How far have we come in providing personalised radiation treatment for cancer patients?

The Hindu

4 days ago

Radiotherapy, also known as radiation oncology or radiation therapy, is an important arm of cancer therapy. It involves the use of high-energy ionizing radiation to predominantly treat malignancies, as well as certain benign conditions.
In India, due to lack of awareness and inadequate cancer screening initiatives, a majority of cancer patients seek medical help when the disease is locally advanced, and hence are candidates requiring multi-modality treatment including various combinations of surgery, radiotherapy, chemotherapy, biological therapy and immunotherapy. Nearly 70% of cancer patients need radiotherapy as a part of their cancer treatment protocol, where its role may be a primary curative treatment, additional or adjunct treatment or palliative therapy to relieve symptoms in advanced disease stages.
Also Read: ICMR study finds only 28.5% of cancer patients receive radiotherapy in India
Understanding radiotherapy
There are 2 primary treatment modalities in radiotherapy: teletherapy or external beam radiotherapy and brachytherapy. In the former, the patient is placed at a distance from the radiation-generating equipment (generating high-energy x rays or gamma radiation) and by virtue of the beam divergence, a homogenous dose is delivered to the tumour tissue. In brachytherapy, radiation-emitting radioactive sources are directly placed in contact with the tumour tissue and subsequently removed after a specific period of time, thereby delivering a high dose to the tumour directly.
The last two decades have seen significant strides in the field of radiation oncology. Technological developments in hardware and software industries have led to development of equipment enabling high precision radiation delivery with sub-millimetre accuracy, resulting in better tumour control and reduction in treatment-related side effects arising out of damage to normal tissues adjacent to the tumour. Until a few years ago, access to this high precision radiotherapy treatment was restricted to large metropolitan cities. With the active involvement of government health agencies (both at the Centre and State levels) along with public private partnerships, there is currently a focussed attempt to reduce this disparity and improve the availability of radiotherapy treatment at most district-level hospitals.
Contemporary radiotherapy treatment
Contemporary high precision radiotherapy treatment techniques such as Intensity modulated radiotherapy (IMRT), Image Guided Radiotherapy (IGRT), Volumated Arc therapy (VMAT/Rapid Arc), Stereotactic Radiosurgery and Stereotactic Radiotherapy (SRS and SRT), have enabled treatment of cancer tissues with higher radiation doses and with preferential sparing of normal tissue. These techniques have also enabled the feasibility of organ preservation in daily practice.
In spite of these benefits, all cancer patients undergoing radiotherapy do not get cured of cancer. An important limitation of present-day cancer treatment, including radiation therapy, is that the response of a tumour to treatment varies from person to person ranging from complete response to partial response and in some cases, disease progression despite treatment. This is due to differences in the genetic and protein composition of the tumours which varies from patient to patient and which can influence treatment outcomes. Another important limitation is treatment-related side effects, which vary from patient to patient and can interfere with treatment compliance necessitating lifestyle modifications during, and post treatment.
In simple terms 'one size does not fit all'. Although the prescribed radiotherapy treatment might be the global established standard of care for a particular disease condition and stage, individual variations in treatment response and tolerance are the norm, which cannot currently be predicted based on any assessment tool. While available radiotherapy guidelines are mainly based on the average response of disease population to treatment, this approach fails to account for individual tumour variations with respect to their molecular and genetic signature as well as patient heterogeneity with respect to their demography, genetic makeup and pattern of lifestyle. There is an unmet need to develop markers which can predict or identify non-responders to radiation and those patients who are likely to develop disease progression while on treatment. There is also an urgent need to identify patients who are likely to suffer significant toxicity and discontinue treatment. In this regard, there exists an unmet need to develop drugs which can reduce radiation- related toxicity without interfering with the radiation's anti-tumour capabilities.
Can newer tech such as proton therapy solve the problem?
The introduction of proton therapy in India along with its dosimetric capability of delivering radiation doses only at a particular range of depth within the patient's body, has significantly reduced early and late complications of radiotherapy with the latter being an important advantage in treatment of paediatric patients. But proton therapy is not a personalised radiotherapy solution and patients can still have residual disease or recurrent disease after proton therapy, based on the radiosensitivity of the tumour. Also, the limited availability of proton therapy presently in India and the high cost of treatment are other inherent issues that render it as a non-viable treatment solution for a majority of Indian patients who cannot afford the cost.
