Response assessment by positron emission tomography-computed tomography as compared with contrast-enhanced computed tomography in childhood Hodgkin lymphoma can reduce the need for radiotherapy in low- and middle-income countries.

INTRODUCTION: The InPOG-HL-15-01, a multicentric prospective study, used a risk-stratified and response-based approach with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) backbone to treat children and adolescents with newly diagnosed Hodgkin lymphoma (HL) and reduce the use of radiation therapy (RT). Children/adolescents with bulky disease or inadequate response at early response assessment (ERA) after two cycles of chemotherapy were assigned to receive RT. For ERA, positron emission tomography computed tomography (PET-CT) was recommended but not mandatory in view of limited access. This study aimed to compare the impact of using contrast-enhanced computed tomography (CECT) and PET-CT on treatment decisions and outcomes. METHODOLOGY: 396 patients were enrolled and 382 had an ERA at the assigned time point. Satisfactory response was defined as Deauville score 3 or less for patients undergoing PET-CT and complete response (CR)/very good partial response (VGPR) for patients undergoing CECT. Outcomes of interest incorporate 5 year event-free survival (EFS), EFS including abandonment (EFSa), and overall survival (OS). RESULTS: At ERA, satisfactory response was documented in 277 out of 382 (72.5%) participants and this was significantly higher in PET-CT (151 out of 186, 81.2%) as compared with CECT-based assessments (126 out of 196, 64.3%) respectively (p value < .001). Amongst the 203 patients with nonbulky disease (wherein the indication for RT was entirely dependent on ERA), 96 out of 114 (84.2%) and 61 out of 89 (68.5%) patients achieved a satisfactory response according to the PET-CT and CECT (p value = .008) respectively and hence a lesser proportion of patients in the PET-CT arm received RT. Despite a lower usage of RT the 5 year OS of both groups, ERA based on CECT (91.8%) versus PET-CT (94.1%) was comparable (p value = .391) and so was the 5 year EFS (86.7 vs. 85.5%, p value = .724). CONCLUSION: Use of PET-CT as the modality for ERA is more likely to indicate a satisfactory response as compared with CECT and thereby decreases the need for RT in response-based treatment algorithm for HL-afflicted children. The reduction in the application of RT did not impact the overall outcome and plausibly would lower the risk of delayed toxic effects.

The impact of COVID-19 pandemic on access to treatment for children with cancer in India and treating center practices.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic led the Indian government to announce a nationwide lockdown on March 23, 2020. This study aimed to explore the impact of the pandemic on the accessibility of care for children with cancer and to view strategies adopted by hospitals for service delivery. METHODS: Weekly average of childhood cancer (≤18 years) patient registrations during pre-lockdown period (January 1 to March 23, 2020) were compared with post-lockdown period (March 24 to May 31, 2020). The effect on the scheduled treatment was investigated for post-lockdown period. A survey of health care providers was conducted to determine centers' adopted strategies. RESULTS: In 30 participating centers, 1146 patients with childhood cancer (797 pre-lockdown period and 349 post-lockdown period) were registered. The weekly average registration was 67.3 and 35.5 patients during pre-lockdown and post-lockdown respectively (decline of 47.9%). Although most centers experienced this decline, there were 4 that saw an increase in patient registrations. The distribution of patients registered post-lockdown was found significantly different by age (lesser older age, P = .010) and distance (lesser travel distance, P = .001). 36.1% of patients, who were scheduled for any of the treatment modalities (chemotherapy, surgery, radiotherapy, and hematopoietic stem cell transplantation) during the post-lockdown period, experienced delays. Centers adopted several strategies including modifications to treatment protocols, increased use of growth factors, and increased support from social organizations. CONCLUSIONS: This multicenter study from India suggests that the COVID-19 pandemic and the lockdown impacted 2 out of 3 children with cancer. The effect of this on survival is yet to be established.

Resilient health care in global pediatric oncology during the COVID-19 pandemic.

