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.

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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.