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Persisting residual masses at treatment completion are known in rhabdomyosarcoma (RMS) treated with definitive radiotherapy (RT) to the primary site, but their prognostic significance is uncertain. Tumor response as assessed by anatomic imaging is not prognostic and studies based on 18F-FDG-PET response are limited. We report the prognostic significance of persistent FDG-avidity in residual masses, assessed 3-month postdefinitive RT, in pediatric RMS.Children aged 15 years or below with Group III/IV RMS who received only definitive radiotherapy for local control from June 2013 to December 2018, and had 18F-FDG-PET CT at 3 months post-RT were retrospectively analyzed for outcomes and other prognostic factors.Sixty-three children were eligible (Group III-55, Group IV-8). 18F-FDG-PET CT scan done 3 months postradiotherapy showed FDG-avid residual masses in 10 patients (15.9%), anatomic residual in 24 (38.1%), and no anatomic/FDG-avid residual in 29(46.0%). At a median follow-up of 38 months (interquartile range, 24 to 55 mo), 3-year EFS of patients with FDG-avid residual masses was 40.0% (95% CI: 18.7% to 85.5%) versus the rest of the cohort, which was 71.9% (95% CI: 59.8% to 86.5%) (P=0.008). Three-year OS of patients with FDG-avid residual masses was 50.8% (95% CI: 25.7% to 100.0%) versus the rest of the cohort, which was 77.0% (95% CI: 65.1% to 91.0%) (P=0.037). Presence of FDG-avid residual disease persisting post-RT affected both EFS [HR-3.34 (95% CI: 1.29 to 8.68) (P=0.013)] and OS [HR-3.20 (95% CI: 1.01 to 10.12) (P=0.048)] on univariate analysis and this significance was retained for EFS in multivariate analysis [HR-3.52 (95% CI: 1.33 to 9.30) (P=0.011)].Persistent metabolic activity in residual disease post-chemoradiotherapy in RMS may portend a poorer prognosis with an increased risk of relapse. This subset of high-risk patients needs to be identified, and further trials are warranted to develop strategies to improve their outcomes.

Thrombotic events (TEs) have been extensively studied in adult cancer patients, but data in children are limited. We prospectively analyzed pediatric cancer-associated thrombosis (PCAT) in children with malignancies.Children below 15 years of age with confirmed malignancies, treated at a large tertiary cancer center in India from July 2015 to March 2020 developing any TE were eligible. A standardized approach for detection and management was followed. Data were collected after informed consent.Of 6132 eligible children, 150 (2.44%) had 152 TEs, with median age 8.5 years and male:female of 1.83:1. Most TEs occurred on chemotherapy: 111 (74.0%). The most common site was central nervous system (CNS) 59 (39.3%), followed by upper-limb venous system 37 (24.7%). Hemato-lymphoid (HL) malignancies were more prone to PCAT than solid tumors (ST) (incidence 3.23% vs. 1.58%; odds ratio [OR] = 2.06, 95% confidence interval [CI] [1.36-2.88]; p .001). Malignancies associated with PCAT were acute lymphoblastic leukemia (ALL) 2.94%, acute myeloid leukemia (AML) 6.66%, and non-Hodgkin lymphomas 5.35%. Response imaging done in 106 (70.7%) children showed complete to partial resolution in almost 90% children. Death was attributable to TE in seven (4.66%) children. Age above 10 years (OR 2.33, 95% CI [1.59-3.41]; p .001), AML (OR 4.62, 95% CI [1.98-10.74]; p = .0062), and non-Hodgkin lymphoma (OR 4.01, 95% CI [1.15-14.04]; p = .029) were significantly associated with TEs. In ALL, age more than 10 years (OR 1.86, 95% CI [1.06-3.24]; p .03), T-ALL (OR 3.32, 95% CI [1.69-6.54]; p = .001), and intermediate-risk group (OR 4.97, 95% CI [1.12-22.02]; p = .035) were significantly associated with thrombosis. The 2-year event-free survival (EFS) for HL malignancies with PCAT was 55.3% versus 72.1% in those without PCAT (p = .05), overall survival (OS) being 84.6% versus 80.0% (p = .32).Incidence of PCAT was 2.4%, and occurred predominantly in older children with hematolymphoid malignancies early in treatment. Most resolved completely with low molecular weight heparin (LMWH) and mortality was low. In hematolymphoid malignancies, PCAT reduce EFS, highlighting the need for prevention.

