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AIMS: Cisplatin-based chemotherapy with radiotherapy is currently the standard treatment for locally advanced carcinoma of the cervix. Recent studies have shown a better response with the addition of newer chemotherapeutic agents. The aim of this phase I study was to establish the maximum tolerated dose (MTD) of paclitaxel in combination with cisplatin as a radiosensitiser along with radiation therapy in the treatment of carcinoma of the cervix and to analyse the toxicity profile of the combination regimen. MATERIALS AND METHODS: In total, 21 newly diagnosed patients with squamous cell carcinoma of the cervix, International Federation of Gynecology and Obstetrics stage IB to IIIB were included in this trial. All patients received external beam radiation therapy to the pelvis (50 Gy in 25 fractions) delivered by conventional four-field box technique followed by low dose rate brachytherapy. Concurrent chemotherapy was administered with weekly cisplatin (30 mg/m(2)) and an escalating dose of weekly paclitaxel starting at 10 mg/m(2) up to 50 mg/m(2) (according to the modified Fibonacci series). RESULTS: The MTD of weekly paclitaxel was found to be 40 mg/m(2). The dose-limiting toxicity that occurred in our patients at a dose of 50 mg/m(2) weekly paclitaxel was grade 3 proctitis and vaginitis. CONCLUSION: In this phase I trial of concurrent radiation and combination chemotherapy with weekly paclitaxel and cisplatin (30 mg/m(2)/week), the MTD of paclitaxel was found to be 40 mg/m(2). This combination was feasible, with an acceptable toxicity profile. [ABSTRACT FROM AUTHOR]

