Adenoid cystic carcinoma of the base of tongue: A population-based study.

BACKGROUND: The objective was to assess demographic and survival patterns in patients with adenoid cystic carcinoma of the base of tongue. METHODS: Patients were extracted from the Surveillance, Epidemiology and End Results (SEER) database from 1973 through 2012 and were categorized by age, gender, race, historical stage A, and treatment. Incidence and survival were compared with Kaplan Meier curves and mortality hazard ratios. RESULTS: A total of 216 patients were included. After adjusting for age, gender, race and tumor-directed treatment, patients over the age of 70years had a significantly increased mortality [HR=2.847, 95% CI (1.499, 5.404) p=0.0014]. Furthermore mortality among patients with distant disease was significantly increased [HR=2.474 95% CI (1.459, 4.195) p=0.00008]. CONCLUSION: By examining the largest collection of patients we have demonstrated that there is a significant difference in mortality based on both the age at diagnosis and in the setting of distant disease.

Marital status as a predictor of survival in patients with human papilloma virus-positive oropharyngeal cancer.

PURPOSE: Determine whether marital status is a significant predictor of survival in human papillomavirus-positive oropharyngeal cancer. MATERIALS AND METHODS: A single center retrospective study included patients diagnosed with human papilloma virus-positive oropharyngeal cancer at Boston Medical Center between January 1, 2010 and December 30, 2015, and initiated treatment with curative intent at Boston Medical Center. Demographic data and tumor-related variables were recorded. Univariate analysis was performed using a two-sample t-test, chi-squared test, Fisher's exact test, and Kaplan Meier curves with a log rank test. Multivariate survival analysis was performed using a Cox regression model. RESULTS: A total of 65 patients were included in the study with 24 patients described as married and 41 patients described as single. There was no significant difference in most demographic variables or tumor related variables between the two study groups, except single patients were significantly more likely to have government insurance (p=0.0431). Furthermore, there was no significant difference in 3-year overall survival between married patients and single patients (married=91.67% vs single=87.80%; p=0.6532) or 3-year progression free survival (married=79.17% vs single=85.37%; p=0.8136). After adjusting for confounders including age, sex, race, insurance type, smoking status, treatment, and AJCC combined pathologic stage, marital status was not a significant predictor of survival [HR=0.903; 95% CI (0.126,6.489); p=0.9192]. CONCLUSIONS: Although previous literature has demonstrated that married patients with head and neck cancer have a survival benefit compared to single patients with head and neck cancer, we were unable to demonstrate the same survival benefit in a cohort of patients with human papilloma virus-positive oropharyngeal cancer.

Somatic Activating ESR1 Mutation in an Aggressive Prolactinoma.

CONTEXT AND OBJECTIVE: The genetic profile of prolactinomas remains poorly understood. Our objective is to identify somatic genetic alterations associated with prolactinomas and to report the identification of an activating ESR1 mutation (ESR1Y537S) in an aggressive prolactinoma. SETTING: Brigham and Women's Hospital. DESIGN: Massively parallel-sequencing panel (OncoPanel) was performed in a cohort of patients with prolactinomas to identify mutations and copy number variation (CNV). RESULTS: Twenty subjects (mean age 38.6 years; 12 women and 8 men) were included in this study. A somatic ESR1Y537S mutation was identified in an aggressive prolactinoma in a post-menopausal woman. No SF3B1 or other somatic mutations were identified. The median number of CNV events identified in our samples was 46; the prolactinoma with ESR1Y537S had the highest number with 233 events. In breast cancer, ESR1Y537S has been shown to activate estrogen receptor alpha independent of ligand binding. In patients with resistant breast cancer and ESR1Y537S, elacestrant, a second-line ER degrader, improves progression-free survival. Therefore, given the lack of response to multimodality therapies, elacestrant was initiated in this patient after the third cycle of radiotherapy. Elacestrant, along with radiotherapy, controlled tumor growth and significantly reduced prolactin levels. CONCLUSION: Molecular profiling allowed the identification of ESR1Y537S, in an aggressive prolactinoma. ESR1Y537S was not detected early in the course of the disease and is likely conferring tumor aggressiveness. This finding emphasizes the significance of estrogen receptor signaling in prolactinomas. It also allowed the use of targeted therapy with successful control of disease progression.