Objective Families of children with cancer undergoing treatment during COVID‐19 pandemic represent a vulnerable population for psychological distress and early identification and remedial measures are imperative for wellbeing of both the children and the caregivers. This article reports the results of assessment of psychological distress in primary caregivers of children with cancer undergoing treatment at a tertiary care center. Methods Primary caregivers of children with cancer (≤15 years) taking treatment at our institute during the period of July 2020 to August 2020 were prospectively evaluated for psychological distress using Patient Health Questionnaire‐9 (PHQ‐9) and Generalized Anxiety Disorder‐7 (GAD‐7) tools over a telephonic call. There were 2 cohorts, A and B (50 participants each) depending on whether child was diagnosed with COVID‐19 or not respectively during the study period. Results The assessment tool, PHQ‐9 showed a score of ≥10 in 13% (n = 13) participants (95%CI:7.1%–21.2%) in the entire cohort and in 16% (n = 8, 95%CI:5.8%–26.2%) and 10% (n = 5, 95%CI:1.7%–18.3%) participants in cohort A and cohort B respectively. GAD‐7 showed a score of ≥8 in 18% (n = 18) participants (95%CI:11.0%–27.0%) in the entire cohort and in 20% (n = 10, 95%CI:8.9%–31.1%) and 16% (n = 8, 95%CI:5.8%–26.2%) participants in cohort A and cohort B respectively. All participants were assessed, and supportive psychotherapeutic interventions administered over telephonic call. Conclusions Primary caregivers should be assessed and followed up for psychological distress irrespective of other co‐existing factors. Robust support systems built over time could help withstand the exceptional strain of a major surge during a pandemic.

Objective To report the experience with COVID-19 in children with cancer at the largest tertiary-cancer care and referral center in India. Methods This study is a single tertiary center experience on COVID-19 in children with cancer and continuation of cancer-directed therapy in them. Children ≤ 15 y on active cancer treatment detected with COVID-19 until September 15th, 2020 were prospectively followed up in the study. Patients were managed in accordance with well-laid guidelines. Treatment was continued for children with COVID-19 who were clinically stable and on intensive treatment for various childhood cancers. Results One hundred twenty-two children (median age 8 y; range 1–15 y, male:female 1.7:1) with cancer were diagnosed with COVID-19. Of 118 children, 99 (83.9%), 60 (50.8%), 43 (36.4%), 26 (22.0%), and 6 (5.1%) had RT-PCR positivity at 14, 21, 28, 35, and 60 d from diagnosis of COVID-19, respectively. Scheduled risk-directed intravenous chemotherapy was delivered in 70 (90.9%) of 77 children on active systemic treatment with a median delay of 14 d (range 0–48 d) and no increased toxicities. All-cause mortality rate was 7.4% (n = 9) and COVID-19 related mortality rate was 4.9% (n = 6). One hundred-fifteen (94.2%) children with COVID-19 did not require any form of respiratory support during the course of infection. Conclusions COVID-19 was not a major deterrent for the continuation of active cancer treatment despite persistent RT-PCR positivity. The long-term assessment of treatment adaptations requires further prospective follow-up and real-time addressal.

Background Despite being mandated by cooperative groups, omission of nodal sampling is the most frequent protocol deviation in surgery for Wilms tumor. The stations as well as the number of nodes that should be sampled are not clearly defined resulting in a marked variation in practices among surgeons. We propose a systematic method for nodal sampling intending to reduce interoperator variation. In this study, we have assessed the feasibility and yield of systematic lymph node sampling and also evaluated the factors influencing nodal metastasis. Methods Prospective evaluation of 113 Wilms tumor patients operated at a single tertiary cancer center between 2015 and 2019. All these patients underwent a systematic 5-station nodal sampling. Results Median lymph node yield was 8 and 13.2% (15/113) patients harbored a histologically positive nodal disease. Of the patients with positive nodal disease, interaortocaval nodes had metastasis in 46.7% (n = 7). They represented isolated sites of nodal disease (skip metastases) in 28.6% (n = 4) of patients. Right-sided tumors had more frequent involvement of interaortocaval nodes and skip disease. Tumors with high-risk histology had 12.5 times more odds of harboring nodal disease as compared to low and intermediate-risk histology Wilms tumor. Conclusions The proposed method of systematic station wise sampling provides a template to guide surgeons in performing lymph node harvesting. Interaortocaval nodes sampling should be performed routinely as the incidence of disease at this station is sufficiently high and metastasis may skip hilar nodes. Study of diagnostic test Level III evidence.