To analyse the compliance of surgical care provided to patients diagnosed with carcinoma endometrium, to the European Society of Gynaeacological Oncology (ESGO) quality indicators. This is a retrospective audit done in the Department of Gynaecologic Oncology. Electronic medical records of patients who underwent surgical management of carcinoma endometrium from January 2020 to December 2021 were assessed. A total of 163 patients had undergone primary surgery, and 2 patients had surgery for recurrence. The audit showed that the target for categories of general indicators and pre-operative work-up was met. There was lack in compliance to the intraoperative management, with only 34% among presumed early-stage disease undergoing successful MIS, 31% undergoing sentinel lymph node procedure and 53% among them being done using indocyanine green with 18% bilateral mapping rate. None of the patients had complete molecular classification. Compliance to adjuvant treatment provided was adequate. Minimal required elements in surgical reports were in 81% and pathological reports in 91% of patients falling short of the set target. The audit helped us identify the need to increase MIS and use and adapt sentinel lymph node procedure with ICG dye more aggressively. There also is a need for improvement in documentation of pertinent information on surgical and pathology reporting. Molecular classification should be routinely incorporated into the diagnostic algorithm to aid in adjuvant therapy., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Indian Association of Surgical Oncology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objective(s): The treatment response to neoadjuvant chemoradiation (nCRT) differs largely in individuals treated for rectal cancer. In this study, we investigated the role of radiomics to predict the pathological response in locally advanced rectal cancers at different treatment time points: (1) before the start of any treatment using baseline T2-weighted MRI (T2W-MR) and (2) at the start of radiation treatment using planning CT., Methods: Patients on nCRT followed by surgery between June 2017 to December 2019 were included in the study. Histopathological tumour response grading (TRG) was used for classification, and gross tumour volume was defined by the radiation oncologists. Following resampling, 100 and 103 pyradiomic features were extracted from T2W-MR and planning CT images, respectively. Synthetic minority oversampling technique (SMOTE) was used to address class imbalance. Four machine learning classifiers built clinical, radiomic, and merged models. Model performances were evaluated on a held-out test dataset following 3-fold cross-validation using area under the receiver operator characteristic curves (AUC) with bootstrap 95% confidence intervals., Results: One hundred and fifty patients were included; 58/150 with TRG 1 were classified as complete responders, and rest were incomplete responders (IR). Clinical models performed better (AUC = 0.68) compared to radiomics models (AUC = 0.62). Overall, the clinical + T2W-MR model showed best performance (AUC = 0.72) in predicting the pathological response prior to therapy. Clinical + Planning CT-merged models could only achieve the highest AUC of 0.66., Conclusion: Merging clinical and baseline T2W-MR radiomics enhances predicting pathological response in rectal cancer. Validation in larger cohorts is warranted, especially for watch and wait strategies., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To develop and validate a novel scoring system for predicting the risk of uterine perforation during brachytherapy (BT) in cervical cancer patients and to stratify patients based on this score to guide the use of ultrasound guidance during BT., Methods: Fifty patients with uterine perforation during BT between January 2018 and December 2020 were included. Common reasons for perforation were identified and a scoring system was developed. This was then applied to a cohort of 50 patients without perforation. The 2 cohorts were compared using the χ² test. To validate the scoring system, all newly diagnosed patients who underwent BT in 2021 were scored, and analysed using χ² test and receiver operator characteristic curves., Results: The mean score in the test cohort was 10.16 (range=7-14) and 5.92 (range=5-8) for patients with and without perforation. In the validation cohort, the mean score was 6.9 (range=5-10) and 9.33 (range=7-11) for those with and without perforation. Patients with a score <8 were classified as low risk, while those with a score ≥8 were classified as high risk. Among the criteria evaluated for validation, response to external beam radiotherapy, uterine position, cervico-uterine angle (uterine flexion), identification of cervical os at BT assessment, and the total score were significant predictors, while previous history of perforation, uterine length, and additional uterine anomaly were not., Conclusion: The novel scoring system is an effective predictor of perforation risk during BT. Implementing this during BT assessment can optimize the need for ultrasound guidance during the procedure., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Background: In order for low and middle income countries (LMIC) to transition to Human Papilloma Virus (HPV) test based cervical cancer screening, a greater understanding of how to implement these evidence based interventions (EBI) among vulnerable populations is needed. This paper documents outcomes of an implementation research on HPV screening among women from tribal, rural, urban slum settings in India., Methods: A mixed-method, pragmatic, quasi-experimental trial design was used. HPV screening on self-collected cervical samples was offered to women aged 30-60 years. Implementation strategies were 1) Assessment of contextual factors using both qualitative and quantitative methods like key informant interviews (KII), focus group discussions (FGDs), pre-post population sample surveys, capacity assessment of participating departments 2) enhancing provider capacity through training workshops, access to HPV testing facility, colposcopy, thermal ablation/cryotherapy at the primary health care centers 3) community engagement, counselling for self-sampling and triage process by frontline health care workers (HCWs). Outcomes were assessed using the RE-AIM (Reach, Effectiveness, adoption, implementation, maintenance) framework., Results: Screening rate in 8 months' of study was 31.0%, 26.7%, 32.9%, prevalence of oncogenic HPV was 12.1%, 3.1%, 5.5%, compliance to triage was 53.6%, 45.5%, 84.6% in tribal, urban slum, rural sites respectively. Pre-cancer among triage compliant HPV positive women was 13.6% in tribal, 4% in rural and 0% among urban slum women. Unique challenges faced in the tribal setting led to programme adaptations like increasing honoraria of community health workers for late-evening work and recalling HPV positive women for colposcopy by nurses, thermal ablation by gynaecologist at the outreach camp site., Conclusions: Self-collection of samples combined with HCW led community engagement activities, flexible triage processes and strengthening of health system showed an acceptable screening rate and better compliance to triage, highlighting the importance of identifying the barriers and developing strategies suitable for the setting., Trial Registration: CTRI/2021/09/036130., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Oommen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Molecular subtyping of endometrial carcinomas (EC) has been shown to classify tumors into prognostically relevant groups. Characterizing EC with a limited number of markers viz., POLE mutations, p53 mutations, and MMR status, can provide valuable information., Design: Paraffin sections of a cohort of 48 EC from a tertiary care center were characterized for the above-mentioned molecular markers and analyzed in the context of survival., Methods: Formalin fixed paraffin embedded tissues from 48 EC were characterized for POLE mutations by Sanger sequencing (exons 9-14), for MMR (MLH1, MH2, MSH6) using immunohistochemistry (IHC) and copy number (high/low) using p53 IHC. Mutational status was integrated along with the clinicopathological details and survival analysis performed., Results: Eleven (22.9%) patients were MMR deficient, 3 (6.3%) had POLE mutation, while 2 (4.1%) had both POLE and P53 mutations (regarded as multiple classifiers). Twelve (25%) patients were found to have P53 mutations, while the remaining 20 (41.7%) had no specific molecular profile (NSMP). Median follow-up duration was 43.5 (2-62) months with 8 recurrences and 9 deaths. Tumors with POLE mutation had the most favorable prognosis followed by the NSMP and the MMR mutated group while the P53 and multiple classifier groups had the worst prognosis in terms of OS (Log-rank p: 0.006) and PFS (Log-rank p: 0.001)., Conclusion: The integration of molecular-clinicopathologic data for endometrial cancer classification, through cost-effective, clinically applicable assays appears to be a highly objective tool that can be adopted even in resource-limited settings. It has the potential to cause a shift in the paradigm of EC pathology and management practice., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Total neoadjuvant therapy (TNT) with pre-operative chemotherapy and chemoradiotherapy results in improved survival and is becoming the new standard of care in locally advanced rectal cancer (LARC). We describe our experience with TNT consisting of induction chemotherapy followed by chemoradiotherapy using full dose 5FU without oxaliplatin., Methods: Adults with biopsy-proven, newly diagnosed LARC with high-risk characteristics on pelvic MRI (T4a or T4b, extramural vascular invasion, N2, mesorectal fascia involvement, enlargement/tumor deposits on lateral lymph nodes) were included. The TNT protocol comprised of six biweekly courses of modified FOLFOX6 followed by pelvic RT with four concurrent cycles of biweekly 5-FU 2600 mg/m2 + LV 200 mg/m2 without oxaliplatin to complete 20 uninterrupted weeks of full dose 5FU. Surgery was planned 11-13 weeks after completing chemoradiotherapy., Results: Eighty-four LARC patients, including 26% with signet-ring cell carcinoma, with high-risk MRI characteristics were treated with the TNT protocol with a 96% completion rate. Significant (> grade 3) toxicities included neutropenia (23.8%), diarrhea (14.2%) anemia (10.7%), and two deaths. The median DFS at 2 years was 22.5 months with better survival noted for those who underwent surgery or had cCR (with NOM) compared to those who did not undergo surgery (due to progression, inadequate regression, or patient preference despite residual disease) -mDFS 27.7 months versus 11.4 months, p =  < 0.0001 and mOS 29.2 months versus 15 months p =  < 0.0001., Conclusion: The hybrid TNT regimen was administered without significant dose delays or interruptions. Toxicity was manageable but with two treatment-related deaths. Ability to undergo surgery after TNT predicted for improved DFS and OS., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: One needs to choose wisely between primary neoadjuvant chemotherapy and primary cytoreductive surgery in ovarian cancer. The aim was to determine the recurrence free survival and overall survival after surgery for epithelial ovarian cancer and also the risk factors for recurrence and death., Methods: Electronic medical records of 322 women operated for ovarian, fallopian or primary peritoneal cancer between 2011 and 2015table were reviewed. Descriptive statistics were used to describe patients and their clinical outcomes. Cox proportional hazard models were used for risk factor analysis. Adjusted hazard ratios were obtained for recurrence and death, adjusted for stage, primary treatment modality, residual disease and histology. Kaplan-Meier curves were drawn for probability of recurrence-free survival and overall survival. The log rank test was used to compare survival probabilities., Results: The majority were stage III or stage IV (78%), serous histology (71%) and high grade (64%). Primary cytoreduction was done in 48% and interval cytoreduction in 52%. The median duration of follow up (survival) was 77 months (95% CI 72-82). There were 179 known recurrences (55.6 %). The estimated median time to recurrence was 22 (95% CI 14.5- 29.5) months. The independent risk factors for recurrence were neoadjuvant chemotherapy [HR 2.14, 95% CI 1.48-3.09], stage III/IV [HR 2.75; 95% CI 1.40-5.41], high grade serous histology [HR 1.69; 95% CI 1.12-2.54] and sub-optimal debulking [HR 3.15, 95% CI 2.19-4.55]. There were 78 known deaths (24.2 %) with a mean time to death of 24.3 (SD 16.1) months. The independent risk factors for death were sub-optimal debulking [HR 3.07; 95% CI 1.78-5.29] and stages III and IV cancer [HR 3.07; 95% CI 1.14-8.27]., Conclusions: Most ovarian cancers recur within 2 years. Risk factors for mortality are advanced stage and sub-optimal debulking. Maximal efforts at down staging and surgical resection will increase survival., (Copyright © 2024 Copyright: © 2024 Indian Journal of Cancer.)

