Q: You are a radiation oncologist with a particular interest in cancer of the prostate. How does the molecular study of prostate, as well as other cancers, including Next Generation Sequencing (NGS), help inform Precision Radiation Oncology?
A: Radiation oncology is a specialty where the accuracy and precision of treatment delivery is vital to the safety and outcomes of our patients. Many specialized techniques are utilized to enhance this precision, including intensity modulated radiation therapy, image-guided radiation therapy, and volumetric arc therapy. Emerging modalities such as proton and carbon therapy take advantage of the physics of heavy ions to potentially minimize normal tissue toxicity. With these methods, we are in essence, performing precision oncology, tailoring radiotherapy to each individual patient. However, precision oncology is much more than that, as novel technologies have expanded our understanding of the drivers of cancer that may be targetable or dictate response to treatment. Currently, emerging evidence has shown the benefits of biomarker-directed systemic treatments, but what about genomic markers to guide radiation therapy? Although the preclinical and retrospective data supports the notion of this possibility, results from prospective studies are not yet available.
Perhaps the most promising and straightforward example of biomarker-directed radiation therapy is in head and neck cancer (HNC). The human papilloma virus (HPV) has been identified as a cause of head and neck cancer. Compared to non-HPV induced HNCs, HPV associated HNCs have better outcomes due to their increased radiation sensitivity. Efforts to de-escalate radiation therapy in this population have yielded encouraging results, and prospective randomized studies are ongoing. However, more work is needed, as not all HPV-associated HNCs have good outcomes. Identifying this subset of patients using genomics and other information is crucial to optimize precision radiation therapy for these patients.
Along these lines, the prediction of tumor sensitivity to radiation would be a powerful tool for precision radiation oncology. The Radiation Sensitivity Index (RSI) is one such test. This molecular signature has been validated for colorectal, head and neck, esophageal, and breast cancers, and patients with tumors that have a radiosensitive signature had improved outcomes. Prospective trials incorporating the RSI to help inform treatment decisions are needed to validate the clinical utility of this signature.
In prostate cancer, a number of genomic signatures have also been reported that can identify more aggressive disease that is at high risk for metastasis or recurrence. Additionally, investigators recently reported the subtyping of prostate cancers using a genomic test approved in breast cancer that could potentially classify prostate cancers that respond well to androgen-deprivation therapy. Similar to the RSI, prospective validation of these findings is needed.
In summary, recent advances in tumor genomics have created potential opportunities to guide and optimize radiation treatment for cancer patients beyond traditional technical improvements. Results are promising, and prospective validation studies are currently ongoing. Given these exciting results, precision radiation oncology will be a part of the standard treatment algorithm in the near future.
Eddy Yang’s contact info is included in the author affiliations at the top of this page.
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