Autologous Stem Cell Transplantation in Adult Hodgkin Lymphoma at a Tertiary Care Center in India: Analysis of Outcomes and Prognostic Factors.

High-dose chemotherapy and autologous stem cell transplant (ASCT) is the standard of care treatment in relapsed/refractory Hodgkin lymphoma (rrHL). Published long-term follow-up data concerning this modality from the Indian subcontinent is lacking. In this retrospective study, the data on adults (> 16 years) with biopsy-confirmed rrHL who were autografted from 1 January 2000 to 31 December 2021 at our transplant unit were analyzed. Progression-free survival (PFS) was defined as time from transplant to disease progression or death due to any cause. Overall survival (OS) was determined from date of transplant to date of death due to any cause. Overall, 134 patients with Hodgkin lymphoma underwent ASCT. At a median follow-up of 38.2 (range, 0.1-240) months, 5 years PFS was 45.3% (95% CI 35.4-54.4). The probability of OS at 5 years was 60.5% (95% CI 49.6-69.6). Eleven (8.2%) patients suffered transplant-related mortality by 100 days. Post-transplant persistent disease, pre-transplant serum hypoalbuminemia (< 3.5 g/dl) and chemo-resistance (< PR after last salvage regimen) of tumour at transplant were independent prognostic factors associated with worse PFS in multivariable analysis. Likewise, age ≥ 30 years, ECOG performance status ≥ 1 and residual disease after transplantation correlated with inferior OS. Long-term outcomes of rrHL patients undergoing ASCT in India match those from the developed world in the era of peripheral blood stem cell transplantation. Pre-transplant performance status, chemo-sensitivity of disease, serum albumin and post-transplant remission status determined survival in our cohort. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01690-x.

Demographic and clinical profile of 1106 adult soft tissue sarcoma patients: A single institutional prospective database experience from India.

BACKGROUND: Adult soft tissue sarcomas (STS) are rare and diverse. Current management is based on limited literature from the West. Therefore, data from different geographical regions is required, including the low-middle-income countries. This is our experience managing adult sarcomas in the tertiary cancer center of North India. MATERIALS AND METHODS: This is a retrospective analysis of the structured sarcoma database of patients treated in the surgical oncology department between 1992 and 2020. The descriptive analysis includes demography, site distribution, diagnosis, histopathology variations, prior surgical interventions, and stage. RESULTS: A total of 1106 soft tissue sarcoma patients were treated in three decades. Age distribution was 13%, 43%, 31%, and 11% in <20, 21-40, and 41-60 and >60 years, respectively. The male-to-female ratio was 1.73. The anatomical distribution was 17%, 42%, 23%, 7%, 7%, and 3% in upper extremity, lower extremity, trunk, retroperitoneum, head and neck, and viscera, respectively. Overall, 49% of patients had undergone prior suboptimal surgeries at community hospitals. Common histology subtypes were synovial sarcoma (18%), undifferentiated pleomorphic sarcoma (UPS) (13%), dermatofibrosarcoma protuberans (12%), and liposarcoma (9%). A pathological discordance of 13% was identified between the initial and the final histologies. Overall, 61% of tumors were high-grade. Memorial Sloan Kettering Stages II and III were present in 33% and 35% of patients, respectively. CONCLUSIONS: This is one of the largest single institutional experiences of STS from the Asian population. Mostly young adults were affected with male preponderance. The lower extremity and trunk were common subsites. Frequent histologies were synovial sarcoma and UPS. A high rate of suboptimal surgical intervention at the community level and pathological discordance was noted. This study highlights the need to establish prospective structured databases for capturing quality information related to rare malignancies and providing insights for future research.

Treatment outcomes in patients with Ewing sarcoma of the spine in a resource-challenged setting: 17-year experience from a single center in India.

