Long-term clinical outcomes of combined modality therapy for advanced-stage Hodgkin lymphoma in the PET era: A retrospective study.

BACKGROUND OBJECTIVES: The role of consolidation radiation therapy (CRT) after complete metabolic response to chemotherapy in advanced-stage (stage III and IV) Hodgkin lymphoma (HL) is controversial. This study was undertaken to assess the clinical outcomes in terms of event free survival, local failure free survival and overall survival in individuals with advanced HL treated with chemotherapy and CRT. METHODS: A retrospective review was conducted to study the long-term clinical outcomes in individuals diagnosed with HL and treated with chemotherapy and CRT from 2012 to 2016 at a tertiary cancer care hospital in India. RESULTS: Data from 203 study participants with advanced-stage HL were analyzed. Positron emission tomography-computed tomography (PET-CT) was done at baseline and after 2 cycles for response assessment. The median age at presentation was 32 yr [interquartile range (IQR): 26-46]. Early metabolic response (after 2 cycles) and delayed metabolic response (after 4 or 6 cycles) were observed in 74.4 and 25.6 per cent of individuals, respectively. With a median follow up of 52 months (IQR: 40-67), the five-year event-free survival (EFS), local failure-free survival (LFFS) and overall survival (OS) were 83.2, 95.1 and 94.6 per cent, respectively. On univariate analysis, extranodal disease was associated with inferior EFS (P=0.043). Haemoglobin <10.5 g/dl (P=0.002) and Hasenclever index >3 (P=0.00047) were associated with poorer OS. Relapses were observed in 28/203 (13.8%) study participants with predominance at central nodal stations. The median time to relapse was 19.4 months (IQR: 13-33). Local relapse alone (at the irradiated site) was observed in 5/28 study participants, systemic (distant) relapse in 14/28 individuals, while both systemic and local relapse was observed in 9/28 participants. Extranodal disease (P=0.05), bulky disease (P=0.005) and haemoglobin concentration ≤10.5 g/dl (P=0.036) were significant predictors for disease relapse. INTERPRETATION CONCLUSIONS: Individuals with advanced-stage HL treated with anthracycline-based chemotherapy (anthracycline-based chemotherapy with doxorubicin, bleomycin, vinblastine and dacarbazine regimen) and CRT had excellent long-term outcomes. As isolated infield failures are uncommon, selective consolidation with conformal RT to high-risk sites improves final disease outcomes.

Exposure-Response Relationship of Posaconazole Suspension in Theprophylaxis of Invasive Fungal Infections in Patients with Acute Myeloid Leukemia.

Purpose: Antifungal prophylaxis with posaconazole has demonstrated a reduction in the risk of death due to Invasive fungal infections (IFI)in patients with acute myeloid leukemia (AML) during induction therapy. However, various factors affect the plasma levels of posaconazole and can potentially limit its efficacy. Therapeutic drug monitoring (TDM) can help optimize the dose, but literature is scant from centers with a high IFI burden. This study aimed to evaluate the proportion of de-novo AML patients on induction who could achieve the target level of 700ng/mL with posaconazole prophylaxis,factors that can influence the plasma levels, and the impact of plasma posaconazole levels on incidence of IFI. Methods: Patients with AML on induction therapy with no baseline IFI were enrolled at our tertiary cancer center which has high prevalence of IFI. These patients received posaconazole suspension as prophylaxis. Daily plasma levels were measured from Day 4 till Day 12 of posaconazole prophylaxis. All patients were monitored for the development of IFI. The data on adverse events, concomitant drugs, mucositis, vomiting, and diarrhea were recorded. Results: A total of 411 samples from fifty patients were collected. Only 177 out of 411 samples had levels > 700 ng/mL. The median trough level was 610 ng/mL (range30-3000 ng/mL). The median time to achieve target trough concentration was four days (range 4-12 days) from the start of induction.Thirty-eight (76%) patients achieved target plasma levels by day 12 of induction.The median plasma level on day 12 was 690 ng/mL (range,30-1270) in patients who achieved target levels as compared to 340 (50-560) ng/mL in those who did not. Twenty-six (52%) patients had IFI in our study, and the median time to develop breakthrough IFI was 14 days (range 4-24 days). Median and range of plasma levels were 690 ng/ml (30-2410; n = 22) in those who developed IFI, while 590 ng/mL (50-2300 n = 24) in those who did not. The odds of developing IFI in patients who did not achieve the threshold trough concentration of 700 ng/mL was 7.14 (95% CI; 1.35-37.75, p = 0.0206). Occurrence of vomiting (p = 0.02), diarrhea (p = 0.0008), mucositis (p = 0.003) had adverse impact on achievement of target plasma posaconazole levels. Conclusion: A significant proportion of patients receiving posaconazole prophylaxis fail to achieve target plasma levels which can result in high risk of development of IFI. Occurrence of diarrhea, vomiting and mucositis can adversely affect the achievement target plasma levels.

