My highlights of SIOP 2010 in Boston

I hope that all those of you who had a chance to attend this year's SIOP meeting in Boston at the Hynes Convention Centre had a great time. It was a personal pleasure to meet so many of my old friends and make new ones. There was a good representation of the paediatric oncology community from India as well as many from the Indian diaspora.

There were 45 presentations (8 oral and 37 poster) from India and I had a chance to hear and see several of them. My personal highlight was Dr Kurkure's presentation on L0w cost rationally designed protocol for treatment of pediatric acute lymphoblastic leukemia in developing countries which was used in motivated families below poverty line at Tata Memorial Hospital. This protocol had a 3 drug induction (VCR, L-Asp, Dex) and 91% of children were in clinical remission at the end of induction. The event-free survival for standard risk patients was 63% (median follow-up 22 months) and for high risk patients was 48% (median follow-up 31 months). Remarkably, only 3% of children abandoned treatment during induction and 1% following induction.

The other presentation I really enjoyed was by Dr Vinay Jain on Building capacity in pediatric oncology in India: efforts of Jiv Daya Foundation 2008-2010 which gave a summary of the excellent work that he and his foundation have done over the last few years in several centres in India. More details of their work can be found on www.jivdayafound.org.

Finally, I heard with great interest two related presentations by Paola Freidrich-Medina who is a fellow at the Dana-Farber Cancer Institute. She was presenting the work done by AHOPCA (Asociacion de Hemato-Oncologica Pediatrica de Centro America) which is collection of seven resource-limited countries from Central America. The presentations were Current barriers for successful treatment of children with sarcomas in low-income countries and High tumor burden, high rate of abandonment and fear of disabling surgery are among the innermost barriers to treatment of pediatric sarcomas in resource-limited settings.

I welcome your thoughts and your highlights of the meeting. If there are any photographs that you want to share from the meeting on this blog, you can email them to me.

In India, should we treat children with High Risk Neuroblastoma (HR NB)?

At the outset, let me clarify two things. Firstly, by no means am I advocating not giving treatment to children with HR NB in India. My only purpose is to generate debate and learn from the more experienced and learned clinicians in India who manage children with this cancer. Secondly, every child irrespective of the type of disease or cancer (including HR NB) has a right to palliation including pain relief and this treatment option should not be denied. So, I guess the question I am really asking is "In India, should we treat children with HR NB with a curative intent?"

Around 50% of all children with NB have HR disease (essentially Stage IV i.e. metastatic NB or NB with mycn gene amplification with some caveats for age and histology). A study from the Children's Oncology Group published last month (Yu et al, 2010) reports a 2-year overall survival of 86% and event-free survival of 66% in children with HR NB who were treated with multi-drug induction + stem cell transplantation + isotretinoin + immunotherapy. Prior to the introduction of immunotherapy, the event-free survival in the developed world had plateaued at less than 50%. Thus, this new report of further improvement in outcomes is significant.

This brings me to the situation in India. As far as I am aware, while multi-drug induction (followed by surgery and radiotherapy) is standard treatment for children with HR NB, use of stem cell transplantation is not standard and immunotherapy has not been tried. In such a setting, what are the outcomes of HR NB? It is difficult to answer this question precisely, because assessment of mycn amplification is not standard practice in India either. Outcome of children with Stage IV i.e. metastatic NB can give us some indication, although very few institutes from India have published their outcomes. This includes 3 long term survivors out of 32 children with Stage IV neuroblastomas reported from Thiruvanathapuram (Kusumakumary et al, 1998); 1 out of 27 reported from Chandigarh (Bansal et al, 2008); and 0 out of 38 reported from Mumbai (Bhatnagar et al, 2007, SIOP).

Based on these reported outcomes i.e. less than 10% reported long-term survivors of HR NB, is there an argument for not offering curative treatment to the above group of patients in India? Has anybody reported better outcomes from India?

What is the outcome of children with Acute Lymphocytic Leukemia (ALL) in India?