Background There is limited data on outcomes in cancer patients with coronavirus disease 2019 (COVID‐19) from lower middle‐income countries (LMICs). Patients and Methods This was an observational study, conducted between 12 April and 10 June 2020 at Tata Memorial centre, Mumbai, in cancer patients undergoing systemic therapy with laboratory confirmed COVID‐19. The objectives were to evaluate cumulative 30‐day all‐cause mortality, COVID‐19 attributable mortality, factors predicting mortality, and time to viral negativity after initial diagnosis. Results Of the 24 660 footfalls and 7043 patients evaluated, 230 patients on active systemic therapy with a median age of 42 (1‐75) years were included. COVID‐19 infection severity, as per WHO criteria, was mild, moderate, and severe in 195 (85%), 11 (5%), and 24 (11%) patients, respectively. Twenty‐three patients (10%) expired during follow‐up, with COVID‐19 attributable mortality seen in 15 patients (6.5%). There were no mortalities in the pediatric cohort of 31 (14%) patients. Advanced stage cancer being treated with palliative intent vs others [30‐day mortality 24%% vs 5%, odds ratio (OR) 5.6, 95% CI 2.28‐13.78, P, COVID‐19 attributable mortality in cancer patients on systemic therapy in LMICs appears lower than published data and slightly more than an unselected patient's cohort. Delayed recovery in terms of SARS COV‐2 negativity is seen in these patients. Treating Cancer remains the priority.

1 Background and Objective Coronavirus disease-2019 (COVID-19) or its complications in children with cancer were not increased as compared to normal children in earlier reports. However, continuing intensive treatment during ongoing COVID-19 infection has not been studied systematically. We report a single tertiary center experience on COVID-19 in children with cancer and continuation of cancer-directed therapy in them. 2 Methods Children ≤15years on active cancer treatment detected with COVID-19 until September 15th, 2020 were prospectively followed-up. Patients were managed in accordance to well-laid guidelines. Treatment was continued for children with COVID-19 infection who were clinically stable and on intensive treatment for various childhood cancers as far as practicable. 3 Results One hundred twenty-two children (median age 8years; range 1-15years, male: female 1.7:1) with cancer were diagnosed with COVID-19. All-cause mortality rate was 7.4%(n=9) and COVID-19 related mortality rate was 4.9%(n=6). Of 118 children, 99 (83.9%), 60 (50.8%), 43 (36.4%), 26 (22.0%) and 6 (5.1%) had RT-PCR positivity at 14, 21, 28, 35 and 60 days from diagnosis of COVID-19 respectively. Scheduled risk-directed intravenous chemotherapy was delivered in 70 (90.9%) of 77 children on active systemic treatment with a median delay of 14days (range, 0-48days) and no increased toxicities. 4 Conclusions COVID-19 was not a major deterrent for the continuation of active cancer treatment despite persistent RT-PCR positivity. The long-term assessment of treatment adaptations requires further prospective follow up and real time addressal.

The management of malnutrition in children with cancer remains a challenge in low-middle-income countries (LMICs). We describe our pediatric oncology nutrition program and its impact over the past decade.We evaluated the impact of our nutrition program in accordance with the International Society of Paediatric Oncology-Paediatric Oncology in Developing Countries (SIOP PODC) Nutritional Program Evaluation in the areas of service delivery (number served, increments in delivery, number of trained care providers), patients at-risk (proportion identified with malnutrition at diagnosis/follow-up), and efficiency of nutritional interventions (proportion assessed, proportion achieved healthy weight, clinicians trained). We analyzed available data for trends between 2009 and 2020, and comparisons were made using the Fisher t test. This study was approved by our institutional ethics committee.From 2010 to 2020, 17 749 children treated at our center were beneficiaries of the nutritional program, including assessment and intervention. During this period, trained pediatric nutritionists increased from 2 to 8; SIOP PODC level from 2 to 3-4, and nutrition budget increased 15-fold. At diagnosis (n = 5618) and six-month follow-up (n = 2674), 59.6% and 51.2% children were undernourished, 34.8% and 43% well nourished, and 4.7% and 5.7% overnourished. From 2016 onward, fewer children were undernourished at follow-up-69.5% (2016), 60% (2018), 54% (2019), and 55% (2020, P 0.001). The program helped train over 500 clinicians in nutrition.Improved financial support and capacity building have helped build and sustain an effective nutrition program. Priority areas include implementation of best practices, early nutritional intervention, continued education, and locally relevant research.

