Medical Oncology

Medical oncologists are cancer specialists who are experts in treating cancer patients with systemic treatments like chemotherapy, endocrine therapy, targeted therapy and immunotherapy. Cancer prevention, diagnosis and supportive care for cancer patients are also delivered by them.

Clinical oncologists are cancer specialists who are usually trained in the United Kingdom in radiation oncology but also can provide systemic treatments.

Medical oncologists are doctors who have undergone specialized training focused on systemic therapy like chemotherapy, targeted therapy, immunotherapy and clinical trials. They can devote themselves to more intensive and advanced forms of systemic therapy.

No, oncologists are trained to clinically examine and evaluate all aspects of cancer from prevention to diagnosis, treatment, supportive care and end of life care. They are also able to discuss the risks of cancer, cancer prevention measures and in case if the tests are positive, they help in guiding about the best treatment possible.

Cancer is a very heterogeneous disease which means it represents hundreds of different varieties of cancer types. It has been seen that some treatments work very well for some cancers but do not have any effect on others. That is because each cancer cell has unique genes and proteins which cause the growth or prevents the growth of cancer cells. In most cancers, if we can ‘target’ these genes or proteins, then the growth of cancer can be stopped and cancer cells die. This is called targeted therapy. The advantages are that the side effects that are usually caused by chemotherapy are not caused by targeted therapy as the normal cells are not affected much.

This is currently being used in a majority of cancers, some of the examples are given below:

• Breast cancer: Anti Her2
  therapy (Trastuzumab, TDM-1, Lapatinib)
• Lung cancer: Anti EGFR therapy: Erlotinib, Osimertinib, Gefitinib Anti-ALK therapy: Crizotinib
• Kidney cancer: Anti-VEGF:Sunitinib
• c-kit positive GIST:Imatinib
• RAS, BRAF wild type Colon cancer:
• Cetuximab
• CD20 positive lymphoma:Rituximab

Targeted therapy has lesser side effects than conventional chemotherapy as they are designed to target the cancer cells rather than normal cells.

The success rate or response rate depends on the drug, stage, site and type of cancer. In most cancers in whom there is a definite target as identified by the diagnostic tests, response rates can be as high as 60-70%.

Targeted therapy and immunotherapy may be used together or separately and each has a different role to play in treating cancer. We have certain markers like microsatellite instability (MSI), tumor mutational burden (TMB) which can predict response to immunotherapy.

Many cancers are “hormone or endocrine driven” which means that the presence of certain hormones in the body increases the growth of cancer. For example, in males, carcinoma prostate is driven by testosterone secreted by testes. In females, breast cancer cell growth may be increased by high levels of oestrogen in the body. In such patients, we can use drugs to reduce the level of hormones or block the actions of hormones on the cancer cells, to control or increase cure rates of cancer. These drugs are called hormonal therapy.

They are useful in prostate cancer, breast cancer, in ovarian, uterine cancers and neuroendocrine cancers.

It depends on the type of hormone action blocked by hormone therapy. The most common side effects are bone and joint pains, fatigue, changes in the level of lipids, osteoporosis, menopausal symptoms like hot flushes, night sweats, vaginal dryness in women.

Immunotherapy is the use of medicines that can potentiate or increase the immune response of the human body towards the cancer cells and result in the death of cancer cells. They are of different types like immune checkpoint inhibitors, cancer vaccines etc.

Many cancers can be currently treated with immunotherapy but there are some tests to be done that can predict response to the immunotherapy like the PDL1 test, MSI and TMB. The most effective data has been seen in cancers. Immunotherapy has been approved irrespective of the cancer type if patients have high TMB and MSI (this is called cancer agnostic approval)

Chemotherapy and immunotherapy have their own important place in the management of cancer. They can be used alone or together to treat some cancers. Not all cancers will benefit from immunotherapy or chemotherapy. The treatment has to be individualized based on the type of cancer and the biomarkers expressed by the cancer cells.

But in some cancers like lung cancers, it has been seen that when immunotherapy was used in selected patients and compared with chemotherapy, immunotherapy fared better than chemotherapy in terms of better responses and side effects profile.

All of us are unique and carry different genetic information (DNA) and so does the cancer that affects individuals. Each cancer is driven by certain factors that are unique to that cancer. Understanding more about the biological basis of cancer and genomic drivers has helped us in individualizing therapy and improving outcomes for patients with advanced cancers and de-escalating treatment for patients with early cancers. The previous approach of “one size fits all” is no longer relevant.

Personalized medicine is the tailoring of medical treatment to the individual characteristics of each patient. This approach is developed on scientific breakthroughs in understanding how a person’s unique molecular and genetic profile makes them susceptible to certain cancers. It separates people into different groups—with medical decisions, practices,interventions and/or products being tailored to the individual patient based on their predicted response or risk of disease.

This is useful because knowledge of a patient’s genetic profile can help doctors select the right medication or treatment and administer it using the proper dose or regimen.

Examples of personalized medicine include using targeted therapies to treat specific types of cancer cells, such as HER2-positive breast cancer cells, or using circulating tumour DNA to detect genomic drivers to help treat patients (liquid biopsy).

