Background Regimens for palliation in patients with head and neck cancer recommended by the US National Comprehensive Cancer Network (NCCN) have low applicability (less than 1-3%) in low-income and middle-income countries (LMICs) because of their cost. In a previous phase 2 study, patients with head and neck cancer who received metronomic chemotherapy had better outcomes when compared with those who received intravenous cisplatin, which is commonly used as the standard of care in LMICs. We aimed to do a phase 3 study to substantiate these findings. MethodsWe did an open-label, parallel-group, non-inferiority, randomised, phase 3 trial at the Department of Medical Oncology, Tata Memorial Center, Homi Bhabha National Institute, Mumbai, India. We enrolled adult patients (aged 18-70 years) who planned to receive palliative systemic treatment for relapsed, recurrent, or newly diagnosed squamous cell carcinoma of the head and neck, and who had an Eastern Cooperative Oncology Group performance status score of 0-1 and measurable disease, as defined by the Response Evaluation Criteria In Solid Tumors. We randomly assigned (1:1) participants to receive either oral metronomic chemotherapy, consisting of 15 mg/m² methotrexate once per week plus 200 mg celecoxib twice per day until disease progression or until the development of intolerable side-effects, or 75 mg/m² intravenous cisplatin once every 3 weeks for six cycles. Randomisation was done by use of a computer-generated randomisation sequence, with a block size of four, and patients were stratified by primary tumour site and previous cancer-directed treatment. The primary endpoint was median overall survival. Assuming that 6-month overall survival in the intravenous cisplatin group would be 40%, a non-inferiority margin of 13% was defined. Both intention-to-treat and per-protocol analyses were done. All patients who completed at least one cycle of the assigned treatment were included in the safety analysis. This trial is registered with the Clinical Trials Registry-India, CTRI/2015/11/006388, and is completed. Findings Between May 16, 2016, and Jan 17, 2020, 422 patients were randomly assigned: 213 to the oral metronomic chemotherapy group and 209 to the intravenous cisplatin group. All 422 patients were included in the intention-totreat analysis, and 418 patients (211 in the oral metronomic chemotherapy group and 207 in the intravenous cisplatin group) were included in the per-protocol analysis. At a median follow-up of 15•73 months, median overall survival in the intention-to-treat analysis population was 7•5 months (IQR 4•6-12•6) in the oral metronomic chemotherapy group compared with 6•1 months (3•2-9•6) in the intravenous cisplatin group (unadjusted HR for death 0•773 [95% CI 0•615-0•97, p=0•026]). In the per-protocol analysis population, median overall survival was 7•5 months (4•7-12•8) in the oral metronomic chemotherapy group and 6•1 months (3•4-9•6) in the intravenous cisplatin group (unadjusted HR for death 0•775 [95% CI 0•616-0•974, p=0•029]). Grade 3 or highe...

Background This study compared the surgical and oncological outcomes of open and minimally invasive pelvic exenteration. Methods Patients who underwent pelvic exenterations for primary locally advanced rectal cancers with invasion of the urogenital organs (central and anterior disease) between August 2013 and September 2020 were reviewed retrospectively. Patients were categorized as undergoing open or minimally invasive surgery (MIS) and these groups were compared for perioperative outcomes and 3-year survival (overall, recurrence-free and local relapse-free survival). Multivariable Cox regression analysis was performed to assess the independent influence of approach of surgery and cancer features on recurrence-free survival (RFS). Results Of the 158 patients who underwent pelvic exenteration, 97 (61.4 per cent) had open exenterations and 61 (38.6 per cent) patients had an MIS resection (44 patients (72 per cent) using laparoscopy and 17 (28 per cent) using robotic surgery). There were 96 (60.8 per cent) total pelvic exenterations and 62 (39.2 per cent) posterior pelvic exenterations. MIS exenterations had significantly longer operative times (MIS versus open: 640 mins versus 450 mins; P < 0.001) but reduced blood loss (MIS versus open: 900 ml versus 1600 ml; P < 0.001) and abdominal wound infections (MIS versus open: 8.2 versus 17.5 per cent; P = 0.020) without a difference in hospital stay (MIS versus open: 11 versus 12 days; P = 0.620). R0 resection rates and involvement of circumferential resection margins were similar (MIS versus open: 88.5 versus 91.8 per cent, P = 0.490 and 13.1 versus 8.2 per cent, P = 0.342 respectively). At a median follow-up of 29 months, there were no differences in 3-year overall survival (MIS versus open: 79.4 versus 60.2 per cent; P = 0.251), RFS (MIS versus open: 51.9 versus 47.8 per cent; P = 0.922) or local relapse-free survival (MIS versus open: 89.7 versus 75.2 per cent; P = 0.491. On multivariable analysis, approach to surgery had no bearing on RFS, and only known distant metastasis, aggressive histology and inadequate response to neoadjuvant radiation (pathological tumour regression grade greater than 3) predicted worse RFS. Conclusion MIS exenterations documented longer procedures but resulted in less blood loss and fewer wound infections compared with open surgeries. In the setting of an experienced centre, the hospital stay, R0 resection rates and oncological outcomes at 3 years were similar to those of open exenterations.

Collision tumor is the occurrence of two histologically and morphologically distinct tumors within the same organ with no histological admixture. Collision tumors of the thyroid are extremely rare constituting < 1% of all thyroid tumors. Clinical profiles and pathological features of Medullary thyroid carcinoma (MTC) and Papillary thyroid carcinoma (PTC) presenting as Collision tumors of thyroid, diagnosed between 2009 and 2019, at a tertiary care cancer center were retrospectively analyzed. Collision tumors comprised 4.7% of all MTC cases diagnosed over 10 years. A total of 21 cases (11males, 11 females, M:F = 1) were retrieved with the mean age of patients being 45.33 years (range 26-77 years). More than half of PTCs involved the right lobe of the thyroid (66.6%). About half (53.4%) of MTCs affected the left lobe. Imaging done preoperatively failed to identify the smaller second tumor in 60% of the cases with both tumours in separate lobes. Pre-operative FNAC showed only MTC in all 8 cases in which it was done. Papillary microcarcinoma (m-PTC) was seen in 85.7% cases, with one case of multifocal m-PTC. MTC (mean size 3.12 cm), on an average, was 3 times larger than the PTC (mean size 0.91 cm). The histological variants of MTC included-oncocytic (1/21, 4.7%), spindle cell (1/21, 4.7%), epithelial (3/21, 14.2%) and classical (16/21, 76.2%) and of PTC included classic PTC (12/21, 57.14%), Hurthle cell (2/21, 9.52%), tall cell (1/21, 4.76%) and follicular variant of PTC (6/21, 28.57%). The microscopic extrathyroidal extension (ETE) due to MTC and PTC component was 42.8% and 9.5% respectively. Lymph node metastasis was seen in 16 (76.2%) cases; 87.5% (14/16) of which were contributed by MTC, 12.5% (2/16) by PTC alone, and 12.5% (2/16) cases showed metastasis from both MTC and PTC. MTC had a higher stage than PTC in 85.5% of cases. Collision tumors of the thyroid are exceedingly rare, and possibly underdiagnosed due to variation in sampling techniques, especially of the grossly "normal lobe". The low incidence in our cohort is in favor of the "Chance theory" of co-occurrence. This diagnosis is important due to its therapeutic and prognostic implications.