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.

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.

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.

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.

Tata Memorial Centre Evidence Based Management of Colorectal cancer.

ABSTRACT: This review article examines the evidence-based management of colorectal cancers, focusing on topics characterized by ongoing debates and evolving evidence. To contribute to the scientific discourse, we intentionally exclude subjects with established guidelines, concentrating instead on areas where the current understanding is dynamic. Our analysis encompasses a thorough exploration of critical themes, including the evidence surrounding complete mesocolic excision and D3 lymphadenectomy in colon cancers. Additionally, we delve into the evolving landscape of perioperative chemotherapy in both colon and rectal cancers, considering its nuanced role in the context of contemporary treatment strategies. Advancements in surgical techniques are a pivotal aspect of our discussion, with an emphasis on the utilization of minimally invasive approaches such as laparoscopy and robotic surgery in both colon and rectal cancers, including advanced rectal cases. Moving beyond conventional radical procedures, we scrutinize the feasibility and implications of endoscopic resections for small tumors, explore the paradigm of organ preservation in locally advanced rectal cancers, and assess the utility of total neoadjuvant therapy in the current treatment landscape. Our final segment reviews pivotal trials that have significantly influenced the management of colorectal liver and peritoneal metastasis.

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.

Management of testicular tumours in patients with undescended testes- a challenging but rewarding task: experience from a tertiary care cancer centre in India.

Objective: Primary objective: To study patients' clinical profile and outcomes with germ cell tumours developing in undescended testes. Materials and methods: Case records of patients enlisted in the prospectively maintained 'testicular cancer database' at our tertiary cancer care hospital from 2014 to 2019 were retrospectively reviewed. Any patient who presented with testicular germ cell tumour with a documented history/diagnosis of undescended testes, whether surgically corrected or not, was considered for this study. The patients were managed along the standard lines of treatment for testicular cancer. We evaluated clinical features, difficulties and delays in diagnosis and complexities in management. We evaluated event-free survival (EFS) and overall survival (OS) using the Kaplan-Meier Method. Results: Fifty-four patients were identified from our database. The mean age was 32.4 years (median age 32, range: 15-56 years). Seventeen (31.4%) had developed cancer in orchidopexy testes, and 37 (68.6%) presented with testicular cancer in uncorrected cryptorchid testes. The median age at orchidopexy was 13.5 years (range: 2-32 years). The median time from symptom onset to diagnosis was 2 months (1-36 months). There was a delay in the initiation of treatment of more than 1 month in 13 patients, with the longest delay being 4 months. Two patients were initially misdiagnosed as gastrointestinal tumours. Thirty-two (59.25%) patients had seminoma, and 22 (40.7%) patients had non-seminomatous germ cell tumours (NSGCT). Nineteen patients had metastatic disease at presentation. Thirty (55.5%) patients underwent orchidectomy upfront while in 22 (40.7%) patients, orchidectomy was done after chemotherapy. The surgical approach included high inguinal orchidectomy, exploratory laparotomy or laparoscopic surgery per the clinical situation. Post-operative chemotherapy was offered as clinically indicated. At a median follow-up of 66 months (95% CI: 51-76), there were four relapses (all NSGCT) and one death. The 5-year EFS was 90.7% (95% CI: 82.9-98.7). The 5-year OS was 96.3% (95% CI: 91.2-100). Conclusions: The tumours in undescended testes, particularly those without prior orchiopexy, often presented late and with bulky masses, requiring complex multidisciplinary management. Despite the complexity and challenges, our patient's OS and EFS matched that of patients with tumours in normally descended testes. Orchiopexy may help in earlier detection. In the first such series from India, we show that testicular tumours in the cryptorchid are also as curable as the germ cell tumours developing in the descended testis.A multidisciplinary disease management group with expertise in managing complex cases is crucial for a favourable outcome in these groups of patients. We also found that orchiopexy done even later in life confers an advantage in terms of early detection in a subsequently developing testicular tumour.

Institutional Patterns of Care of Diffuse Intrinsic Pontine Glioma.