Predictive medicine is a branch of medicine that aims to identify patients at risk of developing a disease, thereby enabling either prevention or early treatment of that disease. Either single or more commonly multiple analyses are used to identify markers of future disposition to disease.

Predicting the probability of disease and instituting preventive measures to prevent the disease altogether or significantly decrease its impact, is beneficial to the patient. There are different prediction methodologies, including cytomics, proteomics, and genomics. But the most fundamental way to predict future disease is based on genetics.

Proteomics and cytomics allow for early detection, but they detect biological markers that exist because disease had already started. Comprehensive genetic testing, on the other hand, allows for the estimation of disease risk, years to decades Gene therapy replaces defective genes with healthy ones, adding new genes to help the body fight or treat disease.

Predictive medicine also applies to certain markers in cancer cells which can predict response to treatment, for eg, patients with oestrogen receptor-positive breast cancer are likely to respond to endocrine therapy.

Precision medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person. This approach allows doctors and researchers to predict more accurately which treatment and prevention strategies for a particular disease will work in which groups of people. It is in contrast to a one-size-fits-all approach, in which disease treatment and prevention strategies are developed for the average person,with less consideration for the differences between individuals.

Personalized medicine refers to an approach to patients that considers their genetic make-up but with attention to their preferences, beliefs, attitudes, knowledge and social context, whereas precision medicine describes a model for health care delivery that relies heavily on data, analytics, and information.

Personalized medicine is an older term used to define the approach currently called precision medicine and in many instances, is used interchangeably with precision medicine.

Precision medicine involves the identification of specific molecules or genetic changes in specific cancers which can then be used for prevention, diagnosis, treatment monitoring etc. This involves higher technologies for genetic and molecular diagnostics and also involves bioinformatics for data analysis and interpretation.

Example is the BRCA gene in breast cancer. The presence of the BRCA gene can be done before the individual develops any cancer. Having BRCA mutation increases the risk of women developing breast and ovarian cancers by 50-60% and hence, if detected, preventive treatments can be undertaken (surgery, medicines, follow-up protocols). Also, if a patient has BRCA mutation-positive cancer like ovarian, breast or pancreas cancer, newer drugs like olaparib can be used for treatment.

There are various tests that are needed as part of precision medicine and they can be costly depending upon the tests. Currently, there are various platforms that offer the tests at lower costs. The precision medicine or drugs also depends on the individual drugs many of which have generic versions which have made the drugs affordable to the vast majority of patients.

Precision medicine has lesser side effects than conventional chemotherapy as they are designed to target the cancer cells rather than normal cells.

The main indications of precision medicine are both in curative and advanced cancer settings. They have revolutionized the treatment of many cancers most commonly breast, skin and lung cancer. They have increased patient survival and reduced the treatment-related side effects caused to the patient due to conventional chemotherapy.

Gene therapy is part of precision medicine and is an experimental technique that uses genes to treat or prevent disease. In the future, this technique may allow doctors to treat a disorder by inserting a gene into a patient’s cells instead of using drugs or surgery. It focuses on the utilization of the therapeutic delivery of nucleic acids into a patient’s cells as a drug to treat disease

Gene therapy replaces defective genes with healthy ones, adding new genes to help the body fight or treat disease.

In cancers, new genes are inserted into a cancerous cell or the surrounding tissue to cause cell death or slow the growth of cancer. This treatment technique is very flexible, and a wide range of genes and vectors are being used in clinical trials.

Genetic testing is a type of medical test that identifies changes in chromosomes, genes, or proteins. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person’s chance of developing or passing on a genetic disorder. More than 1,000 genetic tests are currently in use, and more are being developed. Predictive genetic testing is the type of testing used to look for inherited gene mutations that might put a person at higher risk of getting certain kinds of cancer for example BRCA1 and BRCA2, PALB2, p53 etc

Genetic testing is done for different reasons:

Diagnostic testing, Pre-symptomatic and predictive testing, Carrier testing, Pharmacogenetics, Prenatal testing, Newborn screening, Preimplantation genetics diagnosis (PGD) testing, germline (genetic, what one is born with) and somatic (develops and changes in cancer cells over time) testing.

Molecular genetic tests, chromosomal genetic tests and biochemical genetic tests are different types of genetic tests used in clinical practice.

In general, people at risk for an inherited cancer gene have one or more first- or second-degree family members who were diagnosed with:

• Cancer before age 50
• The same type of cancer
• Two or more different cancers
• Rare cancer, such as male breast cancer or sarcoma

Genetic counseling is an important component of germline genetic testing and should be considered before doing the tests.

Molecular diagnostics is a part of laboratory medicine, which relies on the detection of individual biologic molecules.
Indications:

• Identification of patients with hereditary cancers and is now a routine practice
• There are several tests which help to select the most effective treatment based on molecular characteristics of tumour tissues or some other biologic parameters of cancer.

The main domains where Molecular diagnostics are useful are

• Hereditary cancer syndromes like Li Fraumeni syndrome
• Hereditary NonPolyposis Colorectal cancer (HNPCC) etc
• Molecular markers for the choice of cancer treatment
• Liquid biopsy(circulating tumour DNA)
• The diagnosis of cancers of the unknown primary site
• Management of large amounts of biomedical data