Epidemiological Trend of Esophageal Cancer at a Tertiary Cancer Center in Mumbai, India, Over the Past 15 Years.

BACKGROUND: In developed countries, there has been a definite change in the histopathological spectrum of esophageal cancer towards adenocarcinoma. There are limited data from India regarding the histopathological profile of patients with esophageal cancer. MATERIALS AND METHODS: We retrospectively evaluated patients with histologically proven esophageal cancer who were registered at the Tata Memorial Hospital (Mumbai, India) between 2003 and 2018. The primary aim of the study was to analyze the time-trend of the histological pattern of esophageal cancer. Our secondary objectives included evaluating whether there was any correlation between the histology of the esophageal cancer and the age, sex, socioeconomic status (the paying ability of the patient, which was reflected in the treatment category of the patient, i.e., private [full payment], general [subsidized payment], or no charge), comorbidities, and a history of substance abuse. RESULTS: Among 7874 patients with esophageal cancer, 5092 (64.7%) were men, with a male-to-female ratio of 1.8:1. The median age was 57 years (IQR, 50-65). Of the 4912 patients in whom a history of tobacco or alcohol use had been elicited, 1360 (27.7%) had no history of substance abuse. A majority of the tumors (2942, 37.4%) originated in the middle-third of the esophagus. Squamous cell carcinoma was the predominant histological type, noted in 6413 (81.4%) patients and remained the most common histologic type consistently through the study with no evidence of a time-trend in the histological pattern. On the multivariate analysis, female sex and a history of substance abuse were associated with higher odds of squamous cell carcinoma, while the presence of comorbidities and lower esophageal/gastroesophageal junction primaries were associated with higher odds of adenocarcinoma. CONCLUSIONS: There is no evidence of an epidemiological shift in the histopathologic spectrum of esophageal cancer in India over the last two decades. Four out of five Indian patients with esophageal cancer have squamous cell histology, with the commonest site of origin being the middle third. This is important to recognize, given the varying molecular spectrum and efficacy of therapeutic modalities based on histopathology.

Does Operable Stage IV Gingivobuccal Cancers Need Further Prognostic Subgrouping?

Background: Operable stage IV gingivobuccal complex cancer is classified as Stage IVA and IVB. Among patients with Stage IVA disease, different subgroups with likely different prognoses are combined. Patients with advanced nodal status tend to have a poorer prognosis. We divided these patients into four groups: group I (T4aN0), group II (T4aN1-2), group III (T1-3N2) constituting stage IVA category, and group IV (TanyN3) representing stage IVB. This study assesses if these patients can be prognostically subgrouped based on nodal status. Methods: It is a prospective observational study done at a tertiary care center from July 2017 to June 2020. This study aims to analyze survival outcomes in these subgroups using Kaplan Meir, univariate and multivariate analysis. Results: The study enrolled 113 patients of operable gingivobuccal complex stage IVA cancer with a median follow up of 26 months, disease-free survival (DFS) was 74% for group 1, while it was 55%, 26% and 32.2% for group 2, group 3 and group 4 respectively. Patients with T4N3 disease had DFS of just 15%. Patients in group 3 and 4 had the worst outcomes in terms of DFS and Overall Survival(OS) with HR-3.7 and 3.3 and 3.3 and 3.8 respectively (p value-0.001). Conclusion: The nodal status is the most important prognostic factor affecting DFS and OS. Patients with small primary but advanced nodal stage do poorly than patients with advanced primary and node-negative disease. There is a need for subgrouping patients with Stage IVA tumors based on nodal status for better prognostication.

Translation and Validation of COST - FACIT (Version 2) Questionnaire into Hindi and Marathi to Assess Financial Toxicity in Indian Cancer Patients.