Ewing sarcoma (ES) of the spine is a rare childhood cancer with sparse literature on treatment outcomes. We aimed to describe survival outcomes and prognostic factors in patients with spinal ES treated at a single institute in a resource-challenged setting. We conducted a retrospective analysis of patients with spinal ES registered at a tertiary care oncology center between 2003-2019. Clinical patient data was retrieved from hospital records. Cox regression analysis was used to identify the association of baseline clinical parameters with event free survival (EFS) and overall survival (OS). A cohort of 85 patients was analyzed including 38 (45%) patients with metastatic disease. The median age was 15 years with 73% being male. Local therapy was administered in 62 (72.9%) patients with surgery alone in 8 (9.4%), radiotherapy alone in 36 (42.4%) and both in 18 (21.2%) patients. A higher proportion of males received local therapy than females (80.3% versus 59.1%; p = 0.049). The median EFS and OS were 20.1 and 28.6 months, respectively. On univariable analysis, age ≤ 15 years, female sex, serum albumin ≤3.5 g/dL and hemoglobin ≤11 g/dL were associated with inferior EFS while younger age, female sex, hypoalbuminemia and metastatic disease were associated with inferior OS. On multivariable analysis, only hypoalbuminemia was predictive for inferior EFS (HR:2.41; p = 0.005) while hypoalbuminemia (HR:2.06;p = 0.033) and female sex (HR:1.83; p = 0.046) were associated with inferior OS. We concluded that hypoalbuminemia confers poor prognosis in ES spine. Survival outcomes are poorer in females treated in our setting, possibly due to prevailing sex-based biases.

Malignant Chest Wall Tumors: Complex Defects and Their Management-A Review of 181 Cases.

BACKGROUND: Chest wall tumors are a heterogeneous group of tumors that are managed by surgeons from diverse specialties. Due to their rarity, there is no consensus on their diagnosis and management. MATERIALS: This retrospective, descriptive analysis includes patients with malignant chest wall tumors undergoing chest wall resection. Tumors were classified as primary, secondary, and metastatic tumors. The analysis includes clinicopathological characteristics, resection-reconstruction profile, and relapse patterns. RESULTS: A total of 181 patients underwent chest wall resection between 1999 and 2020. In primary tumors (69%), the majority were soft tissue tumors (59%). In secondary tumors, the majority were from the breast (45%) and lung (42%). Twenty-five percent of patients received neoadjuvant chemotherapy, and 98% of patients underwent R0 resection. Soft tissue, skeletal + soft tissue, and extended resections were performed in 45%, 70%, and 28% of patients, respectively. The majority of patients (60%) underwent rib resections, and a median of 3.5 ribs were resected. The mean defect size was 24 cm2. Soft tissue reconstruction was performed in 40% of patients, mostly with latissimus dorsi flaps. Rigid reconstruction was performed in 57% of patients, and 18% underwent mesh-bone cement sandwich technique reconstruction. Adjuvant radiotherapy and chemotherapy were given to 29% and 39% of patients, respectively. CONCLUSIONS: This is one of the largest single-institutional experiences on malignant chest wall tumors. The results highlight varied tumor spectra and multimodality approaches for optimal functional and survival outcomes. In limited resource setting, surgery, including reconstructive expertise, is very crucial.

Re-operative surgery for differentiated thyroid cancer: A single institutional experience of 182 cases.

INTRODUCTION: Re-operative thyroid surgery (RTS) is performed in patients of differentiated thyroid cancer (DTC) with residual or recurrent disease. However, there is a paucity of literature discussing experience and technique of RTS. This study aims to address this gap by providing a comprehensive review of RTS for DTC, utilizing experiences from a dedicated complex thyroid surgical oncology program at the apex hospital in a developing country. METHODS: A retrospective analysis was conducted using data from the Department of Surgical Oncology's thyroid cancer database. The study period spanned from 2006 to 2022. Clinical presentation, prior surgical history, operative details of RTS, and post-operative outcomes were assessed. Descriptive analysis was performed. RESULTS: During the study period, a total of 182 patients underwent re-operative thyroid surgery (RTS). The primary surgeries performed prior to RTS included near-total or total thyroidectomy in most cases (69.2%), and approximately half of the patients (48.4%) had prior neck node interventions. The RTS procedures consisted of completion total thyroidectomy in 30.8% of cases and surgery for thyroid bed recurrence in 9.9% of cases, while central node dissection was performed in 46.2% of patients and unilateral or bilateral template neck dissection was performed in 41.8% of cases. Extended resections were required in 9.3% of patients. Post-operative complications included permanent hypoparathyroidism (2.7%) and unilateral recurrent laryngeal nerve palsy (1.6%). CONCLUSIONS: RTS is a complex procedure with high rates of post-operative morbidity reported in literature. Optimal outcomes require a multidisciplinary approach, thorough assessment, and skilled surgeons.