BACKGROUND: In the face of unprecedented challenges because of coronavirus disease 2019, interdisciplinary pediatric oncology teams have developed strategies to continue providing high-quality cancer care. This study explored factors contributing to health care resilience as perceived by childhood cancer providers in all resource level settings. METHODS: This qualitative study consisted of 19 focus groups conducted in 16 countries in 8 languages. Seven factors have been previously defined as important for resilient health care including: 1) in situ practical experience, 2) system design, 3) exposure to diverse views on the patient's situation, 4) protocols and checklists, 5) teamwork, 6) workarounds, and 7) trade-offs. Rapid turn-around analysis focused on these factors. RESULTS: All factors of health care resilience were relevant to groups representing all resource settings. Focus group participants emphasized the importance of teamwork and a flexible and coordinated approach to care. Participants described collaboration within and among institutions, as well as partnerships with governmental, private, and nonprofit organizations. Hierarchies were advantageous to decision-making and information dissemination. Clinicians were inspired by their patients and explained creative trade-offs and workarounds used to maintain high-quality care. CONCLUSIONS: Factors previously described as contributing to resilient health care manifested differently in each institution but were described in all resource settings. These insights can guide pediatric oncology teams worldwide as they provide cancer care during the next phases of the pandemic. Understanding these elements of resilience will also help providers respond to inevitable future stressors on health care systems.

Deviation from delivery of radiation therapy to childhood cancer patients: A retrospective audit.

BACKGROUND: Planning and coordination of the delivery of radiation therapy (RT) can be challenging in resource-limited settings. In this retrospective study, we describe the profile of children undergoing radiation and analyze deviation from some accepted norms. PROCEDURE: Data on all children (<18 years of age) with cancer who completed RT from January 2009 to December 2019 were retrieved. Diagnostic groups with more than five patients were included in the analysis for deviations in RT (time to start [TTS]; total dose delivered [TDD] in gray; and time to complete [TTC]). We investigated reasons for deviation. RESULTS: Two hundred seven children received RT as front-line treatment (68% Indian, 59% male). Most common diagnoses were brain tumors (44%), lymphomas (13%), leukemias, and soft tissue sarcomas (10% each). TTS deviation was seen in 23.6%, TTD in 6.0%, and TTC in 24.7%, while 43.4% had at least one deviation in any of these three parameters. Deviation in TTS varied significantly by location of preceding treatment and by cancer (greatest deviation in sarcomas), with issues around access to health care being the most common reason. Deviation in TTC varied significantly by cancer (greatest deviation in sarcomas and medulloblastoma), with myelotoxicity being the most common reason. CONCLUSIONS: Our study adds to the limited literature on RT quality for children with cancer in resource-limited settings. Certain cancers (sarcomas and medulloblastomas) and patient groups (preceding treatment outside our institute) had the maximum deviation. Barriers to accessing care and myelotoxicity were the two main reasons for this deviation.

Treating early-stage Hodgkin lymphoma in resource-limited settings: InPOG-HL-15-01 experience.

BACKGROUND: Hodgkin lymphoma (HL) in childhood is an eminently curable disease. Excellent outcomes can be achieved even in resource-limited settings and increasingly, the focus is on limiting long-term toxicity. Contemporary treatment incorporates a risk-stratified, response-adapted approach using multiagent chemotherapy with or without low-dose radiotherapy (RT). Many developing countries continue to use ABVD (adriamycin, bleomycin, vinblastin, and dacarbazine)-based regimen owing to limited acute toxicity, cost, and ease of delivery. We report outcomes of children with early-stage HL using limited cycles of ABVD-based treatment in the first prospective multicentric collaborative study from India InPOG-HL-15-01. METHODS: Children <18 years with biopsy-proven HL were enrolled. Patients with stages I and IIA with or without bulky disease were classified as having early-stage disease. Patients were planned to receive four cycles of ABVD subject to satisfactory early response assessment (ERA) scheduled after two cycles of chemotherapy. RT was limited to patients with bulky disease or those with suboptimal ERA. RESULTS: Four hundred ten patients were enrolled over 30 months from 27 centers. One hundred thirty-four were classified as having early-stage disease. Fifty-three (40%) of these had bulky disease. One hundred ten (83%) of this cohort achieved complete or very good partial ERA. Fifty-four (40%) received RT. At a median of 52 months since diagnosis, 5-year event-free survival (EFS) and overall survival (OS) is 94% and 95.5%, respectively. Treatment-related mortality and abandonment were <1%. CONCLUSION: Limited cycles of ABVD with RT to selected patients is a very effective option for patients with early-stage disease in resource-limited settings.