The answer to this question, depends on whose asking it and to what purpose. At an individual level (when access to treatment is not a barrier), currently the standard 5-year survival in most of the developed world is 80-90% with that for low-risk ALL even higher than 90%. The best published results from India are 59% 5-year survival for children with ALL treated from 1985 to 2003 in CMC Vellore (Bajel et al, 2008), and of 57% in those treated from 1990 to 1993 in Tata Memorial Hospital, Mumbai (Advani et al, 1999). For low-risk ALL, these survival figures are around 73-77%. It is important to point out, that these results from India are calculated after censoring (removing) those children with ALL who refused to start treatment or abandoned ongoing active treatment. There are some unpublished data suggesting better outcomes - 70% 4-year survival of children with ALL treated at Sir Ganga Ram Hospital in Delhi (Sachdeva et al, SIOP 2007); and 94% survival after median follow-up of two years of children with ALL treated at Apollo Hospital in Delhi (Mahajan et al, SIOP 2008). A more accurate reflection of outcomes of children with ALL in India can be obtained when we include all those who refused and abandoned treatment and then calculate the survival. This is particularly relevant to clinicians, epidemiologists and health planners. To my knowledge, the recent paper from PGI in Chandigarh is the only one to publish such data. It shows a 4-year overall survival of 33% and a 10-year overall survival of 30% for children with ALL diagnosed at that institute from 1990 to 2006 (Kulkarni et al, 2009). Other sources of such information are the population-based cancer registries. Only two reports have ever been published looking at population-based 5-year survival in children with cancer and these were 35% from Bangalore for the period 1982 to 1987 (Nandakumar et al, 1996); and 39% for Chennai for the period 1990 to 2001 (Swaminathan et al, 2008). In a nutshell, 6 out of 10 children with ALL in India will have long term survival (and cure) if they are compliant with their treatment. If treatment uptake and compliance is variable, only 1 out of 3 children in such settings would be cured. These outcomes apply only to those treated in specialist tertiary centres in urban areas. For those in rural areas or non-specialist centres, the outlook is certain to be worse.

Childhood Cancer Survival in Philippines (and India) lags by >30 years than in Developed Countries

Survival of childhood cancer has enormously improved in the developed world with current 5-year survival for leukemia and lymphoma now around 80% and 90% respectively. An interesting recent paper shows that for the period 2001-2005 the 5-year survival of children with these cancers in Philippines is much lower (32.9% for leukemias and 47.7% for lymphomas) (Redaniel et al, Br J Cancer, 2010). These figures are even less than the survival seen in USA during 1976-1980 (57.7% for leukemias and 60.9% for lymphomas). These observations although not unexpected, do highlight the enormous gap in the outlook of children with cancer in the developing world.

What about India? There is limited population-based childhood cancer survival data. The most recent data from Madras Metropolitan Tumour Registry shows that for the period 1990-2001 the 5-year survival of children with leukemias in Chennai was 36.3% and lymphomas was 55.3% respectively (Swaminathan et al, Int J Cancer, June 2008). In this study, a combination of completeness of treatment and type of hospital emerged as significant prognostic factors for survival.

CNS disease at presentation in childhood ALL

Hi all,

Recently, management experience of CNS disease at presentation in childhood ALL from PGIMER, Chandigarh, India was published (Ref - Marwaha et al, Leukemia and Lymphoma, Feb 2010). The summary is as below

The spectrum of central nervous system (CNS) disease at diagnosis, traumatic lumbar puncture (TLP), role of cranial irradiation, prognostic parameters, and survival outcome in patients with CNS involvement amongst 747 patients with acute lymphoblastic leukemia managed at PGIMER was analysed. The overall outcome and management experience has been described elsewhere (Ref - Kulkarni et al, Pediatric Blood Cancer, Aug 2009).

25 and 6 patients out of these had CNS disease and TLP, respectively. Patients with CNS disease had significantly higher mean presenting leukocyte count and incidence of hyperleukocytosis compared to those without it. Contemporary immunophenotyping and molecular data was unavailable in majority of the patients especially managed in the 1990s. Other usual prognostic parameters were not significantly associated with CNS disease at presentation. The outcome was poor with three patients in continuous complete-remission, nine relapsers, eight deaths, and eight therapy defaulters.

