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Abstract Metastatic Ewing's sarcoma is a challenging disease for oncology care providers with wide spectrum of disease at presentation, widely varying approach to the treatment and varied outcomes. The paucity of randomized evidence is a barrier in developing a consensus. This perspective provides the evidence ”for and against” the benefit of aggressive approach including local and systemic therapy in patients presenting with metastatic Ewing's sarcoma and provide general recommendations so as to help select patients who will benefit with definitive intent treatment and also, avoid aggressive approach in patients with dismal outcome.

Advances in the diagnosis and management of childhood cancers have significantly improved survival, and 80% of those who have access to contemporary treatment are expected to survive into adulthood. Multimodality protocols incorporating high-intensity cytotoxic chemotherapy and radiotherapy may be associated with increased acute and delayed adverse effects, thereby compromising the quality of life. Furthermore, curative therapeutic options remain limited in the context of metastatic, relapsed or refractory disease as well as rare tumour entities. This has prompted a paradigm shift in pediatric oncology care in the contemporary era, encompassing multiple domains including cancer predisposition, immunotherapy, precision medicine and survivorship, aimed at optimising survival while minimising treatment-related toxicity and improving quality of life. While these advances are increasingly evident in high-income countries, several hurdles and challenges exist in the implementation of these strategies in low-income and middle-income countries (LMICs). Key barriers include restricted accessibility and affordability of newer and advanced diagnostic modalities and therapeutic agents, deficient infrastructure, non-availability of targeted agents and newer immunotherapy drugs, logistical and regulatory hurdles, limited access to clinical trials and inadequate long-term follow-up. Substantial changes are requisite to facilitate the translation of these changing paradigms into reality in India and LMICs.

While factors influencing outcomes of rhabdomyosarcoma (RMS) in developed countries have evolved from clinical characteristics to molecular profiles, similar data from developing countries are scarce. This is a single-centre analysis of outcomes in treated cases of RMS, with emphasis on prevalence, risk-migration and prognostic impact of Forkhead Box O1 (FOXO1) in non-metastatic RMS. All children with histopathologically proven RMS, treated between January 2013 and December 2018 were included. Intergroup Rhabdomyosarcoma Study-4 risk stratification was used, with treatment based on a multimodality-regimen with chemotherapy (Vincristine/Ifosfamide/Etoposide and Vincristine/Actinomycin-D/Cyclophosphamide) and appropriate local therapy. Formalin-fixed paraffin-embedded tissues were tested using Reverse Transcriptase-Polymerase Chain Reaction for FOXO1-fusions (PAX3(P3F); PAX7(P7F)). A total of 221 children (Cohort-1) were included, of which 182 patients had non-metastatic disease (Cohort-2). Thirty-six (16%), 146 (66%), 39 (18%) patients were low-risk (LR), intermediate-risk (IR) and high-risk, respectively. FOXO1-fusion status was available in 140 patients with localised RMS (Cohort 3). P3F and P7F were detected in 25/49 (51%) and 14/85 (16.5%) of alveolar and embryonal variants, respectively. The 5-year-event-free survival (EFS)/overall survival (OS) of Cohorts 1, 2 and 3 was 48.5%/55.5%, 54.6%/62.6% and 55.1%/63.7%, respectively. Amongst the localised RMS, presence of nodal metastases and primary tumour size > 10 cms were adverse prognostic factorvs ( < 0.05). On incorporating fusion-status in risk-stratification, 6/29 (21%) patients migrated from LR (A/B) to IR. All patients who re-categorised as LR (FOXO1 negative) had a 5-year EFS/OS of 80.81%/90.91%. FOXO1-negative tumours had a better 5-year relapse-free survival (58.92% versus 44.63%; = 0.296) with a near-significant correlation in favourable-site tumours (75.10% versus 45.83%; = 0.063). While FOXO1-fusions have superior prognostic utility compared to histology alone in localised, favourable-site RMS, traditional prognostic factors (tumour size and nodal metastases) impacted outcome the most in this subset. Strengthening of early referral systems in community and timely local intervention can help in improving outcome in resource-constrained countries.

To report an innovative technique of interstitial brachytherapy developed for treatment of orbital soft tissue tumors. A 4-month-old child diagnosed with rhabdomyosarcoma of orbit was treated with multiagent chemotherapy (CTh) and brachytherapy. Pre-planning computed tomography (CT) images were obtained and clinical target volume (CTV) was defined using the pre-treatment magnetic resonance imaging (MRI). Brachytherapy plan was generated for deciding optimal catheter placement. With the child under general anesthesia, catheter entry points were extrapolated and marked on the skin as determined from the pre-planning CT scan. Implantation of catheters was performed as per pre-determined catheter position and depths. Brachytherapy plan was generated and evaluated using dose volume histograms (DVH). A comparative external beam radiotherapy (EBRT) plan using RapidArc was also generated for the CTV with a 3 mm margin as the planning target volume (PTV). The mean CTV dose with brachytherapy was 158% compared to 101% with RapidArc. The CTV V was 90% for brachytherapy vs. 95% for RapidArc. The mean dose to Lt Lens were 51% and 60%, respectively for brachytherapy and RapidArc, while the corresponding mean doses to the bony orbit were 39% and 68%, respectively. Follow-up MRI at 3 months showed complete response of the tumor. Interstitial brachytherapy for orbit using this innovative technique is a safe and effective modality of local treatment for appropriately selected orbital soft tissue tumors. Brachytherapy resulted in excellent disease control with significant reduction of dose to surrounding ocular structures compared to EBRT.