Correlation Between Research Productivity During Medical School and Radiation Oncology Residency.

Purpose: This analysis investigates whether research productivity during medical school predicts future research productivity during radiation oncology residency. Methods and Materials: At our institution, there have been 20 medical students who graduated between 2005 and 2015 and subsequently completed their residency training in radiation oncology. We built a database of all PubMed-indexed publications in which these former students were the first author or coauthor. Mean publication rates with 95% confidence intervals (95% CI) were computed. The paired t test and McNemar-Bowker test of symmetry were used to examine differences in first-author and coauthor publications between the medical school and residency periods. An ordinal logistic regression model was employed to measure the odds ratio of publishing during residency versus during medical school. A Spearman correlation coefficient was calculated for the relationship between the number of publications during medical school and the number during residency. Results: A total of 14 and 60 first-author publications (46 and 117 coauthor publications) were identified for 20 individuals during medical school and residency, respectively. There was an average of 0.7 (95% CI, 0.17-1.23) first-author publications during medical school and 3.08 (95% CI, 1.56-4.44) first-author publications during residency (P = .003). Only 15% (3/20) had ≥2 publications during medical school, and 50% (10/20) had ≥2 publications during residency (P = .012). The Spearman correlation coefficient between research publications before and during residency was .457 (P = .043). The mean number of coauthor publications during medical school and residency was 2.3 (95% CI, 0.92-3.68) and 5.85 (95% CI, 3.50-8.20), respectively (P = .004). Conclusions: Based on this retrospective analysis from our institution, student research productivity during medical school, as defined by the number of first-author publications, does correlate with future research productivity during radiation oncology residency.

Deformable registration of preoperative PET/CT with postoperative radiation therapy planning CT in head and neck cancer.

In intensity-modulated radiation therapy (IMRT), precise target delineation is important to avoid underdosing areas at risk for recurrence and overdosing adjacent normal tissue. In postoperative radiation therapy of patients with head and neck cancer (HNC), surgical extirpation of tumor, anatomic changes resulting from tissue removal, and surgical reconstruction often obscure anatomic detail and may make it difficult to identify high-risk target volumes at postoperative planning computed tomography (CT). Positron emission tomography (PET)/CT can significantly affect CT-based tumor contours by providing information on both biologic and metabolic features of cancer. To incorporate diagnostic PET/CT into target delineation at postoperative CT, an advanced image registration method is required to overcome significant differences in patient position and anatomy between the imaging studies. Rigid registration can account for only linear or uniform transformation between the imaging datasets within six degrees of freedom (three rotations and three translations). However, deformable registration can account for significant temporal and anatomic changes between the corresponding images by computing nonlinear and nonuniform relationships between the volume elements across the imaging datasets. Use of deformable registration to integrate preoperative PET/CT with postoperative treatment planning CT is a powerful tool for target volume delineation in HNC patients undergoing postoperative IMRT.

Use of 18F-FDG PET/CT as a predictive biomarker of outcome in patients with head-and-neck non-squamous cell carcinoma.