Formulation and validation of a baseline prognostic score for osteosarcoma treated uniformly with a non-high dose methotrexate-based protocol from a low middle income healthcare setting: a single centre analysis of 594 patients.

Introduction: The outcomes of osteosarcoma in low middle income countries (LMICs) are different due to patients presenting in advanced stages, resource constraints and the use of non-high-dose-methotrexate (HDMTX)-based regimens. This study derived and validated a prognostic score for osteosarcoma that integrates biologic and social factors and is tailored for patients from an LMIC setting using a non-HDMTX-based protocol. Materials and methods: A retrospective study including osteosarcoma patients enrolled for treatment at a single tertiary care centre in India between 2003-19 was conducted. Baseline biologic and social characteristics were extracted from medical records and survival outcomes were noted. The cohort was randomised into a derivation and validation cohort. Multivariable Cox regression was used to identify baseline characteristics that were independently prognostic for survival outcomes in the derivation cohort. A score was derived from the prognostic factors identified in the derivation cohort and further validated in the validation cohort with estimation of its predictive ability. Results: 594 patients with osteosarcoma were eligible for inclusion in the study. Around one-third of the cohort had metastatic disease with 59% of the patients residing in rural areas. The presence of metastases at baseline (HR 3.39; p<0.001; score=3), elevated serum alkaline phosphatase (SAP) >450 IU/L (HR 1.57; p=0.001; score=1) and baseline tumour size > 10 cm (HR 1.68; p<0.001; score=1) were identified to be independent factors predicting inferior event free survival (EFS) and were included in development of the prognostic score. Patients were categorized as low risk (score 0), intermediate risk (score 1-3) and high risk (4-5). Harrell's c-indices for the score were 0.682, 0.608 and 0.657 respectively for EFS in the derivation, validation and whole cohort respectively. The timed AUC of ROC was 0.67 for predicting 18-month EFS in the derivation, validation and whole cohorts while that for 36-month EFS were 0.68, 0.66 and 0.68 respectively. Conclusions: The study describes the outcomes among osteosarcoma patients from an LMIC treated uniformly with a non-HDMTX-based protocol. Tumor size, baseline metastases and SAP were prognostic factors used to derive a score with good predictive value for survival outcomes. Social factors did not emerge as determinants of survival.

Central nervous system metastasis from epithelial ovarian cancer- predictors of outcome.

Management of central nervous system (CNS) metastases from epithelial ovarian cancer (EOC) is an unmet need. We analyzed data on 41 such patients to evaluate predictors of outcome. Between January, 2010 and December 2020, among 1028 patients with EOC treated at our institute 41 (3.98%) developed CNS metastasis. Median age of patients was 48 years, ranging from 22 to 75 years. Primary outcome measure was progression free survival (PFS). Overall survival (OS), and analysis of prognostic factors were secondary outcome measures. An intention to treat analysis was done. We also performed review the literature (n=2253) as regards to clinicopathological and radiological features, treatment received, survival outcomes and prognostic factors. Median time from diagnosis of EOC to CNS metastasis was 27 months (range: 0 to 101 months). 33(80.5%) patients had FIGO stage III-IV at baseline and serous carcinoma (75.6%) was common pathology subtype. Thirteen (31.7%) patients had isolated CNS metastasis and 28 (68.3%) had intra-abdominal disease in addition. Nineteen (46.3%) patients achieved complete response post treatment with surgery, radiation and chemotherapy. Median PFS and OS from the time of CNS metastasis is 12 (range:1 to 51) months and 33 (range: 1 to 71) months, respectively. Absence of extracranial disease and lower serum CA-125 at diagnosis of CNS metastasis were predictive of superior PFS and OS on multivariate analysis. CNS metastasis is a late event in EOC, post multiple lines of treatment. Patients with disease limited to brain and treated with surgical resection and chemoradiation have best outcome.

