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Head and neck cancer is the fifth most common cancer in the United States, with an overall survival rate of approximately 40-50%. In an effort to improve patient outcomes, research efforts designed to maximize benefit and reduce toxicities of therapy are in progress. Basic research in cancer biology has accelerated this endeavor and provided preclinical data and technology to support clinically relevant advances in early detection, prognostic and predictive biomarkers. Recent completion of the Human Genome Project has promoted the rapid development of novel "omics" technologies that allow more broad based study from a systems biology perspective. However, clinically relevant application of resultant gene signatures to clinical trials within cooperative groups has advanced slowly. In light of the large numbers of variables intrinsic to biomarker studies, validation of preliminary data for clinical implementation presents a significant challenge and may only be realized with large trials that involve significant patient numbers. The Radiation Therapy Oncology Group (RTOG) Head and Neck Cancer Translational Research Program recognizes this problem and brings together three unique features to facilitate this research: (1) availability of large numbers of clinical specimens from homogeneously treated patients through multi-institutional clinical trials; (2) a team of physicians, scientists, and staff focused on patient-oriented head-and-neck cancer research with the common goal of improving cancer care; and (3) a funding mechanism through the RTOG Seed Grant Program. In this position paper we outline strategic plans to further promote translational research within the framework of the RTOG.

Purpose The purpose of this critical review is to summarize the literature specific to single-fraction stereotactic radiosurgery (SRS) and multiple-fraction stereotactic radiation therapy (SRT) for postoperative brain metastases resection cavities and to present practice recommendations on behalf of the ISRS. Methods and Materials The Medline and Embase databases were used to apply the Preferred Reporting Items for Systematic Reviews and Meta-Analyses approach to search for manuscripts reporting SRS/SRT outcomes for postoperative brain metastases tumor bed resection cavities with a search end date of July 20, 2018. Prospective studies, consensus guidelines, and retrospective series that included exclusively postoperative brain metastases and had at minimum 100 patients were considered eligible. Results The Embase search revealed 157 manuscripts, of which 77 were selected for full-text screening. PubMed yielded 55 manuscripts, of which 23 were selected for full text screening. We deemed 8 retrospective series, 1 phase 2 prospective study, 3 randomized controlled trials, and 1 consensus contouring paper appropriate for inclusion. The data suggest that SRS/SRT to surgical cavities with prescription doses of 30 to 50 Gy equivalent effective dose (EQD) 210, 50 to 70 Gy EQD25, and 70 to 90 EQD22 are associated with rates of local control ranging from 60.5% to 91% (median, 80.5%). Randomized data suggest improved local control with single-fraction SRS compared with observation and improved cognitive outcomes compared with whole-brain radiation therapy (WBRT). The toxicity of SRS/SRT in the postoperative setting was limited and is reviewed herein. Conclusions Although randomized data raise concern for poorer local control after resection cavity SRS than WBRT, these findings may be driven by factors such as conservative prescription doses used in the SRS arm. Retrospective studies suggest high rates of local control after single-fraction SRS and hypofractionated SRT for postoperative brain metastases. With a superior neurocognitive profile and no survival disadvantage to withholding WBRT, the ISRS recommends SRS as first-line treatment for eligible postoperative patients. Emerging data suggest that fractionated SRT may provide superior local control compared with single-fraction SRS, in particular, for large tumor cavity volumes/diameters and potentially for patients with a preoperative diameter greater than 2.5 cm.

Purpose Chemoradiation therapy (CRT) for patients with locally advanced pancreatic cancer (LAPC) provides survival benefits but may result in considerable toxicity. Health-related quality of life (HRQL) measurements during CRT have not been widely reported. This paper reports HRQL data from the Selective Chemoradiation in Advanced Localised Pancreatic Cancer (SCALOP) trial, including validation of the QLQ-PAN26 tool in CRT. Methods and Materials Patients with locally advanced, inoperable, nonmetastatic carcinoma of the pancreas were eligible. Following 12 weeks of induction gemcitabine plus capecitabine (GEMCAP) chemotherapy, patients with stable and responding disease were randomized to a further cycle of GEMCAP followed by capecitabine- or gemcitabine-based CRT. HRQL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EORTC Pancreatic Cancer module (PAN26). Results A total of 114 patients from 28 UK centers were registered and 74 patients randomized. There was improvement in the majority of HRQL scales during induction chemotherapy. Patients with significant deterioration in fatigue, appetite loss, and gastrointestinal symptoms during CRT recovered within 3 weeks following CRT. Differences in changes in HRQL scores between trial arms rarely reached statistical significance; however, where they did, they favored capecitabine therapy. PAN26 scales had good internal consistency and were able to distinguish between subgroups of patients experiencing toxicity. Conclusions Although there is deterioration in HRQL following CRT, this resolves within 3 weeks. HRQL data support the use of capecitabine- over gemcitabine-based chemoradiation. The QLQ-PAN26 is a reliable and valid tool for use in patients receiving CRT.

