Background: Patients with HPVþ oropharyngeal squamous cell carcinoma were assigned to dose and volume de-escalated radiotherapy (RT) or chemoradiotherapy (CRT) based on response to induction chemotherapy in an effort to limit treatmentrelated toxicity while preserving efficacy. Patients and methods: Patients were classified as low-risk (T3, N2B, 10 pack-year history) or high-risk (T4 or N2C or >10 PYH). After three cycles of carboplatin/nab-paclitaxel, response was assessed using Response Evaluation Criteria in Solid Tumors 1.1. Low-risk patients with 50% response received 50 Gray (Gy) RT (RT50) while low-risk patients with 30%-50% response or high-risk patients with 50% response received 45 Gy CRT (CRT45). Patients with lesser response received standardof-care 75 Gy CRT (CRT75). RT/CRT was limited to the first echelon of uninvolved nodes. The primary end point was 2-year progression-free survival compared with a historic control of 85%. Secondary end points included overall survival and toxicity. Results: Sixty-two patients (28 low risk/34 high risk) were enrolled. Of low-risk patients, 71% received RT50 while 21% received CRT45. Of high-risk patients, 71% received CRT45. With a median follow-up of 29 months, 2-year PFS and OS were 95% and 100% for low-risk patients and 94% and 97% for high-risk patients, respectively. The overall 2-year PFS was 94.5% and within the 11% noninferiority margin for the historic control. Grade 3þ mucositis occurred in 30%, 63%, and 91% of the RT50, CRT45, and CRT75 groups, respectively (P ¼ 0.004). Rates of any PEG-tube use were 0%, 31%, and 82% for RT50, CRT45, and CRT75 groups, respectively (P < 0.0001). Conclusions: Induction chemotherapy with response and risk-stratified dose and volume de-escalated RT/CRT for HPVþ OPSCC is associated with favorable oncologic outcomes and reduced acute and chronic toxicity. Further evaluation of induction-based de-escalation in large multicenter studies is justified. Clinical trial registration: Clinical trials.gov identifier: NCT02258659.

The term “oligometastatic prostate cancer” refers to a heterogeneous group of disease states currently defined solely on the basis of clinical features. Oligorecurrent disease, de novo oligometastases, and oligoprogressive disease likely have unique biologic underpinnings and natural histories. Evidence suggesting the existence of a subset of patients who harbor prostate cancer with limited metastatic potential currently includes disparate and overwhelmingly retrospective reports. Nevertheless, emerging prospective data have corroborated the “better‐than‐expected,” retrospectively observed outcomes, particularly in the setting of oligorecurrent prostate cancer. Improved functional imaging with prostate‐specific membrane antigen‐targeted strategies may enhance the identification of patients with oligometastatic prostate cancer in the short term. In the long term, refinement of the oligometastatic case definition likely will require biologic risk‐stratification schemes. To determine optimal treatment strategies and identify patients most likely to benefit from metastasis‐directed therapy, future efforts should focus on conducting high‐quality, prospective trials with much‐needed molecular correlative studies.

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BackgroundPreclinical studies suggest enhanced anti-tumor activity with combined radioimmunotherapy. We hypothesized that radiation (RT) + immunotherapy would associate with improved overall survival (OS) compared to immunotherapy or chemotherapy alone for patients with newly diagnosed metastatic non-small-cell lung cancer (NSCLC).MethodsThe National Cancer Database was queried for patients with stage IV NSCLC receiving chemotherapy or immunotherapy from 2013 to 2014. RT modality was classified as stereotactic radiotherapy (SRT) to intra- and/or extracranial sites or non-SRT external beam RT (EBRT). OS was analyzed using the Kaplan-Meier method and Cox proportional hazards models.ResultsIn total, 44,498 patients were included (13% immunotherapy, 46.8% EBRT, and 4.7% SRT). On multivariate analysis, immunotherapy (hazard ratio [HR]:0.81, 95% confidence interval [CI]:0.78–0.83) and SRT (HR:0.78, 95%CI:0.70–0.78) independently associated with improved OS; however, the interaction term for SRT + immunotherapy was insignificant (p = 0.89). For immunotherapy patients, the median OS for no RT, EBRT, and SRT was 14.5, 10.9, and 18.2 months, respectively (p < 0.0001), and EBRT (HR:1.37, 95%CI:1.29–1.46) and SRT (HR:0.78, 95%CI:0.66–0.93) associated with OS on multivariate analysis. In the SRT subset, median OS for immunotherapy and chemotherapy was 18.2 and 14.3 months, respectively (p = 0.004), with immunotherapy (HR:0.82, 95%CI:0.69–0.98) associating with OS on multivariate analysis. Furthermore, for patients receiving SRT, biologically effective dose (BED) > 60 Gy was independently associated with improved OS (HR:0.79, 95%CI:0.70–0.90, p < 0.0001) on multivariate analysis with a significant interaction between BED and systemic treatment (p = 0.008).ConclusionsTreatment with SRT associated with improved OS for patients with metastatic NSCLC irrespective of systemic treatment. The high survival for patients receiving SRT + immunotherapy strongly argues for evaluation in randomized trials.

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