Topic of cancer: New forms, targeted therapies and more

As the disease shape-shifts and affects more Indians than ever before, hope lies in the evolving line of targeted therapies

The images were gut-wrenching. There was Manohar Parrikar, looking dapper in one picture, and skeletal in another. The Goa chief minister’s death at the age of 63 followed the demise of another BJP stalwart. Union minister Ananth Kumar was just 59 when he breathed his last. The two leaders had the world’s best medical care at their disposal, but fell prey to a disease that has been haunting India — cancer.

There has been a steady increase in India in deaths caused by cancer — a group of diseases that leads to an abnormal increase in affected cells. Today, nearly 10 Indians die of cancer every second, more than double the lives lost in 1990.

The incidence of cancer is still lower in India than in most developed countries, but globally it ranks 10th in overall cancer rates. And in the number of cancer patients, it is third in the world, after China and the US.

A spate of deaths — along with cases of celebrities fighting cancer — has turned the spotlight on the disease in recent times in India. Parrikar’s death from pancreatic cancer came four months after Kumar succumbed to lung cancer last November.

Manohar Parrikar (63), chief minister of Goa, died of pancreatic cancer last month despite having the best medical care at his disposal   –  PTI

 After Lisa Ray successfully fought blood cancer, several others in Bollywood came out with stories of their battle with the disease. Among them were Sonali Bendre, Manisha Koirala, Irrfan Khan and Rakesh Roshan. Cricketer Yuvraj Singh was also diagnosed with a form of lung cancer.

News of celebrities such as Irrfan Khan, Manisha Koirala, Yuvraj Singh and Sonali Bendre fighting cancer has turned the spotlight on the disease in recent times in India.   –  v sreenivasa murthy; pti/ashok bhaumik; pti/shashank parade

“The crude number of new cases due to cancer increased substantially in India over the last two decades,” says Krithiga Sridhar, epidemiologist with the Public Health Foundation of India (PHFI). But this, Sridhar believes, is mainly because of population growth and the increasing urbanisation of India.

A report published by a consortium of senior oncology researchers from India and abroad, in the journal Lancet Oncology last October, identified new trends in the Indian cancer landscape. It gave a comprehensive picture of the patterns and time trends of the burden of total cancer and specific cancer types in each state of India, estimated as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016. This was the first dataset of its kind.

The report states that while cancers linked to sanitation and personal hygiene are on the decline, those associated with lifestyle changes and a sedentary life are on the rise.

According to the GBD data, cancers accounted for 8.3 per cent of all deaths in India in 2016, the second highest cause after cardiovascular diseases, which led to 17.8 per cent of deaths. Among cancers, stomach was the most prevalent (9 per cent), followed by breast cancer (8.2 per cent) and lung cancer (7.5 per cent).

“What’s intriguing is that in India we’re not only seeing an increase in cancer, but we’re also seeing changes in a particular portfolio of cancers. So the cancers we’re looking at in 2016 are not the same cancers that were driving the public health agenda 15 years ago,” says Ken Buetow, an Arizona University professor who specialises in cancer studies. The human genetics and genomics researcher studying cancer, liver disease and obesity was recently in India at the invitation of the US-based non-governmental Open Health System Laboratory.

So, instead of cervical cancer, leukaemia and other cancers that were once the most common forms of the disease in India, there are many more cases of breast cancer, he points out. Lifestyle choices — smoking, unhealthy diets or lack of exercise, for instance — can lead to breast, colorectal or stomach cancers. Lack of sanitation and personal hygiene and unprotected sexual intercourse are linked to cancers of the cervix and penis.

“The incidence of lung cancer, head and neck cancer and colon cancer is now rapidly increasing,” he says.

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Doctors, however, stress that there is no data — yet — to indicate that there is an unusual increase in cancer incidence in India. ”The increasing trend observed in cancer-specific incidence rates is because of population growth and ageing, but also the increasing prevalence of risk factors,” says Sridhar.

The number of cancer cases may be increasing, but there is not much evidence that it is becoming more virulent. “There is no data to suggest that cancer is becoming aggressive in India. But 60-75 per cent of cancers are diagnosed at later stages (stage 3 or 4), leading to a lower chance of survival,” says Dr Arvind Krishnamurthy, head of surgical oncology at the Adyar Cancer Institute, Chennai.

Significantly, Krishnamurthy’s team has discovered that 80-90 per cent of lung cancer in India shows up only at an advanced stage. Why that happens is something doctors are still to figure out, he says. But this could explain why Ananth Kumar died within a few months of his diagnosis.

Cancers account for five per cent of disability-adjusted life-years (DALYs) — a tool to track the disease burden of a country, as it covers both mortality (death) and morbidity (ill-health or disability). DALY is a measure of the overall disease burden, expressed as the number of years lost due to ill-health, disability or early death.

According to Buetow, the cancer burden is a significant economic cost to a country such as India, which is in the midst of an economic makeover. Life years lost to cancers have doubled in the last 15 years, he says. A life year is an additional year of life lost — or gained — because of a disease or health intervention.

