Wilms Tumour in India

Carl Max Wilhelm Wilms was a German pathologist and surgeon who worked extensively on renal tumours towards the end of the 19th century. One of the most common solid tumours in children, nephroblastoma, is also known as Wilms tumour in recognition of his work. In resource-rich countries, the five-year survival for this cancer is 90% and the focus now is on reducing the treatment-related morbidity while maintaining similar outcomes.

Despite being a relatively common childhood cancer, there have been no published studies from India on the outcome of this cancer for over a decade. It is for this reason, that the recently published report from PGI Chandigarh (Trehan et al, JPHO, 2011) is so timely. 23 children with Wilms tumour were seen over a five year time period (1999 to 2003). Three did not start treatment and abandoned after diagnosis. In the remaining 20 treatment was based on the SIOP philosophy of neoadjuvant or preoperative chemotherapy. There was one treatment related mortality (5%), three relapses (15%) and one abandonment on therapy (5%) leading to a five-year event-free survival of 75%.

Detailed analysis of causes of treatment failure would be needed to further improve outcomes. What is noteworthy is that the three relapses happened in two Stage II patients and one Stage III patients. Staging of the chest was done by x-ray which would be standard practice in many centres in India. I wonder whether a CT Chest may have upstaged these patients at diagnosis and consequently they might have received more intensive chemotherapy leading to reduced risk of relapse. I think it is a question worth answering in the future.

How does this compare to other centres in India? The difficulty is the lack of published and peer-reviewed literature. Nevertheless, long term event-free survival of 73% and 77% have been reported from Tata Memorial Hospital (SIOP 2005) and AIIMS (SIOP 2009) based on data obtained from scientific presentations of annual SIOP congresses.

Good old, Ginger

The recent Pediatric Blood cancer made for happy reading when I saw the very interesting piece of work from AIIMS on the use of GINGER in the control of nausea and vomiting in children with cancer (Pillai et al, PBC, 2011). It is encouraging to see that this root, which is so essential to Indian cooking, has been harnessed for therapeutic use. Dr Bakshi and his team should be congratulated on a simple well-designed trial with a clear message. I look forward to use of ginger and its effect in other settings, other centres, and other chemothrapy regimens.

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.