Despite the fact that the percentage of pateints with CNS disease was lower than published literature, outcome was not inkeeping with the contemporary outcomes. Once again this highlights the difficulties faced by a pediatric Oncologist in the developing world in holistic management of ALL. CNS involvement was significantly associated with inferior survival. CNS involvement was thus a high-risk indicator. Poor outcome in this cohort indicated the need for the revaluation of our treatment protocols with the inclusion of risk-stratified systemic therapy, categorization of CNS involvement according to published criteria into CNS 1, 2 and 3 which is also often difficult in resource limited settings. The rate of traumatic lumbar puncture was however very low. Problably reflecting the fairly good skills of the operators given the large number of patients managed.

Communication in Paediatric Cancer Patients: A Parent's Perspective

Clear and honest communication done sensitively is important in the holistic management of children with cancer and their parents. Little research has been done in India to assess the health information needs of sick children (and their parents). Also the quality and adequacy of information given by health professionals not been looked at.

To address this knowledge gap, Dr Tullika Seth, a haematologist at All India Institute of Medical Sciences has done a pilot study where she interviewed parents of children aged 10 to 18 years with acute lymphocytic leukaemia (Seth T, Indian Journal of Palliative Care, Jan-Apr 2010). The results clearly show that in the Indian context, parents wanted little information to be shared with their children (65% did not want their children to be informed of the diagnosis; 60% did not want the child to be informed about side effects of therapy and especially about long term effects). There was even a stronger opinion about not involving children with decision-making (95% did not want them to involved with making any decision about the treatment; 100% did not want them to involved with making any decision about stopping curative treatment when such a situation arose).

These findings would be useful to health professionals in "forging an alliance with the family to facilitate communication" as Dr Seth says. They also offer us insight into the different attitudes and practices in India compared to the Western context, where patient autonomy is more visible.

Vincristine Neurotoxicity and Malnutrition

Vincristine is an important weapon in the chemotherapeutic arsenal against several childhood cancers including acute lymphoblastic leukaemia, lymphomas, Wilm's tumour and various brain tumours. It does have side-effects, notable neurotoxicity which manifests in various ways. It is accepted that malnutrition (more common in resource-poor nations) can exacerbate vincristine-related neurotoxicity.

A report from Delhi highlights the prevalence of vincristine-related neurotoxicity (at dose of 1.4 mg/m2) which was seen in 10 out ot 20 children with various cancers treated over a two year period (Ref - Gomber et al, Indian J Pediatrics, Jan 2010). This is much higher than that reported from resource-rich nations. In 6 cases, the severity of the toxicity warranted temporary discontinuation of the drug. The weight of all patients who developed neurotoxicity was below the 3rd centile for age and was significantly lower than those children who did not develop neurotoxicty.

Clues to the mechanism by which malnutrition can increase vincristine-related neurotoxicity can be found in another recent paper (ref - Israel et al, European Journal of Cancer, 2010). The pharmacockinetics of vincristine (at dose of 1.5 mg/m2) were studied in 11 children with Wilm's tumour from Malawi and 8 children from UK. The children from Malawi had significantly lower weight-for-height than those in UK. The clearence of vincristine was significantly slower in Malawian children and as a result the exposure to vincristine (measured by area under the curve) was almost two times longer. There was a linear corelation between the extent of malnutrition and the area under the curve for vincristine.

The above two studies would suggest that in children with cancer who are malnourished, we may have to reconsider the dose of vincristine. Clearly, this area merits more research in India and in other resource-poor settings.

Brain Tumour Foundation of India

Brain tumours, the second most common group of childhood tumours, pose special challenges in diagnosis, management and long-term follow-up. A close co-operation between neurosurgeons, radiation oncologists, paediatric oncologists, neuroradiologists and neuropathologists is needed for optimal management of these children

The Brain Tumour Foundation of India is a non-profit organisation which is committed to reducing the physical, emotional and financial suffering associated with diagnosis, treatment and rehabilitation of patients with these tumours, and their families. Various health professionals and allied professionals from Tata Memorial Hospital and King Edward Memorial Hospital, along with other organisations in Mumbai who share an interest in patients with brain tumours came together and set up this foundation nearly 10 years ago.