Amit JoshiBackground Cancer is one of the most expensive and exhaustive medical conditions with a huge impact on the financial condition of the patient and their family members. A lot of advancements have led to improvement in the survival of the patients but at a raised cost. Comprehensive Score for financial Toxicity - Functional Assessment of Chronic Illness Therapy (COST - FACIT Version 2) is one such validated and widely used tool. Assessing the financial burden in our country is still far more challenging as COST - FACIT is available in the English language but not in any regional language. Hence, we decided to validate this tool in Hindi and Marathi languages. Material and Methods A single-center, cross-sectional study was conducted in the Department of Uro-Oncology at the Tata Memorial Hospital. The original version of the COST - FACIT (Version 2) was translated from English into Hindi and Marathi languages, following the FACIT translation method and tested for content validity that included two forward translations, followed by reconciliation and a backward translation. The questionnaires were then approved by the FACIT team, and pilot testing was done for 20 patients (10 for each Hindi and Marathi language). Each of these 20 patients, after filling up the questionnaire themselves, was interviewed for any difficulty encountered during answering the questionnaire. Based on the suggestions or interpretations of this pilot testing, the necessary changes were incorporated in the final Hindi and Marathi questionnaires. Results A total of 20 patients (10 each for Hindi and Marathi) were included for pilot testing of the questionnaire. The median age of the entire cohort was 61 years (27-79). The questionnaires showed good content and face validity and demonstrated a high internal consistency (Cronbach's α: 0.85 for Hindi, 0.89 for Marathi). Conclusion The questionnaire COST - FACIT (Version 2) has been approved and validated in Hindi and Marathi languages by the FACIT team for use in clinical practice and studies.

Outcomes of Ewing sarcoma in adults over 40 years of age from a low-middle income country.

Introduction: The data on outcomes and toxicity in adult Ewing sarcoma (ES) patients, particularly those aged ≥40 years, is exceedingly scarce around the world, particularly in low- and middle-income countries (LMICs) and mandates research. Methods: The study involved histologically ascertained ES patients aged ≥40 years who registered at our institute from 2013 to 2018. Prospectively collected data were analysed for overall survival (OS), event-free survival (EFS) and chemotherapy-related toxicities. Results: There were 66 patients, of which 34 were non-metastatic, and 32 were denovo metastatic, recurrent or had doubtful metastasis. At presentation, median age was 46 years, and 42 (63.6%) had extra-skeletal primary and 24 (36.3%) had extremity tumours. Curative treatment was offered to 40 (60.6%) patients. Significant grade 3/4 toxicities in non-metastatic and metastatic cohort, respectively, were febrile neutropenia (61.3%, 37.5%), anaemia (58.1%, 37.5%), thrombocytopenia (45.2%, 25.0%), peripheral neuropathy (25.8%, 12.5%) and dyselectrolytemia (25.8%, 6.25%). Chemotherapy-related toxicity led to death in three patients in the metastatic cohort, versus none in the non-metastatic patients. The 5 year EFS and OS for non-metastatic cohort were 53.8% and 67.8%, while the same for metastatic cohort were 20.7% and 27.5%, respectively. On multivariate analysis, Eastern Cooperative Oncology Group-performance status >2 and metastasis at presentation predicted poorer EFS and OS. Additionally, raised lactate dehydrogenase, larger tumours (>8 cm) and palliative intent treatment predicted worse EFS, while extra-skeletal primary and female gender were indicators of worse OS. Conclusions: Older adult ES patients benefit from aggressive multimodality treatment even in LMIC infrastructure. However, careful patient selection, close monitoring and pertinent dose modifications is imperative due to higher propensity for potential toxicities.

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.

G8 and VES-13 as screening tools for geriatric assessment and predictors of survival in older Indian patients with cancer.