Objective  The aim of this study was to characterize the tissue involving the margin and study if this information will affect margin prediction on restaging magnetic resonance imaging (MRI) in low rectal adenocarcinoma (LRC) patients treated with neoadjuvant long-course chemoradiotherapy (LCCRT). Methods  In this retrospective study of nonmetastatic LRC (distal margin <5 cm from the anal verge) treated with LCCRT followed by surgery, a radiologist blinded to outcome reread the restaging MRI and documented if the radial margin was involved by tumor, fibrosis, or mucin reaction using T2 high-resolution (HR) and diffusion-weighted imaging (DWI). The diagnostic performance of tumor-involving margin on restaging MRI was assessed using surgical histopathology as a reference. Interobserver agreement between three independent radiologists was assessed in a subset. Results  We included 133 patients (80 males and 53 females) with a mean (range) age of 44.7 (21-86) years and 82% of them had well or moderately differentiated adenocarcinoma. Baseline MRI showed T3 ( n  = 58) or T4 ( n  = 60) disease in 89% of the patients. The pathological margin was positive in 21% ( n  = 28) cases. In restaging MRI, the circumferential resection margin (CRM) ≤1 mm in 75.1% ( n  = 100) cases and MRI predicted tumor, fibrosis, and mucin reaction at the margin in 60, 34, and 6%, respectively, and histopathology showed tumor cells in 33, 14.7, and 16.6% of them, respectively. LRC with tumor-involving margin and bad response (MR tumor regression grade [mr-TRG] 3-5) on restaging MRI had fourfold increased risk of positive pathological circumferential resection margin (pCRM). There was moderate and fair inter-reader agreement for the tissue type involving the CRM ( κ  = 0.471) and mr-TRG ( κ  = 0.266), p  < 0.05. The use of both distance criteria and tumor-involving margins improved the diagnostic accuracy for margin prediction from 39 to 66% on restaging MRI. Conclusions  Margin prediction on restaging MRI can be improved by characterizing the tissue type involving the margin in low rectal cancer patients. The inter-reader agreement was moderate for determining the tissue type., Competing Interests: Conflict of Interest None declared., (Indian Radiological Association. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Introduction: Squamous cell carcinoma antigen (SCC Ag) is a sub-fraction of the tumor antigen TA-4, first isolated by Kato and Torigoe, the most commonly used tumor marker in cervical cancer. It can be used as a serum marker to detect residual disease, early local recurrence, or distant metastasis in locally advanced cervical cancer even before the clinical symptoms of recurrence or metastasis., Methods and Materials: Between January 2018 and August 2018, 30 patients with squamous cell carcinoma cervix (FIGO) stages IB2-IVA, who received concurrent chemoradiation, followed by brachytherapy, were included in the study. Serum SCC Ag levels were collected at four time points during the course of the treatment, and their correlation with tumor and treatment factors were analyzed., Results: As the FIGO stage increases, mean pre-treatment SCC Ag also increases. Node-positive patients had higher pre-treatment SCC Ag as compared to those who were negative (P = 0.05). There was a statistically significant decreasing trend in the mean SCC Ag at the end of EBRT (P = 0.015). After completion of treatment, 78% had a complete response, 8% had a partial response, and 14% had progressive disease with statistically significant elevation of SCC Ag at 6 weeks of follow-up (P = 0.01). Patients who progressed or had the residual disease at follow-up were found to have high pre-treatment SCC Ag values., Conclusion: SCC Ag can be potentially used as a reference indicator of biological behavior of cervical cancer, to monitor the treatment response, and as a prognostic marker, especially in those with node-positive disease.

