MedicalResearch.com Interview with:
Heiko Enderling, Ph.D.
Associate Member & Director for Education and Outreach
Dept. of Integrated Mathematical Oncology
Dept. of Radiation Oncology
H. Lee Moffitt Cancer Center & Research Institute
Tampa, FL 33612
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Although radiation therapy after breast-conserving surgery for early-stage breast cancer has significantly improved patient prognosis, many patients will face a second cancer diagnosis within 20 years of primary treatment. Experimental and clinical studies have shown that local radiation therapy can activate an immune response that can propagate systemically to attack distant untreated metastases. However, current radiotherapy practice has not specifically focused on enhancing immune responses.
We asked the question if pre-operative irradiation, when applied to the bulk of disease, could have potentially higher immune stimulatory effects. To study this, we analyzed historic outcomes of breast cancer patients treated with either adjuvant (radiation after surgery) or neoadjuvant (radiation before surgery) radiotherapies.
Our analysis showed that the risk of developing a second tumor after neoadjuvant compared with adjuvant RT was significantly lower, especially for estrogen receptor-positive women who underwent breast conserving surgery or mastectomy. Historic data revealed an increase in disease-free survival of 12% over 20 years after treatment of the original tumor.
MedicalResearch.com: What should clinicians and patients take away from your report?
Response: Our report highlights the importance of identifying the optimal sequencing of potentially synergistic treatments to improve patient outcomes, both increased tumor control and lowered treatment toxicities. If changing the order of the same two treatments shows different outcomes, this motivates the quest to identify the best treatment protocol. Better understanding of the synergy of radiation and surgery is especially intriguing as both treatments are standard of care with plenty of experimental and historic clinical data available. As exciting as the reported data is, however, it is important to point out that this is a retrospective analysis without conclusive information on potentially confounding factors. It is unclear why some patients received neoadjuvant radiotherapy, and information about additional treatment are absent in the database used for this analysis.
Therefore, to conclusively evaluate the long-term outcomes after adjuvant and neoadjvuant radiation for early stage breast cancer, a controlled prospective clinical trial is required.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Leveraging neoadjuvant radiation with the immune system to recognize the tumor, overcome tumor-mediated immunosuppression, and generate a protective systemic response to eradicate micrometastatic disease is an idea which is worthy of a prospective trial which attempts to improve local control while decreasing the risk of distant metastases.
Furthermore, the biological mechanism of the potential benefit of neoadjuvant radiation remains speculative. Whilst immune activation is a strong possibility, immune correlates will need to be collected in experimental studies to conclusively confirm that radiation-induced mechanisms contribute to outcome. If radiation-induced immunity is confirmed to vaccinate against residual and future disease, future work will have to include the quest for the optimal radiation dose and dose fractionation to harness the synergy with the patient’s immune system. We suspect that a full 5-weeks course of daily radiation may not be required. If the purpose of radiation is not to eradicate a large number of cancer cells but to activate an immune response to assist in tumor cell kill, then short courses of immune-priming radiation may be an attractive clinical alternative.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Jan Poleszczuk, Kimberly Luddy, Lu Chen, Jae K. Lee, Louis B. Harrison, Brian J. Czerniecki, Hatem Soliman, Heiko Enderling. Neoadjuvant radiotherapy of early-stage breast cancer and long-term disease-free survival. Breast Cancer Research, 2017; 19 (1) DOI: 10.1186/s13058-017-0870-1
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