BACKGROUND: Geriatric 8 (G8) and Vulnerable Elders Survey-13 (VES-13) are quick and easy-to-use screening tools, developed and validated in older patients living in North America and Europe for predicting abnormalities in the subsequent geriatric assessment. The applicability of these screening tools in older Indian patients with cancer is not known. METHODS: An observational study in 308 Indian patients with cancer aged ≥60 years, who were evaluated in the Geriatric Oncology clinic at the Tata Memorial Hospital, Mumbai, India, between June 2018 and November 2020. Patients underwent the G8 and VES-13 screening tools followed by a geriatric assessment. The objectives were to determine the diagnostic accuracy of the G8/VES-13 screening tools to detect an abnormal geriatric assessment, to determine their association with the Eastern Cooperative Oncology Group (ECOG) performance status (PS)/Cancer Aging and Research Group (CARG) scores, to determine the optimal cut-off value on the G8 scale for older Indian patients with cancer, and to determine whether an abnormal G8/VES-13 score was associated with shorter survival. We also aimed to assess the utility of combining the G8 and VES-13 scores to predict for an abnormal geriatric assessment and poorer survival. RESULTS: The sensitivity and specificity of the G8 (cut-off, ≤14) score were 84.4% and 17.6%, respectively, whereas those for the VES-13 score (≥3) were 34.9% and 82.4%, respectively. The appropriate abnormal G8 cut-off score was noted to be 12. Abnormal G8 (≤14) and VES-13 scores were not associated with an abnormal subsequent geriatric assessment [p = 0.736 (G8)], while abnormal G8 (≤14) scores did not predict for worse survival outcomes. Lowering the cut-off of the G8 score to <12 and/or combining an abnormal G8 (<12) with the VES-13 score were found to be associated with an abnormal subsequent geriatric assessment [p < 0.001 (G8), p < 0.001(G8 + VES-13)] and predicted for worse survival. CONCLUSIONS: An abnormal G8 cut-off score < 12 is therefore appropriate in older Indian patients with cancer. G8 < 12 predicts for the presence of non-oncological vulnerabilities and shorter survival. Lowering the cutoff of G8 to 12translated to a 35% reduction in the number of patients undergoing a complete geriatric assessment. Combined with VES-13, the G8 can be reliably used to identify those patients who would benefit the most from a geriatric assessment and help in optimal resource utilization especially in busy Indian centers.

Selecting lymph node-positive patients for adjuvant therapy after radical prostatectomy and extended pelvic lymphadenectomy: An outcome analysis of 100 node-positive patients managed without adjuvant therapy.

Objective: The aim of the study is to evaluate the effect of deferred androgen deprivation therapy on biochemical recurrence (BCR) and other survival parameters in node-positive prostate cancer patients after robot-assisted radical prostatectomy with bilateral extended pelvic lymph node dissection (RARP + EPLND). Materials and methods: Of the 453 consecutive RARP procedures performed from 2011 to 2018, 100 patients with no prior use of androgen deprivation therapy were found to be lymph node (LN) positive and were observed, with initiation of salvage treatment at the time of BCR only. Patients were divided into 1 or 2 LNs (67)-and more than 2 LNs (33)-positive groups to assess survival outcomes. Results: At a median follow-up of 21 months (1-70 months), the LN group (p < 0.000), preoperative prostate-specific antigen (PSA, p = 0.013), tumor volume (TV, p = 0.031), and LND (p = 0.004) were significantly associated with BCR. In multivariate analysis, only the LN group (p = 0.035) and PSA level (p = 0.026) were statistically significant. The estimated BCR-free survival rates in the 1/2 LN group were 37.6% (27%-52.2%), 26.5% (16.8%-41.7%), and 19.9% (9.6%-41.0%) at 1, 3, and 5 years, respectively, with a hazard of developing BCR of 0.462 (0.225-0.948) compared with the more than 2 LN-positive group. Estimated 5-year overall survival, cancer-specific, metastasis-free, and local recurrence-free survival rates were 88.4% (73.1%-100%), 89.5% (74%-100%), 65.1% (46.0%-92.1%), and 94.8% (87.2%-100.0%), respectively, for which none of the factors were significant. Based on cutoff values for PSA, TV, and LND of 30 ng/mL, 30%, and 10%, respectively, the 1/2 LN group was substratified, wherein the median BCR-free survival for the low- and intermediate-risk groups was 40 and 12 months, respectively. Conclusions: Nearly one fourth and one fifth of 1/2 node-positive patients were BCR-free at 3 and 5 years after RARP + EPLND. Further substratification using PSA, TV, and LN density may help in providing individualized care regarding the initiation of adjuvant therapy.

Radical D2 gastrectomy with adjuvant chemotherapy for stage IB/II/III distal gastric cancers in the era of perioperative chemotherapy: A propensity matched comparison.

AIM: This study aimed to assess the impact of treatment sequencing on long-term survival, in distal gastric cancers (GCs) (stage IB/II/III). METHODS: This retrospective study included patients with distal GC undergoing D2 resection. Outcomes were compared between group 1 (surgery with adjuvant chemotherapy) and group 2 (perioperative chemotherapy with surgery). 1:1 matching for baseline characteristics (age, cT, and cN stage) was performed for outcome comparison. RESULTS: At a median follow-up of 47.5 months in the included 342 patients, the 5-year overall survival (OS) was 61.1% and disease-free survival (DFS) was 50.5%. OS was comparable in the unmatched (group 1, n = 118; group 2, n = 224) (HR 0.905, 95%CI 0.64-1.33, P = 0.615) and matched groups (group 1, n = 97; group 2, n = 97) (HR 0.77, 95% CI 0.48-1.26, P = 0.3). CONCLUSION: D2 resection followed by adjuvant chemotherapy provides similar long-term outcomes as compared to perioperative chemotherapy approach for stage IB/II/III distal GCs.

