Purpose To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials. Methods and Materials One male pelvis computed tomography (CT) data set and one female pelvis CT data set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The following were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified. Results The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa_R, Adnexa_L, Prostate, SeminalVesc, PenileBulb, Femur_R, and Femur_L. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed. Conclusions Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research.

◥Purpose: Pembrolizumab improved survival in patients with recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC). The aims of this study were to determine if pembrolizumab would be safe, result in pathologic tumor response (pTR), and lower the relapse rate in patients with resectable human papillomavirus (HPV)-unrelated HNSCC.Patients and Methods: Neoadjuvant pembrolizumab (200 mg) was administered and followed 2 to 3 weeks later by surgical tumor ablation. Postoperative (chemo)radiation was planned. Patients with high-risk pathology (positive margins and/or extranodal extension) received adjuvant pembrolizumab. pTR was quantified as the proportion of the resection bed with tumor necrosis, keratinous debris, and giant cells/histiocytes: pTR-0 (<10%), pTR-1 (10%-49%), and pTR-2 (≥50%). Coprimary endpoints were pTR-2 among all patients and 1-year relapse rate in patients with high-risk pathology (historical: 35%). Correlations of baseline PD-L1 and T-cell infiltration with pTR were assessed. Tumor clonal dynamics were evaluated (Clin-icalTrials.gov NCT02296684).Results: Thirty-six patients enrolled. After neoadjuvant pembrolizumab, serious (grades 3-4) adverse events and unexpected surgical delays/complications did not occur. pTR-2 occurred in eight patients (22%), and pTR-1 in eight other patients (22%). One-year relapse rate among 18 patients with high-risk pathology was 16.7% (95% confidence interval, 3.6%-41.4%). pTR ≥10% correlated with baseline tumor PD-L1, immune infiltrate, and IFNg activity. Matched samples showed upregulation of inhibitory checkpoints in patients with pTR-0 and confirmed clonal loss in some patients.Conclusions: Among patients with locally advanced, HPVunrelated HNSCC, pembrolizumab was safe, and any pathologic response was observed in 44% of patients with 0% pathologic complete responses. The 1-year relapse rate in patients with high-risk pathology was lower than historical.

Purpose: Severe artifacts in kilovoltage-CT simulation images caused by large metallic implants can significantly degrade the conspicuity and apparent CT Hounsfield number of targets and anatomic structures, jeopardize the confidence of anatomical segmentation, and introduce inaccuracies into the radiation therapy treatment planning process. This study evaluated the performance of the first commercial orthopedic metal artifact reduction function (O-MAR) for radiation therapy, and investigated its clinical applications in treatment planning. Methods: Both phantom and clinical data were used for the evaluation. The CIRS electron density phantom with known physical (and electron) density plugs and removable titanium implants was scanned on a Philips Brilliance Big Bore 16-slice CT simulator. The CT Hounsfield numbers of density plugs on both uncorrected and O-MAR corrected images were compared. Treatment planning accuracy was evaluated by comparing simulated dose distributions computed using the true density images, uncorrected images, and O-MAR corrected images. Ten CT image sets of patients with large hip implants were processed with the O-MAR function and evaluated by two radiation oncologists using a five-point score for overall image quality, anatomical conspicuity, and CT Hounsfield number accuracy. By utilizing the same structure contours delineated from the O-MAR corrected images, clinical IMRT treatment plans for five patients were computed on the uncorrected and O-MAR corrected images, respectively, and compared. Results: Results of the phantom study indicated that CT Hounsfield number accuracy and noise were improved on the O-MAR corrected images, especially for images with bilateral metal implants. The γ pass rates of the simulated dose distributions computed on the uncorrected and O-MAR corrected images referenced to those of the true densities were higher than 99.9% (even when using 1% and 3 mm distance-to-agreement criterion), suggesting that dose distributions were clinically identical. In all patient cases, radiation oncologists rated O-MAR corrected images as higher quality. Formerly obscured critical structures were able to be visualized. The overall image quality and the conspicuity in critical organs were significantly improved compared with the uncorrected images: overall quality score (1.35 vs 3.25, P = 0.0022); bladder (2.15 vs 3.7, P = 0.0023); prostate and seminal vesicles/vagina (1.3 vs 3.275, P = 0.0020); rectum (2.8 vs 3.9, P = 0.0021). The noise levels of the selected ROIs were reduced from 93.7 to 38.2 HU. On most cases (8/10), the average CT Hounsfield numbers of the prostate/vagina on the O-MAR corrected images were closer to the referenced value (41.2 HU, an average measured from patients without metal implants) than those on the uncorrected images. High γ pass rates of the five IMRT dose distribution pairs indicated that the dose distributions were not significantly affected by the CT image improvements. Conclusions: Overall, this study indicated that the O-MAR function can remark...