Background and hypothesis Bone and lung are the common sites of metastasis in pediatric round cell tumors and its presence indicates poor outcomes. Staging workup for these malignancies thus includes bone marrow biopsy (BMB) along with evaluation of thorax, and tissue analysis for N MYCN status in neuroblastoma. BMB is an invasive procedure requiring general anesthesia with known disadvantages.With an aim of avoiding an invasive BMB a study was taken up to evaluate efficacy of FDG PET CT in detecting marrow involvement in neuroblastoma and rhabdomyosarcoma at staging. Materials and method Prospective observational study evaluated 83 newly diagnosed treatment naive patients of neuroblastoma (n = 43) and rhabdomyosarcoma (n = 42) who underwent conventional imaging of PETCT with CECT of local region along with a CT thorax and BMB (both iliac crest) done within 1 week. Findings of FDG PETCT were compared with bone marrow histology and accuracy parameters were calculated. Result The overall sensitivity, specificity, accuracy, positive-predictive value (PPV), negative-predictive value (NPV) of FDG PETCT for detection of marrow disease was 100%, 86.1%, 89.4%. 68.9% and 100%, respectively. Subset analysis showed sensitivity, specificity, PPV and NPV of 100%, 66%, 71.4% and 100%, respectively, for neuroblastoma, with rhabdomyosarcoma patients having few events NPV of 100% accuracy of 97.6%. Conclusion FDG PETCT with sensitivity and NPV of 100% can be considered as a first stop imaging and biopsy can be avoided in patients with a negative scan.

Clinicopathologic profile and outcome of 15 children (15 years or above) with diffuse large B-cell lymphoma treated with MCP-842 protocol are reported. Eleven of 15 presented with advanced (stage-III/IV) disease. Post-2 cycles of chemotherapy, complete metabolic and morphologic response was documented in 10 (66%) and rest 5 (33%) with partial response achieved complete metabolic remission by end of treatment. At a median follow-up of 44 months (range: 16 to 79 mo), the 3-year event-free survival and overall-survival were 77.1%±11.7% and 85.7%±9.4%, respectively. Though majority of our patients had advanced disease, outcome on MCP-842 protocol was satisfactory.

Indian studies on EBV in childhood classic Hodgkin Lymphoma (cHL) have mainly analyzed the epidemiology of EBV-positive [EBV(+)HL] or negative HL [EBV(-)HL], with limited data on outcomes. We studied a large cohort of children with intermediate and high-Risk cHL for tumor EBV status and its impact on outcomes retrospectively. Of evaluable 189 patients, 84.7% had EBV(+)HL. Positive status was significantly associated with age ≤ 10 years (

Comment on: The COVID-19 Pandemic: A rapid global response for children with cancer from SIOP, COG, SIOP-E, SIOP-PODC, IPSO, PROS, CCI and St. Jude Global.Chetan Dhamne MSc MD1, Tushar Vora MD1, Maya Prasad MD1, Nirmalya Roy Moulik MD PhD1, Badira C Parambil MD DM1, Akanksha Chichra MD1, Girish Chinnaswamy MD1, Shripad Banavali MD1, Gaurav Narula MD11 Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India2. Homi Bhabha National Institute, Anushaktinagar, Mumbai, IndiaCorrespondence to:Gaurav Narula Pediatric Hematolymphoid Disease Management Group, Department of Medical Oncology, Tata Memorial Center, Parel Mumbai, 400012 Email: narulag@tmc.gov.inText word count: 576Brief running title: Letter to Editor (COVID-19) Global responseKeywords: COVID-19, SARS-CoV2, Pediatric Oncology, Children with cancerTables: 1Abbreviations