Elevated CEA with negative PET scan on surveillance of colorectal cancers-a role of CEA kinetics.

INTRODUCTION: The management of patients with elevated CEA after curative treatment of colorectal cancers without structural disease is uncertain. The aim was to study the clinical risk factors, CEA thresholds, and kinetics that could predict relapses. METHODS: Retrospective study of colorectal cancers patients that were detected to have an elevated CEA (> 5 ng/ml on 2 separate occasions) and normal clinical exam, colonoscopy, and positron emission tomography (PET). Receiver operating characteristic (ROC) curves were generated to determine the optimal cutoff for absolute CEA values and proportional rise that could predict recurrences. RESULTS: 162 patients were followed for a median of 42 months. 32 patients (19.7%) relapsed of which 11 (34.4%) had a peritoneal disease. Besides known clinical risk factors, higher CEA at the time of negative PET and rising CEA trend predicted disease recurrence on multivariate logistic regression. CEA threshold of 10.05 ng/ml provided a sensitivity/specificity of 53%/86.2%, while CEA velocity of 1.36 ng/ml over 3 months presented a sensitivity/specificity of 80%/70.6% for subsequent relapse. CONCLUSIONS: The discriminatory value of CEA kinetics was more than that of a single absolute value. An algorithm for managing these patients based on clinical risk factors, absolute CEA value, and its kinetics is suggested.

Management of Abdominal Ewing's Sarcoma: A Single Institute Experience.

Ewing's sarcoma (ES)/primitive neuroectodermal tumors (PNETs) are a rare group of tumors commonly arising from bones, uncommonly from soft tissues, and rarely from abdomen. The aim of the study was to analyze the outcome (recurrence-free survival[RFS]), patient characteristics, role of FDG-PET (fluorodeoxyglucose positron emission tomography) computerized scan, chemotherapy and radiation, and prognostic factors. We retrospectively studied patients diagnosed with abdominal ES/PNET and treated surgically between June 2005 and November 2019. Ten patients were included in the study, with a median age of 36.5 years (19-46 years). The median follow-up was 25 months (3-178 months). The site of origin was the retroperitoneum, small bowel, and abdominal wall in six, two, and two patients, respectively. 70% of patients were treated with induction chemotherapy. R0 resection was achieved in 90% of patients. With chemotherapy, there was significant reduction in tumor size (p = 0.034) with non-significant reduction in SUV max (p = 0.31). The 1- and 2-year RFS were 88.90% and 76.20%, respectively. Pathological peritoneal metastasis and ability to achieve R0 resection were prognostic factors affecting RFS. These patients must be offered multimodality treatment. Induction chemotherapy significantly reduces the tumor size. Pathological peritoneal metastasis and ability to achieving R0 resection significantly affect survival.

Can We Avoid Axillary Lymph Node Dissection (ALND) in Patients with 1-2 Positive Sentinel/Low Axillary Lymph Nodes (SLN/LAS+) in the Indian Setting?

The ACOSOG Z0011 study, heralded as a "practice changing" trial, suggested that women with T1-2 breast cancer with 1-2 SLN+, undergoing breast conservation therapy, need not be offered further ALND. However, whether these results are applicable to all women in the Indian setting, it remains debatable. A retrospective audit of all cN0 operated from 2013 to 2018 was conducted. We analyzed the percentage of additional LN positive (LN+) in the ALND group and compared it to the ACOZOG Z11 trial. Of the 2350 cN0 with EBC who underwent LAS, 687 (29%) had positive lymph nodes on final histopathology. Five hundred ninety-seven (86.9%) patients had 1-2 LN+, 40 (5.8%) patients had 3 LN+, and 50 (7.3%) had 4 or more nodes positive. Demographic features in the ACOSOG Z11 are different from those in our study, looking at ACOZOG Z11 versus our cohort-median pT 1.7 cm versus 3 cm, 45% micrometastasis versus 99.16% macrometastasis, and 28-30% grade 3 tumors versus 73.7%. In our cohort 31.82% of the 1-2 LN positive had additional LN+ on ALND. Keeping in mind the difference in clinicopathological features between our cohort and that of ACOZOG Z0011 and that 31.82% of women had additional LN+ on ALND, it may not be appropriate to apply the results of the ACOSOG Z0011 trial directly to our general population. Possibly, only a select subset of patients who match the trial population of the ACOSOG Z11 could be offered observation of the axilla and validated nomograms can be used to identify high-risk patients.

