuvant concurrent chemoradiation with the intention of downstaging and facilitating R0 resection of these tumors. PATIENTS AND METHODS: Twenty-eight patients with locally advanced carcinoma gallbladder (stage III, having deep liver infiltrations and/or large portal nodes) underwent prior positron emission tomography/computed tomography to rule out metastatic disease. All were treated with concomitant chemoradiation using helical tomotherapy (dose of 57 Gy over 25 fractions to the gross tumor and 45 Gy over 25 fractions to the surrounding nodes) with injectable gemcitabine (300 mg/m(2)/week × 5 weeks). RESULTS: Of the 28 patients, 25 (89 %) successfully completed planned chemoradiation and 20 (71 %) achieved partial or complete radiologic response. Eighteen (64 %) patients were surgically explored, of whom 14 (56 %) achieved R0 resection. At the median follow-up of 37 months for the surviving patients, the median overall survival (OS) was 20 months for all patients. Only one patient recurred in the common bile duct postsurgery, whereas six patients had distant metastasis. The 5-year OS was 24 % for all patients and 47 % for patients with R0 resection. Biliary leak was seen in 6 (43 %) patients, of whom two required interventions. CONCLUSION: Locally advanced unresectable cancers may benefit from neoadjuvant chemoradiation to facilitate a curative resection with a good survival.

Modified FOLFIRINOX (mFOLFIRINOX) as neoadjuvant therapy and 'salvage' in patients with high risk locally advanced rectal cancers - tolerance and early outcomes.

BACKGROUND: There is limited data with regard to the use of modified 5-fluoroural-leucovorin-irinotecan-oxaliplatin (mFOLFIRINOX) in terms of tolerance and enabling total mesorectal excision (TME) of locally advanced rectal adenocarcinomas (LARC) with high-risk characteristics (T4b status, signet ring histology etc) post standard neoadjuvant long course chemoradiation (NACTRT) or short course radiation (SCRT) and chemotherapy. MATERIALS AND METHODS: Patients with LARC from January 2018 to December 2020 receiving mFOLFIRINOX post NACTRT/SCRT to facilitate TME were evaluated. The primary endpoint was assessment of grade 3 and grade 4 treatment related toxicity and TME rates. Event free survival (EFS), where event was defined as disease progression or recurrence post resection after mFOLFIRINOX, was calculated by Kaplan Meier method. RESULTS: Forty-seven patients were evaluated with a median age of 33 years (Range:18-59), 45% T4b status, 96% radiological circumferential margin (CRM) involved (79% CRM positive post NACTRT/SCRT), 43% extramural venous invasion (n=33) and 36% signet ring histology. 62% had received prior NACTRT and 38% had received SCRT with chemotherapy before receiving mFOLFIRINOX. The most common grade 3 and grade 4 treatment related side effects included diarrhoea (7%), anaemia (4%) and infections (4%). Intended duration of mFOLFIRINOX or beyond was completed in 94% of patients. 60% of patients underwent curative local resection with R0 resection rates of 100% (n=28) and pathological complete response rates of 21%. The most common surgeries done were exenterations and abdominoperineal in 22% and 17% patients respectively. With a median follow up of 19 months, 24 patients had recurred or progressed for a median EFS of 20 months [95% confidence interval (CI): 15-24]. CONCLUSIONS: Locally advanced rectal cancers with high-risk characteristics are a niche group of cancers with less-than-optimal outcomes post standard neoadjuvant strategies. mFOLFIRINOX appears to be well tolerated and enables TME in a significant proportion of these patients.

Non-operative management in low-lying rectal cancers undergoing chemoradiation.

PURPOSE: To evaluate the outcomes of post-neoadjuvant chemoradiation (NACTRT) wait-and-watch Strategy (WWS) in distal rectal cancers. MATERIALS AND 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 wishing for the non-surgical treatment option of WWS were included in this study. Patients were observed with 3 monthly magnetic resonance imaging (MRIs), sigmoidoscopies, and digital rectal examination for 2 years and 6 monthly thereafter. Organ preservation rate (OPR), local regrowth rate (LRR), non-regrowth recurrence-free survival (NR-RFS) and overall survival (OAS) 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 at a dose of 45-50Gy conventional fractionation and concurrent capecitabine. An additional boost dose with either an 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 the disease, as they refused surgery. The overall OPR, NR-RFS, and OS were 83%, 95%, and 98%, respectively. Seven (11%) patients developed distant metastasis, of which six underwent metastatectomy and are alive and well. LRR was higher in patients with nCR versus cCR (P = 0.05). CONCLUSION: The WWS is a safe non-operative alternative management for selected patients attaining cCR/nCR after NACTRT with excellent outcomes.

Translation and pilot validation of Hindi, Marathi, and Bangla translation of quality of life EORTC module (QLQ-SH-22) for assessing sexual health-related quality of life.