Autologous stem cell transplant for multiple myeloma: Impact of melphalan dose on the transplant outcome.

We evaluated impact of melphalan dose on transplant outcomes for multiple myeloma. Between 1995 and 2019 459 consecutive patients received a transplant; 69(15%) received melphalan ≤150 mg/m2 (Mel 150 cohort) and 390 (85%) melphalan 200 mg/m2 (MEL 200 cohort). The primary outcome was overall survival (OS) from the date of transplant. Progression-free survival (PFS), engraftment, transplant response, and cumulative relapse at 2 years were secondary outcome measures. Patients in Mel 150 cohort had adverse clinical and laboratory parameters at base line. Transplant response was better for Mel 200 cohort (p < 0.024). Median OS at a median follow-up of 88 months was similar in the two cohorts; 100 Vs 102 months (Mel 200), p = 0.817. Median PFS (60.0 Vs 53 months, p = 0.746), relapse at two years (32.4% Vs 30.9%, p = 0.745) and grade 3-4 mucositis (p = 0.823) were similar. Initial treatment prepares patients better for subsequent similar transplant outcomes despite differences in baseline characteristics.

Real World Presentation and Treatment Outcomes with a Predominant Induction Chemotherapy Based Approach in Nasopharyngeal Carcinoma: A Sixteen Year Report from a Teaching Hospital in India.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) is a rare malignancy in India except in north-eastern states. We present our institutional experience of 16 years highlighting management, outcomes, responses and toxicities. MATERIALS AND METHODS: NPC patients registered at our center during the period of 2000-2015. The primary objective of the study was to assess the overall survival (OS). Secondary outcome included determinations of response rates, progression free survival (PFS) and to assess treatment-related toxicity (CTCAE v4.0). Institute ethics committee approval was obtained prior to initiation of this study. RESULTS: Data was retrieved from complete records of 222 patients out of 390 registered during study period. There were 163 males (73.4%) and 59 females (26.6%) with a male to female ratio of 2.8:1. The median age was 35 years (range 6-73). Only 5.6% (n = 12) presented in early-stage disease (stage I and II) while 89.6% (n = 199) were advanced stage (stage III, IVA, IVB). Five patients (2.2%) presented as metastatic disease. Majority of patients were treated with induction chemotherapy followed by concurrent chemoradiation (CCRT) {76.1%, n = 169}. Relapses were documented in 10.4% patients. 5% patients had loco-regional relapse while distant metastases were seen in 4% patients. The 3-year PFS and OS rates are 60.9% and 68.4%, respectively. Achieving a CR predicted superior OS on multivariate analysis. CONCLUSIONS: NPC is a rare malignancy and majority presented with advanced stages. This data outlines our experience and outcomes with a predominantly induction chemotherapy followed by definitive CCRT based approach.

Efficacy and Safety of Percutaneous Radiological Gastrostomy (PRG) as a Rescue Measure for Enteral Feeding in Patients with Advanced Head, Neck, and Upper Digestive Malignancies.