OBJECTIVE: The purpose of this article is to establish whether pretreatment (18)F-FDG uptake predicts disease-free survival (DFS) and overall survival in patients with head-and-neck non-squamous cell carcinoma (SCC). MATERIALS AND METHODS: Eighteen patients (six women and 12 men; mean [± SD] age at diagnosis, 57.89 ± 13.54 years) with head-and-neck non-SCC were included. Tumor FDG uptake was measured by the maximum standardized uptake value (SUV(max)) and was corrected for background liver FDG uptake to derive the corrected SUV(max). Receiver operating characteristic analyses were used to predict the optimal corrected SUV(max) cutoffs for respective outcomes of DFS (i.e., absence of recurrence) and death. RESULTS: The mean corrected SUV(max) of the 18 head-and-neck tumors was 5.63 ± 3.94 (range, 1.14-14.29). The optimal corrected SUV(max) cutoff for predicting DFS and overall survival was 5.79. DFS and overall survival were significantly higher among patients with corrected SUV(max) < 6 than among patients with corrected SUV(max) ≥ 6. The mean DFS for patients with corrected SUV(max) < 6 was 25.7 ± 11.14 months, and the mean DFS for patients with corrected SUV(max) ≥ 6 was 7.88 ± 7.1 months (p < 0.018). Among patients with corrected SUV(max) < 6, none died, and the mean length of follow-up for this group was 35.2 ± 9.96 months. All of the patients who died had corrected SUV(max) ≥ 6, and the overall survival for this group was 13.28 ± 12.89 months (p < 0.001). CONCLUSION: FDG uptake, as measured by corrected SUV(max), may be a predictive imaging biomarker for DFS and overall survival in patients with head-and-neck non-SCC.

Reduced-Dose Radiation Therapy for HPV-Associated Oropharyngeal Carcinoma (NRG Oncology HN002).

PURPOSE: Reducing radiation treatment dose could improve the quality of life (QOL) of patients with good-risk human papillomavirus-associated oropharyngeal squamous cell carcinoma (OPSCC). Whether reduced-dose radiation produces disease control and QOL equivalent to standard chemoradiation is not proven. PATIENTS AND METHODS: In this randomized, phase II trial, patients with p16-positive, T1-T2 N1-N2b M0, or T3 N0-N2b M0 OPSCC (7th edition staging) with ≤ 10 pack-years of smoking received 60 Gy of intensity-modulated radiation therapy (IMRT) over 6 weeks with concurrent weekly cisplatin (C) or 60 Gy IMRT over 5 weeks. To be considered for a phase III study, an arm had to achieve a 2-year progression-free survival (PFS) rate superior to a historical control rate of 85% and a 1-year mean composite score ≥ 60 on the MD Anderson Dysphagia Inventory (MDADI). RESULTS: Three hundred six patients were randomly assigned and eligible. Two-year PFS for IMRT + C was 90.5% rejecting the null hypothesis of 2-year PFS ≤ 85% (P = .04). For IMRT, 2-year PFS was 87.6% (P = .23). One-year MDADI mean scores were 85.30 and 81.76 for IMRT + C and IMRT, respectively. Two-year overall survival rates were 96.7% for IMRT + C and 97.3% for IMRT. Acute adverse events (AEs) were defined as those occurring within 180 days from the end of treatment. There were more grade 3-4 acute AEs for IMRT + C (79.6% v 52.4%; P < .001). Rates of grade 3-4 late AEs were 21.3% and 18.1% (P = .56). CONCLUSION: The IMRT + C arm met both prespecified end points justifying advancement to a phase III study. Higher rates of grade ≥ 3 acute AEs were reported in the IMRT + C arm.

Systematic review of postoperative therapy for resected squamous cell carcinoma of the head and neck: Executive summary of the American Radium Society appropriate use criteria.