AIM: To translate and validate the European Organization for Research and Treatment for Cancer (EORTC) module for assessing the sexual health-related quality of life in cancer patients (QLQ-SH22), in Hindi, Marathi, and Bangla languages for clinical use. METHODS AND RESULTS: The EORTC QLQ-SH-22 was translated into Hindi, Marathi, and Bangla by adopting standard guidelines given by EORTC. Initially, the original questionnaire was forward translated by two separate translators, followed by the reconciliation of the forward translations by a third person. This was followed by two back translations of the reconciled version into English by two other translators. These back-translated questions were then compared with the original EORTC questions for accuracy, and once acceptable, a preliminary questionnaire was prepared in all three languages. These questionnaires were then pilot tested with 30 patients (10 for each language) diagnosed with any of the cancers in the pelvic region who are expected to be at risk of sexual quality of life due to tumor or treatment like pelvic radiotherapy. Participated patients had never seen or filled the questionnaire before, each patient was interviewed after filling the questionnaire for difficulty in answering, confusion, difficulty understanding, or if any of the questions were upsetting and if patients would have asked the question differently. RESULTS: None of the patients reported any changes or suggestions for all the three translations. All the translated questionnaires were well understood by all the patients. Pilot testing reports were sent to EORTC. After reviewing the entire report of Hindi, Marathi, and Bangla translations, these questionnaires were approved by the EORTC translation unit. The questionnaires are reliable with Cronbach's α for Hindi, Marathi, and Bangla being 0.69, 0.66, and 0.86, respectively. CONCLUSION: The final Hindi, Marathi, and Bangla translations of SH 22 have been approved by the EORTC and can be used to assess the sexual health of cancer patients in routine oncology practices and/or clinical studies.

Translation and Pilot Validation of Hindi, Marathi, and Bangla Translation of Quality-of-Life EORTC Radiation Proctitis Module (PRT-20) for Routine Clinical Use.

Rahul Krishnatry The aim of this study was to translate and validate the European Organization for Research and Treatment for Cancer (EORTC) "Radiation Proctitis" (PRT-20) module in Hindi, Marathi, and Bangla languages. The EORTC PRT-20 was translated into Hindi, Marathi, and Bangla using EORTC guidelines. Two separate translators first translated the original questionnaire into the three regional languages, following which a reconciled forward translation was compiled. This reconciled version in each language was then back-translated into English by two other translators. This back-translated version was then compared with the original the EORTC questionnaire for correctness, and the preliminary questionnaires were formed in all three languages. The EORTC translation unit approved the questionnaires. The preliminary questionnaires were administered to 30 patients (10 for each language) diagnosed with rectal or anal canal cancer who had received pelvic radiotherapy and were at risk of developing PRT. None of the patients had seen the questionnaire before. After filling out the questionnaire, each patient was interviewed for difficulty in answering, confusion, understanding, or if any of the questions were upsetting and if patients would have asked the question differently. No changes were suggested for Marathi and Bangla translations. Two modifications were suggested in the Hindi translation, which was then retested in five patients and finalized. All the suggestions were incorporated into the preliminary questionnaires, which were sent back to the EORTC for final approval. After reviewing the entire report of pilot testing for the translated quality-of-life questionaire-PRT-20 in three languages, it was approved by the EORTC translation unit. The translated questionnaires were reliable, with Cronbach α values of 0.767, 0.799, and 0.898 for Hindi, Marathi, and Bangla, respectively. The Hindi, Marathi, and Bangla translations of PRT-20 have been approved by the EORTC and can be used in routine clinical practice.

Adjuvant Gemcitabine Plus Cisplatin and Chemoradiation in Patients With Gallbladder Cancer: A Randomized Clinical Trial.

Importance: There is limited evidence with regard to the benefit of adjuvant chemotherapy chemoradiotherapy in resected gallbladder cancers (GBCs). Objective: To establish a baseline survival rate for operated GBCs in patients receiving either gemcitabine plus cisplatin (GC) or capecitabine and capecitabine concurrent with chemoradiation (CCRT). Design, Setting, and Participants: The GECCOR-GB study was a multicenter, open-label, randomized phase 2 noncomparator "pick the winner" design trial of adjuvant GC and CCRT in patients with resected histologically confirmed adenocarcinoma or adenosquamous carcinoma of the gallbladder, (stage II/III) with no local residual tumor (R0) or microscopic residual tumor (R1). The study was carried out in 3 tertiary cancer institutions in India. Patients 18 years or older with adequate end-organ functions, and Eastern Cooperative Oncology Group Performance Status of 1 or lower between May 2019 and February 2022 were enrolled. The cutoff date for data analysis was February 28, 2023. Interventions: Patients were randomized 1:1 to receive either GC every 3 weeks (maximum of 6 cycles) or CCRT comprising capecitabine with concurrent chemoradiation (capecitabine concurrent with radiotherapy) sandwiched between capecitabine chemotherapy. Main Outcomes and Measures: The primary outcome was disease-free survival (DFS) at 1 year in randomized patients. This study was conducted as 2 parallel, single-stage phase 2 clinical trials. Within each treatment arm, a 1-year DFS rate of less than 59% was considered as insufficient activity, whereas a 1-year DFS rate of 77% or higher would be considered as sufficient activity. Results: With a median follow-up of 23 months, 90 patients were randomized, 45 in each arm. Overall, there were 31 women (69%) and 14 men (31%) in the GC arm with a mean (range) age of 56 (33-72) years and 34 women (76%) and 11 men (24%) in the CCRT group with a mean (range) age of 55 (26-69) years. In the GC and CCRT arms, 1-year DFS and estimated 2-year DFS was 88.9% (95% CI, 79.5-98.3) and 74.8% (95% CI, 60.4-89.2), and 77.8% (95% CI, 65.4-90.2) and 74.8% (95% CI, 59.9-86.3), respectively. Completion rates for planned treatment was 82% in the GC arm and 62% in the CCRT arm. Conclusions and Relevance: In this randomized clinical trial, GC and CCRT crossed the prespecified trial end points of 1-year DFS in patients with resected stage II/III GBCs. The results set a baseline for a larger phase 3 trial evaluating both regimens in operated GBCs. Trial Registration: ClinicalTrials.gov Identifier: CTRI/2019/05/019323I.