Although based primarily in Mumbai, the foundation is keen to reach out to patients with brain tumour across the country. Its three main objectives are

1. Quality Treatment and Care: Support for chemotherapy drugs, materials/medicines needed during surgery and radiotherapy.
2. Social and Psychological Support: Activities included monthly support group meetings, celebrating festivals, organising art events, producing greeting cards (see figures) educational support, advocacy and other similar activities.
3. Research

.

First Month of Blogging!

It has been a month since I started this blog. I had some idea in my head as to what I wanted to achieve, but was completely unsure of the shape the blog would take, and the reception it would receive. I am immensely grateful to those who have given me encouragement. My gratitude also extends to those "silent" readers across India and the world. You readers are the life of this blog and your comments are most welcome.

In this first month I have published 13 blog posts. These posts have been viewed in 45 cities in 9 countries including 63 visits from 18 cities in India. Posts from the blog have been shared on Twitter and Facebook. All this is very encouraging and gives me lot of motivation to continue putting my thoughts via this medium.

In the coming months, I plan to continue to do more of the same. In addition, I hope to encourage more "active" participation of the readers of the blog, while at the same time increasing the visibility of this blog. The expectation is that the readers not only read and comment on the blog posts, but also write posts of their own and put it on this blog. This blog can then act as a forum for them to express their opinion and generate debate.

Dismal Outcome of Diffuse Intrinsic Pontine Glioma

Around 10-15% of all childhood tumours of the brain are in the brain-stem. A majority of these are diffuse and infiltrating lesions of the pons called Diffuse Intrinsic Pontine Glioma (DIPG). Surgical removal of these tumours is not feasible and focal radiation in combination with experimental chemo/biologic therapeutic agents is the mainstay of treatment. Current outcomes across the world are dismal overall survival less than 10 to 15%.

In a recently published report from Tata Memorial Hospital in Mumbai, clinicians describe the outcome of 20 children with DIPG who were treated with focal radiotherapy (54 Gy in 30 fractions over 6 weeks) along with oral temozolomide during and after radiotherapy (Ref - Jalali et al, Int J Radiat Oncol Biol Phys, May 2010). This was done as a phase 2 feasibility clinical trial. Although the treatment was generally fairly well tolerated, only 35% of children were alive at 12 months after diagnosis and only 6% after 18 months.

In summary, this is one of the very few case-series on DIPG from India and the dismal outcome of these children is similar to that reported from rest of the world. I am fascinated by the complete absence of treatment refusal and abandonment in these group of patients. In a cancer, where treatment is intense and the outcome generally fatal, refusal/abandonment of treatment should theoretically be a relatively common occurrence.

Health-Related Quality of Life in Children with Cancer

Historically, outcomes of children with cancer has been measured in terms of mortality, relapses and survival. As these QUANTITATIVE measures of life have improved in resource-rich countries, measurement of QUALITY OF LIFE (QOL) has become standard practice. For various reasons, resource-poor countries including India have under-used and under-reported these outcomes (Ref - Pandey, Psycho-Oncology, June 2004).

A recent paper reports health-related QOL outcomes in children with cancer from a physicians perspective (Ref - Chirivella et al, Indian J Pediatrics, Dec 2009). 45 patients and their physicians were recruited from two centres in Hyderabad. Using questionnaires, the physicians were interviewed for their assessment of the various HRQOL domains (sensation, vision, hearing, speech, mobility, dexterity, emotion, cognition, self-care, pain). Although its primary objective was a feasibility study, it does show an interesting (and not unexpected) observation of the pain domain having one of the lowest and most variable scores. This is in line with the recent report by Human Rights Watch which found that pain relief during palliation was sub-optimal in India.

A brief search of Medline did not reveal any other articles from India looking at health-related QOL in children with cancer. The efforts of the authors of this paper is laudable in this context. I wonder how the authors propose to progress from here?

