Clinico-Radiological Outcomes in WNT-Subgroup Medulloblastoma.

Medulloblastoma (MB) comprises four broad molecular subgroups, namely wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4, respectively, with subgroup-specific developmental origins, unique genetic profiles, distinct clinico-demographic characteristics, and diverse clinical outcomes. This is a retrospective audit of clinical outcomes in molecularly confirmed WNT-MB patients treated with maximal safe resection followed by postoperative standard-of-care risk-stratified adjuvant radio(chemo)therapy at a tertiary-care comprehensive cancer centre. Of the 74 WNT-MB patients registered in a neuro-oncology unit between 2004 to 2020, 7 patients accrued on a prospective clinical trial of treatment deintensification were excluded, leaving 67 patients that constitute the present study cohort. The median age at presentation was 12 years, with a male preponderance (2:1). The survival analysis was restricted to 61 patients and excluded 6 patients (1 postoperative mortality plus 5 without adequate details of treatment or outcomes). At a median follow-up of 72 months, Kaplan-Meier estimates of 5-year progression-free survival and overall survival were 87.7% and 91.2%, respectively. Traditional high-risk features, large residual tumour (≥1.5 cm2), and leptomeningeal metastases (M+) did not significantly impact upon survival in this molecularly characterized WNT-MB cohort treated with risk-stratified contemporary multimodality therapy. The lack of a prognostic impact of conventional high-risk features suggests the need for refined risk stratification and potential deintensification of therapy.

A National Cancer Grid pooled procurement initiative, India.

In health systems with little public funding and decentralized procurement processes, the pricing and quality of anti-cancer medicines directly affects access to effective anti-cancer therapy. Factors such as differential pricing, volume-dependent negotiation and reliance on low-priced generics without any evaluation of their quality can lead to supply and demand lags, high out-of-pocket expenditures for patients and poor treatment outcomes. While pooled procurement of medicines can help address some of these challenges, monitoring of the procurement process requires considerable administrative investment. Group negotiation to fix prices, issuing of uniform contracts with standardized terms and conditions, and procurement by individual hospitals also reduce costs and improve quality without significant investment. The National Cancer Grid, a network of more than 250 cancer centres in India, piloted pooled procurement to improve negotiability of high-value oncology and supportive care medicines. A total of 40 drugs were included in this pilot. The pooled demand for the drugs from 23 centres was equivalent to 15.6 billion Indian rupees (197 million United States dollars (US$)) based on maximum retail prices. The process included technical and financial evaluation followed by contracts between individual centres and the selected vendors. Savings of 13.2 billion Indian Rupees (US$ 166.7million) were made compared to the maximum retail prices. The savings ranged from 23% to 99% (median: 82%) and were more with generics than innovator and newly patented medicines. This study reveals the advantages of group negotiation in pooled procurement for high-value medicines, an approach that can be applied to other health systems.

Lorsque les systèmes de santé reçoivent peu de fonds publics et que leurs processus d'achat sont décentralisés, le prix et la qualité des médicaments contre le cancer ont un impact direct sur l'accès aux traitements efficaces contre la maladie. Des facteurs tels que l'application de prix différenciés, les négociations en fonction des volumes ainsi que la confiance placée dans des génériques bon marché dont la qualité n'a pas été évaluée peuvent entraîner des décalages entre l'offre et la demande, d'énormes dépenses non remboursables pour les patients et de piètres résultats thérapeutiques. Bien que les acquisitions groupées de médicaments puissent contribuer à résoudre certains de ces problèmes, le suivi du processus d'achat requiert un engagement considérable au niveau administratif. Les négociations collectives en vue de fixer les tarifs, l'établissement de contrats types assortis de conditions générales standardisées, mais aussi les achats effectués par des hôpitaux en particulier peuvent également faire baisser les coûts et améliorer la qualité sans nécessiter d'importants investissements. Le National Cancer Grid, un réseau réunissant plus de 250 centres d'oncologie en Inde, a testé un dispositif d'achat groupé visant à assurer une meilleure négociabilité pour des médicaments et soins de soutien essentiels contre le cancer. Au total, 40 substances ont été prises en compte dans ce projet pilote. La demande groupée en médicaments émise par 23 centres équivalait à 15,6 milliards de roupies indiennes (197 millions de dollars américains) d'après le prix maximal de vente au détail. Ce processus prévoyait une évaluation technique et financière, puis des contrats entre chaque centre et les distributeurs sélectionnés. Des économies de 13,2 milliards de roupies indiennes (166,7 millions de dollars américains) ont pu être réalisées par rapport au prix maximal de vente au détail. Ces économies étaient comprises entre 23 et 99% (médiane: 82%) et concernaient davantage les médicaments génériques que les marques et les médicaments récemment brevetés. La présente étude révèle les avantages que représentent les négociations collectives lors des achats groupés de médicaments essentiels, une approche applicable à d'autres systèmes de santé.