Serous endometrial intraepithelial carcinoma: A clinico-pathological study of 48 cases and its association with endometrial polyps - A tertiary care oncology centre experience.

BACKGROUND: Endometrial serous carcinoma (ESC) is an aggressive neoplasm wherein the recent studies have shown that it arises from its putative precursor namely the serous endometrial intraepithelial carcinoma (SEIC). SEIC usually arises in inactive/ atrophic endometrium but surprisingly is frequently associated endometrial polyps (EPs). The aim of this study was to assess the incidence of SEIC with or without invasion, its clinical behaviour and association with endometrial polyp. MATERIALS AND METHODS: After Institutional review board approval, a total of 205 samples (belonging to 120 patients); diagnosed as ESC from January 2009 to December 2015 were retrieved and reviewed for presence of in situ carcinoma and also for associated endometrial polyp. RESULTS: The mean age at diagnosis was 62.40 years with postmenopausal bleeding being the most common presenting symptom. The incidence of SEIC with or without invasive tumor was 40% (48/120). Of these 48 cases; 25 cases were associated with in-situ carcinoma arising in the EPs which amounted to 52% of the total cases. The overall three year survival and disease free survival in SEIC with or without invasion were 1.9% and 0.25%, indicating the aggressive nature of the disease. CONCLUSION: SEIC is a difficult histopathological diagnosis and one should carefully look for these lesion, especially in the EPs which are frequently associated with them. Extensive sampling of the EP will be helpful to pick up in-situ carcinoma arising in EP. SEIC is an aggressive disease on its own with a propensity to develop distant metastasis even in the absence of myometrial invasion and hence should be treated with optimum surgical staging and if indicated aggressive adjuvant treatment protocols.

Efficacy and safety of palbociclib and ribociclib in patients with estrogen and/or progesterone receptor positive, HER2 receptor negative metastatic breast cancer in routine clinical practice.

BACKGROUND: There is scant data from India on efficacy and safety of palbociclib and ribociclib in routine clinical practice. METHODS: This retrospective, observational, single institution study included patients with estrogen and/or progesterone receptor positive and human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancers, who received palbociclib or ribociclib with any partner endocrine therapy in any line of treatment between January 2016 and June 2019. Data were analyzed for progression-free survival (PFS), overall survival (OS) and toxicity. RESULTS: The study included 101 female patients with median age of 57 (IQR 48-62) years, of whom 80 (79.2%) were postmenopausal, 79 (78.2%) received palbociclib or ribociclib in second- or later-line treatment, 59 (58.4%) received fulvestrant and 41 (40.6%) received an aromatase inhibitor. In first-line treatment, at a median follow-up of 21.7 (0.5-41.9) months, median PFS and OS were 21.1 (95%CI 16.36-not estimable) months and not reached, respectively. In second- or later-line setting, at a median follow-up of 17.2 (0.5-43.7) months, median PFS and OS were 5.98 (95%CI 4.96-7.89) months and 20.2 (95%CI 14.1-not estimable) months, respectively. Grade 3-4 neutropenia and febrile neutropenia were seen in 45 (45.0%) and 9 (9.0%) patients, respectively while dose reduction was required in 32 (31.7%) patients. In multivariable Cox regression analysis, first-line setting (HR 0.49, 95%CI 0.25-0.97, p = 0.043) and ECOG performance status 1 (HR 0.43, 95%CI 0.20-0.91, p = 0.028) were significantly associated with PFS while only ECOG PS 1 was significantly associated (HR 0.04, 95%CI 0.008-0.206, p = 0.000) with OS. CONCLUSION: Palbociclib and ribociclib, when used in routine clinical practice in first or subsequent lines of treatment, resulted in efficacy and toxicity outcomes in concordance with those expected from pivotal trials.

Adolescent-adult nonmetastatic Ewing sarcoma-Experience from a large developing country.