To describe the outcomes of elective cancer surgeries and adverse consequences on the patients and medical staff due to the surgical interventions in children during the Coronavirus Disease 2019 (COVID-19) pandemic.The study included children younger than 15 years who underwent elective cancer surgeries from March 4, 2020 and December 3, 2020.A total of 121 patients (62% male; median age, 3 years) underwent surgery. The surgical procedures included nephrectomies (n = 18), neuroblastoma (n = 26) and soft tissue tumor resections (n = 24) and complex surgical procedures like extended liver resections (n = 2), intra-atrial thrombectomy under cardiopulmonary bypass (n = 2), pancreatoduodenectomy (n = 1), and free microvascular flaps (n = 7). Clavien-Dindo Grade III complications were 5% (n = 6), and there were no postoperative deaths. Preoperative COVID-19 testing was performed in 82% of children, and only 2% showed severe acute respiratory syndrome coronavirus 2 positivity. Postoperatively, 26 children were tested because of specific symptoms and, 6 tested positive for severe acute respiratory syndrome coronavirus 2. Except for a median delay of 23 days in treatment, none of the patients with COVID-19 required critical hospital management. None of the surgical residents or faculty acquired COVID-19, while 4 each medical and support staff were tested positive in the study period.COVID-19 was not a deterrent for continued cancer care, and surgeries could be safely performed adopting universal preventive measures without any added morbidity from COVID-19. Caregivers and centers dealing with childhood cancers can be encouraged to sustain or seek early healthcare.

The current multidisciplinary approach in the treatment of Ewing sarcoma has improved cure rates, with contemporary dose-dense chemotherapy attaining 5-year event-free survival (EFS) of 73% in localized cases. Dose-intense and dose-dense chemotherapy is difficult in the majority of resource-limited settings with limited access to optimal supportive care. We report on patients with Ewing sarcoma treated on EFT-2001, a nondose-dense chemotherapy protocol.A retrospective analysis was conducted of patients (15 years) with Ewing sarcoma treated with curative intent during January 2013-June 2017 with an institutional ethics committee-approved nondose-dense protocol (EFT-2001). Local therapy was planned after 9-12 weeks of chemotherapy with metastatic sites addressed with radiotherapy. The study assessed outcomes and prognostic factors.We analysed 200 patients with M:F ratio of 1.27:1 and metastases in 41 patients (20.5%). At a median follow up of 41.5 months (range 4.5-81.8 months), respective 3-year EFS and overall survival (OS) of the whole cohort is 65.3% (95% confidence interval [CI]: 58.1-71.7%) and 79.3% (95% CI: 72.8-84.5%); for localized and metastatic cohort, 70.9% (95% CI: 62.9-77.5%) and 82.8% (95% CI: 75.7-89.0%); and for metastatic cohort, 42.8% (95% CI: 28.0-58.6%) and 65.3% (95% CI: 47.7-78.3%). Presence of residual disease (morphologic/metabolic) on positron emission tomography-computed tomography scan done 3 months post definitive radiotherapy (hazard ratio [HR] 7.92 [95% CI: 3.46-18.14]) and delay in any form of local control4 months (HR 3.42 [95% CI: 1.32-8.89]) affected outcomes. Nonrelapse mortality during treatment was 6.5%, mainly due to cardiomyopathy (3.0%) and bacterial sepsis (1.5%). Cardiotoxicity was seen in 11.5% of patients.Nondose-dense chemotherapy provides good outcomes with manageable toxicities in a multidisciplinary treatment approach, while reducing cumulative drug exposures in the developing world where dose-intense or dose-dense chemotherapy could potentially increase toxicity, and hence seems a feasible approach in resource-limited settings. Presence of any residual disease post definitive radiotherapy or delay in local control portends poor outcome.

BACKGROUND Classical Hodgkin lymphoma (cHL) has excellent survival rates, but late effects are an issue and dictate modern approaches. We analyzed the clinical profile and outcome of cHL treated on a risk-adapted approach aimed at reducing late effects while improving historical outcomes at our center. PROCEDURE Children (≤15 years) consecutively treated for cHL from January 2013 through December 2016 were retrospectively analyzed. 18 FDG-PET-CT-based staging and response assessment was done after two cycles for early response (ERA) and end of chemotherapy (late-response assessment [LRA]) if not in complete response (CR; Deauville