En los sistemas sanitarios con escasa financiación pública y procesos de adquisición descentralizados, el sistema de fijación de precios y la calidad de los medicamentos contra el cáncer afectan directamente al acceso a una terapia eficaz contra dicha enfermedad. Factores como los diferentes sistemas de determinación de precios, la negociación en función del volumen y la dependencia de genéricos de bajo precio sin evaluación de su calidad pueden generar retrasos en la oferta y la demanda, elevados gastos para los pacientes y malos resultados en el tratamiento. Aunque la adquisición conjunta de medicamentos puede ayudar a abordar algunos de estos retos, el seguimiento del proceso de adquisición requiere una inversión administrativa considerable. La negociación colectiva a la hora de determinar los precios, la emisión de contratos unificados con términos y condiciones estandarizados y la adquisición por parte de algunos hospitales también reducen los costes y mejoran la calidad sin necesidad de realizar una gran inversión. La Red Nacional de Cáncer, una red que cuenta con más de 250 centros oncológicos en la India, puso a prueba la adquisición conjunta con el fin de mejorar la negociabilidad de medicamentos oncológicos y de tratamiento complementario que resultaban costosos. En esta prueba piloto se incluyó un total de 40 medicamentos. La demanda conjunta de medicamentos por parte de 23 centros fue equivalente a 15 600 millones de rupias indias (197 millones USD) según los precios minoristas máximos. El proceso incluyó una evaluación técnica y financiera, así como contratos entre centros independientes y proveedores seleccionados. Se logró un ahorro de 13 200 millones de rupias indias (166,7 millones USD) en comparación con los precios minoristas máximos. El ahorro osciló entre el 23 y el 99% (media: 82%) y fue más alto con los medicamentos genéricos que con los de marca y los recién patentados. Este estudio pone de manifiesto las ventajas de la negociación colectiva en lo que respecta a la adquisición conjunta de medicamentos costosos, un enfoque que se puede aplicar a otros sistemas sanitarios.

Long-Term Outcomes in Survivors of Childhood Cancer: A 30-Year Experience From India.

PURPOSE: Despite an increasing number of survivors of childhood cancer (CCS) in low- and middle-income countries, survivorship care is in its nascent stages. We describe the spectrum of late effects seen, challenges faced, and lessons learnt over three decades of a late effects program in India. METHODS: We describe the demographics and profile of late effects of all CCS survivors enrolled in our After Completion of Treatment Clinic from February 5, 1991 (inception) to February 4, 2021. We analyzed the trends by the decade of diagnosis. RESULTS: There were 3,067 CCS survivors, the median age was 18 years (range, 3-57 years), and the median follow-up was 11 years (range, 2-46 years). Two thirds (62.4%) had either no or mild late effects, 480 (15.6%), 497 (16.2%), and 162 (5.3%) had grades 2, 3, and 4 late effects, with 67 deaths reported. Notable late effects were chronic viral hepatitis (7.8%), thyroid dysfunction (7.5%), other endocrine issues (13.6%), psychosocial issues (57%), neurocognitive impairment (4.1%), and metabolic syndrome (4%). The cumulative incidence and severity of late effects showed a consistent decline by the decade of diagnosis. Twenty-two percent of survivors are lost to follow-up. CONCLUSION: Survivors of childhood cancer treated on contemporary treatment protocols have a significantly lower side-effect profile. Attrition to long-term follow-up and psychosocial issues are significant concerns. Understanding the unique spectrum of late effects and establishing a holistic support system go a long way in ensuring the long-term physical and mental health and psychosocial concerns of childhood cancer survivors in low- and middle-income countries.

Impact of a pediatric oncology nutrition program: Lessons learnt over a decade.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Impact of the COVID pandemic on survivors of childhood cancer and survivorship care: lessons for the future.