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. 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. 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. 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.

Introduction Primary cervical (CN) and cervicothoracic neuroblastoma (CTN) is generally associated with good outcome; however, surgical resection can be challenging and not without morbidity. The aim of this study is to assess the overall outcome and compare the clinico-radiological features, treatment, and complications of CN and CTN. Materials and methods Sixteen consecutive patients, (CN = 9, CTN = 7) treated between November 2006 and December 2012 were selected from the prospective database for this analysis. Results The 2-year overall and event-free survival of entire cohort is 100 and 72 %, respectively. Respiratory symptoms due to compression of airway and intraspinal extension were common in CTN. Gross total resection was feasible in all patients with CN; in contrast, incomplete excision along with significantly longer duration of surgery and more blood loss occurred in CTN. Postoperative morbidity was seen in three patients with CN and only one patient with CTN. The extent of surgery did not affect the overall and event-free survival of CTN ( p  = NS). Conclusion CN and CTN have characteristic clinico-radiological presentation and surgical specification. However, both have a favorable outcome, even though with a distinct but acceptable morbidity. The favorable outcome in CTN is unrelated to the extent of surgical excision.

Background: 2008 World Health Organization (WHO) classification of hematolymphoid neoplasms (HLN) has classified them based on morphology, results of various ancillary techniques, and clinical features.[1] There are no studies looking at the applicability of WHO classification. Aims: The aim of the study was to calculate proportions of all HLN subtypes seen during 1-year period based on 2008 WHO classification of HLN and study applicability and also shortcomings of practices in a tertiary care center in India. Materials and Methods: This was a 1-year retrospective study (January 1st, to December 31st, 2010) where cases were identified using hospital/laboratory electronic records. Old follow-up and referral cases were excluded from the study. Only newly diagnosed cases classified into categories laid down by 2008 WHO classification of HLN included. Results: Out of 2118 newly diagnosed classifiable cases, 1602 (75.6%) cases were of lymphoid neoplasms, 489 (23.1%) cases of myeloid neoplasms, 16 (0.8%) cases of histiocytic and dendritic cell neoplasms, and 11 (0.5%) cases of acute leukemias of ambiguous lineage. Overall, most common HLN subtype was diffuse large B-cell lymphoma (n = 361, 17.0%). Precursor B-lymphoblastic leukaemia/lymphoma (n = 177, 48.2%) was the most common subtype within pediatric age group. Conclusions: All major subtypes of HLN were seen at our center and showed trends almost similar to those seen in other Indian studies. Molecular/cytogenetic studies could not be performed on a significant number of cases owing to logistic reasons (unavailability of complete panels and also cost-related issues) and such cases could not be classified as per the WHO classification system.

Abstract Background: Vascular endothelial growth factor (VEGF) is an angiogenic marker and is implicated in the carcinogenesis and prognostication of cancers. However, its prognostic potential in Ewing sarcoma (ES) merits exploration. Methods: Histopathologically confirmed consecutive ES cases registered at our institute from 2014 to 2018 were analyzed. Immunohistochemical staining for VEGF was performed on tumor tissues, and they were further classified based on VEGF intensity. Results: There were 105 patients (53 non-metastatic and 52 metastatic). VEGF immunostaining in non-metastatic and metastatic cohorts was negative in 20 (37.7%) and 21 (40.4%), mildly positive in 13 (24.5%) and 9 (17.3%) cases, moderately positive in 14 (26.4%) and 16 (30.8%), and was intensely positive in 6 (11.3%) and 7 (13.5%) patients, respectively. VEGF immunoexpression of up to 25% was seen in 14 (13.3%) and 10 (9.5%) patients within the non-metastatic and metastatic cohorts, respectively. For the non-metastatic cohort, the median EFS (months) was 78.6 (95% CI: 61.34-NA), whereas the median OS was not reached. The median EFS and OS (months) were 10.8 (95% CI: 6.41-17.1) and 13.5 (95% CI: 8.08-21.2), respectively, for the metastatic cohort. Metastatic ES patients having either VEGF immunostaining in >25% of tumor cells or moderate/strong immunostaining were found to have inferior OS (P = 0.008, HR = 10.565). In addition, metastatic patients who were treatment naïve had inferior OS, whereas patients who underwent definitive surgery and completed treatment had superior OS (P = 0.003, P = 0.015, and P = 0.009, respectively). Conclusion: VEGF was found to be an independent prognostic marker in metastatic ESs. This may translate to therapeutic relevance but needs validation in the subsequent, larger prospective studies.