BACKGROUND: Outcome and toxicity data in adolescent-adult Ewing sarcoma (AA-ES) patients are sparse and merits exploration. METHODS: Histopathologically confirmed, nonmetastatic AA-ES patients, who received standard institutional combination chemotherapy regimen (Ewing's family of tumors-2001 [EFT-2001]) comprising of ifosfamide plus etoposide and vincristine, doxorubicin plus cyclophosphamide, lasting a total of 12 months between 2013 and 2018, were analyzed for treatment-related toxicities, event-free survival (EFS), and overall survival (OS). RESULTS: There were 235 patients (primary safety cohort [PSC]) with median age of 23 (15-61) years; 159 (67.7%) were males, 155 (65.9%) had skeletal primary and 114 (48.5%) had extremity tumors. One hundred ninety-six (83.4%) were treatment naïve (primary efficacy cohort [PEC]) and of these 119 (60.7%) had surgery. In PEC, at a median follow-up of 36.4 (interquartile range [IQR] 20-55) months, estimated 3-year EFS and OS were 67.3% (95% CI 60.3-75.1%) and 91.1% (95% CI 86.7-95.7%), respectively. Of these, 158 (80.6%) complying with intended treatment, at a median follow-up of 39 (IQR 26-57) months had an estimated 3-year EFS of 68.2% (95% CI 60.3-76.1%). In multivariable analysis, good prognostic factors included longer symptom(s) duration (HR 0.93, 95% CI 0.86-0.994), ≥99% necrosis (HR 0.30, 95% CI 0.11-0.77), and treatment completion (HR 0.32, 95% CI 0.14-0.74). Among PSC, grade 3-4 toxicities were febrile neutropenia (119, 50.6%), anemia (130, 55.3%), peripheral neuropathy (37, 15.7%), with three (1.3%) chemo-toxic deaths. CONCLUSIONS: The outcomes of AA nonmetastatic ES patients treated with EFT-2001 regimen were comparable to those reported by others, with acceptable toxicity. This regimen can be considered a standard of care in AA-ES.

Multinational Study to Assess Stress Levels Among the Health Care Workers of Radiation Oncology Community at the Outset of the COVID-19 Pandemic.

PURPOSE: To evaluate stress levels among the health care workers (HCWs) of the radiation oncology community in Asian countries. METHODS: HCWs of the radiation oncology departments from 29 tertiary cancer care centers of Bangladesh, India, Indonesia and Nepal were studied from May 2020 to July 2020. A total of 758 eligible HCWs were identified. The 7-Item Generalized Anxiety Disorder, 9-Item Patient Health Questionnaire, and 22-Item Impact of Events Scale-Revised were used for assessing anxiety, depression, and post-traumatic stress disorder. Univariate and multivariate analysis was done to identify the causative factors affecting mental health. RESULTS: A total of 758 participants from 794 HCWs were analyzed. The median age was 31 years (IQR, 27-28). The incidence of moderate to severe levels of anxiety, depression, and stress was 34.8%, 31.2%, and 18.2%, respectively. Severe personal concerns were noticed by 60.9% of the staff. On multivariate analysis, the presence of commonly reported symptoms of COVID-19 during the previous 2 weeks, contact history (harzard ratio [HR], 2.04; CI, 1.15 to 3.63), and compliance with precautionary measures (HR, 1.69; CI, 1.19 to 2.45) for COVID-19 significantly predicted for increasing anxiety (HR, 2.67; CI, 1.93 to 3.70), depression (HR, 3.38; CI 2.36 to 4.84), and stress (HR, 2.89; CI, 1.88 to 4.43) (P < .001). A significant regional variation was also noticed for anxiety, stress, and personal concerns. CONCLUSION: This survey conducted during the COVID-19 pandemic revealed that a significant proportion of HCWs in the radiation oncology community experiences moderate to severe levels of anxiety, depression, and stress. This trend is alarming and it is important to identify and intervene at the right time to improve the mental health of HCWs to avoid any long-term impacts.

Outcomes and prognostic factors in adolescents and young adults with ALL treated with a modified BFM-90 protocol.

The use of pediatrics-inspired protocols in adolescent and young adult (AYA) acute lymphoblastic leukemia (ALL) results in superior survival compared with the adult protocols. Pediatrics-inspired protocols carry an increased risk of toxicity and treatment-related mortality in low resource settings, which can offset the potential benefits. We studied the outcomes and prognostic factors in the treatment of AYA ALL with a pediatrics-inspired regimen. We retrieved data regarding demographics, investigations, treatment details, and toxicities from the electronic medical records of patients diagnosed with ALL in the 15- to 25-year-old age group who were initiated on a modified Berlin-Frankfurt-Münster 90 (BFM-90) protocol between January 2013 and December 2016 at the Tata Memorial Centre. A total of 349 patients in the 15- to 25-year-old age group were treated with a modified BFM-90 protocol. The use of this pediatrics-inspired protocol resulted in a 3-year event-free survival (EFS) and overall survival (OS) of 59.4% and 61.8%, respectively. Only 15 patients underwent an allogeneic stem cell transplant. Minimal residual disease (MRD) persistence postinduction emerged as the only factor predictive of poor outcomes. A modified BFM-90 protocol is an effective and safe regimen for AYA ALL with an OS and EFS comparable to the published literature.