Background Percutaneous radiologic gastrostomy is an established mode of enteral feeding for nutritional support for patients with dysphagia from upper digestive tract malignancy. Its role as a rescue measure in patients with advanced malignancy, presenting with absolute dysphagia and failure of nasogastric tube insertion has not been well established. Purpose This study was performed to assess technical success and long-term outcomes of percutaneous radiologic gastrostomy (push type) for nutritional support for patients with absolute dysphagia as a last ditch nonsurgical rescue effort for enteral access. Materials and Methods This was a prospective observational study of 31 patients who underwent push-type percutaneous radiologic gastrostomy over a period of 2 years (March 2017-March 2019). The study was a part of a larger trial approved by the institutional ethics committee. Patients were followed till the removal of tube, death, or 1 year, whichever was earlier. Gastrostomy tube-related problems and complications were documented. Descriptive summary statistics were employed to analyze the success rate and complications. Results Thirty-one patients with mean age 56 years (26-78 years) including 18 males and 13 females with head and neck squamous cell cancer and esophageal cancer presenting with absolute dysphagia or significant dysphagia with failed nasogastric or endoscopic enteral access were included. Overall technical success was 93.5% (29/31), achieved in 26/31 patients with just fluoroscopy guidance and 3/5 patients with computed tomography guidance. One major (3.3%) and two minor (6.5%) complications were encountered. Five out of 29 gastrostomy tubes had to be exchanged, after a mean of 44 days (1-128 days) after insertion. Conclusion Percutaneous radiologic gastrostomy is a safe and effective intervention even as a rescue measure in patients with absolute dysphagia from advanced upper digestive tract malignancies.

Robotic ultrasound: An initial feasibility study.

BACKGROUND: Performing ultrasound during the current pandemic time is quite challenging. To reduce the chances of cross-infection and keep healthcare workers safe, a robotic ultrasound system was developed, which can be controlled remotely. It will also pave way for broadening the reach of ultrasound in remote distant rural areas as well. AIM: To assess the feasibility of a robotic system in performing abdominal ultrasound and compare it with the conventional ultrasound system. METHODS: A total of 21 healthy volunteers were recruited. Ultrasound was performed in two settings, using the robotic arm and conventional hand-held procedure. Images acquired were analyzed by separate radiologists. RESULTS: Our study showed that the robotic arm model was feasible, and the results varied based on the organ imaged. The liver images showed no significant difference. For other organs, the need for repeat imaging was higher in the robotic arm, which could be attributed to the radiologist's learning curve and ability to control the haptic device. The doctor and volunteer surveys also showed significant comfort with acceptance of the technology and they expressed their desire to use it in the future. CONCLUSION: This study shows that robotic ultrasound is feasible and is the need of the hour during the pandemic.

Multiple Myeloma: Impact of Time to Transplant on the Outcome.

BACKGROUND: Autologous stem cell transplant (ASCT) is a standard therapy for transplant eligible patients of multiple myeloma (MM). To evaluate impact of time to transplant on subsequent outcomes, we analyzed data on consecutive MM patients who received novel agents-based induction prior to transplant. METHODS: Between 2006 and 2019, 363 MM patients underwent ASCT. Patients' median age was 52 years, ranging from 20 to 72 years, 233 (64.2%) were males. Median interval from diagnosis to transplant was 11.5 months (range, 4-67.5); 201 (55.4%) patients underwent ASCT within 12 months (early) and 162 (44.6%) beyond 12 months since diagnosis (delayed ASCT). Primary objective was progression-free survival. Secondary objectives were-response rate to transplant, overall survival (OS), and transplant-related mortality (TRM). RESULTS: Post-ASCT complete response (CR) (77.1% vs. 64.8%; P < .025) and CR+ very good partial response rate (89% vs. 81.5%; P < .03) was higher for early ASCT cohort. Engraftment characteristics, regimen-related toxicities, and day +100 TRM (3.5% vs 3.7%; P = .564) were similar in 2 cohorts. Median OS for early versus late cohort from date of diagnosis is 127.0 (95% CI, 98.9-155.1) versus 104.5 months (95% CI, 79.3-129.6; P = .356) and from date of transplant is 119.0 (95% CI, 93.4-144.6) versus 89.5 months (95% CI, 57.4-121.6), P < .02. Median PFS is better for early transplant cohort; 69.5 (95% CI, 56.7-82.3) versus 50.0 months (95% CI, 35.6-64.4), P < .05, respectively. CONCLUSION: Early transplant for myeloma is associated with higher response rate and better progression-free survival.