Purpose Between 2000 and 2010, the American Society for Radiation Oncology (ASTRO) awarded 22 Junior Faculty Career Development Awards (JFA) totaling $4.4 million. This study aimed to evaluate the impact of these awards on the grantees' career development, including current position, publications, and subsequent independent grant funding. Methods Each awardee was requested via email and telephone to provide an updated curriculum vitae, a National Institutes of Health (NIH) biosketch, and information regarding current position of employment. Twenty-one of the 22 JFA recipients complied. Reported grant funding was extracted from each candidate's CV, and the amounts of NIH grants obtained were confirmed via NIH REPORTER. Reported publications were confirmed via PubMed. Results All survey respondents (21 of 21) have remained in academic positions. Subsequent aggregate grant funding totaled more than $25 million (range, $0-$4.1 million), 5.9 times the initial investment. NIH grant funding totaled almost $15 million, 3 times the initial investment. Awardees have published an average of 34.6 publications (range, 0-123) for an overall rate of 4.5 papers/year (range, 1-11). Conclusions ASTRO JFAs over the past decade have been strongly associated with grantees remaining in academic positions, success in attracting private and NIH grants, and publication productivity. In an era of dwindling federal research funding, the support provided by the ASTRO JFA may be especially helpful to support the research careers of promising junior faculty members.

PURPOSE/OBJECTIVE: Rotterdam and Brussels have independently published guidelines for the definition and delineation of CT-based neck nodal Levels I-VI. This paper first reports on the adequacy of contouring of the Rotterdam delineation protocol. Rotterdam and Brussels differed slightly in translating the original surgical level definitions as proposed by the 2002 American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) to CT guidelines. To adapt to the surgical level definitions to come to a unifying concept, adjustments of both CT-based classifications are proposed. METHODS AND MATERIALS: The clinical neck nodal target volumes of patients irradiated in Rotterdam by three-dimensional conformal radiotherapy (3D-CRT) between December 1998 and March 2001 were reviewed. Thirty-four patients with N0 and 27 patients with N+ disease with primary tumors located in the oral cavity (n = 1) oropharynx (n = 24), hypopharynx (n = 7), and larynx (n = 29) were evaluated. Seven patients underwent unilateral (3 N0 patients, 4 N+ patients) and 54 underwent bilateral (31 N0 patients, 23 N+ patients) irradiation of the neck. In 11 N+ patients, 3D-CRT of the neck was followed by unilateral neck dissection. The dose to the primary and nonresected N+ necks was 70 Gy and to the N0 neck was 46 Gy. Neck levels were analyzed for adequacy of contouring, dose distribution, and patterns of relapse. The mean dose and the percentage of the volume receiving a minimum of 95% (V95) or >107% (V107) of the prescribed dose was computed. RESULTS: In 4 patients treated with bilateral 3D-CRT, contouring was not in concordance with the guidelines of the protocol. The V95 and V107 in the 81 adequately contoured N0 necks (63 irradiated N0 necks from 33 N0 patients, 18 irradiated N0 necks from 24 N+ patients) was 95.6% and 6.3%, respectively. For the 26 N+ necks (15 N+ necks from 13 N+ RT-only patients, 11 N+ necks from 11 preoperatively irradiated patients), the V95 and V107 was 94.6% and 6.7%, respectively. With a median follow-up of 29 months, in 4 (8.6%) of 46 patients treated by 3D-CRT only, regional relapse was found. An actuarial regional and locoregional relapse-free survival and disease-free survival rate at 3 years of 90%, 78%, and 68%, respectively, was observed. All regional relapses were observed in the N0 necks of patients with supraglottic laryngeal carcinoma. Taking the surgical 2002 AAO-HNS classification as a reference, adjustments are proposed for the Rotterdam and Brussels delineation protocols to arrive at a unified CT-based neck nodal classification. CONCLUSION: Adequate dose coverage for the Rotterdam CT-based contours of the neck nodal levels was found. In the RT-only patients, only four failures were observed: one regional and three locoregional relapses. As a next step in optimizing the current Rotterdam and Brussels CT-based delineation protocols, adaptations are proposed to resolve the discrepancies compared with the 2002 AAO-HNS surgical classification.

Radioactive 125 I seeds have been used increasingly in intraoperative permanent interstitial implants of certain tumors. Dosimetry calculations of dose distribution in the implants have been based on the assumption of isotropic radiation emission from the 125 I seeds. This paper presents experimental results which show that the radiation fluence around single 125 I seeds is highly anisotropic. Dosimetry calculations based on the measured radiation distribution pattern indicate unusual dosage inhomogeneity within the implant volume. The clinical significance of this effect and approaches to circumvent this potential problem are discussed.