Pregnancy associated breast cancer (PABC): Report from a gestational cancer registry from a tertiary cancer care centre, India.

BACKGROUND: Pregnancy associated breast cancer (PABC) is a rare entity and defined as breast cancer diagnosed during pregnancy or one-year post-partum. There is sparse data especially from low and middle-income countries (LMIC) and merits exploration. METHODS: The study (2013-2020) evaluated demographics, treatment patterns and outcomes of PABC. RESULTS: There were 104 patients, median age of 31 years; 43 (41%) had triple-negative disease, 31(29.8%) had hormone-receptor (HR) positive and HER2 negative, 14 (13.5%) had HER2-positive and HR negative and 16(15.4%) had triple positive disease. 101(97%) had IDC grade III tumors and 74% had delayed diagnosis. 72% presented with early stage (24, EBC) or locally advanced breast cancer (53, LABC) and received either neoadjuvant (n = 49) or adjuvant (n = 26) chemotherapy and surgery. Trastuzumab, tamoxifen, and radiotherapy were administered post-delivery. At a median follow up of 27 (IQR:19-35) months, the estimated 3-year event-free survival (EFS) for EBC and LABC was 82% (95% CI: 65.2-100) and 56% (95% CI: 42-75.6%) and for metastatic 24% (95% CI: 10.1%-58.5%) respectively. Of the 104 patients, 34 were diagnosed antepartum (AP) and 15 had termination, 2 had preterm and 16 had full-term deliveries(FTDs). Among postpartum cohort (n = 70), 2 had termination, 1 had preterm, 67 had FTDs. 83(including 17 from AP) children from both cohorts were experiencing normal milestones. CONCLUSION: Data from the first Indian PABC registry showed that the majority had delayed diagnosis and aggressive features(TNBC, higher grade). Treatment was feasible in majority and stage matched outcomes were comparable to non-PABCs.

Prostate-Only Versus Whole-Pelvic Radiation Therapy in High-Risk and Very High-Risk Prostate Cancer (POP-RT): Outcomes From Phase III Randomized Controlled Trial.

PURPOSE: We report the clinical outcomes of a randomized trial comparing prophylactic whole-pelvic nodal radiotherapy to prostate-only radiotherapy (PORT) in high-risk prostate cancer. METHODS: This phase III, single center, randomized controlled trial enrolled eligible patients undergoing radical radiotherapy for node-negative prostate adenocarcinoma, with estimated nodal risk ≥ 20%. Randomization was 1:1 to PORT (68 Gy/25# to prostate) or whole-pelvic radiotherapy (WPRT, 68 Gy/25# to prostate, 50 Gy/25# to pelvic nodes, including common iliac) using computerized stratified block randomization, stratified by Gleason score, type of androgen deprivation, prostate-specific antigen at diagnosis, and prior transurethral resection of the prostate. All patients received image-guided, intensity-modulated radiotherapy and minimum 2 years of androgen deprivation therapy. The primary end point was 5-year biochemical failure-free survival (BFFS), and secondary end points were disease-free survival (DFS) and overall survival (OS). RESULTS: From November 2011 to August 2017, a total of 224 patients were randomly assigned (PORT = 114, WPRT = 110). At a median follow-up of 68 months, 36 biochemical failures (PORT = 25, WPRT = 7) and 24 deaths (PORT = 13, WPRT = 11) were recorded. Five-year BFFS was 95.0% (95% CI, 88.4 to 97.9) with WPRT versus 81.2% (95% CI, 71.6 to 87.8) with PORT, with an unadjusted hazard ratio (HR) of 0.23 (95% CI, 0.10 to 0.52; P < .0001). WPRT also showed higher 5-year DFS (89.5% v 77.2%; HR, 0.40; 95% CI, 0.22 to 0.73; P = .002), but 5-year OS did not appear to differ (92.5% v 90.8%; HR, 0.92; 95% CI, 0.41 to 2.05; P = .83). Distant metastasis-free survival was also higher with WPRT (95.9% v 89.2%; HR, 0.35; 95% CI, 0.15 to 0.82; P = .01). Benefit in BFFS and DFS was maintained across prognostic subgroups. CONCLUSION: Prophylactic pelvic irradiation for high-risk, locally advanced prostate cancer improved BFFS and DFS as compared with PORT, but OS did not appear to differ.