Background and Aim: Despite recent advances, the outcomes of diffuse intrinsic pontine glioma (DIPG) remain dismal. This is a retrospective study to understand the pattern of care and its impact on DIPG patients diagnosed over 5 years in a single institute. Subjects and Methods: DIPGs diagnosed between 2015 and 2019 were retrospectively reviewed to understand the demographics, clinical features, patterns of care, and outcomes. The usage of steroids and response to treatment were analyzed as per the available records and criteria. The re-irradiation cohort was propensity matched with patients with a progression-free survival (PFS) >6 months treated with supportive care alone based on PFS and age as a continuous variable. Survival analysis was performed using the Kaplan-Meier method, and Cox regression model was used to identify any potential prognostic factors. Results: One hundred and eighty-four patients were identified with demographic profiles similar to western population-based data in the literature. Of them, 42.4% were residents from outside the state of the institution. About 75.2% of patients completed their first radiotherapy treatment, of which only 5% and 6% had worsening clinical symptoms and persistent need for steroids 1 month posttreatment. On multivariate analysis, Lansky performance status <60 (P = 0.028) and cranial nerve IX and X (P = 0.026) involvement were associated with poor survival outcomes while receiving radiotherapy with better survival (P < 0.001). In the cohort of patients receiving radiotherapy, only re-irradiation (reRT) was associated with improved survival (P = 0.002). Conclusion: Many patient families still do not choose radiotherapy treatment, although it has a consistent and significant positive association with survival and steroid usage. reRT further improves outcomes in the selective cohorts. Involvement of cranial nerves IX and X needs improved care.

Utilising alternative cystoscopic schedules to minimise cost and patient burden after trimodality therapy for muscle-invasive bladder cancer.

BACKGROUND: To assess urinary symptoms and urine cytology as screening tools for cystoscopic detection of local recurrence after bladder-preserving trimodality treatment (TMT). METHODS: Patients with muscle-invasive bladder cancer receiving definitive TMT follow-up three monthly for 2 years, six monthly for the next 3 years and then yearly, with a clinical review, urine cytology and cystoscopy at each visit (triple assessment, TA). Grade 2+ cystitis/haematuria absent/present was scored 0/1, and urine cytology reported negative/suspicious or positive was scored 0/1, respectively. The performance of these two parameters for predicting local recurrence in cystoscopic biopsy was tested. Other hypothetical surveillance schedules included cystoscopy on alternate visits (COAV), or suspected recurrence (COSR), six-monthly COSR and six-monthly TA. RESULTS: A total of 630 follow-up visits in 112 patients with 19 recurrences (7 muscle invasive, 12 non-muscle invasive) at a median follow-up of 19 months were analysed. The sensitivity and specificity of clinical symptoms were 47.4% and 92%, and for urine cytology 58% and 85%, respectively. The combination of clinical symptoms and cytology (COSR) was 95% sensitive and 78% specific for local recurrence but 100% sensitive for muscle-invasive recurrence. Both COAV and COSV schedules showed a high area under the curve (AUC) for detecting local recurrence (COAV = 0.84, COSR = 0.83), muscle-invasive recurrence (AUC = 0.848 each) and non-muscle-invasive recurrence (COAV = 0.82, COSR = 0.81); reducing the need for TAs by 64% and 67% respectively, and overall cost by 18% and 33%, respectively. CONCLUSION: Cystoscopy at suspected recurrence during follow-up is safe and the most cost-effective for detecting muscle-invasive local recurrences, while cystoscopy at alternate visits may be more optimal for detecting any local recurrence.

Optimizing Target Volume for Adjuvant Radiation Therapy in Penile Cancer.

PURPOSE: Recent studies have reported improved outcomes with adjuvant radiation therapy in penile cancer. However, the appropriate target volumes to be irradiated in this group of patients for optimal outcomes are still unclear. This study aims to report the patterns of failure and define target volumes to be irradiated in patients with pN3 penile cancer. METHODS AND MATERIALS: Patients with pT1-T4, pN3, cM0, and squamous cell carcinoma of the penis who received adjuvant radiation therapy (involved field or extended field), with or without concurrent chemotherapy were included in the study. Complete information on disease characteristics, radiation therapy target details, and patterns of failure were available for 75 patients. Disease-free (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and log-rank test was used to compare survival outcomes between the involved field and extended field radiation therapy groups. Multivariate analysis was performed using the Cox proportional hazards model to analyze factors correlating with survival outcomes. RESULTS: At a median follow-up of 39 months, 38.6% (29/75) of patients had relapsed either locally, regionally, or at distant sites. Of the 24 patients who received extended field radiation therapy (EFRT), only 1 (4%) patient experienced relapse. Twenty-eight (55%) patients experienced relapse after involved-field radiation therapy (IFRT), of which 28.5% were regional-only relapses and 64% relapses were associated with a regional component. The 2-year DFS and OS of the entire cohort were 62.2% and 70.8%, respectively. The 2-year DFS was 67.9% in patients who received IFRT and 94.1% in those who received EFRT (P = .002), and the 2-year OS was 62.4% with IFRT and 91.1% with EFRT (P = .014). Extended field radiation therapy was associated with an improved DFS (hazard ratio, 12.2; 95% confidence interval, 1.5-97.4; P = .02) and OS (hazard ratio, 4.6; 95% confidence interval, 1-21.5; P = .05) on multivariate analysis. CONCLUSIONS: Extended field radiation therapy significantly improves clinical outcomes compared with involved-field radiation in patients with pN3 penile cancer.