BACKGROUND: The aims of this systematic review are to (a) evaluate the current literature on the impact of postoperative therapy for resected squamous cell carcinoma of the head and neck (SCCHN) on oncologic and non-oncologic outcomes and (b) identify the optimal evidence-based postoperative therapy recommendations for commonly encountered clinical scenarios. METHODS: An analysis of the medical literature from peer-reviewed journals was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. Prospective studies and methodology-based systematic reviews and meta-analyses of postoperative therapy for SCCHN were identified by searching Medline (OVID) and EMBASE (Elsevier) using controlled vocabulary terms (ie, National Library of Medicine Medical Subject Headings [MeSH], EMTREE). Study screening and selection was performed with Covidence software and full-text review. The RAND/UCLA appropriateness method was used by the expert panel to rate the appropriate use of postoperative therapy, and the modified Delphi method was used to come to consensus. RESULTS: A total of 5660 studies were identified and screened using the title and abstract, leading to 201 studies assessed for relevance using full-text review. After limitation to the eligibility criteria, 101 studies from 1977 to 2020 were identified, including 77 with oncologic endpoints and 24 with function and quality of life endpoints. All studies reported staging prior to the implementation of American Joint Committee on Cancer (AJCC-8). CONCLUSIONS: Prospective clinical studies and systematic reviews identified through the PRISMA systematic review provided good evidence for consensus statements regarding the appropriate use of postoperative therapy for resected SCCHN. Further research is needed in domains where consensus by the expert panel could not be achieved for the appropriateness of specific postoperative therapeutic interventions.

Comparing survival outcomes in early stage desmoplastic melanoma with or without adjuvant radiation.

Desmoplastic melanoma (DM) due to its rare and locally aggressive nature, can be difficult to study and to treat effectively. Whether the optimal treatment approach for these tumors should include adjuvant radiation has been unclear in the literature. In this retrospective study of the National Cancer Database, 2390 patients with localized DM were included for analysis. 2082 were treated with wide local excision (WLE) and 308 were treated with wide local excision and adjuvant radiation therapy (WLE + RT). Overall survival (OS) in these groups was compared on crude and adjusted analyses utilizing Cox proportional hazards regression modeling. There was no difference in OS at 1, 3, and 5 years on initial analysis. Subsequent multivariate analysis and propensity score analysis showed a survival benefit in those treated with WLE + RT. Multivariate analysis demonstrated significantly decreased OS in cases of residual tumor following surgical excision. Adjuvant radiation was more likely to be performed for tumors on the head and neck, tumors with higher pathologic American Joint Committee on Cancer stage and T classifications, and tumors with positive surgical margins. This is the first study to demonstrate significantly improved OS in early-stage DM patients treated with WLE + RT compared to WLE alone.

Racial disparities in laryngeal cancer treatment and outcome: A population-based analysis of 24,069 patients.

OBJECTIVES: To determine the impact of race on laryngeal preservation strategies and overall survival (OS) for laryngeal squamous cell carcinoma (SCC). STUDY DESIGN: Retrospective, national cancer database analysis. METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results database. Chi-square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 20.0 (Armonk, NY: IBM Corp.) for data analyses. RESULTS: A total of 24,069 patients with laryngeal SCC were identified. Of these, 18,166 (75.5%) patients were white, 3,475 (14.4%) were black, 1,608 (6.7%) were Hispanic, and 820 (3.4%) were Asian. Compared with other races, black patients were more likely to be diagnosed at a younger age (P < 0.001), undergo lymph node dissection (P < 0.001), have nodal metastasis (P < 0.001), be with advanced stage disease (P < 0.001), and be unmarried (P < 0.001). Black patients with T1 to T2 and T3 disease were more likely to undergo total laryngectomy as compared with white patients (T1-2: 8.2% vs. 4.3%; P < 0.001; T3: 28.4% vs. 24.3%; P = 0.023). For patients with T4 disease, however, rates of primary radiotherapy among black patients were higher (40.5% vs. 35.7%; P = 0.015). The 5-year OS for white, black, Hispanic, and Asian patients were 60.6%, 52.7%, 59.5% and 65.7% (P < 0.001). This significant 5-year OS difference by race persisted regardless of age, gender, year of diagnosis, primary treatment, nodal status, or tumor grade. On multivariate analysis, race remained an independent prognostic factor for OS. CONCLUSIONS: Race is an independent prognostic factor for OS. Further studies are warranted to evaluate causes for racial disparities and discrepancies in OS and laryngeal preservation strategies.