Objectives: This study aimed to assess sexual health and quality of life (QoL) in endometrial cancer survivors and the factors influencing these variables., Methods: A mixed method design comprising quantitative (cohort design) and qualitative (face-to-face interviews) aspects was chosen. A total of 132 patients who underwent surgery alone, surgery followed by adjuvant vaginal brachytherapy, or surgery followed by chemotherapy and radiation were included. Female Sexual Function Index (FSFI) and Functional Assessment of Cancer Therapy General (FACT-G) questionnaires were used to assess the participants' sexual health and QoL at 6 months and 1 year post-treatment. Multivariate logistic regression models were used to analyze the factors associated with general and sexual well-being., Results: At 1 year, 89% of the participants still had low sexual function scores. Survivors over 50 years (OR 284.7, 95% CI 13 to 364, p<0.001) and educated below graduate level (OR 26.8, 95% CI 2 to 370, p=0.014) had low sexual function scores. Patients who had surgery alone had better QoL than those who received adjuvant radiation. Women who had surgery, chemotherapy, and radiation had the lowest QoL scores (OR 6.4, 95% CI 2.1 to 19.5, p=0.001). All scores improved with time., Conclusions: This study demonstrated the high prevalence of low sexual function and poor QoL in endometrial cancer survivors. There was a communication gap between the women and their partners as well as their healthcare providers. This study highlights the need for discussion about the survivors' sexual well-being and QoL., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background & Introduction: Serous cancers are a biologically aggressive variety of endometrial cancer (EC) with a high rate of recurrence and mortality among all the subtypes. Herein we describe our experience with serous endometrial cancer., Objective: This study was conducted to identify the clinicopathological characteristics, treatment modalities and survival outcomes in women diagnosed with serous endometrial malignancies., Methods: This was a retrospective descriptive analysis of data on patients diagnosed with serous endometrial tumours between January 2010 to September 2019 in our institute collected from electronic medical records. Descriptive statistics such as proportions, means and standard deviations and Cox regression hazards model on risk factors were performed. Survival was plotted by Kaplan-Meier curves., Results: During the study period, 32 (5.7%) patients out of 564 diagnosed cases of endometrial cancer had serous histology. The mean age at diagnosis was 62.5 years (SD 7.6) while mean BMI was 26.4 kg/m 2 (SD 4.6). Staging laparotomy was done in 27(84%) of the patients. Advanced stages (III and IV) were detected in 16 patients (50%) at primary surgery.Adjuvant chemo therapy and radiation was received by 21(65.6%) patients therapy. Out of 32 patients, 13 (40%) developed recurrence while another 13 expired. Stage at diagnosis and type of adjuvant therapy were important factors in determining the outcome. Median recurrence free and overall survival was 22(95% CI 1.4-42) and 36 months (95% CI 10.1-61.8) respectively., Conclusion: Serous endometrial cancers are an intrusive subtype of EC. Comprehensive surgical staging with optimal cytoreduction should be aimed at. Adequate upfront molecular categorization of these tumors is mandated. Adjuvant therapy with chemotherapy and radiation is given in postoperative setting. Targeted therapies and immunotherapy could be considered in recurrences., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Background: The administration of 5-fluorouracil (5FU) in the treatment of gastrointestinal (GI) malignancies is associated with common side effects such as mucositis, diarrhoea, and myelosuppression, which are easily managed with supportive measures and dose adjustments. Cardiotoxicity and neurotoxicity are rare but reversible side effects of 5-FU and are treated with withdrawal of the drug and conservative measures. The presenting symptoms of 5-FU-induced leukoencephalopathy are often confusing and pose a diagnostic dilemma in routine clinical practice., Methods: We report a series of five patients with GI malignancies who developed 5-FU-induced leukoencephalopathy., Results: All (n = 5) had Naranjo scores of 6-7, predictive of 5-FU-related adverse effects, with clinical and radiological findings suggestive of 5-FU-induced encephalopathy as described in prior literature. The median time to onset of symptoms from initiation of 5FU was 3 days (range: 2-4 days). All patients improved after conservative management with complete neurological recovery., Conclusion: Prompt recognition of this rare yet severe adverse effect of 5-FU-based chemotherapy aids early withdrawal of the offending agent (5-FU) and timely initiation of supportive measures and helps plan alternative oncological interventions., (© 2022. The Author(s).)

Aim: To study the prognostic significance of MRI identified tumour deposits (TD), extramural vascular invasion (EMVI), lymph node metastases (LNM) and pelvic sidewall (PSW) disease in rectal cancer., Methods: This IRB approved study was conducted on patients with stage IIA-IIIC rectal adenocarcinoma treated with neoadjuvant long course chemoradiotherapy (LCCRT) and total mesorectal excision (TME) type of surgery between 2012-2018. A radiologist blinded to outcome reviewed staging and restaging magnetic resonance imaging (MRI) for TD, EMVI, LNM and PSW. The agreement between four radiologists was studied and we obtained outcome data from a prospectively maintained database. The prognostic significance of imaging findings was assessed., Results: A total of 297 (186 males) patients with a mean age of 47.3 (SD14.4) years were included in the study. The majority had T3 (n = 206) or T4 (n = 59) stage disease. The mean duration of follow-up was 49.3 ± 25 months (6.6-101 months). 5-year overall (OS) and disease-free survival (DFS) was 84% and 74%, respectively. Staging and restaging MRI had EMVI in 49.5% and 31.3%; TD in 47.5% and 31.6%; LNM in 61.1% and 38.1% and PSW in 11.4% and 6.1%. OS was adversely affected by EMVI, TD and PSW with the adjusted HR (aHR) of 3.32, 3.31, 3.27 for staging MRI and 2.99, 3.1, 2.81 for restaging MRI, respectively, p < 0.05. DFS was affected by EMVI (aHR = 1.85, 2.33) and TD (aHR = 1.83, 2.19), p < 0.05. Persistence of these findings after LCCRT led to worst outcome. Intra- and interobserver agreement for EMVI, TD and LN was 0.789, 0.734, 0.406 and 0.449, 0.354, 0.376, respectively, p < 0.001., Conclusions: MRI identified that TD, EMVI and PSW disease are independent poor prognostic indicators in rectal cancer patients. Interobserver agreement for these findings was moderate to fair., (© 2021 The Association of Coloproctology of Great Britain and Ireland.)