Impact of immobilisation and image guidance protocol on planning target volume margins for supine craniospinal irradiation.

Background: The setup errors during supine-CSI (sCSI) using single or dual immobilisation (SM, DM) subsets from two institutions were reviewed to determine if DM consistently decreased the required planning target volumes (PTV) margins and to identify the optimal image guidance environments. Materials and methods: Ours and a sister institutional cohort, each with a subset of SM or DM sCSI and daily 3-dimensional online image verification sets, were reviewed for the cranial and spinal regions translational shifts. Using descriptive statistics, scatter plots and independent sample Mann-Whitney test we compared shifts in each direction for two subsets in each cohort deriving PTV margins (Van Herk: VH, Strooms: St recipes) for the cranial and spinal regions. Three image guidance (IG) protocols were simulated for two regions on the combined cohort with SM and DM subsets to identify the most optimal option with the smallest PTV margin. The IG protocols: 3F, 5F and 5FB where the systematic error correction was done using the average error from the first three, five and in the cranium alone (applied to both the cranium and spine, otherwise) for the first five set-ups, respectively. Results: 6968 image sets for 179 patients showed DM could consistently reduce the PTV margin (VH/St) for the cranium from 6/5 to 4/3.5 (31.8/30.8%) and 6/4 to 4/3.5 mm (30.5/16.8%) for primary and validation cohort, respectively. Similarly, for the spine it was 10/8.5 to 6/5.5 (38.6/38.4%) and 9/7.7 to 7/6 (21.6/21.4%), respectively. The "5F-IG" resulted in the smallest margins for both the cranial (3 mm) and spinal region (5 mm) for DM with estimated 95% CTV coverage probability. Conclusion: DM with 5F-IG would significantly reduce the required PTV margins for sCSI.

Quality and Safety With Technological Advancements in Radiotherapy: An Overview and Journey Narrative From a Low- and Middle-Income Country Institution.

PURPOSE: To present an overview of quality and safety in radiotherapy from the context of low- and middle-income countries on the basis of a recently conducted annual meeting of our institution and our experience of implementing an error management system at our center. METHODS: The minutes of recently concluded annual Evidence-Based Medicine (EBM-2021) meeting on the basis of technology in radiation oncology were reviewed. The session on quality and safety, which had international experts as speakers, was reviewed. Along with this, we reviewed the literature for preventive and reactive measures proposed to manage errors including error reporting and learning systems (ILSs). Concise summary for the same was prepared for this article. RESULTS: We also reviewed the journey of development of our institutional ILS and present here a summary of achievements, challenges, and future vision. CONCLUSION: Preventive and reactive measures must be followed to achieve high-quality and safe radiotherapy. Despite resource constraints, a successful ILS program can be developed in a low- and middle-income country center by first understanding the patterns of error and developing one that suits the working ecosystem.

Access to Radiation Therapy: From Local to Global and Equality to Equity.

The discipline of radiation oncology is the most resource-intensive component of comprehensive cancer care because of significant initial investments required for machines, the requirement of dedicated construction, a multifaceted workforce, and recurring maintenance costs. This review focuses on the challenges associated with accessible and affordable radiation therapy (RT) across the globe and the possible solutions to improve the current scenario. Most common cancers globally, including breast, prostate, head and neck, and cervical cancers, have a RT utilization rate of > 50%. The estimated annual incidence of cancer is 19,292,789 for 2020, with > 70% occurring in low-income countries and low-middle-income countries. There are approximately 14,000 teletherapy machines globally. However, the distribution of these machines is distinctly nonuniform, with low-income countries and low-middle-income countries having access to < 10% of the global teletherapy machines. The Directory of Radiotherapy Centres enlists 3,318 brachytherapy facilities. Most countries with a high incidence of cervical cancer have a deficit in brachytherapy facilities, although formal estimates for the same are not available. The deficit in simulators, radiation oncologists, and medical physicists is even more challenging to quantify; however, the inequitable distribution is indisputable. Measures to ensure equitable access to RT include identifying problems specific to region/country, adopting indigenous technology, encouraging public-private partnership, relaxing custom duties on RT equipment, global/cross-country collaboration, and quality human resources training. Innovative research focusing on the most prevalent cancers aiming to make RT utilization more cost-effective while maintaining efficacy will further bridge the gap.