Long-Term Outcomes and Safety Trends of Autologous Stem-Cell Transplantation in Non-Hodgkin Lymphoma: A Report From A Tertiary Care Center in India.

PURPOSE: Published experience with autologous stem-cell transplantation (ASCT) in non-Hodgkin lymphoma (NHL) from the Indian subcontinent is extremely limited. Here, we describe the activity and outcomes of this treatment modality at a large tertiary care center in India. PATIENTS AND METHODS: We retrospectively analyzed adult patients with NHL who were eligible for ASCT and autografted between January 1, 2002, and December 15, 2020, at our transplant unit. Toxicities, complications, and long-term outcomes were compared between patients who underwent transplant during 2002-2012 (group A) and 2013-2020 (group B). RESULTS: Overall, 80 patients (group A, n = 37; group B, n = 43) underwent ASCT using peripheral blood stem cells. At a median follow-up of 57.6 months, the 5-year event-free survival (EFS) and overall survival (OS) were 43.5% and 47.6%, respectively, for all patients. More recently (group B), patients had reduced 100-day transplant-related mortality (2.3% v 21.6%, P < .01), improved 3-year EFS (52.9% v 37.3%, P = .04), and superior OS (at 3-year; 63.4% v 43.2%, P = .02). Patients in group B also tolerated the procedure better, with improved resource utilization. In multivariate analysis, an International Prognostic Index (IPI) ≥ 3 at diagnosis adversely affected EFS (hazard ratio [HR] = 2.82, P = .009) and OS (HR = 2.84, P = .01) after ASCT. Low pretransplant serum albumin levels were associated with inferior EFS (HR = 2.68, P = .02) and transplant-related mortality (odds ratio = 10.80, P = .02) after ASCT. CONCLUSION: It is feasible to achieve comparable short- and long-term outcomes in patients with NHL undergoing ASCT in a resource-poor country with improved supportive care and expertise of the transplant team and center.

Patterns of Multimodality Management of Gastric Cancer-Single Institutional Experience of 372 Cases From a Tertiary Care Center in North India.

Introduction: Worldwide gastric cancer is the 5th most commonly diagnosed cancer and the leading cause of gastrointestinal cancer-related deaths. Alone surgery provides long-term survival improvements in 20% of the patients with local advanced gastric cancer. The results can be improved considering multimodal management including chemotherapy and radiotherapy. However, in low middle-income countries like India, multimodal management is challenging. Herein, we evaluated the experience of multimodal management of gastric cancer and the long-term outcome. Methods: Retrospective analysis of the data of 372 patients was done from a prospectively maintained computerized database from 1994 to 2021. Records were analyzed for demographic details, treatment patterns, recurrences, and long-term outcomes (DFS and OS). Statistical analysis was done with the package SPSS version 26 (IBM Corp, Chicago, Illinois, USA). Results: This study included 372 patients. The mean age of the patients was 54.07. A total of 307 patients (82.5%) were operated upfront, 45 (12%) received NACT, and 20 (5.5%) underwent the palliative procedure. A total of 53.2% underwent curative resection. R0 resection rate was achieved in 95% of patients. A total of 72.58% of patients required adjuvant treatment, and the majority of the patients underwent chemoradiotherapy. The most common site of metastasis was the liver. Median follow-up was 50.16 months. The 3-year disease-free survival and overall survival were 36.28% and 67.8%, and the 5-year disease-free survival and overall survival were 30.15% and 37.7%, respectively. Conclusion: Our study suggested that multimodal management is required in locally advanced gastric cancer to achieve good long-term outcomes. The treatment sequence can be tailored based on the available resources.

Modified Protocol of Nivolumab in Relapsed/Refractory Hodgkin Lymphoma: A Brief Communication of Real World Data.