Exploring the Financial Toxicities of Patients with Locally Advanced Head and Neck Malignancies, Being Treated in a Private Sector Hospital in North India: A Thematic Analysis.

BACKGROUND: The high cost of cancer diagnosis and treatment is a global concern. Evidence derived, mostly from high-income countries, shows how it gradually impacts the personal and household financial condition causing the increased psychosocial burden of the patient and their families (termed "financial toxicity"). AIM: To qualitatively explore the financial toxicities in patients with advanced head and neck malignancies in India, and to consider how it impacts the patient and his family. METHODS: Interviewing a purposive sample of 8 patients using semi-structured interviews face to face. Interviews were transcribed verbatim, and a thematic content analysis was carried out. RESULTS: Four major themes were identified: burden and amplifying factors, impact, rescue and relieving factors, and learning and innovation. The burden of cost relates to diagnosis, treatment and non-medical costs which gets amplified while navigating the healthcare labyrinth. Emerging themes describe financial journey of cancer patients, the issues faced by them and the ways they tackle these issues during their treatment. Healthcare system factors like limited availability of adequate/comprehensive/meaningful insurance and reimbursements potentiate the toxicity. The financial toxicity leads to a significant adverse financial, psychological and social impact on the patient and the family. While moving through the process of care, there were a few learnings and innovations which patients proposed. CONCLUSION: This study provides qualitative evidence of the considerable and pervasive nature of financial toxicity in head and neck cancer patients in India. The findings have implications for all cancer patients and highlight the unmet need of psychosocial support for these patients.

Sustainable care for children with cancer: a Lancet Oncology Commission.

We estimate that there will be 13·7 million new cases of childhood cancer globally between 2020 and 2050. At current levels of health system performance (including access and referral), 6·1 million (44·9%) of these children will be undiagnosed. Between 2020 and 2050, 11·1 million children will die from cancer if no additional investments are made to improve access to health-care services or childhood cancer treatment. Of this total, 9·3 million children (84·1%) will be in low-income and lower-middle-income countries. This burden could be vastly reduced with new funding to scale up cost-effective interventions. Simultaneous comprehensive scale-up of interventions could avert 6·2 million deaths in children with cancer in this period, more than half (56·1%) of the total number of deaths otherwise projected. Taking excess mortality risk into consideration, this reduction in the number of deaths is projected to produce a gain of 318 million life-years. In addition, the global lifetime productivity gains of US$2580 billion in 2020-50 would be four times greater than the cumulative treatment costs of $594 billion, producing a net benefit of $1986 billion on the global investment: a net return of $3 for every $1 invested. In sum, the burden of childhood cancer, which has been grossly underestimated in the past, can be effectively diminished to realise massive health and economic benefits and to avert millions of needless deaths.

Childhood cancer survivorship and late effects: The landscape in India in 2020.

Survivorship care is a major area of focus in the holistic management of childhood cancer with current knowledge and information almost exclusively from high-income countries. In this review, we summarize the state of scientific knowledge, service delivery, advocacy initiatives, and research efforts in this field in India. Twenty-one single-center studies published until today (20 in the last decade) confirm some of the well-documented issues in childhood cancer survivors and highlight the high prevalence of hepatitis B and hepatitis C infection in our survivors. Heterogeneity in methodology, outcome metrics, and quality precludes drawing further conclusions, and the ongoing multicenter Indian Pediatric Oncology Group study would address this. Besides the usual model of follow-up clinics in hospital settings, innovative models of service delivery led by not-for-profit organizations are being developed. Advocacy initiatives driven by survivors and support groups are also under way. All of these portend a promising future.

Access to care for childhood cancers in India: perspectives of health care providers and the implications for universal health coverage.