A prognostic volumetric threshold of gross tumor volume in head and neck cancer patients treated with radiotherapy.

OBJECTIVES: To determine the prognostic utility of a volumetric threshold for gross tumor volume (GTV) of the primary and nodal disease when accounting for the TNM classification in head and neck cancer (HNC) patients treated with definitive radiotherapy (RT). MATERIALS AND METHODS: From 2004 to 2011, 79 HNC patients were treated to a median dose of 70 Gy, using intensity-modulated RT in 78.5% and 3-dimensional conformal RT in 21.5% with 83.5% receiving concurrent chemotherapy. Primary (GTV-P) and nodal (GTV-N) GTVs were derived from computed tomography (CT)-based contours for RT planning, of which 89.7% were aided by positron emission tomography-computed tomography. Local (LC), nodal (NC), distant (DC) control, and overall survival (OS) were assessed using the Kaplan-Meier product-limit method. RESULTS: With a median follow-up of 27.1 months GTV-P, threshold of <32.9 mL (mean value) compared with ≥32.9 mL, correlated with improved 2-year LC (96.2% vs. 63.9%, P<0.0001), NC (100% vs. 69.2%, P<0.0001), DC (87.9% vs. 64.2%, P=0.001), and OS (88.4% vs. 58.6%, P=0.001). GTV-P demonstrated its prognostic utility in multivariate analyses when adjusted for tumor category, cancer site, and chemotherapy regimen. Nodal GTV (mean, 34.0 mL) was not predictive of nodal control and survival. CONCLUSIONS: A volumetric threshold of the primary tumor may be used as an independent prognostic factor in patients with HNC undergoing definitive RT.

Results of surgical resection for progression of brain metastases previously treated by gamma knife radiosurgery.

OBJECTIVE: To determine treatment outcome after surgical resection for progressive brain metastases after gamma knife radiosurgery (GKR) and to explore the role of dynamic contrast agent-enhanced perfusion magnetic resonance imaging (MRI) and proton spectroscopic MRI studies (MRS/P) in predicting pathological findings. METHODS: Between 1997 and 2002, 32 patients underwent surgical resection for suspected progression of brain metastases from a cohort of 245 patients with brain metastases treated with GKR. Postradiosurgery MRI surveillance was performed at 6 and 12 weeks, and then every 12 weeks after GKR. In some cases, additional MRI scanning with spectroscopy or perfusion (MRS/P) was used to aid differentiation of radiation change from tumor progression. The decision to perform neurosurgical resection was based on MRI or clinical evidence of lesion progression among patients with a Karnofsky performance score of 60 or more and absent or stable systemic disease. RESULTS: Thirteen percent (32 out of 245) of patients and 6% (38 out of 611) of lesions required surgical resection after GKR. The median time from GKR to surgical resection was 8.6 months (range, 1.7-27.1 mo). The 6-, 12-, and 24-month actuarial survival from time of GKR was 97, 78, and 47% for the resected patients and 65, 40, and 19% for the nonresected patients (P < 0.0001). The two-year survival rate of patients requiring two resections after GKR was 100% compared with 39% for patients undergoing one resection (P = 0.02). The median survival of resected patients was 27.2 months (range, 7.0-72.5 mo) from the diagnosis of brain metastases, 19.9 months (range, 5.0-60.7 mo) from GKR, and 8.9 months (range, 0.2-53.1 mo) from surgical resection. Tumor was found in 90% of resected specimens and necrosis alone in 10%. MRS/P studies were performed in 15 resected patients. Overall, MRS/P predicted tumor in 11 lesions, confirmed pathologically in nine lesions, and necrosis alone was found in two. The MRS/P predicted necrosis alone in three, whereas pathology revealed viable tumor in two and necrosis in one lesion. CONCLUSION: Surgical intervention of progressive brain metastases after GKR in selected patients leads to a meaningful improvement in survival rates. Further studies are necessary to determine the role of MRS/P in the postradiosurgery surveillance of brain metastases.