PURPOSE: The COVID pandemic has greatly impacted cancer care, with survivorship care being accorded low priority. We aimed to assess the impact of the COVID pandemic on survivorship services at our centre, as well as on survivors of childhood cancer (CCS). METHODS: We analyzed the trends in survivorship care at our centre from March 2020 to June 2021 compared to previous years. We also conducted an online survey of adolescent and young adult (AYA-CCS) following up at the After Completion of Treatment Clinic, Mumbai, to assess the impact of the COVID pandemic and ensuing restrictions on our cohort of survivors. Sibling responses were used as comparator (CTRI/2020/11/029029). RESULTS: There was a decrease in in-person follow-ups and increase in remote follow-ups over the first few months of the pandemic. While in-person visits steadily increased after October 2020 and reached pre-pandemic numbers, distant follow-ups continue to be higher than pre-pandemic. Evaluable responses from the survey of 88 AYA-CCS and 25 siblings revealed new-onset health concerns in 29.5% of AYA-CCS, missed follow-up visit in 52% and varying degrees of mental health issues in 12.5%. While most survivors were able to cope with the stresses of the pandemic, 20% of siblings reported being unable to cope. CONCLUSIONS: Survivorship services continue to be affected well into the pandemic, with increased use of distant follow-ups. While AYA-CCS experienced significant physical, mental health issues and psychosocial concerns as a result of the COVID pandemic, they coped better than siblings during this stressful time, possibly due to multiple, holistic support systems including family, peer support groups and healthcare team.

Clinical Audit of Survival Outcomes and Prognostic Factors in Adolescents and Adults with Medulloblastoma.

Purpose: Medulloblastomas, comprising 20%-25% of all primary brain tumors in children are much rarer in adulthood. Disease biology varies substantially across different age groups; however, owing to rarity, adults with medulloblastoma are traditionally treated using pediatric protocols. This is a retrospective audit of adolescent and adult medulloblastoma from a comprehensive cancer center. Methods: Data regarding demography, clinical presentation, imaging characteristics, histopathological features, molecular profiling, risk stratification, treatment details, and outcomes were retrieved from medical records. All time-to-event outcomes were analyzed using Kaplan-Meier method and compared with the log-rank test. Univariate and multivariate analysis of relevant prognostic factors was done with p value <0.05 being considered statistically significant. Results: A total of 162 patients ≥15 years of age with medulloblastoma were included. The median age was 25 years (range: 15-59 years) with leptomeningeal metastases seen in 31 (19%) patients at initial diagnosis. Following surgery, patients were treated with appropriate risk-stratified adjuvant therapy comprising of craniospinal irradiation plus boost with or without systemic chemotherapy. At a median follow-up of 50 months, 5-year Kaplan-Meier estimates of progression-free survival and overall survival were 53.5% and 59.5%, respectively. The addition of adjuvant systemic chemotherapy did not impact upon survival in standard-risk medulloblastoma. High-risk (HR) disease and anaplastic histology emerged as significant and independent predictors of poor survival on multivariate analysis. Conclusion: Medulloblastoma is a rare tumor in adolescents and adults with key differences in disease biology and resultant outcomes compared with the pediatric population. Contemporary management comprising maximal safe resection followed by appropriate risk-stratified adjuvant therapy provides acceptable survival outcomes.

Efficacy of ready-to-use therapeutic food in malnourished children with cancer: Results of a randomized, open-label phase 3 trial.

BACKGROUND: The adverse influence of undernutrition in children with cancer may be remediated by early nutritional intervention. This study assessed the efficacy of ready-to-use therapeutic food (RUTF) in improving nutritional status and reducing treatment-related toxicities (TRTs) in such children. METHODS: In a randomized controlled phase-3 open-label trial, severely and moderately undernourished children with cancer were randomized 1:1 to receive standard nutritional therapy (SNT) or SNT+RUTF for 6 weeks. The primary outcome (weight gain >10%) and secondary outcomes (improved/maintained nutritional status, improved body composition) were assessed after 6 weeks. TRTs were assessed over 6 months. RESULTS: Between July 2015 and March 2018, 260 subjects were enrolled, 126 were analyzable in both arms at 6 weeks. More children on RUTF had weight gain (98 [77.8%] vs. 81 [64.2%], p = .025) with a greater increase in fat mass as a percentage of body mass (median 2% [IQR -0.12 to 4.9] vs. 0.5% [IQR -1.45 to 2.27, p = .005]) but a greater loss of lean mass (median -1.86% [IQR -4.4 to 0.50] vs. -0.4% [IQR -2.4 to 1.4, p = .007]) compared to the SNT arm. Fewer subjects on the RUTF arm had episodes of severe infection (10.6% vs. 31%, p < .0001), treatment delays (17.7% vs. 39%, p < .0001), and severe mucositis (11% vs. 23.8%, p = .006) compared to the SNT arm. The odds of developing TRTs on the RUTF arm were lower even after adjusting for improvement in nutritional status. CONCLUSIONS: RUTF is efficacious in improving weight gain and nutritional status in undernourished children with cancer and decreases TRTs. Incorporating RUTF into a healthy, balanced diet should be considered in undernourished children with cancer.