Adopting Health Economic Research in Radiation Oncology: A Perspective From Low- or Middle-Income Countries.

Establishing a new radiation therapy (RT) setup is resource-intensive as it involves substantial capital costs and the recruitment of a skilled workforce. It is essential to incorporate health economic analysis that estimates recurring and nonrecurring expenses on the basis of the national and local needs, infrastructure, and future projections. RT costing exercises can be especially relevant for low- or middle-income countries (LMICs) with more than 70% of the global cancer burden, with access to < 20% of the available resources. This review article summarizes the scope of RT costing exercises in LMICs, the hurdles in conducting them, and possible ways to circumvent them. The purpose of performing costing studies in RT lies in their utility to improve the efficiency of the investment while at the same time helping to address the issues of uniformity and equitable distribution of resources. This will help assess the net benefit from RT in terms of utility and outcome-linked parameters like Quality-Adjusted Life Years. There are numerous barriers to conducting economic evaluations in LMICs, including the lack of national costing values for equipment, data on manpower salary, cost for public and private setups, and indirect costs. The situation is further complicated because of the nonuniform pay structure, lack of an organizational framework, robust real-world data on outcomes, and nonavailability of country-specific reference utility values. Collaborative national efforts are required to collect all elements required to perform health technology assessments. Information from the national and hospital databases can be made available in the public domain to ease access and broader adoption of health economic end points in routine care. Although resource-intensive at the onset, costing studies and health economic assessments are essential for improving the coverage and quality of RT in LMICs.

Modern Radiotherapy Technology: Obstacles and Opportunities to Access in Low- and Middle-Income Countries.

Low- and middle-income countries (LMICs) have a large burden of cancer with differential population needs and outcomes compared to high-income countries. Access to radiotherapy, especially modern technology, is a major challenge. Modern radiotherapy has been demonstrated with better utility in overall cancer outcomes. We deliberate various challenges and opportunities unique to LMICs' set up for access to modern radiotherapy technology in the light of discussions and deliberations made during the recently concluded annual meeting of Tata Memorial Centre, India. We take examples available from various LMICs in this direction in our manuscript.

Expert survey on management of prostate cancer in India: Real-world insights into practice patterns.

To gain insights on the diverse practice patterns and treatment pathways for prostate cancer (PC) in India, the Urological Cancer Foundation convened the first Indian survey to discuss all aspects of PC, with the objective of guiding clinicians on optimizing management in PC. A modified Delphi method was used, wherein a multidisciplinary panel of oncologists treating PC across India developed a questionnaire related to screening, diagnosis and management of early, locally advanced and metastatic PC and participated in a web-based survey (WBS) (n = 62). An expert committee meeting (CM) (n = 48, subset from WBS) reviewed the ambiguous questions for better comprehension and reanalyzed the evidence to establish a revote for specific questions. The threshold for strong agreement and agreement was ≥90% and ≥75% agreement, respectively. Sixty-two questions were answered in the WBS; in the CM 31 questions were revoted and 4 questions were added. The panelists selected answers based on their best opinion and closest to their practice strategy, not considering financial constraints and access challenges. Of the 66 questions, strong agreement was reached for 17 questions and agreement was achieved for 22 questions. There were heterogeneous responses for 27 questions indicative of variegated management approaches. This is one of the first Indian survey, documenting the diverse clinical practice patterns in the management of PC in India. It aims to provide guidance in the face of technological advances, resource constraints and sparse high-level evidence.

Machine-learning approach to predict molecular subgroups of medulloblastoma using multiparametric MRI-based tumor radiomics.

OBJECTIVE: Image-based prediction of molecular subgroups of Medulloblastoma (MB) has the potential to optimize and personalize therapy. The objective of the study is to distinguish between broad molecular subgroups of MB using MR-Texture analysis. METHODS: Thirty-eight MB patients treated between 2007 and 2020 were retrospectively analyzed. Texture analysis was performed on contrast enhanced T1(T1C) and T2 weighted (T2W) MR images. Manual segmentation was performed on all slices and radiomic features were extracted which included first order, second order (GLCM - Grey level co-occurrence matrix) and shape features. Feature enrichment was done using LASSO (Least Absolute Shrinkage and Selection Operator) regression and thereafter Support Vector Machine (SVM) and a 10-fold cross-validation strategy was used for model development. The area under Receiver Operator Characteristic (ROC) curve was used to evaluate the model. RESULTS: A total of 174 and 170 images were obtained for analysis from the Axial T1C and T2W image datasets. One hundred and sixty-four MR based texture features were extracted. The best model was arrived at by using a combination of 30 GLCM and six shape features on T1C MR sequence. A 10-fold cross-validation demonstrated an AUC of 0.93, 0.9, 0.93, and 0.93 in predicting WNT, SHH, Group 3, and Group 4 MB subgroups, respectively. CONCLUSION: Radiomic analysis of MR images in MB can predict molecular subgroups with acceptable degree of accuracy. The strategy needs further validation in an external dataset for its potential use in ab initio management paradigms of MBs. ADVANCES IN KNOWLEDGE: Medulloblastoma can be classified into four distinct molecular subgroups using radiomic feature classifier from non-invasive Multiparametric Magnetic resonance imaging. This can have future ramifications in the extent of surgical resection of Medulloblastoma which can ultimately result in reduction of morbidity.

