Expanding treatment options for breast cancer. Enhancing immunotherapy. Addressing disparities in access to cutting-edge treatment.
These are some of the highlights from ASTRO, the largest scientific and educational forum for radiation oncology. Members of OHSU’s Department of Radiation Medicine made 11 research presentations and contributed to many more at the annual meeting of the American Society for Radiation Oncology in San Diego.
Enhancing the effect of radiotherapy in a difficult-to-treat form of breast cancer
Allison DuRoss presented early findings on a strategy to treat triple-negative, non-BRCA associated breast cancers, for which there is a lack of treatment options when tumors become chemo-resistant. DuRoss described in vitro studies of the co-delivery of two anti-tumor drugs, a PI3K inhibitor and a PARP inhibitor, using a nontoxic polymer alginate that degrades in response to ionizing radiation. “Our findings indicate that co-delivery of these drugs can enhance the efficacy of ionizing radiation in a difficult to treat subset of breast cancer,” she reported.
Intraoperative radiotherapy could expand options for treating breast cancer
Intraoperative radiotherapy – irradiating the tumor bed during surgery – appears to be a safe and effective alternative to whole breast radiotherapy with relatively low toxicity and excellent local control, Shushan Rana, M.D., reported. And for patients with locally recurrent breast cancer previously treated with whole-breast radiotherapy, it offers an alternative to mastectomy. Rana presented data from a retrospective review of 127 breast cancer patients receiving intraoperative radiotherapy from 2009-2016. Ipsilateral breast tumor recurrence was detected in four patients (3%) with median time to recurrence of 25 months. Two patients had recurrences within the same quadrant, and there were no in-field recurrences. Additional follow-up and analysis remains ongoing to understand the long-term efficacy of IORT.
Enhancing immunotherapy with radiation treatment
Adding radiotherapy to immunotherapy could provide a way to reverse tumor-associated T cell dysfunction, according to results presented by Joshua Walker, M.D., Ph.D. Tumors alter their surroundings and infiltrating immune cells in ways that result in two kinds of CD8 T cell dysfunction: anergy, a lack of proliferative response to stimulation, and exhaustion, the inability of T cells to kill or produce effector cytokines in response to stimulation. Walker’s group used a mouse model to show that radiotherapy given in combination with αOX40 and αCTLA-4 antibodies reverses T cell anergy and exhaustion. Walker said the data provide rationale for early-phase clinical trials.
Synergistic effect of stereotactic radiosurgery and immunotherapy for metastatic melanoma
The anti-CTLA-4 and anti-programmed cell death-1 (PD-1) antibody therapies have significantly improved survival of patients with metastatic melanoma. Blair Murphy, M.D., presented data on 26 patients who received immunotherapy for melanoma combined with stereotactic radiosurgery for brain metastases (13 patients received ipilimumab, 2 received pembrolizumab, and the rest received both). Concurrently delivered stereotactic radiosurgery was safe and well tolerated. And the data showed increased regional control, suggesting radiotherapy may augment the regional effects of immunotherapy.
Disparities in access to Stereotactic Body Radiation Therapy
Stereotactic body radiation therapy has been gaining favor over conventional external beam radiation therapy as a treatment for spinal metastases. But there are wide disparities in access based on race and insurance status, according to data presented by Woody McClelland, M.D. African-Americans were 20 percent less likely to receive the newer therapy, and people covered by Medicaid (the government program for low-income and disabled citizens) were 30 percent less likely. McClelland and colleagues analyzed National Cancer Data Base records from 2004-2013 and used a multivariable logistic regression model adjusted for patient age, sex, income, medical comorbidities, insurance status, facility, and region of the United States. Stereotactic body radiation therapy for spine metastases more than quadrupled during the ten year span, the researchers found. The racial and insurance status disparities are concerning and deserve further investigation, McClelland said.
Christina Binder, M.D., Ph.D.: Radiation Retinopathy Following I-125 Plaque Brachytherapy for Uveal Melanoma as Evaluated by OCT Angiography
Aaron Grossberg, M.D., Ph.D.: The Roles of Neuroinflammation and Orexin Signaling in Brain Radiation-induced Fatigue
OHSU faculty and staff contributed contributed to several more research presentations now on view at the Department of Radiation Medicine’s web page.