Immune check point inhibitors such as nivolumab are changing the treatment paradigm of relapsed/refractory Hodgkin lymphoma (r/rHL). Data from single arm studies have shown nivolumab to be an effective and safe therapy. Real world data from resource constrained settings are limited. Our study is a retrospective single center analysis of nivolumab in r/rHL from India. Data regarding baseline and pretreatment characteristics were collected for 20 patients treated with nivolumab from January 2016 to March 2021. Of 20, 15 patients received nivolumab in modified protocol, because of financial limitations. Postnivolumab therapy, the overall response rate was 90%, with 40% in complete remission. The median progression free survival was 13.1 month (95% confidence interval 8.33 mo, not reached) and median overall survival not reached, at a follow up of 24.3 months. No patients discontinued nivolumab because of side effects. Univariate and multivariate analysis showed no effect of dose reduction or increased duration of administration. Most common adverse effect seen was autoimmune hypothyroidism. Possible delayed immune-related side effects were seen in 3 out 5 patients in peritransplant period, in those who received nivolumab as salvage regimen before autologous stem cell transplant. In conclusion, nivolumab shows comparable efficacy and safety even with compromised dosing and schedule of administration of the drug in real world setting.

Development and validation of a prognostic score at baseline diagnosis for Ewing sarcoma family of tumors: a retrospective single institution analysis of 860 patients.

INTRODUCTION: Prognostic scores in Ewing sarcoma including baseline clinical and laboratory characteristics are necessary for pre-treatment risk stratification. In this study, we formulated and validated a prognostic model for baseline risk categorization in Ewing sarcoma. MATERIALS AND METHODS: A retrospective single-institutional study was conducted on Ewing sarcoma patients treated uniformly between January 2003 and December 2018. Baseline clinical/pathological characteristics and survival outcomes were noted from medical records. The cohort was randomised into a derivation and validation cohort. A prognostic score was formulated by including independent prognostic factors from the derivation cohort by multivariable analysis. The prognostic model was validated in the validation cohort along with estimation of its predictive ability. RESULTS: A total of 860 patients were included with 40.3% having baseline metastases. Tumor diameter >5 cm (HR 2.04; P<0.001; score 2), baseline metastases (HR 2.33; P<0.001, score 2), and total leucocyte count >11000/mm3 (HR 1.44; P=0.015; score 1) were independent predictors of overall survival in derivation cohort and included for prognostic score calculation. Patients were categorized into low (score 0), intermediate (score 1-3) and high-risk (score 4-5) groups. Harrell's c-indexes of the model were 0.625, 0.622 and 0.624 in the derivation, validation and whole cohort respectively. The timed AUC of ROC of the prognostic score-group for 5-year survival was 0.72, 0.71 and 0.73 in the derivation, validation and whole cohort respectively. CONCLUSIONS: We have formulated and validated a prognostic score for Ewing sarcoma incorporating baseline clinical and laboratory parameters, with fair predictive ability for risk stratification and facilitating risk-adapted personalized therapy.

Outcome and prognostic factors in childhood B non-Hodgkin lymphoma from India: Report by the Indian Pediatric Oncology Group (InPOG-NHL-16-01 study).

The literature on B-non-Hodgkin lymphoma (NHL) in India is restricted to individual hospital data. The study aimed to evaluate the epidemiology and outcome of B-NHL in our country. One hundred and ninety-one patients of B-NHL from 10 centers diagnosed between 2013 and 2016 were analyzed retrospectively. B/T lymphoblastic lymphoma and patients with inadequate data were excluded. The median age was 88 months (IQR: 56, 144) with an M:F ratio of 5.6:1. Undernourishment and stunting were seen in 36.5% and 22%. Primary site was abdomen in 66.5%. Hypoalbuminemia was noted in 82/170 (48.2%). Histological subtypes: Burkitt lymphoma (BL): 69.6%, Burkitt-like: 10.4%, and diffuse large B cell lymphoma (DLBCL): 13.6%, unclassified and others (6.4%). Stage distribution: I/II, 33 (17.3%), III, 114 (59.7%), and IV, 44 (23%). One-eighty-six patients took treatment. Protocols used were LMB and BFM in 160/186 (86%). At a median follow-up of 21.34 (IQR: 4.34, 36.57) months, the disease-free-survival (DFS) was 74.4% and event-free-survival (EFS) was 60.7%. Treatment-related mortality (TRM), relapse/progression and abandonment were 14.3%, 14.5%, and 8.4%, respectively. Bone marrow positivity, stage IV disease, and lactate dehydrogenase (LDH) > 2,000 U/l predicted inferior EFS. Stage IV disease, LDH > 2,000 U/l, bone marrow positivity, tumor lysis syndrome and low albumin predicted TRM; LDH retained significance on multivariate analysis for EFS and TRM [OR: 4.54, 95% CI: 1.14-20, p 0.03; OR 20, 95%CI: 1.69-250, p 0.017]. BL was the main histological subtype. High TRM and relapse/progression are hampering survival. An LDH > 2,000 U/l was adversely prognostic. These data demonstrate a need to develop a national protocol that balances toxicity and potential for cure.

