Personalised Cancer Treatment: From Chemotherapy to NGS

Personalised cancer treatment means choosing therapy by how a specific cancer behaves in an individual patient, not by the diagnosis alone. Tests on the biopsy, from immunohistochemistry to next-generation sequencing (NGS), identify targets for targeted therapy and show who is likely to benefit from immunotherapy. At Fortis Hospital, Shalimar Bagh, New Delhi, a comprehensive NGS report is usually available by about the seventh day.

Dr. Mohit Agarwal, Principal Director & Head Medical Oncology, Fortis Hospital, Shalimar Bagh, New Delhi, India, makes a comparison that captures how oncology has changed. If two patients with fever walk into his clinic, he will probably give both the same treatment: an antibiotic and a paracetamol. If three women with breast cancer walk in on the same day, of the same age, height, weight and stage, he may give each of them a different treatment, and their outcomes may differ widely. One may be cured, one may live for only a year or two, and one may live for ten years. The oncologist, in his phrase, is not treating the cancer. He is treating how that specific cancer behaves in that individual's body.

This article follows that idea through the medical treatment of cancer: chemotherapy and the myths around it, the standards that make chemotherapy safe, targeted therapy, immunotherapy, the genomic testing that decides between them, and what the newer drugs now cost. Biopsy, staging and surgery are covered in Does a Biopsy Spread Cancer? Staging and Surgery Myths, and the wider picture of risk, screening and prevention in the complete guide to cancer myths, facts and advances.

Chemotherapy myths: is it painful, and does hair grow back?

Chemotherapy is painless, it need not stop a patient working, and the hair loss it causes is temporary. Chemotherapy carries a reputation as poison, and Dr. Agarwal addresses the myths that follow from it one by one.

"It is extremely painful." It is painless. Giving chemotherapy is much like giving intravenous fluids. A patient who receives it may barely notice that it has been given.

"I will be under house arrest." Not at all. Dr. Agarwal's patients take their treatment, have a normal night's sleep, and are back at work the next day.

"It will cause lasting damage." Chemotherapy can have long-term side effects. Preventing them is the expert's job: the oncologist stops treatment at the right point, as the guidelines direct, so that cumulative toxicity does not develop.

"I will lose my hair for good." Hair loss troubles most patients, and women in particular. It is temporary: once chemotherapy stops, the hair grows back. At Fortis, patients can also use scalp cooling during treatment. Cooling the scalp narrows its blood vessels, so less of the drug reaches the hair follicles. In randomised trials, about half of women treated with scalp cooling kept enough hair not to need a wig, with results depending on the drug regimen.

Why does chemotherapy cause side effects?

Chemotherapy acts on cells that multiply quickly. Cancer cells divide fast, which is why chemotherapy kills them, but so do the cells of the hair follicles, the lining of the mouth and the lining of the gut. That is the origin of the familiar side effects: hair loss, mouth ulcers and diarrhoea. Traditional chemotherapy and radiotherapy affect healthy cells as well as cancerous ones. The newer treatments described below were designed to break that link.

Chemotherapy safety: why the way it is given matters

Chemotherapy is not a simple pill, and its safety depends on a chain of technical standards in how it is dosed, prepared and delivered. Doctors in Africa frequently face a pointed question from patients whose local team has recommended chemotherapy: what is the difference between chemotherapy given at home and chemotherapy given at an advanced centre? Dr. Agarwal's answer lies in those standards, each of which affects safety.

• Individual dosing. A paracetamol tablet of 500 mg works the same way for most adults. Chemotherapy does not. Each dose is calculated from the patient's height and weight, which together give the body surface area, and adjusted for the patient's overall condition.
• Controlled mixing. Chemotherapy drugs cannot be mixed and hung like an antibiotic. They are prepared in dedicated mixing units where contamination and dosing accuracy are tightly controlled.
• Exact infusion times. Infusion times are part of the protocol. In Dr. Agarwal's example, a drug written to run over 30 minutes that instead runs over an hour causes many more side effects. Adhering to the exact protocol keeps toxicity down.
• Continuous monitoring. Patients are monitored throughout the infusion so that a reaction is caught as it begins and the infusion stopped immediately, rather than the patient developing symptoms and needing intensive care. Such reactions are uncommon overall, but with some drugs, such as taxanes, platinum agents and monoclonal antibodies, they affect several per cent of patients, and they are serious when they occur.
• Temperature control. Targeted therapies and immunotherapies must be kept within specified temperatures during mixing and administration.
• Protection from light. Some drugs are photosensitive. They are covered with dedicated equipment so that the drug reaches the patient without exposure to sunlight.

None of these steps is visible to a patient, which is exactly why they are easy to overlook. Together they determine how much of the intended benefit a patient receives, and at what cost in toxicity. Indicative prices are on the chemotherapy cost page.

How targeted therapy works: the sniper, not the shotgun

Targeted therapy attacks a specific protein or receptor on the surface of the cancer cell, instead of every fast-dividing cell. If a patient's tumour carries such a receptor, and a drug exists that binds to it, the drug attaches to the cancer cells and leaves normal cells alone.

