Abstract
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. 21 single centre studies published till date (20 in the last decade) confirm some of the well-documented issues in childhood cancer survivors and also 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 organisations are being developed. Advocacy initiatives driven by survivors and support groups are also underway. All of these portend a promising future.
Outcomes of childhood cancer have improved steadily and consistently over the last several decades and now more than eight out of 10 children with cancer in high-income countries are long-term survivors and considered cured of their disease. With an estimated half a million long-term survivors of childhood cancer in USA1 and a similar number in Europe2, survivorship practice and research are major areas of focus for healthcare professionals, policy makers and patient advocates. Approximately, two of every three childhood cancer survivors will experience at least one late effect, and 40% may develop a “severe, disabling, or life-threatening condition” 30 years after cancer diagnosis.3 Not surprisingly, the focus of the pediatric oncology professionals has shifted for “Cure at all cost” to “Equivalent cure with minimal cost”. Contemporary treatment protocols give considerable importance to minimizing long-term impacts of treatment while maintaining high cure rates.
In contrast to the progress seen in high income countries, low and middle income countries like India have continued to confront the triple challenges of high treatment abandonment, toxicity-related mortality and disease progression.4,5 Consequently improvements in survival are more modest and till recently, survivorship has not been a priority at service, research or policy level.6,7 The last few years have witnessed an increased momentum in issues related to survivors and survivorship. In this review we aim to summarize the current state of scientific knowledge, service delivery, advocacy initiatives and research efforts in this field in India.

Review of published literature from India

We identified references for this review through searches of PubMed using the following search terms or combinations of search terms: “Survivors”, “Neoplasms”, “India”, “Child”, “Late effects” and “Long-Term Follow Up”. Reference lists of the shortlisted studies were reviewed to identify potentially relevant previous studies. Similarly Google Scholar was used to see citations of the shortlisted studies in order to identify potentially relevant subsequent studies. Each of the co-authors was also asked to review their own files to ensure that the literature search had been comprehensive. The final list was generated on the basis of originality and relevance to the scope of this review.
Summary of results of 21 studies7-27 are tabulated (Table 1) and categorized by organ systems and late effects as used in the Children’s Oncology Group Survivorship Guidelines.28 All except one7 of these studies, has been published in the last decade, highlighting the recent expansion in work in this area in India. These were all single centre studies with 15 of the 21 studies from All India Institute of Medical Sciences, New Delhi and Tata Memorial Hospital, Mumbai. Sample sizes ranged from 20 to 1285 with median of 119 patients. Median follow-up was 4.5 years (range >1 year to 12 years). Most studies lacked controls,7-14,17-21,23-27 which is important to quantify the increased risk of the problem as compared to the general population. Importantly, with few exceptions9,11,24, most studies had not examined dose-effect relationship of exposure or the effect of combined modality of treatment. Heterogeneity in methodology (of patient selection, defining outcomes and tools used) made it unfeasible to pool data and give a summative risk for each category. The data is hence displayed as a table to allow the reader to get an overview of the methodology and results.
Despite the above limitations, several important observations can be made. These studies confirmed some of the well-documented issues in childhood cancer survivors including the previously reported detrimental effects of cranial radiation on neurocognition9-12 and neuroendocrine axis11, of neck radiation on thyroid function7,10, and of alkylating agents on fertility.10,12, 24,25 Contrary to published literature,28 a single study from India showed bone mineral density in leukemia survivors was similar to that of controls.22 The prevalence of overweight/obesity varied from 1% to 32% and may reflect the heterogeneity in patient selection, methodology and study design.10,12,19-23For late-effects of the heart the duration of follow-up was not sufficient to conclude on the magnitude of increased risk. The risk of secondary malignancy was 0.7% to 1.8% with median follow-up of 4.7 to 12 years.
Studies from three major centres in India, which included patients treated in the 21st century, also highlighted the specific challenge of transmitted viral infections with high prevalence of Hepatitis B (20% to 54%) and Hepatitis C (6% to 25%) infection in survivors.7,10,12 Blood product transfusion played a major role in this although they were likely to be other factors.12,29 Improvements in standards of screening of blood products has led to major decreases in transfusion transmitted viral-infections globally30 although the risk of acquiring these infections is still unacceptably high in low and middle income countries.31 Although, standards of testing including NAT testing have gradually improved, the progress has been patchy and tardy.32

