6.7 Personalized Radiation Therapy

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Radiation therapy is a form of cancer treatment that uses high-energy photons, in the form of x-rays or gamma rays, or charged particles, such as electrons or alpha particles, to induce irreversible DNA damage in tumour cells and thereby cause apoptosis. The effects of radiation therapy, unlike chemotherapy, are localized to the tumour region, meaning that patients given radiation treatments do not experience the whole-body side effects common during chemotherapy treatments. Radiation therapy also has an advantage over surgery for some tumours, as it can be precisely targeted to spare essential, healthy tissues surrounding the tumour (1). For example, radiation therapy is useful in treating prostate cancers, where more invasive surgical treatments can lead to incontinence and impotence (1). However, radiation treatments are not suitable for systemic cancers (cancers existing throughout the body) and also cannot be used when a tumour surrounds a vital organ that could be damaged during treatment (1).

 

Other cancer therapies, including immunotherapy and chemotherapy, have only recently entered a time of greater personalization for individual patients, in the form of autologous immunotherapies and pharmacogenomics for chemotherapy. Radiation therapy, on the other hand, has an established history of personalized treatment plans, beginning in the planning stages of treatment and ending with adjustments made as treatments are being delivered.

 

To begin a patient’s course of radiation therapy, an imaging tool is used to construct a three-dimensional model of an individual patient’s tumour. The tumour images may be taken with a magnetic resonance imaging (MRI) instrument, which shows contrast between different tissue types and does not expose the patient to additional radiation, or with a computed tomography (CT) instrument, which uses x-rays to reveal contrast between areas of high and low absorption of x-ray energy and delivers a small radiation dose to the patient (1). With either imaging tool, many two-dimensional slices of a patient’s body are imaged and reconstructed to build a three-dimensional, computerized model of the tumour and its surrounding region (1). The treatment planning team, typically comprised of a medical physicist, dosimetrist, radiation therapist, and radiation oncologist, consults the model and designs a treatment plan that will deliver sufficient radiation to eradicate the full extent of the tumour plus a small region surrounding it, where there may be microscopic metastases (1). The treatment is simulated, using Monte Carlo simulations, further CT scans of the patient, and other computational techniques to insure that it will have the desired effect (1). One of two main methods of radiation dose delivery may be chosen: external beam radiation therapy or brachytherapy. External beam radiation uses a focused beam of photons or charged particles coming from outside the body to deliver radiation to a tissue, while brachytherapy uses radioactive isotopes implanted directly in or near the tumour region to deliver radiation (1). The method selected for an individual patient depends on the location, type, and size of tumour to be treated. External beam radiation treatments often require special molds of some part of the patient’s body to be constructed in order to immobilize the patient during the treatment (1). A uniquely shaped filter may be also placed between the beam and the patient to precisely match the shape of their tumour and insure uniform dose delivery to every part of the tumour (1).

 

Recent advances in radiation therapy include finding better solutions for motion management, where patients move during treatment and thereby change the actual tumour dosage profile compared to the predicted dosage profile (2). A range of techniques are currently used, from teaching patients particular breathing techniques to imaging patient movement concurrently with treatment and adjusting treatment accordingly; both have improved the effectiveness of radiation therapy in certain situations (2). The future in personalized radiation therapy is the use of biomarkers to aid in treatment plan customization (3).  Possible treatment options include different doses and dose fractionation, and combining radiation therapy with surgery or chemotherapy (3). By personalizing the amount of exposure to radiation, therapeutic effects can be maximized while the toxicity minimized (3). Examples of potential biomarkers in various types of cancer will be discussed.

 

In glioma, deletion of both the 1p and 19q chromosomal arms in tumour cells has been correlated with an increased survival time for patients compared to those without the deletion (3). This brings up the possibility of delaying radiation therapy in patients who have the codeletion (3). In the majority of head and neck squamous cell carcinomas (HNSCC), the gene for epithelial growth factor receptor (EGFR) is overexpressed and has been associated with decreased survival (3). Increasing the rate at which the dose is delivered might improve the outcome of these patients (3). In breast cancer, the rate of local recurrence is lowered when breast conserving therapy is followed up by radiation therapy (3). Patients with a high expression of human epidermal growth factor receptor 2 (HER2) or high expression of the protein Ki-67 have an increased risk of relapse and might benefit from radiation therapy (3). Also, the drug trastuzumab has been shown to increase the cancer cells’ sensitivity to radiation without an increase in toxicity, and thus could be used concurrently with radiation therapy (3). In prostate cancer, increasing the dose of radiation has benefited patients with high levels of prostate-specific antigen (PSA) while having no effects on those with low levels of PSA (3). Patients with tumours that express the B-cell lymphoma 2 protein (Bcl-2) have also had better response with increased dose (3).

 

Despite the multitude of potential biomarkers, the clinical use of them has yet to flourish due to the lack of sufficient evidence (3). Further research must be done to not only validate these biomarkers, but also provide simple integration of biomarker testing into the clinical setting (3). Biomarker usage in radiation therapy will allow for decreased exposure to radiation when possible, and identify when a more rigorous regimen can benefit the patient (3).

 

 

References

  1. Washington, C. M. and D. Leaver. Principles and Practice of Radiation Therapy, 2e. 2004. Mosby, St. Louis, MO.
  2. Cole, A. J., G. G. Hanna, S. Jain, and J. M. O’Sullivan. 2014. Motion Management for Radical Radiotherapy in Non-small Cell Lung Cancer. 26(2): 67 – 80.
  3. Bibault, J., Fumagalli, I., Ferte, C., Chargari, C., Soria, J., and Deutsch, E. (2013). Personalized radiation therapy and biomarker-driven treatment strategies: a systematic review. Cancer Metastasis Rev 32, 479-492.