Advances In Pediatric Oncology

Introduction

Outcome of childhood cancer has improved significantly in the past two decades. In developed countries, it has reached to the tune of 70-90% in most of the diseases. Though steady progress has been achieved in India as well, still we are far behind from what has been witnessed in the west. Therefore, it is crucial for us to analyse the past, evaluate the current scenario and devise strategies for future so as to achieve desirable goals in long-term. For the sake of clarity and better understanding, we have discussed these aspects of Pediatric- Oncology in four domains: diagnostics, therapeutics, research, education and services.

Diagnostics

Historically, clinicians were reliant on conventional cytology, histology and radiological studies for diagnosis of cancer. Though even today these are still very important tools, in addition we have plethora of other new tests which may help in confirmation of diagnosis in difficult cases. Detection of certain pahogonomic genetic alteration by FISH/ PCR in cases where morphology and immunohistochemistry is inconclusive is one such example. Application of flow cytometry in diagnosis and response assessment has revolutionized management of acute leukemia in children and adolescents. Another important addition in diagnostic armamentarium has been inclusion of functional imaging like PET-Scan for staging and response assessment. Application of these modalities has helped us to escalate/deescalate treatment of certain subset of patients and thus in a way has paved way for personalized treatment. Another major advancement has been incorporation of next generation sequences (NGS) which has provided overwhelming genomic information pertaining to childhood cancers. This information has revealed an unprecedented view of the tumor genome, thus enabling clinicians to identify certain bad players for whom treatment can be modified. Furthermore, newer molecular technique platforms perform massively parallel sequencing, during which millions of fragments of DNA from a single sample are sequenced in unison. Massively parallel sequencing technology facilitates high-throughput sequencing, which allows an entire genome to be sequenced in less than one day. This information may be used for functional and therapeutic genomics in future.

Therapeutics

When we talk about treating children with cancer, it is not just a matter of improving the survival rate but it is about ensuring a qualitative leap, improving the quality of life for patients and survivors and reducing the sequelae of the disease and its treatment. Major modalities of treatment include systemic chemotherapy, surgery, radiotherapy and stem cell transplant. The introduction of chemotherapy, in the middle of the last century, ushered in an era of improvement in the prognosis of malignant diseases in children. Since then many new drugs have been introduced and with experience we have learnt how to optimize use of these drugs effectively. With the better understanding of biology of the disease, newer targeted therapy and immunotherapy has given promising hope to many patients who otherwise were deemed incurable. Imatinib and other TKI for CML, blinatumomab and inotuzumab for ALL, brentuximab and nivolumab for HL are some of such examples. More recently the possibility of engineering T lymphocytes to produce a chimeric receptor (chimeric antigen receptor [CAR]) for an antigen expressed by tumour cells and thereby provoking a cellular immune response, killing tumour cells, has opened up a new therapeutic strategy for diseases considered resistant to conventional treatments. Another area where things have rapidly changed in last one decade is success of haploidentical stem cell transplant. Feasibility and its success has opened an option for those who deserve allogenic BMT and do not have a match related or an unrelated donor. In addition, advances in newer techniques of radiotherapy delivery and proton therapy has increased the precision of radiation delivery and thus increasing the effectiveness while keeping late effects in check.

Research

A major contributor to the success of childhood cancer can be attributed to well designed systematic cooperative trials from Europe and North America. Participation in clinical trials not only improves the outcome of patient, but also provides important insight about various aspects of disease which may be targeted in subsequent studies. The clinical research landscape outside of these large and well-established groups is almost non-existent. In India, the Indian Pediatric Oncology Group (InPOG) was founded in 2008 to create a platform for multicenteric cooperative group research. After several years of building clinical trial infrastructure, InPOG started recruiting pediatric patients for its first collaborative trial in 2015. Few clinical multicentric collaborative studies are going on yet it has a long way to go before it makes a meaningful and lasting impact. The interfaces between large consortia and smaller regional or national clinical trial groups must be customized to account for a variety of organizational structures and the particular logistical realities and local research priorities of the countries.

Education and services

There was no formal structured fellowship program in Pediatric Haematology–Oncology until 2008. However, since then many institutes are offering 2-3 year training program in this subspecialty accredited by Medical council of India, National board of examination and Indian academy of Pediatrics. With time we have now sizeable number of trained Pediatric oncologist from these institutes and abroad. Also, in last two decades, we have witnessed a rapid rise in dedicated Pediatric Oncology and BMT units. Though these numbers are quite insufficient compared to what is required, still it’s a welcome change.

In conclusion, we have learnt from the west that Pediatric oncology is the prime example of how bench to bedside – research can bring about positive changes in lives of children with cancer. This model is essential to strengthen Pediatric Oncology in India. A concrete, collaborative and multidimensional effort from all stakeholders is essential to achieve international standards. Though many challenges remain, promising initial results provide hope that the future will bring personalized, less toxic, curative treatments to all children with cancer.

Dr. Sandeep Jain, DNB, FIAP
Senior Consultant Pediatric Hematology – Oncology & BMT
Rajiv Gandhi Cancer Institute and Research Centre, Delhi