Dr. Agarwal's example is trastuzumab, which targets the HER2 receptor (human epidermal growth factor receptor 2) found on a subset of breast cancers. When the receptor is present, trastuzumab binds to the cancer cells specifically, and those cells are killed. He likens it to a sniper's rifle: identify the target, and hit only the target. The advantage is that side effects are fewer, because normal cells are largely spared, although trastuzumab can weaken the heart muscle in a minority of patients, so heart function is monitored during treatment.

The precondition is that the target must be present. Not every patient's cancer carries one, though many do, and for those patients specific drugs exist. That is why finding the target comes before choosing the drug.

How immunotherapy works: removing the curtain

Immunotherapy works by removing the "curtain" that cancer cells draw around themselves to hide from the immune system, so that the patient's own immune cells can find and kill them. Everyone, Dr. Agarwal explains, has abnormal cells in the body that could become cancer. Most people never develop cancer because their immune cells recognise and kill those cells. In a patient with cancer, the tumour cells have hidden themselves behind that curtain. Immunotherapy drugs remove it. Once it is gone, the patient's own immune system identifies the cancer cells and kills them.

The "curtain" corresponds to immune checkpoints, such as the PD-1 and PD-L1 proteins, which tumours exploit to switch off the immune cells that would otherwise attack them. Checkpoint-inhibitor drugs block that signal.

Who should receive immunotherapy?

Immunotherapy is not a blanket treatment. Dr. Agarwal stresses that specific criteria govern who should receive it, and that it is given according to its approved indications and standard guidelines. It is now indicated for a large share of advanced cancers. Given outside those criteria, it will not help the patient and becomes, in his words, a financial waste. Indicative prices are on the immunotherapy cost page.

Which tests guide personalised cancer treatment?

Three layers of testing on the biopsy specimen guide personalised cancer treatment, because both targeted therapy and immunotherapy depend on the biology of the individual tumour. The specimen therefore does far more work than confirming the diagnosis. Dr. Agarwal describes the three layers:

1. Immunohistochemistry. The specimen is cut into sections and set in blocks, and special stains are applied. The staining can reveal targets on the surface of the cells.
2. Mutation testing. The tumour's genes are examined for mutations that point to further targets for which drugs are available.
3. PD-L1 testing. This indicates whether the patient is likely to benefit from immunotherapy.

Combined, these results show the best path for the individual patient.

What is next-generation sequencing (NGS)?

Next-generation sequencing, or NGS, reads the DNA of the cancer cells in a biopsy to find where it has gone wrong, and so points to drugs that can act on those changes. It is the most comprehensive layer of testing, and Dr. Agarwal's centre runs it as a dedicated pipeline. Before treatment begins, he already knows the type of cancer, its stage and the probable treatment. NGS adds a further question: why did this cancer develop in this person?

The process extracts DNA from the cancer cells in the biopsy and sequences it, identifying where the DNA or RNA has gone wrong. The mutations found point to the probable reason the cancer arose. Dr. Agarwal describes these as switches that have been turned on. If a drug exists to counteract a particular switch, giving it can switch the process off. Research aims to find a drug for every change NGS can detect; at present, drugs exist for a limited number of specific mutations. When a patient's tumour carries one of them, that drug is given and the patient benefits.

The lung cancer patient described in the complete guide, alive more than a decade after a diagnosis of stage four disease on a sequence of daily oral targeted pills, illustrates what this approach can achieve.

How long does NGS testing take?

At Fortis, the NGS turnaround is about five to six working days, so a comprehensive report is usually available by about the seventh day, including a weekend. That a sequencing step would delay treatment was a concern raised in the masterclass Live Discussion. NGS was once expensive and slow, with results taking around 30 days, and, Dr. Agarwal says, in most institutes it still does. In India it is now much cheaper. With an advanced sequencing platform, a tailor-made treatment can begin within a week or so of the biopsy.

Cost of cancer treatment and newer drugs in India

The cost of cancer treatment varies enormously with the type and stage of cancer, from a few thousand rupees to a million rupees, according to Dr. Agarwal. Doctors counselling patients are often asked about cost long before a formal treatment plan exists.

The most significant change concerns the newer drugs. Targeted therapies and immunotherapies were very expensive when they first arrived. Generic versions are now available at far more reasonable prices. Dr. Agarwal gave an example: an immunotherapy drug that once cost about US$5,000 for a single dose now costs about US$1,000 per dose. Where possible, his team also arranges patient assistance programmes offered by the drug manufacturers for approved indications, to make treatment financially viable for the patient.

The fall in price matters most when it is paired with the discipline Dr. Agarwal describes throughout. A cheaper drug given to a patient whose tumour lacks the target, or who falls outside the criteria for immunotherapy, is still a wasted drug. The value of modern oncology treatment depends on matching the right drug to the right patient, and that match begins with the biopsy and the tests performed on it.