Profile of Pathogenic Mutations and Evaluation of Germline Genetic Testing Criteria in Consecutive Breast Cancer Patients Treated at a North Indian Tertiary Care Center.

BACKGROUND: The burden of hereditary breast cancer in India is not well defined. Moreover, genetic testing criteria (National Comprehensive Cancer Network [NCCN] and Mainstreaming Cancer Genetics [MCG] Plus) have never been validated in the Indian population. METHODS: All new female breast cancer patients from 1st March 2019 to 28th February 2020 were screened. Those providing informed consent and without previous genetic testing were recruited. Multigene panel testing (107 genes) by next-generation sequencing was performed for all patients. The frequency of pathogenic/likely pathogenic (P/LP) mutations between patients qualifying and not qualifying the testing criteria was compared and their sensitivity was computed. RESULTS: Overall, 275 breast cancer patients were screened and 236 patients were included (median age 45 years); 30 patients did not consent and 9 patients previously underwent genetic testing. Thirty-four (14%) women had a positive family history and 35% had triple-negative breast cancer. P/LP mutations were found in 44/236 (18.64%) women; mutations in BRCA1 (22/47, 46.8%) and BRCA2 (9/47, 19.1%) were the most common, with 34% of mutations present in non-BRCA genes. Patients qualifying the testing criteria had a higher risk of having a P/LP mutation (NCCN: 23.6% vs. 7.04%, p = 0.03; MCG plus: 24.8% vs. 7.2%, p = 0.01). The sensitivity of the NCCN criteria was 88.6% (75.4-96.2) and 86.36% (72.65-94.83) for MCG plus. More than 95% sensitivity was achieved if all women up to 60 years of age were tested. Cascade testing was performed in 31 previous (16/44 families), with 23 testing positive. CONCLUSIONS: The frequency of P/LP mutations in India is high, with significant contribution of non-BRCA genes. Testing criteria need modification to expand access to testing.

Risk based and response adapted radiation therapy for children and adolescents with newly diagnosed advanced stage Hodgkin lymphoma treated with ABVD chemotherapy: a report from the Indian pediatric oncology group study InPOG-HL-15-01.

This multi-centric prospective study (InPOG-HL-15-01) assessed epidemiological, clinical and outcome data of advanced stage Hodgkin Lymphoma (IIB, III and IV) in children and adolescents (N = 262). Chemotherapy regimen was ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and radiotherapy (RT) was restricted to patients with bulky disease at diagnosis or with suboptimal response at early response assessment (ERA). ERA revealed complete response in 175 (68.1%), partial response in 77 (29.9%), stable disease in 2 (0.8%), and progressive disease in 3 (1.2%) patients. RT was administered to 111 (97 bulky disease, 14 suboptimal response) patients. Five-year event free (EFS) and overall survival for the whole cohort was 81.1% and 90.8% respectively. On multivariate analysis, the only statistically significant predictor of EFS was use of RT (89% versus 74.2%; p-value <0.001). This study reinforces the benefit of consolidative RT in bulky disease and in those with suboptimal response at ERA on an ABVD backbone.