However, though more people are dying of cancer in India, the prevalence rate has not changed much over the years, the experts maintain. According to Rajendra Badwe, director of the Tata Memorial Centre (TMC), Mumbai, who also contributed to the Lancet Oncology study, the incidence of cancer in Indian villages has been a constant 40-50 per lakh population per year.

“In mid-sized towns, it is 60-70 per lakh and in metropolitan areas, 90-100 per lakh per year. This hasn’t changed in the last 20 years, unlike China and Russia, where the incidence itself has gone up,” he says.

Too little, too late: Almost 80-90 per cent of lung cancers in India shows up at an advanced stage   –  V SREENIVASA MURTHY

If there is a rise in the prevalence of some forms of cancers, there is also a fall in some others, he points out. Cancers of the breast, ovary and the lungs are rising, but the incidence of cervical cancer has come down “remarkably”, he says. “Stomach cancer prevalence has come down to some extent. There is also a 13-16 per cent reduction in oral cancer, thanks to the ban on gutka (chewable tobacco),” he says.

Among men, the doctors point out, lung cancer is on the rise, while penile and stomach cancers are on the wane (though stomach cancers are still among the most prevalent cases). But the mortality rate of stomach cancer is almost 90 per cent. Mortality is also high in the case of liver and gall bladder cancers, which, the doctors stress, are found more in India than elsewhere.

“Most of the liver and gall bladder cases are distributed along the Ganges and Brahmaputra rivers and they are not seen much anywhere else. We still do not know what causes them. Most likely they are caused by a parasitic infection,” says Badwe. “We hope to crack this mystery very soon, as we have received some leads,” he adds.

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Cancer studies have shown that some forms of the disease are declining because of improved hygienic conditions. Take the case of cervical cancers. In certain rural pockets, the incidence rate of cervical cancer — caused by, among other factors, human papilloma virus (HPV), a sexually transmitted virus, and poor hygiene — continues to be 24 per lakh per year. In Mumbai, on the other hand, it dropped from 22 to 7 per lakh per year, which is comparable to figures in the US. Similarly, penile cancer, which was common earlier, is almost disappearing in pockets. The experts believe this could be because of improvement in personal hygiene.

“In places where municipal corporations are providing running water and where people have the privacy of their bathrooms, there is a tremendous improvement in personal hygiene, and this has helped in the reduction of such cancers,” Badwe says.

Barshi, in Maharashtra, which maintains a cancer registry like several cities in India, bears this out. The penile cancer incidence rate — earlier 28 per lakh a year — has now dropped to 15 per lakh. The incidence rate in rural Barshi is expected to come down to 5 per lakh, which is the case in semi-urban Barshi as well as in Mumbai.

“Running water and electricity have had a great impact in reducing certain types of cancers in the country. With refrigeration becoming quite common in semi-urban as well as many rural households, there has also been a drastic reduction in the stomach cancer incidence,” the Mumbai-based oncologist says.

But while that’s good news, what worries health experts is India’s inability to adapt to advanced ways of treating cancers. Medical scientists have started characterising cancers on the basis of the biomarkers involved. Such additional insights help clinicians dovetail treatments based on these unique signatures.

Take lung cancer. Not very long ago, non-small cell lung cancer was broadly classified as one form of cancer, but now there are 34 different types of non-small cell lung cancers, says Buetow.

Similarly, multiple myeloma — a white blood cell cancer — has a dozen different classifications of the disease, based on the characteristics of the cell’s molecules. Thus, the health experts say, for something like breast cancer, there may not be any one treatment. “We have to worry about all the unique molecular signatures that are producing these different types of cancer,” says Buetow.

On the other hand, this also means more-specific treatment. Doctors in the West are already dealing with disparate forms of cancer within one broad cancer. “In this era of personalised medicine, clinicians are tailoring treatments based on molecular signatures,” he says. “In the current precision medicine paradigm, we’re going to be targeting these molecular characteristics of a tumour and the unique genetic constitution of the population that’s underpinning it,” he says.

For India, this may pose a challenge. For one, he says, India is not well represented in the large-scale international registries, or repositories, that have been generated to map the molecular profiles of these diseases. And where Indians are represented (for instance, in the Thousand Genomes Project — which seeks to catalogue human genetic variations) they are present in small numbers, and mostly comprise those who migrated to western countries from India.

“This is nowhere near capturing the diversity of the genetics of the Indian population,” Buetow says. He adds that there is no guarantee that the studies developed in Europe or the US will be applicable to the Indian population.

Modern medicines, particularly immunotherapy drugs, are often based on the genetic makeup of a patient. There are subtle variations in the genetic composition, depending on the ethnic communities they belong to — Caucasians, blacks, Indian, East Asians and so on. The experts stress that it is important to have the representation of Indians while clinical trials are conducted.

“There are improved treatment modalities available now, such as targeted therapy and immunotherapy. They are still work-in-progress. But not all patients respond to such treatments. For instance, immunotherapy — where the immunity of the patient is primed to suit the cancer treatment — works effectively only in one out of four cases. Besides, the treatment is expensive,” Krishnamurthy adds.

Bad news, clearly, can come hand-in-hand with hope. Meanwhile, doctors recommend a healthy diet, exercise — and early detection.

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