During the coronavirus disease 2019 (COVID-19) pandemic, providers and patients must engage in shared decision making regarding the pros and cons of early versus delayed interventions for localized skin cancer. Patients at highest risk of COVID-19 complications are older; are immunosuppressed; and have diabetes, cancer, or cardiopulmonary disease, with multiple comorbidities associated with worse outcomes. Physicians must weigh the patient's risk of COVID-19 complications in the event of exposure against the risk of worse oncologic outcomes from delaying cancer therapy. Herein, the authors have summarized current data regarding the risk of COVID-19 complications and mortality based on age and comorbidities and have reviewed the literature assessing how treatment delays affect oncologic outcomes. They also have provided multidisciplinary recommendations regarding the timing of local therapy for early-stage skin cancers during this pandemic with input from experts at 11 different institutions. For patients with Merkel cell carcinoma, the authors recommend prioritizing treatment, but a short delay can be considered for patients with favorable T1 disease who are at higher risk of COVID-19 complications. For patients with melanoma, the authors recommend delaying the treatment of patients with T0 to T1 disease for 3 months if there is no macroscopic residual disease at the time of biopsy. Treatment of tumors ≥T2 can be delayed for 3 months if the biopsy margins are negative. For patients with cutaneous squamous cell carcinoma, those with Brigham and Women's Hospital T1 to T2a disease can have their treatment delayed for 2 to 3 months unless there is rapid growth, symptomatic lesions, or the patient is immunocompromised. The treatment of tumors ≥T2b should be prioritized, but a 1-month to 2-month delay is unlikely to worsen diseasespecific mortality. For patients with squamous cell carcinoma in situ and basal cell carcinoma, treatment can be deferred for 3 months unless the individual is highly symptomatic.

BACKGROUND Oropharyngeal squamous cell carcinoma (SCC) rates have been increasing significantly in recent years, despite a decreasing incidence of head and neck cancer in general. Oropharyngeal cancer has many characteristics that are distinctively different from other head and neck cancers, and thus it is important to focus specifically on cancers arising here, with the goal of improving patient outcomes. One important goal is to identify patients who are likely to fail standard therapy and who could potentially benefit from alternative or targeted treatments. METHODS In this study, we evaluated the prognostic value of microRNAs (miRNAs) in oropharyngeal SCC. miRNAs are small non-coding RNAs that are master regulators of many important biological processes. In total, 150 oropharyngeal tumors were analyzed using our recently developed quantitative PCR-based method for miRNA expression profiling. In addition, the expression of miRNAs was also correlated to human papillomavirus (HPV) transcriptional activities. RESULTS AND CONCLUSION Our study identified six miRNAs that were significantly associated with cancer survival. A combined expression signature of these miRNAs was prognostic of oropharyngeal SCC, independent of common clinical features or HPV status. Importantly, this new miRNA signature was experimentally validated in an independent oropharyngeal SCC cohort. Furthermore, five HPV-related miRNAs were identified which may help to characterize HPV-induced cancers including both oropharyngeal and cervical SCC.

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Background Complete Response (CR) at the primary tumor site as assessed by clinical examination following induction chemotherapy with cisPlatin and 5-Fluorouracil (5-FU)[PF] is a favorable predictive factor for overall survival and disease-control in patients with locally advanced squamous cell carcinoma of the head and neck. In most series, the rate of CR at the primary site after induction PF was 20–30%. We evaluated the efficacy and feasibility of induction nAb-paclitaxel and Cetuximab given with PF (ACPF) followed by definitive chemoradiation (CRT) in a phase II trial. Methods Patients with HNSCC were treated with ACPF (nab-paclitaxel 100 mg/m2/week; cetuximab 250 mg/m2/week; cisplatin 75 mg/m2 Day 1; 5-fluorouracil 750 mg/m2/day Days 1–3) every 21 days for 3 cycles followed by CRT (cisplatin 100 mg/m2 on days 1,22 and 43 of RT). CR at the primary tumor site after 2 cycles of ACPF was the primary endpoint. Results Thirty patients were enrolled, of which 22 (73%) had large (T3/T4) primary tumors. The CR rate at the primary tumor site after 2 cycles of ACPF was 53% and the overall response rate was 100%. Twenty-nine (96%) patients completed 3 cycles of ACPF, 26 (90%) completed definitive radiation therapy (RT) per protocol and 22 of the 27 evaluable patients (81%) received > 2 of the 3 planned doses of cisplatin with RT. The estimated 2-year overall and progression-free survivals were 84% and 65%, respectively. Conclusion Induction ACPF resulted in a high CR rate (53%) at the primary tumor site even in large tumors and did not adversely affect delivery of definitive CRT. Further investigation of ACPF is warranted.

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