Introduction: Chemoradiation is the standard of care in locally advanced carcinoma of the anal canal. However, the irregular surface and elective inguinal treatment poses a challenge for radiation planning and treatment with associated significant toxicity. In this retrospective study, we analysed the outcome of patients treated with intensity-modulated radiation therapy (IMRT) at our centre from 2012 to 2019., Methods and Materials: Records of patients treated with IMRT at our centre from 2012 to 2019 were reviewed. Patients with non-squamous histology and previous irradiation were excluded. Thus, 25 patients were found suitable for the study., Results: Twenty-five patients with squamous cell carcinoma of the anal canal were treated at our centre from 2012 to 2019 using IMRT based chemoradiation. RTOG guidelines were followed for contouring and Varian Eclipse version 13(Palo Alto, California) was used for planning. Clinical response could be assessed in 20 patients and dosimetric data of all patients was available for review. The target volumes coverage goals as per ICRU 83 were achieved in all patients. The organ at risk constraints for bladder and femoral heads as per LATE-QUANTEC were achieved in most patients; however, the constraints for the rectum, testis and bowel bag were not achieved in the majority of the patients. The median duration of treatment break was 7 days. Mitomycin C and 5-FU or capecitabine were given concurrently with radiation. Eighteen patients (72%) received 2 cycles of chemotherapy, three (12%) received 1 cycle of chemotherapy while 4(16%) patients did not receive any chemotherapy. Median follow-up was 7.5 months. At median follow-up, 15(75%) patients were disease-free and asymptomatic, 2(10%) had residual disease and 3(15%) had progressive disease. Toxicity was assessed using CTCAE Version 5.0. Grade III skin toxicity was reported in 9(36%) of the patients and Grade III gastrointestinal toxicity was reported in 1 (4%) of the patients, no other grades III-IV toxicity was reported. Overall, the disease control was comparable to previous 3D-CRT studies but with much less toxicity., Conclusion: IMRT-based chemoradiation should be the standard of care in locally advanced carcinoma of the anal canal., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Outbreak of Corona Virus Disease in late 2019 (COVID-19) has become a pandemic global Public health emergency. Since there is no approved anti-viral drug or vaccine declared for the disease and investigating existing drugs against the COVID-19., Objective: AYUSH-64 is an Ayurvedic formulation, developed and patented by Central Council of Research in Ayurvedic Sciences, India, has been in clinical use as anti-malarial, anti-inflammatory, anti-pyretic drug for few decades. Thus, the present study was undertaken to evaluate AYUSH-64 compounds available in this drug against Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2) Main Protease (M pro ; PDB ID: 6LU7) via in silico techniques., Materials and Methods: Different molecular docking software's of Discovery studio and Auto Dock Vina were used for drugs from selected AYUSH-64 compounds against SARS-CoV-2. We also conducted 100 ns period of molecular dynamics simulations with Desmond and further MM/GBSA for the best complex of AYUSH-64 with M pro of SARS-CoV-2., Results: Among 36 compounds of four ingredients of AYUSH-64 screened, 35 observed to exhibits good binding energies than the published positive co-crystal compound of N3 pepetide. The best affinity and interactions of Akuammicine N-Oxide (from Alstonia scholaris ) towards the M pro with binding energy (AutoDock Vina) of -8.4 kcal/mol and Discovery studio of Libdock score of 147.92 kcal/mol. Further, molecular dynamics simulations with MM-GBSA were also performed for M pro - Akuammicine N-Oxide docked complex to identify the stability, specific interaction between the enzyme and the ligand. Akuammicine N-Oxide is strongly formed h-bonds with crucial M pro residues, Cys145, and His164., Conclusion: The results provide lead that, the presence of M pro - Akuammicine N-Oxide with highest M pro binding energy along with other 34 chemical compounds having similar activity as part of AYUSH-64 make it a suitable candidate for repurposing to management of COVID-19 by further validating through experimental, clinical studies., Competing Interests: None., (© 2021 The Authors.)

The global increase in cancer burden is a challenge for countries with scarce resources. Amongst all the malignancies, gynaecological cancer still continues to have a high incidence and prevalence leading to significant morbidity and mortality. While a multipronged strategy of decreasing the gynaecological cancer burden is a global priority, one of the key strategies to decrease the morbidity and mortality is to train gynaecological oncology specialists. Most of the developed nations have an established gynaecologic oncology training programme in the form of a well-designed curriculum and skill training. However, in developing countries where the actual disease burden of these cancers is highest, such focused training programmes have only started emerging and evolving over the past two decades. While it is a positive step to initiate such training programmes in a country like India, there are still gaps in the uniformity of curriculum and training. Also, exposure to modern practices in gynaecologic oncology surgery, chemotherapy and technology in radiation oncology, especially brachytherapy, is still insufficient in many centres. This review discusses some of the challenges and opportunities in the still evolving programmes for training gynaecologic oncologists in India., Competing Interests: None

Kimura's disease (KD) is a rare, chronic inflammatory disorder of unknown aetiology, which commonly affects men of the Asian race. Here, we present a case capsule of a 39- year-old man with KD of the left cheek, managed initially by surgery alone. He developed local recurrence after 6 months and was treated with steroids and isotretinoin. Eventually, steroids were discontinued due to toxicity and the lesion progressively increased in size. The patient was successfully treated using intensity-modulated radiotherapy with simultaneous integrated boost as a primary modality with minimal adverse effects. The patient has good local control and cosmetic outcome with no radiation-related toxicity at a follow-up period of 28 months., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

This study aimed to compare the treatment outcomes in carcinoma cervix before and after gynecologic oncology sub-specialization at a tertiary care hospital, in India. This was a retrospective cohort study comparing women with operable cervical cancer who underwent radical hysterectomy before and after gynecologic oncology sub-specialization. Electronic medical records of women operated for early carcinoma cervix between 2001 and 2010 and 2011-2015 were reviewed and compared for treatment and oncological outcomes. Seventy-four patients were operated over 5 years after sub-specialization as against 59 over 10 years before sub-specialization, with similar clinical characteristics. After surgical-pathological examination, both cohorts were comparable with regard to mean tumor size, lymph nodes retrieved, deep stromal invasion, and involvement of lymph nodes, parametrium, and vaginal margins. After sub-specialization, the rate of intraoperative (3% versus 14%, p  = 0.018) and postoperative complications (15% versus 46%, p  < 0.001) was lower. Adjuvant radiation was used more after sub-specialization (50% versus 24%, p  < 0.001). The follow-up rates were similar in both groups with comparable 5-year recurrence-free survival and overall survival rates. The hazard ratio for death after sub-specialization was 0.39 (95% CI 0.12 to 1.22) after adjusting for histology, stage, grade, and presence of intermediate or high risk factors. Gynecological oncologic sub-specialization decreased intraoperative and postoperative complications, improved pathological reporting, and enabled appropriate tailoring of adjuvant therapy., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© Indian Association of Surgical Oncology 2020.)