Thus there is an inherent need for developing personalised radiotherapy treatment practises which can allow a physician to predict the possible treatment response and risk of recurrence of a particular disease based on its molecular and genetic composition. Such a personalised radiotherapy protocol would have the following advantages in that it can:
Provide optimal radiation treatment tailored to each patient tumour's unique biological and clinical characteristics
Predict tumour response to radiotherapy prior to initiation of treatment thereby avoiding treatment- related toxicity in potential non-responders
Then the pertinent question which arises is whether such a personalised radiotherapy protocol or assessment tool is in existence or whether it can be developed? The answer is a resounding yes.
The promise of research into genetics and AI
In recent years, probing research in the field of molecular oncology, genetics and artificial intelligence (AI) are bringing the concept of personalized radiotherapy closer to actual realization. At one end, data-driven AI and deep learning models are being developed to identify predictors of radiation sensitivity. This information is being gathered by accessing huge quantities of data regarding tumour behaviour and their associated pathological and molecular characteristics collected over the years, and corelating them with the outcomes of radiotherapy treatment already delivered. The following areas of medical research are contributing in a big way to the development of personalised radiotherapy treatment in the near future. These include –
Digital pathology – This involves acquisition and interpretation of pathology information in digital format and environment. This, in turn, improves rapid referral of cases between hospitals and doctors for expert opinions or second opinions and facilitates incorporation of digital training resources into pathology reporting, paving the way for integration of AI in pathological reporting.
Radiomics in prognostication – This involves analysis of certain patterns and disease characteristics from radiological scans, and the use of this information to predict patient outcomes and treatment responses to cancer. Radiomics aims to provide more precise information to guide treatment decisions.
Genomics and proteomics-based treatment decisions – The development of bioinformatics and its integration with tumour-related genetics and molecular information is being used to develop genomic and proteomic-based tumour biology panels, which can help in early diagnosis as well as predict response to treatment. This can lead to more personalised and effective cancer treatment strategies.
AI-based adaptive radiotherapy – A revolutionary concept in radiotherapy, this involves the use of AI-based tools to analyse tumour-related changes during a course of radiotherapy. In adaptive RT, before a patient receives his scheduled daily radiotherapy treatment, he is subjected to a CT scan or MR images which are acquired on the radiotherapy machine, prior to treatment. These images acquired are interpreted by AI-based programmes, which then calculate changes in tumour geometry based on daily radiation response. The radiation plan is then altered real time, and adjusted on a daily basis to effectively target the tumour and reduce damage to healthy tissues. This approach enhances the therapeutic ratio of the treatment, potentially improving cure rates while minimising side effects.
One other area of research which is going to influence personalised radiotherapy services positively, is work on nanoparticle technology, which can enable a higher concentration of drugs delivered directly inside the tumour or its related microenvironment thereby increasing radiotherapy associated tumour damage and minimising normal tissue damage. AI-driven assessment of oral and gastrointestinal microbiome changes in response to radiotherapy are also being assessed as a prognostic tool to predict radiation responses. Another important development is research aimed at integrating daily PET CT scans into adaptive radiotherapy (biological adaptive RT), which adds functional information of the treatment along with anatomical data to refine adaptive radiotherapy plans.
Although a lot of research efforts are currently underway in multi-directional fields with a single-minded focus on enabling personalised cancer treatment strategies, a lot of validation needs to be further done in this regard to enable these modalities to be incorporated into daily treatment protocols. However, the good news is that we have indeed covered a lot of ground in realising this dream and the day is not far when the concept of personalised radiotherapy will be translated from the laboratory bench to bedside practise.
(Dr. K. Satish Srinivas is professor and head of the department of radiation oncology, SRIHER, Chennai. [e-mail])