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Background Radiotherapy impacts the local immune response to cancers. Prostate Stereotactic Body Radiotherapy (SBRT) is a highly focused method to deliver radiotherapy often used to treat prostate cancer. This is the first direct comparison of immune cells within prostate cancers before and after SBRT in patients. Methods Prostate cancers before and 2 weeks after SBRT are interrogated by multiplex immune fluorescence targeting various T cells and macrophages markers and analyzed by cell and pixel density, as part of a clinical trial of SBRT neoadjuvant to radical prostatectomy. Results Two weeks after SBRT, CD68, and CD163 macrophages are significantly increased while CD8 T cells are decreased. SBRT markedly alters the immune environment within prostate cancers.

BackgroundHundreds of ongoing clinical trials combine radiation therapy, mostly delivered as stereotactic body radiotherapy (SBRT), with immune checkpoint blockade. However, our understanding of the effect of radiotherapy on the intratumoral immune balance is inadequate, hindering the optimal design of trials that combine radiation therapy with immunotherapy. Our objective was to characterize the intratumoral immune balance of the malignant prostate after SBRT in patients.MethodsSixteen patients with high-risk, non-metastatic prostate cancer at comparable Gleason Grade disease underwent radical prostatectomy with (n = 9) or without (n = 7) neoadjuvant SBRT delivered in three fractions of 8 Gy over 5 days completed 2 weeks before surgery. Freshly resected prostate specimens were processed to obtain single-cell suspensions, and immune-phenotyped for major lymphoid and myeloid cell subsets by staining with two separate 14-antibody panels and multicolor flow cytometry analysis.ResultsMalignant prostates 2 weeks after SBRT had an immune infiltrate dominated by myeloid cells, whereas malignant prostates without preoperative treatment were more lymphoid-biased (myeloid CD45+ cells 48.4 ± 19.7% vs. 25.4 ± 7.0%; adjusted p-value = 0.11; and CD45+ lymphocytes 51.6 ± 19.7% vs. 74.5 ± 7.0%; p = 0.11; CD3+ T cells 35.2 ± 23.8% vs. 60.9 ± 9.7%; p = 0.12; mean ± SD).ConclusionSBRT drives a significant lymphoid to myeloid shift in the prostate-tumor immune infiltrate. This may be of interest when combining SBRT with immunotherapies, particularly in prostate cancer.

For women with a personal history of breast cancer (PHBC), no validated mechanisms exist to calculate future contralateral breast cancer (CBC) risk. The Manchester risk stratification guidelines were developed to evaluate CBC risk in women with a PHBC, primarily for surgical decision making. This tool may be informative for the use of MRI screening, as CBC risk is an assumed consideration for high-risk surveillance. Three hundred twenty-two women with a PHBC were treated with unilateral surgery within our multidisciplinary breast clinic. We calculated lifetime CBC risk using the Manchester tool, which incorporates age at diagnosis, family history, genetic mutation status, estrogen receptor positivity, and endocrine therapy use. Univariate and multivariate logistic regression analyses (UVA/MVA) were performed, evaluating whether CBC risk predicted MRI surveillance. For women with invasive disease undergoing MRI surveillance, 66% had low, 23% above-average, and 11% moderate/high risk for CBC. On MVA, previous mammography-occult breast cancer [odds ratio (OR) 18.95, p

To report a single-institutional experience with the use of magnetic resonance imaging (MRI)-guided radiotherapy for cancers of the head and neck. Between October 2014 and October 2016, 18 patients with newly diagnosed cancers of the head and neck were prospectively enrolled on an institutional registry trial investigating the feasibility and efficacy of external-beam radiotherapy delivered using on-board MRI. All patients had biopsy-proven evidence of malignancy, measurable disease, and the ability to provide consent. None had previously received any treatment. Median dose was 70 Gy (range 54–70 Gy). MRI scans were obtained as part of an image-guided registration protocol for alignment prior to and during each treatment. Concurrent chemotherapy was administered to 14 patients (78%). Patient-reported outcomes were assessed using the University of Washington quality of life instrument. Seventeen of 18 patients completed the planned intensity-modulated radiotherapy (IMRT) treatment of which 15 (83%) had a complete response and 2 (11%) had a partial response based on initial post-therapy positron emission tomography (PET) at 3 months. The 1-year estimates of progression-free survival, overall survival, and local–regional control were 95, 96, and 95%, respectively. There were no treatment-related fatalities. The incidence of grade 3+ acute toxicity was 44%. The proportion of patients rating their health-related quality of life as “very good” or “outstanding” at 6 months and 1 year after completion of radiation therapy was 60 and 70%, respectively. MRI-guided radiotherapy achieves clinical outcomes comparable to contemporary series reporting on IMRT for head and neck cancer.

Breast cancer is the second most common cancer to metastasize in the brain. Little is known about how receptor subtype, including luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) enriched, and triple negative (TN) affect response to radiation and distant intracranial recurrence (ICR) following radiation therapy. We conducted a single-institution retrospective analysis of 38 breast cancer brain metastasis (BCBM) patients who underwent 93 treatment courses of stereotactic radiosurgery, stereotactic radiotherapy, post-operative radiation, or whole brain radiation therapy. Endpoints included overall survival (OS), treatment response (partial/complete response, PR/CR, or progression), ICR after treatment, and time from breast cancer diagnosis to the first BCBM (time to metastasis, TTM). Subset analyses were performed for triple receptor subtype as well as estrogen receptor (ER) positive versus negative, HER2+ versus HER2-, and age ≤ 50 versus >50 years old. Median OS for the population was 22.5 months, with median follow-up after treatment of 20.5 months. TTM was shortest for HER2 enriched, TN, ER−, and younger patients. TN, HER2-, and younger patients showed the poorest OS. ICR was also greatest in TN and HER2− patients. Radiation failure at the treated BCBM was seen most prominently in HER2+ and ER− patients. Receptor subtypes that demonstrated poorer OS tended to demonstrate higher intracranial recurrence. A positive response to radiation was not associated with better OS or lower ICR. Identifying patterns based on receptor subtype may guide clinicians in management and surveillance for BCBM.