Purpose: To assess the diagnostic performance, interobserver agreement and confidence level for determining response to neoadjuvant chemoradiotherapy (NACRT) using morphology based MR-tumour regression grade (MR TRG), diffusion weighted imaging (DWI) patterns and their combination in patients with locally advanced rectal cancer., Methods: This was a retrospective study including patients with locally advanced rectal cancer treated with NACRT and subsequent surgery. Two independent radiologists blinded to the histopathology reviewed staging and restaging MRI. Diagnostic performance of morphology based MR-TRG, DWI patterns and their combination for determining complete (CR) and incomplete (IR) response was assessed with pathological response as the reference. Likert's scale was used to assess the radiologist's level of confidence. Interobserver agreement was determined using Kappa statistics., Results: The study included 251 patients (mean age of 47.9+/-14 (range 19-86) years, M:F = 164:87). Rate of pathological CR was 14.7 % (n = 37). Pattern based interpretation of DWI and combined approach (DWI + T2-HR) had superior diagnostic performance than morphology based assessment alone with area under curve (AUC) for T2HR, DWI and their combination being 0.531, 0.887, 0.874 respectively for observer 1 and 0.558, 0.653, 0.678 respectively for observer 2, p < 0.001. Interobserver agreement was substantial (k = 0.688) for combined approach, moderate (k = 0.402) for DWI patterns and fair (k = 0.265) for T2 HR MRI with both observers exhibiting highest level of confidence for determining response with the combined approach., Conclusion: Complete response to neoadjuvant chemoradiotherapy can be determined with excellent accuracy, substantial interobserver agreement and high level of confidence by combined interpretation of DWI and T2 high resolution MRI., Competing Interests: None of the authors have any conflict of interests., (© 2020 The Authors.)

Haemostatic radiation was effectively used as a novel rescue therapy in a 60-year-old man who presented with recurrent melaena refractory to all conventional medical and surgical measures. He needed multiple transfusions and was diagnosed to be bleeding from an intraductal papillary biliary neoplasm which was not amenable to surgical resection in view of the background liver disease. He received conventional radiation therapy (RT) of a dose of 3 Gy per fraction for 3 consecutive days after which he stabilised. After cessation of the RT, he did not require transfusion for the next 2 months. His quality of life improved and it gave us time to evaluate for other definitive measures., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Paraneoplastic Pemphigus (PNP) is an autoimmune bullous disease characterized by severe stomatitis, polymorphous skin eruptions, and underlying neoplasms. Diagnosis of cutaneous paraneoplastic disorders requires high index of suspicion. We describe a patient with PNP associated with follicular dendritic cell (FDC) tumor in the mediastinum, a rare neoplasm originating from follicular dendritic cells. Its management requires identification of underlying malignancy and treatment of the same. Our patient showed remission of PNP upon excision of the tumor and remained disease-free for 8 years.

Background: Cervical cancer is the most common gynecological cancer in Indian women. This study was initiated to assess whether the combination of paclitaxel and cisplatin with radiation was feasible in Indian women., Aims and Objectives: The aim of this study was to assess the immediate tumor response and toxicity of weekly cisplatin and paclitaxel along with radiotherapy in the treatment of cervical cancer., Materials and Methods: Women with primary untreated squamous cell carcinoma of the cervix with FIGO stages IB2 to IIIB were treated with weekly injections of cisplatin 30 mg/m2 and paclitaxel 40 mg/m2 for 4 weeks along with radiotherapy. A total of 25 patients were enrolled in this study. Disease was assessed prior to treatment by pelvic examination and contrast enhanced computed tomography scan of the abdomen and pelvis. Response was assessed 6 weeks after completion of treatment using the same parameters. Clinical and radiological response was documented. The toxicity was assessed and was graded using the common toxicity criteria Version 3.0. Intention to treat analysis was used when reporting results., Results: A total of 23 patients completed the intended treatment. There was a complete response rate of 88%, 12% were not available for response assessment. The major toxicity was Grade 3 diarrhea (48%). The mean duration of treatment was 58 days., Conclusions: Combination chemotherapy with cisplatin and paclitaxel along with radiotherapy in patients with locally advanced squamous cell carcinoma of cervix had a high incidence of acute toxicity. There was no increase in immediate tumor response and progression free survival with this treatment regimen. Hence, this regimen offers no added benefit when compared to the chemo radiation with cisplatin alone.

Background: Stereotactic body radiation therapy is an advanced technique, which delivers ablative doses to lung lesions. Target verification is done either by orthogonal x-rays or cone beam CT. This study was undertaken to compare these two verification methods., Aim: To evaluate the efficacy of ExacTrac and Cone Beam Computed Tomography (CBCT) for target repositioning while delivering Stereotactic Body Radiation Therapy (SBRT) for lung lesions and derive the population-based margin., Materials and Methods: All patients who had undergone SBRT for lung lesions from February to September 2009 were involved. Patients were immobilized using the BodyFix double vacuum immobilization system, indexed to the computed tomography (CT) simulator and treatment machine. Four-dimensional (3-D) scan was done to generate internal target volume (ITV) and a free breathing CT scan for planning was done on the BrainLab iPlan 4.1 software. During treatment, patient's position was verified using ExacTrac and CBCT. The resulting vertical, lateral, and longitudinal shifts were noted. The random and systematic error were calculated and the margin recipe derived using the Van Herk formula., Results: Sixteen patients had undergone SBRT for lung tumors from February to September 2009. Data from eight patients who had undergone 34 sessions of SBRT was analyzed. The systematic error for lateral, longitudinal, and vertical shifts for ExacTrac and CBCT were 3.68, 4.27, 3.5 mm and 0.53, 0.38, 0.70 mm, respectively. The random error were 1.10, 1.51, 1.96 mm and 0.32, 0.81, 0.59 mm. The lateral, longitudinal and vertical Van Herk margin recipe for ExacTrac were 9.98, 11.72, 10.18 mm, respectively, and for CBCT was 2.17, 1.53,1.55 mm., Conclusions: The systematic and random errors for CBCT were significantly lesser as compared to the errors with Exactrac.