Service delivery and models

The burgeoning number of childhood cancer survivors in high income countries with their morbidity burden necessitated steady and sustained efforts in developing services for their needs. While there is variation in provision of these services, there is universal agreement on their need.33,34 Few specific services are worth highlighting.
Firstly, is the model of long-term follow-up (FU) care. There is no universally agreed “best” model and the choice depends on patient volumes, complexity of needs, resources available and travel distances. Some of these models include FU in primary pediatric oncology setting, transitioning to an adult oncology setting, specialized long-term FU clinic or shared care.34 The second noteworthy development is that of guidelines to support lifelong risk-based follow up for this population. A clear understanding of the association between therapeutic exposures and specific long-term complications, and an understanding of the magnitude of the burden of morbidity borne by childhood cancer survivors, has led to this.28,35 It is worth pointing out that the data supporting these guidelines have come exclusively from research done in high income countries and hence their relevance when applying to low-middle income countries remains to be established. The increasing use of Survivor Passports is another highlight in the service delivery of these survivors.36,37 These passports not only provide a summary of each survivor’s clinical history, with detailed information about the original cancer and of treatments received, but also give personalised follow-up and screening recommendations based on guidelines thus ensuring high quality uniform care.
Surveys from high-income countries demonstrate service delivery for these survivors.38-41 Such information is absent in the Indian context. We recently conducted an online survey with the objective of determining the current service provided to childhood cancer survivors in India.42 It was sent to primary/senior consultants treating children with cancer in 86 centres in India.
Responses from 52(61%) centres in 24 cities have been received (private 46%, public 31%, charitable trust 23%). Upper age cut-off for FU of survivors was no age cut-off (63%), 18 years (21%), 21 years (10%). Similarly, cut-off based on duration from end of treatment was no cut-off (60%), 5 years (38%). In 90% of the centres, FU of survivors (more than 2 years off treatment) was in the regular pediatric oncology clinic while 10% had a dedicated clinic. The current level of service was thought to be inadequate or very inadequate 19%, neither adequate nor inadequate by 56% of centres, and adequate or very adequate 25%. The most important barriers were distance to clinic and patients/parents lack of knowledge about the need for FU.
Below are some examples of current models of service delivery to childhood cancer survivors in India
Model 1 – Follow up driven by healthcare establishments in hospital setting

As described above, these follow up clinics are multidisciplinary, mainly pediatric oncology physician led. They mainly cater to children and adolescents and follow-up duration is short. Some centres give survivorship summaries and 10-15 centres have dedicated survivorship clinics, most of whom have started in the last 5 years. Below are a couple of examples of well-established dedicated survivor clinics.

Tata Memorial Hospital, Mumbai

The After Completion of Therapy Clinic (ACT) Clinic at Tata Memorial Hospital, Mumbai was established in 1991, the first such clinic in India. From its inception, the functioning has been multidisciplinary with pediatric oncologist, psychologist and social worker. Additionally, over the years, there are dedicated weekly clinics for cardio-oncology and endocrinology follow-up of survivors of childhood cancer. Currently there are 3000 survivors registered, of whom 60% follow-up regularly. The median age of these survivors is 18 years, with a median follow-up duration of 10 years. Owing to the longstanding nature of this clinic, survivors are predominantly adolescent and young adults, with over 2/3rd of survivors being adults. Thanks to generous financial support from donors and liaison with Indian cancer society, the ACT clinic is now able to provide holistic support to its survivors.

All India Institute of Medical Sciences, New Delhi

The Pediatric Cancer Survivor Clinic of the department of Pediatrics, AIIMS is a weekly after treatment completion clinic where all children who have completed their treatment for the primary cancer are followed. The team at the clinic comprises of pediatric oncologists, nurses, counselors, dietician and non-governmental organization staff. On an average 150 new patients are registered into the clinic annually. A detailed counseling session is done with the family wherein the importance of long-term follow-up is explained. A bilingual After Treatment Completion Card is provided to all patients which records the treatment given (dates, types of treatment, cumulative doses) and possible late effects (Figure 1).43 Information regarding healthy lifestyle and vaccination is given. Girls are advised to take Human Papilloma Virus vaccine. Details of growth and disease status are captured and necessary tests conducted. A detailed psychosocial evaluation and intelligence quotient assessment are done for children who received central nervous system directed therapy in the form of chemotherapy/radiation. Information on social adjustment into the home, school and society are recorded. Information regarding education and peer relationships is acquired from all children and grades of disability ascertained. Regular follow-up is scheduled.
Model 2 – Follow-Up Driven by Not for Profit Organisations in hospital or community settings
Identifying the deficiency in survivorship services, a couple of not for profit organisations have stepped in. Besides managing medical issues, they are also able to provide social support, engage survivors through peer groups and advocate.