Timing of Ga68-PSMA PETCT and patterns of recurrence after prostate radiotherapy: Implications for potential salvage.

PURPOSE: To study patterns of recurrence in Ga68-PSMA PETCT at rising serum PSA after radical radiotherapy for non-metastatic prostate cancer. METHODS: Among patients with non-metastatic prostate cancer treated with radical external beam radiotherapy and androgen deprivation therapy, those who underwent Ga68-PSMA PETCT for rising PSA during follow up were analysed. Patterns of recurrence in Ga68-PSMA PETCT were studied. Extra-prostatic recurrences ≤5 were considered oligometastases. Local and oligometastatic recurrences were deemed suitable for focal salvage therapy. Probabilities of identifying recurrent lesion and potentially salvageable recurrences in Ga68-PSMA PETCT in relation to PSA were calculated. RESULTS: Total 114 patients were included (69% high-risk). Radiotherapy was hypofractionated in 57% (moderate 40%, extreme 17%), with median prostate EQD2 78.5 Gy. Median time from radiotherapy to Ga68-PSMA PETCT was 4.3 years (IQR 2.4-6.4), with median PSA 4.7 ng/mL (IQR 2.6-10.7) at scan. Uptake suggesting recurrence was observed in 91.2% patients, with positivity of 75%, 87%, 89%, and 100% at PSA thresholds ≤2, ≤5, ≤10, and >10 ng/mL respectively. Probability of detecting recurrence in Ga68-PSMA PETCT increased with higher PSA at scan (AUC = 0.82). Uptake was local in 20 (17.5%), oligometastatic in 39 (34.2%), and polymetastatic in 45 (39.5%) patients. Recurrence was potentially salvageable in 59/104 (56.7%) patients, being 67% at PSA ≤2 ng/mL but only 38% at PSA >10 ng/mL. Probability of recurrence being potentially salvageable declined with increasing PSA at scan (AUC = 0.68). CONCLUSION: Early Ga68-PSMA PETCT for rising PSA after definitive prostate radiotherapy detected majority of recurrent lesions and identified oligorecurrences amenable to focal salvage therapy.

Prognostic impact of semantic MRI features on survival outcomes in molecularly subtyped medulloblastoma.

PURPOSE: Imaging features are known to reflect inherent disease biology in various cancers including brain tumors. We report on the prognostic impact of magnetic resonance imaging (MRI) features on survival in patients with medulloblastoma treated between 2007 and 2018 at our institute. METHODS: Sixteen semantic imaging features (with predefined categories) were extracted from pre- and postcontrast T1-weighted and T2-weighted MRI by consensus. Univariate analysis and multivariate Cox regression analysis were performed to assess the correlation of semantic features with relapse-free survival (RFS) and overall survival (OS). RESULTS: The study cohort comprised 171 medulloblastoma patients (median age 9 years) treated with maximal safe resection followed by risk-stratified adjuvant radio(chemo)therapy. A total of 55 patients experienced recurrent/progressive disease (commonly neuraxial metastases) resulting in 44 deaths, including one treatment-related death. At a median follow-up of 45 months (interquartile range 19-65 months), 5­year Kaplan-Meier estimates of RFS and OS were 64% and 71%, respectively. Semantic MRI features such as non-central tumor location on vertical axis, absence of brainstem involvement, ≤ 80% solid tumor area with contrast uptake, heterogenous pattern of contrast enhancement, necrosis, calcification, and T2-weighted heterogeneity were associated with significantly worse RFS and/or OS in univariate analysis. Cox regression analysis identified tumor location on the vertical axis, brainstem involvement, and calcification as independent prognostic factors impacting outcomes. Distinctive MRI features correlated with survival even within individual molecular subgroups of medulloblastoma. CONCLUSION: Distinctive semantic MRI features correlate significantly with survival outcomes in medulloblastoma, also within individual molecular subgroups, reflecting their prognostic impact.