Objective and Importance: The aim of this paper is to report an unusual presentation of extranodal follicular dendritic cell tumor of neck with spinal metastasis. Follicular dendritic cells are nonlymphoid immune accessory cells present in the germinal centers of lymphoid follicles and play a crucial role in the induction and maintenance of the humoral immune response. Tumors from these cells are rare and treatment modality poorly defined., Clinical Presentation: A 37-year-old lady presented with recurrent neck swelling which was initially reported as malignant paraganglioma. The primary disease was treated with surgery and radiotherapy. Eleven years later, the patient presented with metastasis to the spinal cord. Subsequent immunohistochemical analysis of the primary site tumor and the metastatic deposits revealed it to be a follicular dendritic cell tumor., Intervention: The patient was treated with surgery followed by radiotherapy to spine, and one and half year after treatment, the patient is doing well and has regained complete motor functions., Conclusion: Metastasis to spinal cord for follicular dendritic cell tumor is very rare, and to the best of our knowledge, no such case has been previously reported in the scientific literature so far. In the present case, good local control was achieved with initial surgery and radiotherapy but resulted in distant failure after 11 years. This underlines the need for adjuvant systemic therapy, and understanding the biology of the tumor may help in formulating targeted therapy in the future for this rare disorder.

Hypothesis: Assessment of the prevalence and type distribution of human papillomavirus (HPV) in squamous cell carcinomas (SCC) of the cervix across India was undertaken to estimate the impact of available prophylactic HPV-L1 vaccines in the country and to find out additional types that might be needed to be incorporated in second-generation vaccines., Methods: High-risk (HR) HPVs were genotyped from 667 histopathologically confirmed cases of SCC from 6 different centers representing 4 regions across India: Advanced Centre for Treatment, Research and Education in Cancer, Mumbai; All India Institute of Medical Sciences, New Delhi; Cancer Foundation of India, Kolkata; Christian Medical College, Vellore; Kidwai Memorial Institute of Oncology, Bangalore; and Regional Cancer Center, Thiruvananthapuram. Human papillomaviruses in tumor biopsies were analyzed by Xcytonscreen HPV based on PGMY09/11 multiplex polymerase chain reaction and reverse dot blot assay., Results: Overall viral prevalence across India was not different; 92.1% of 667 cases harbored HPV; 8% were negative. Infection with single HR type was seen in 86.8%: predominant types being HPV-16 followed by HPV-18, -45, -73, -31, -56, -52, -58, -59, -33, -68, -51, -35, -26, and -39. Human papillomavirus types 16/18-positive fraction formed 79.6%; other types comprised 12.4%., Conclusions: Prophylactic HPV-16/18-L1 vaccines would provide greater than 75% protection against SCC in India. Ranking and frequencies of non-16/18 types were different from earlier reports. Hence, considering the possibility of promotion of persistence of nonvaccine types in the vaccinees due to original antigenic sin and the lack of organized screening programs in India, a broad-based vaccine approach would be appropriate.

Objective: HPV infection is a necessary but insufficient cause of cervical cancer. The significance of HPV DNA in blood however is debatable because of variable detection rates due to the differences in the methodology used. The aim of this study was to detect and quantitate HPV 16 and 18 plasma viremia in women with cervical neoplasia., Methods: HPV DNA was detected in cervical tissue using consensus PGMY primers and genotyped using reverse line blot hybridization. HPV 16 and 18 quantitation in tissue and detection and quantitation in plasma was performed using sensitive real time PCRs targeting E6/E7 region of HPV 16/18 genome respectively. Results were correlated with viral loads in corresponding tissue and with clinical disease stage., Results: Viremia was detected in 56.4% of HPV 16 positive women and 20% of HPV 18 positive women. The prevalence of HPV 16 DNA in plasma increased with advancing disease stage (p=0.001), although HPV 16 absolute plasma viral load was not significantly associated with advancing disease stage (p=0.281). There was no correlation between absolute plasma viral load and viral load in corresponding cervical tissue (Spearman's rho=0.184, p=0.187). The prevalence of HPV 18 viremia and absolute HPV 18 plasma viral load were not associated with advancing disease stage (p=0.620, p=0.508)., Conclusion: The presence of HPV 16 in plasma is a marker of advancing cervical disease.

Objective: Human papillomavirus (HPV) contributes to the development of cervical cancer. We hypothesize that HPV DNA and messenger RNA (mRNA) levels may be associated with increasing stages of cervical cancer., Materials and Methods: In this study, we measured DNA and mRNA viral loads of the most common high-risk HPV-16 and HPV-18 in cervical biopsy tissue of women with cervical neoplasia using real-time polymerase chain reaction., Results: Median HPV-16 and HPV-18 DNA viral loads were 58,342 copies and 71,367 per 5000 cells, respectively. We found that HPV-16 and HPV-18 DNA levels did not correlate with advancing tumor stage (P = 0.977 and P = 0.263). Messenger RNA transcripts were detected in 81 (86%) of HPV-16 DNA-positive women and in 16 (84.2%) of HPV-18-positive women. Median HPV-16 and HPV-18 transcript copy numbers were 5964 and 6158, respectively. In women with squamous cell carcinoma, HPV-16 mRNA loads showed an increasing but not statistically significant trend with advancing disease stage (rho = 0.231, P = 0.058)., Conclusions: We conclude that HPV mRNA levels and not DNA levels may be associated with advancing stages of cervical cancer.

Human papilloma virus is a causative factor in the etiology of cervical cancer with HPV16 being the most prevalent genotype associated with it. Intratype variations in oncogenic E6/E7 and capsid L1 proteins of HPV 16 besides being of phylogenetic importance, are associated with risk of viral persistence and progression. The objective of this multicentric study was to identify HPV-16 E6, E7 and L1 variants prevalent in India and their possible biological effects. Squamous cell cervical cancer biopsies were collected from 6 centres in India and examined for the presence of HPV 16. Variants of HPV-16 were characterized by full length sequence analysis of L1, E6 and E7 genes in 412 samples. Similar distribution of the variants was seen from the different centres/regions, with the European variant E350G being the most prevalent (58%), followed by American Asian variant (11.4%). Fifty six changes were seen in E6 region, 31 being nonsynonymous. The most frequent being L83V (72.3%), Q14H (13.1%) and H78Y (12.1%). Twenty-nine alterations were seen in E7 region, with 12 being nonsynonymous. The most frequent being F57V (9%). L1 region showed 204 changes, of which 67 were nonsynonymous. The most frequent being 448insS (100%), and 465delD (100%), H228D (94%), T292A (85%). The identified variants some new and some already reported can disrupt pentamer formation, transcriptional regulation of the virus, L1 protein interface interaction, B and T cell epitopes, p53 degradation, and thus their distribution is important for development of HPV diagnostics, vaccine, and for therapeutic purpose.