Eeshwar Child Welfare Foundation - Support Group from Lucknow

I hope to use this blog to generate awareness of the excellent work done by the various cancer support organisations in the country. I will focus on those groups which either exclusively work with children with cancer and their families, or who provide support to this group of patients along with other similar activities.

The focus of this post is on the Eeshwar Child Welfare Foundation which was set up in 2005 by Sapna Upadhyaya. They provide assistance to the children with cancer and their families who are being treated at Chhatrapati Sahuji Maharaj Medical University (formerly known as King George Medical College) in Lucknow under the care of the local paediatric oncologist, Dr Archana Kumar. In this time the have supported over 1200 children with direct medical costs (chemotherapy, diagnostic tests), indirect medical costs (food, clothing), access to social and educational services. Currently, the support group is involved in building a "Home away from Home" so that these children who travel from long distances have a suitable accommodation available for themselves and their families.

Immunisation Practice in Children with Cancer

Immunisation (also known as vaccination) of children to provide immunity against various infectious diseases is a standard practice all over the world. Children who develop cancer, can lose the protective effect of these vaccines, mainly as a result of immunosupression from chemotherapy. These children thus need additional doses of various vaccines, which are generally given once treatment is complete. According to UK guidelines, these include additional boosters of diptheria, tetanus, acellular pertussis, injectable polio vaccine, H influenza B, meningococcal C and MMR to be given >6 months after completion of standard chemotherapy (non-myeloablative) for leukaemia and solid cancers (Ref - RCPCH Guidelines, 2002). In addition repeat BCG vaccination is recommended for those at high risk for tuberculosis and who have a negative tuberculin test after treatment.

Two interesting papers have come out in Pediatric Blood Cancer recently, in relation to this topic. The first is a survey of immunisation practices among paediatric oncology and shared care oncology consultants in UK which shows a high level of compliance with the above mentioned RCPCH guidelines (Ref - Bate et al, Pediatric Blood Cancer, July 2010). The exception to this was use of pneumococcal conjugate vaccine (which is not specified in the RCPCH guidelines) and 58% of respondents routinely administered it.

Similar guidelines are available in other European countries and North America, but none exist in resource-poor countries (and as far as I am aware there are no guidelines in India). To address this deficiency, a recent review from authors in Pakistan has given recommendations for immunisation against infectious diseases prevalent in resource-poor countries (Ref - Naqvi et al, Pediatric Blood Cancer, Jan 2010). In addition to the recommendations by RCPCH, these authors also recommend boosters for hepatitis A, hepatitis B, typhoid and varicella.

To extend the above discussion in the Indian context, it would be useful to know the practice by health professionals in India who manage children with cancer. For this purpose, I invite readers of this blog to comment on their personal practice - do they give vaccination boosters after completion of treatment to children with cancer; what boosters are the children given; how long after completion of the treatment are these boosters given; and any other comments.

What is the Prevalence of Complementary and Alternative Medicine for Children with Cancer in India?

A collection of health care systems, practices and products which does not fall within conventional medicine is called Complementary and Alternative Medicine (CAM). When it is used as an adjunct to conventional medicine it is called Complementary, and when used as a substitute, it is called Alternative. Included among these are homeopathy, ayurveda, yoga, acupuncture, herbal remedies, nutritional-based therapies and others.

The use of CAM is particularly prevalent in those with cancer. Reasons for use include hope for therapeutic benefit, reduced risk as well as alleviation of adverse-effects. In a recently published systematic review (Ref - Bishop et al, Pediatrics, April 2010) the overall prevalence of CAM was 6% to 91%. Use of individual therapies were 2% to 48% for herbal remedies, 3% to 47% for nutritional interventions, 3% to 30% for faith healing and 1% to 17% for homeopathy. Notably, 23 of the 28 studies in the systematic review were from North America and Europe, and none of the studies were from India. By doing a literature search on Pubmed I was unable to identify any studies which could give me the information of CAM in this context in India.