BACKGROUND: There are multiple barriers impeding access to childhood cancer care in the Indian health system. Understanding what the barriers are, how various stakeholders perceive these barriers and what influences their perceptions are essential in improving access to care, thereby contributing towards achieving Universal Health Coverage (UHC). This study aims to explore the challenges for accessing childhood cancer care through health care provider perspectives in India. METHODS: This study was conducted in 7 tertiary cancer hospitals (3 public, 3 private and 1 charitable trust hospital) across Delhi and Hyderabad. We recruited 27 healthcare providers involved in childhood cancer care. Semi-structured interviews were audio recorded after obtaining informed consent. A thematic and inductive approach to content analysis was conducted and organised using NVivo 11 software. RESULTS: Participants described a constellation of interconnected barriers to accessing care such as insufficient infrastructure and supportive care, patient knowledge and awareness, sociocultural beliefs, and weak referral pathways. However, these barriers were reflected upon differently based on participant perception through three key influences: 1) the type of hospital setting: public hospitals constituted more barriers such as patient navigation issues and inadequate health workforce, whereas charitable trust and private hospitals were better equipped to provide services. 2) the participant's cadre: the nature of the participant's role meant a different degree of exposure to the challenges families faced, where for example, social workers provided more in-depth accounts of barriers from their day-to-day interactions with families, compared to oncologists. 3) individual perceptions within cadres: regardless of the hospital setting or cadre, participants expressed individual varied opinions of barriers such as acceptance of delay and recognition of stakeholder accountabilities, where governance was a major issue. These influences alluded to not only tangible and structural barriers but also intangible barriers which are part of service provision and stakeholder relationships. CONCLUSION: Although participants acknowledged that accessing childhood cancer care in India is limited by several barriers, perceptions of these barriers varied. Our findings illustrate that health care provider perceptions are shaped by their experiences, interests and standpoints, which are useful towards informing policy for childhood cancers within UHC.

A health care labyrinth: perspectives of caregivers on the journey to accessing timely cancer diagnosis and treatment for children in India.

BACKGROUND: Cure rates for children with cancer in India lag behind that of high-income countries. Various disease, treatment and socio-economic related factors contribute to this gap including barriers in timely access of diagnostic and therapeutic care. This study investigated barriers to accessing care from symptom onset to beginning of treatment, from perspectives of caregivers of children with cancer in India. METHODS: Semi-structured in-depth interviews were conducted with caregivers of children (< 18 years) diagnosed with cancer in seven tertiary care hospitals across New Delhi and Hyderabad. Purposive sampling to saturation was used to ensure adequate representation of the child's gender, age, cancer type, geographical location and socioeconomic status. Interviews were audio recorded after obtaining informed consent. Thematic content analysis was conducted and organised using NVivo 11. RESULTS: Thirty-nine caregivers were interviewed, where three key themes emerged from the narratives: time intervals to definitive diagnosis and treatment, the importance of social supportive care and the overall accumulative impacts of the journey. There were two phases encapsulating the experiences of the family: referral pathways taken to reach the hospital and after reaching the hospital. Most caregivers, especially those from distant geographical areas had variable and inconsistent referral pathways partly due to poor availability of specialist doctors and diagnostic facilities outside major cities, influence from family or friends, and long travel times. Upon reaching the hospital, families mostly from public hospitals faced challenges navigating the hospital facilities, finding accommodation, and comprehending the diagnosis and treatment pathway. Throughout both phases, financial constraint was a recurring issue amongst low-income families. The caregiver's knowledge and awareness of the disease and health system, religious and social factors were also common barriers. CONCLUSION: This qualitative study highlights and explores some of the barriers to childhood cancer care in India. Our findings show that referral pathways are intrinsically linked to the treatment experience and there should be better recognition of the financial and emotional challenges faced by the family that occur prior to definitive diagnosis and treatment. This information would help inform various stakeholders and contribute to improved interventions addressing these barriers.

Improved outcome at end of treatment in the collaborative Wilms tumour Africa project.