Impact of COVID-19 on cancer care in India: a cohort study.

BACKGROUND: The COVID-19 pandemic has disrupted health-care systems, leading to concerns about its subsequent impact on non-COVID disease conditions. The diagnosis and management of cancer is time sensitive and is likely to be substantially affected by these disruptions. We aimed to assess the impact of the COVID-19 pandemic on cancer care in India. METHODS: We did an ambidirectional cohort study at 41 cancer centres across India that were members of the National Cancer Grid of India to compare provision of oncology services between March 1 and May 31, 2020, with the same time period in 2019. We collected data on new patient registrations, number of patients visiting outpatient clinics, hospital admissions, day care admissions for chemotherapy, minor and major surgeries, patients accessing radiotherapy, diagnostic tests done (pathology reports, CT scans, MRI scans), and palliative care referrals. We also obtained estimates from participating centres on cancer screening, research, and educational activities (teaching of postgraduate students and trainees). We calculated proportional reductions in the provision of oncology services in 2020, compared with 2019. FINDINGS: Between March 1 and May 31, 2020, the number of new patients registered decreased from 112 270 to 51 760 (54% reduction), patients who had follow-up visits decreased from 634 745 to 340 984 (46% reduction), hospital admissions decreased from 88 801 to 56 885 (36% reduction), outpatient chemotherapy decreased from 173634 to 109 107 (37% reduction), the number of major surgeries decreased from 17 120 to 8677 (49% reduction), minor surgeries from 18 004 to 8630 (52% reduction), patients accessing radiotherapy from 51 142 to 39 365 (23% reduction), pathological diagnostic tests from 398 373 to 246 616 (38% reduction), number of radiological diagnostic tests from 93 449 to 53 560 (43% reduction), and palliative care referrals from 19 474 to 13 890 (29% reduction). These reductions were even more marked between April and May, 2020. Cancer screening was stopped completely or was functioning at less than 25% of usual capacity at more than 70% of centres during these months. Reductions in the provision of oncology services were higher for centres in tier 1 cities (larger cities) than tier 2 and 3 cities (smaller cities). INTERPRETATION: The COVID-19 pandemic has had considerable impact on the delivery of oncology services in India. The long-term impact of cessation of cancer screening and delayed hospital visits on cancer stage migration and outcomes are likely to be substantial. FUNDING: None. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

Holistic support coupled with prospective tracking reduces abandonment in childhood cancers: A report from India.

BACKGROUND: High cure rates of over 80% in childhood cancers reported from high-income countries (HICs) are not replicated in low- and middle-income countries (LMICs). Treatment abandonment (TxA) is an important reason for this poorer outcome. We assessed the effect of a holistic support group approach coupled with prospective tracking on TxA in children with cancer in a limited-resources environment. METHODS: In 2010, all existing nongovernmental organizations (NGOs) working with childhood cancer at our hospital were brought together to form a pediatric cancer foundation with the aim of providing holistic support to the patient and family, including financial, psychosocial, lodging, educational, and bereavement support. Simultaneously, prospective tracking of all children with a Time-Responsive Electronic Abandonment Tracking (TREAT) system was also established. The impact of these measures on TxA over the 2009-2016 period was compared using the log-rank test. RESULTS: The annual rate of abandonment reduced from 20% in 2009 to 10.4% in 2010 and 5.2% in 2011. It has been consistently between 3% and 6% from 2012 to 2016 (P -0.04). TxA after the initiation of treatment dropped from 9% in 2009 to 1% in 2016 (P -0.02), while refusal to initiate treatment dropped from 11% to 2.7% (P -0.23) over the same period. CONCLUSIONS: A holistic support group consisting of the hospital team, as well as existing NGOs and governmental organizations, along with a systematic and prospective tracking system significantly reduced abandonment in a resource-constrained setting. This cost-effective holistic support group may be applicable in other LMICs with similar healthcare systems.

Ifosfamide induced renal rickets.

Ifosfamide is commonly used as a chemotherapeutic agent in children. The authors report a 4-y-old boy who developed proximal renal tubulopathy with florid rickets a year after completion of ifosfamide therapy for Ewing's sarcoma. After initiation of treatment, there was complete healing of rickets and he did not need supplements beyond 18 mo. Growth monitoring and musculoskeletal system examination is important in all children who have received ifosfamide therapy. Routine monitoring for nephrotoxicity during and after ifosfamide therapy helps in early identification and intervention.