CAM is associated with children with cancer in India in a multitude of ways. Prior to accurate diagnosis and appropriate treatment, children with cancer in India often have been receiving some form of treatment from CAM practitioners. This leads to a delay in presentation which then contributes to a higher stage, more intense treatment and poorer outcomes. Then during treatment with chemotherapy and radiotherapy, these children often take some form of complementary therapy to reduce the adverse effects. Lack of adequate supportive care and good, honest communication lead families to expend valuable energy and resources in the pursuit of CAM. Finally, when treatment is refused or abandoned (not an uncommon outcome in India) parents try to find answers with CAM practitioners. There is a need to study and better understand CAM use in children with cancer in India.

CHK4WTK4Z4R9

Music Therapy Reduces Procedural Pain in Children with Cancer

Repeated procedures like lumbar puncture and bone marrow aspiration are routine part of management of several childhood cancers (in particular acute lymphoblastic leukaemia). Adequate sedation and analgesia for these procedures in a safe environment is desirable and there are guidelines available in Europe and North America in this context. The mainstay of sedation in such settings is general anaesthesia.

A recent survey shows that the practice of sedation and analgesia for lumbar punctures and bone marrow aspiration in children with cancer in India is varied and includes no sedation/analgesia, local anaesthesia or some systemic sedation/analgesia but no general anaesthesia (unpublished data). Further research is needed to identify reasons for these variations.

The recently published report from Vietnam (in collaboration with Swedish investigators) shows reduced pain and anxiety in children aged 7-12 years with leukaemia during and after lumbar puncture who were randomised to receive music therapy compared to no music. (Ref - Nguyen et al, Journal of Pediatric Oncology Nursing, May-June 2010). What makes this clinical trial particularly relevant to the Indian context is the fact that besides music therapy, there was no use of any form of sedation/analgesia for the procedure. Such a practice of lack of any sedation/analgesia during the procedure is standard in Vietnam and also a common occurrence in India. Music therapy is a low cost, safe and easily available option which should be considered (in isolation or as an adjunct) for these procedures.

Incidence of Childhood Cancer in Rural India

Although 70% of the Indian population lives in villages, we have relatively little real information about cancer in them as most of the population-based cancer registries (PBCRs) are urban. The incidence and mortality patterns of these urban PBCRs cannot provide an accurate picture for the entire country as the environmental exposures and the gene-environment interactions leading to cancer could be substantially different within different part of India.

In such a context the first report of the rural PBCR at Dindigul Ambilikkai in Tamil Nadu provides us useful information about cancer incidence (including childhood cancer incidence) in rural India (Ref - Swaminathan et al, Cancer Epidemiology, Nov 2009). The reported incidence of cancer in boys less than 15 years of age of 56 million person years and in girls of 46 million person years is similar to reports from the two other rural PBCRs in India and much less than that reported from the urban PBCRs in India and from other parts of the world (Ref - Arora et al, Indian Journal of Cancer, Oct-Dec 2009).

Under-diagnosis (and consequently under-registration) of childhood cancer due to lack of adequate access to diagnostic and clinical services is likely to be the main reason for the lower incidence of childhood cancer seen in rural India (Ref - Arora, Cancer Epidemiology, Feb 2010) and (Ref - Swaminathan et al, Cancer Epidemiology, Feb 2010)

Enabling Timely Diagnosis of Brain Tumours in Children

Worldwide, tumours of the brain (and other parts of the central nervous system) constitute nearly 25% of all childhood cancer (second only to acute leukaemias). Their incidence in India is lower and this is partly related to underdiagnosis as a result of inadequate neuro-radiological and neuro-surgical facilities (Ref - Arora et al, Indian Journal of Cancer, Oct-Dec 2009)

Presenting features of the brain tumour depend on the age of the child as well as the location of the tumour in the brain. However, they can be varied and include headache, nausea/vomiting, visual changes, motor changes, seizures, altered sensorium and others. The non-specificity of some of these symptoms can lead to a delay in parents seeking medical advice and in physicians reaching a diagnosis. These delays can have negative impact on outcomes.