Methyl-accepting chemotaxis proteins (MCPs) are receptors that play an important role in bacterial chemotaxis. Methylation of Tsr, the MCP that mediates chemotaxis towards serine in Escherichia coli, is thought to be facilitated by binding of the methyltransferase to a flexible tether region at the C-terminal end of Tsr. This study analysed natural length variants of the tether that occur in E. coli due to genetic instability in tandem repeat DNA sequences that code for glutaminyl (Q) residues, creating polyQ sequences of variable lengths in the tether region. The tsr gene of E. coli K-12 (strain MG1655) codes for 4Q at the beginning of its 35 aa tether region. The tether varies in length from 35 to 47 residues among pathogenic and non-pathogenic strains of Escherichia, Shigella spp., Salmonella, Yersinia and Photorhabdus. Among previous sequences, Escherichia and Shigella mostly have 4Q and 7Q variants, and one strain (E. coli HS) has 10Q. In E. coli isolated from 50 humans and 75 animals (dogs, cats, horses, birds, etc.), polyQ up to 13Q (44 aa tether) were identified (6 strains); relative frequencies were 7Q ( approximately 77 % of the total) >4Q (14 %) >13Q (5 %) >10Q (4 %). Phylogenetic analysis revealed that E. coli strains with 10Q or 13Q largely fell within two clusters. Serine chemotaxis was not significantly different among 7Q, 10Q and 13Q strains, and was comparable to chemotaxis in the frequently studied K-12 strain. These results are consistent with models indicating that polyQ sequences from 7Q to 13Q are flexible, and that longer tethers, within this range, would not change the precision of adaptation mediated by methylation. Studies of this naturally variable polyQ region in E. coli may also have relevance to mechanisms that mediate polyQ instability in human genetic diseases.

Brahmavaivartapurana is one of the important Mahapurana, which is considered as a Vaisnavapurana. The text is divided into four parts called khanda i.e., Brahma, Prakrti, Ganapati, and Srikrsnajanmakhanda. The total number of chapters are 276 and comprising about 20,500 verses. Brahmavaivartapurana comprises both ancient and medieval materials. It considers Ayurveda as Pancama Veda and devoted 16th chapter of Brahmakhanda which describes the origin of Ayurveda its propagaters headed by Bhaskara (sun god) and his 16 students and their corresponding books in detail. An account of the Jvara (Fever) and other diseases, Dinacarya (daily routine), Rtucarya (seasonal regimen), Tridosa (three humours), their Prakopa (Vitiation) and Praśamana (palliation) etc are described in this book. BVP deals with the do's and dont's of food intake, sleep and sexual indulgance in detail which are deemed to be Trayopastambha (three sub pillers of health). The book provides an account of Plant Tulsi's origin and its spiritual importance. Prakrti (nature's) origins, Pañcamahabhuta nature of the body are described in Prakrtikhanda. At the flag end of the book there is a legend describing the origin of Lord Dhanvantari and describes his scholarship in the field of Veda and śastra. On the whole purana provides glimpse of the life style of a Vaisnava devoutee and the people of the time when it was compiled. It serves the purpose of a practical manual to lead a healthy life and ensure spiritual growth in the life of any individual who believes in the precepts of this book.

The purpose of this study is to determine the extracranial dose in patients treated for pituitary adenoma with conventional and stereotactic radiotherapy (SRT). Twelve patients receiving treatment with radiation for pituitary adenoma were selected. Six patients underwent SRT, and six patients underwent conventional radiotherapy. Extracranial doses were measured with pre-irradiation annealed lithium fluoride thermoluminscent dosimetry (TLD) chips. The chips were wrapped and placed on the patients' skin, over each eyelid, the thyroid, chest, and scrotum for males and over the suprapubic region for females. Postradiation annealing was done, and the TLDs were read in a TLD reader system. The results were analyzed using the Wilcoxon matched-pairs signed rank test by SPSS, version 6.01. The doses to the thyroid, center, and gonads were significantly higher (74.62 +/- 9.12 mrad, 65.42 +/- 9.35 mrad, and 58.42 +/- 5.36 mrad, respectively) in patients receiving SRT than in conventional radiotherapy portals (69.45 +/- 21.19 mrad, 38.33 +/- 19.44 mrad, and 31.41 +/- 18.25 mrad). But the average doses to the right eye (84.84 +/- 8.80 mrad) and to the left eye (85.68 +/- 5.82 mrad) in the stereotactic group were less when compared with the patients treated with conventional radiotherapy, who received 127.5 +/- 37.90 mrad and 117.29 +/- 34.01 mrad, respectively. In conclusion, SRT is definitely superior to conventional radiotherapy as far as dose to the surrounding normal structures is concerned. The higher extracranial doses in SRT seem to be within the acceptable range; however, the clinical significance of this is still unclear and needs longer followup.

Novel bis-andrographolide ether (1) and six known compounds andrographolide, 14-deoxy-11,12-didehydroandrographolide, andrograpanin, 14-deoxyandrographolide, (+/-)-5-hydroxy-7,8-dimethoxyflavanone, and 5-hydroxy-7,8-dimethoxyflavone have been isolated from the aerial parts of Andrographis paniculata and their structures were established by spectral data. All the isolates were tested for the anti-HIV and cytotoxic activity.

Chemical examination of the aerial parts of Cleistanthus collinus afforded the arylanphthalide lignans, cleistanone (1), diphyllin (2), cleistanthins A (3), C (4) and D (5), and 4-O-(3"-O-methyl-beta-D-glucopyranosyl)-diphyllin (6). The first compound is a new member of the rare group of arylnaphthalide lignans containing an alkoxy group on the lactone ring. The structure of the compound was determined from its spectral data, chemical transformations and partial synthesis from diphyllin (2). The new lignan, 1 and its acetyl derivative, 7 were found to exhibit cytotoxicity against MT(2) cell lines.