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.