The Children's Brain Tumour Research Centre in Nottingham University has developed evidence-based guidelines to help clinicians recognise and diagnose brain tumours in children in a timely fashion. These guideline have application across all settings and populations including in the Indian context and deserve to be widely disseminated.

(Ref - Wilne et al, Archives of Diseases in Childhood, 2010) and (Ref - Royal College of Paediatrics and Child Health Guidelines)

Proportion of Translocations in Childhood ALL in Pakistan is similar to that in India

TEL gene rearrangement due to the 12;21 chromosome translocation is the most common molecular genetic abnormality in childhood acute lymphoblastic leukemia (ALL) and is seen in around 25% of children with pre-B cell ALL (studies mainly from Europe and North America). In this translocation the 5’ part of the TEL (ETV6) gene fuses with almost the entire AML1 (CBFA2) gene, producing the chimeric transcript ETV6-CBFA2.

Figure from www.kreatech,com

It is associated with a better prognosis in ALL . In contrast to the West, the frequency of the translocation TEL/AML1 in children in India with ALL is around 7% (Ref - Siraj et al, Leukemia, June 2003). Now in a study of 50 children with ALL from two institutes in Lahore, Pakistan the frequency of the TEL/AML1 translocation was a similar 6% (Ref - Faiz et al, Journal of Pediatric Hematology Oncology, April 2010). Interestingly, the frequency of another translocation which confers a poor prognosis, t(9;22) or BCR/ABL, was 24% and is much higher than that reported from India and elsewhere.

Clearly, these results are from a hospital-based case series and further larger studies in Pakistan would be necessary. The fact that 42 of these 50 ALL children with ALL were boys illustrates the limitation of such hospital-based case series.

Addendum (08/06/2010) - A recent report shows that the frequency of TEL/AML1 in Far East Asia (Japan, Korea, China, Hong Kong, Chinese in Singapore, and Taiwan) based on a pooled analysis of 1321 children with ALL was 13.4% (Ref - Liang et al, Pediatr Blood Cancer, 2010). This is lower than that reported from the West but higher than that from the Indian subcontinent.

Ovarian Germ Cell Tumours in Children

Tumours of the ovaries represent around 4% of tumours overall in females and around 2% of all tumours in children less than 15 year of age. In children and adolescents, germ cell tumours of the ovary are by far the most common pathology (around 70%) among ovarian tumours while in adults, carcinoma of the ovarian epithelium accounts for 85-90% of the ovarian tumours.

Dr Biswajit and his colleagues from a tertiary cancer centre from Chennai have recently published outcomes of 40 girls less than 18 years of age with ovarian germ cell tumours who were managed in their institute from 1990 to 2002 with cisplatin-based chemotherapy and surgery (Ref - Biswajit et al, Journal of Pediatric Hematology Oncology, March 2010). Nearly 2/3^rd of the patients presented in Stage III-IV. Delays in diagnosis and treatment could have been due to patient-related factors or due to healthcare-related delays although this was not specifically studied. The 5 years disease-free survival was 72.8% (mainly because of relapses in 25% of patients) and overall survival was 94.9%. Similar results were reported from Tata Memorial Hospital in Mumbai nearly 15 years ago although they had less relapses (Ref - Kapoor et al, Journal of Pediatric Hematology Oncology, November 1995).

Treatment Refusal and Abandonment

The outlook of childhood cancer has improved enormously in the developed world with 5 year survival overall ~80%. Unfortunately we have not been unable to translate this success to much of the developing world including India. Treatment related mortality and relapse are important causes of treatment failure. However they are overshadowed by the widespread prevalence of treatment refusal and abandonment which are the main causes of treatment failure. These are as much a social problem as they are a medical problem. Any attempts to improve the outlook of children with cancer in a country like India has to have at its core strategies to deal with this problem. Such successful models are now being increasingly reported from Central and South America. Most notable has been the reduction of treatment abandonment in children with acute leukaemia as a result of the “twinning programs” between St. Jude Children’s Research Hospital in Memphis USA and Instituto Materno Infantil de Pernambuco in Recife, Brazil (see graph below)