BACKGROUND: The Collaborative Wilms Tumour (WT) Africa Project has implemented an adapted WT treatment guideline in sub-Saharan Africa as a multi-centre prospective clinical trial. A retrospective, baseline evaluation of end-of-treatment outcome was performed for a 2-year period prior to the introduction of this guideline. The collaborative project aims to reduce both treatment abandonment and death during treatment to less than 10% for improving survival. PROCEDURE: All participating centres obtained local Institutional Research Board (IRB) approval and implemented the adapted WT treatment guideline. End-of-treatment outcome was documented for 2 years. It was divided into alive without evidence of disease, treatment abandonment, death during treatment and persistent disease. The outcome of children enroled in the first 2 years of the prospective clinical trial has been compared to the outcome before the start of the project. RESULTS: One hundred twenty-two patients were included in the baseline evaluation (2011-2012) and 133 in the first 2 years of the collaborative clinical trial (2014-2015). The percentage of patients alive without evidence of disease at the end of treatment increased from 52% (63/122) to 68% (90/133; P = 0.01). Treatment abandonment decreased from 23% (28/122) to 13% (17/133; P = 0.03). Death during treatment decreased from 21% (26/122) to 13% (17/133; P = 0.07). CONCLUSION: This collaboration, using relatively simple and low-cost interventions, led to a significant decrease in treatment abandonment and increase in survival without evidence of disease at the end of treatment.

A framework to develop adapted treatment regimens to manage pediatric cancer in low- and middle-income countries: The Pediatric Oncology in Developing Countries (PODC) Committee of the International Pediatric Oncology Society (SIOP).

Many children with cancer in low- and middle-income countries are treated in hospitals lacking key infrastructure, including diagnostic capabilities, imaging modalities, treatment components, supportive care, and personnel. Childhood cancer treatment regimens adapted to local conditions provide an opportunity to cure as many children as possible with the available resources, while working to improve services and supportive care. This paper from the Adapted Treatment Regimens Working Group of the Pediatric Oncology in Developing Countries committee of the International Society of Pediatric Oncology outlines the design, development, implementation, and evaluation of adapted regimens and specifies levels of services needed to deliver them.

Improving Care for Children With Cancer in Low- and Middle-Income Countries--a SIOP PODC Initiative.

The Paediatric Oncology in Developing Countries (PODC) committee of International Society of Paediatric Oncology (SIOP) has 10 working groups that provide a forum for individuals to engage, network, and implement improvements in the care of children with cancer in low- and middle-income countries. The development of adapted guidelines (medulloblastoma, retinoblastoma, Wilms tumor, neuroblastoma, retinoblastoma, Burkitt lymphoma, supportive care), advocacy and awareness (on hospital detention and essential drugs), education and training, and global mapping (nutritional practice, abandonment rates, and twinning collaborations) have been the initial areas of focus, and the impact of some of these activities is evident, for example, in the SIOP Africa PODC Collaborative Wilms tumor project.

A practical approach to reporting treatment abandonment in pediatric chronic conditions.

Treatment abandonment, the failure to complete therapy that is required for definitive disease control, frequently causes treatment failure for pediatric patients in low- and middle-income countries with chronic conditions, particularly cancer. Other forms of incomplete treatment affecting children in all settings, such as nonadherence and loss to follow-up, are often confused with treatment abandonment. Unclear definitions of incomplete treatment dramatically affect reported outcomes. To facilitate disease-specific and cross-sector analyses, we outline a practical approach to categorize forms of incomplete treatment, present distinct semantic categories with case examples and provide an algorithm that could be tailored to disease- and context-specific needs.

Profile of Childhood Cancers From Hospital-Based Cancer Registries in India, 2012-19.

OBJECTIVE: To describe the clinical pattern of childhood and adolescent cancers across India using hospital-based data in the National Cancer Registry Program. METHODS: Records of 60720 cancer cases in the 0-19 year age group for the period 2012-2019 from 96 hospital-based cancer registries were reviewed. Childhood cancers were classified based on the International Classification of Childhood Cancer (ICCC). Descriptive analysis was used to examine the distribution of cancer by five-year age groups, sex and ICCC diagnostic groups and subgroups. Data were analysed using IBM SPSS software and visualised using R software. RESULTS: 3.2% and 4.6% of all cancer cases in India were among children in the 0-14 year and 0-19 year age groups respectively. The male-to-female ratio for all cancers was 1.72 for 0-14 years and 1.73 for 0-19 years. The four leading groups of cancers among 0-14 year olds were leukemia (40%), lymphoma (12%), central nervous system tumor (11%) and bone cancer (8%). The four leading cancers among the 0-19 year age group were leukemia (36%), lymphoma (12%), bone (11%) and central nervous system tumor (10%). CONCLUSION: Cancers in the 0-14 and 0-19 age groups accounted for a considerable proportion of all cancers with significant male preponderance. Such information helps to fine-tune research and planning strategies.