Ref - Howard et al, JAMA, May 2004

Attempts have been made in the past to contact the children and families of those who abandon treatment. There are a very few studies looking at this and their dissemination has been limited to scientific proceedings. The recently published paper from Indonesia (Ref - Sitaresmi et al, Psycho-Oncology, April 2010) is the first extensive analysis of child and parent attitudes and behaviour to explain this complex problem. The authors conducted home-visits to interview families of 37 acute leukaemia patients, diagnosed between January 2004 and August 2007, who refused or abandoned treatment. There was no relation of abandonment with age, risk stratification of leukaemia, class of hospitalization (marker of economic status), parental education level and travel time. Girls abandoned slightly more often but this difference did not reach statistical significance.

Financial difficulties and a belief in the incurability of acute leukemia were the leading reasons given by parents for abandoning treatment. Additionally, treatment-related toxicity, painful procedures performed with inadequate analgesia and sedation, inadequate communication provided by health care providers and transportation difficulties were contributing reasons.

Extraocular Retinoblastoma in India

Retinoblastoma is the most common cancer of the eye in children and accounts for 2.5 to 4% of all childhood cancers. When a child is diagnosed with retinoblastoma, the cancer may be limited to the eye globe (intraocular) or have spread beyond the eye globe (extraocular). The spread may be local (to the orbit and local lymph nodes) or more distant i.e metastatic. Delays in presentation in India lead to more than half of the children with retinoblastoma having the cancer spread outside the globe at diagnosis.

Ref - Sahu et al, Pediatric Hematology Oncology, Nov-Dec, 1998

Sameer Bakhshi and his colleagues describe the treatment and outcome of 25 children with extraocular but non-metastatic retinoblastoma over a 5 year period (2003 to 2008) from one of the premier treatment centres in India. The overall survival figures are not given but at a median follow up of 28.5 months (nearly 2½ years) 13 of the 25 children had progressed/relapsed.

Ref - Bakhshi et al, Journal of Pediatric Hematology Oncology, Mar 2010

All those who progressed or relapsed, either refused or did not respond to second line treatment which implies that they would all ultimately die of the cancer. One also needs to consider that there were 51 children with extraocular non-metastatic retinoblastoma during this time period but only 25 opted for treatment. Many if not all of those who did not opt for treatment for various reasons are also likely to have succumbed to the cancer. These poor outcomes are all the more significant as majority of the children in India with retinoblastoma present late and the disease has spread locally or systemically. Hence, it is not surprising that the five year overall survival of children with retinoblastoma (all stages combined) is less than 50% while that in Europe and North America is 95% and above.

Ref – Swaminthan et al, International Journal of Cancer, June 2008

Childhood Cancer in India: An Introduction

Globally, it is estimated that 250,000 children under the age of 15 years develop cancer every year. Around 50,000 (20% or 1/5th) of these children are in India.
Both the above estimates are based on the incidence of childhood cancer being 125 to 150 per million per year.

We do not know, how many of these 50,000 children with cancer in India get diagnosed. Of those who are diagnosed, we do not know how many of them seek treatment. A significant proportion of those who do seek treatment, either refuse treatment when it is offered or abandon treatment within the first few weeks. Based on information derived from published studies and presentations at scientific meets we know that treatment refusal and abandonment rates vary from 17 to 62% depending on the type of cancer and treatment center.
Ref – Arora et al, Pediatric Blood Cancer, Dec 2007

Currently, nearly 8 out of 10 children with cancer get cured in resource-rich countries like those in North American and Europe. If we exclude those who refuse or abandon treatment, comparable outcomes for specific cancers are achieved in India in those treated at tertiary institutes like the Tata Memorial Hospital in Mumbai. However, at a population level, the five-year overall survival for all childhood cancers combined has been reported to be 37-40% from Bangalore and Chennai. This cancer registry data is a much more accurate representation of cancer outcomes across India although as it is from urban areas, it is also likely to be an over-estimate of the true survival.
Ref – Arora et al, Indian Journal of Cancer, Oct-Dec 2009