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Introduction: It was hypothesized that use of proton beam therapy (PBT) in patients with locally advanced non–small cell lung cancer treated with concurrent chemoradiation and consolidative immune checkpoint inhibition is associated with fewer unplanned hospitalizations compared with intensity‐modulated radiotherapy (IMRT). Methods: Patients with locally advanced non–small cell lung cancer treated between October 2017 and December 2021 with concurrent chemoradiation with either IMRT or PBT ± consolidative immune checkpoint inhibition were retrospectively identified. Logistic regression was used to assess the association of radiation therapy technique with 90‐day hospitalization and grade 3 (G3+) lymphopenia. Competing risk regression was used to compare G3+ pneumonitis, G3+ esophagitis, and G3+ cardiac events. Kaplan–Meier method was used for progression‐free survival and overall survival. Inverse probability treatment weighting was applied to adjust for differences in PBT and IMRT groups. Results: Of 316 patients, 117 (37%) received PBT and 199 (63%) received IMRT. The PBT group was older (p <.001) and had higher Charlson Comorbidity Index scores (p =.02). The PBT group received a lower mean heart dose (p <.0001), left anterior descending artery V15 Gy (p =.001), mean lung dose (p =.008), and effective dose to immune circulating cells (p <.001). On inverse probability treatment weighting analysis, PBT was associated with fewer unplanned hospitalizations (adjusted odds ratio, 0.55; 95% CI, 0.38–0.81; p =.002) and less G3+ lymphopenia (adjusted odds ratio, 0.55; 95% CI, 0.37–0.81; p =.003). There was no difference in other G3+ toxicities, progression‐free survival, or overall survival. Conclusions: PBT is associated with fewer unplanned hospitalizations, lower effective dose to immune circulating cells and less G3+ lymphopenia compared with IMRT. Minimizing dose to lymphocytes may be warranted, but prospective data are needed. The use of proton beam therapy in locally advanced non–small cell lung cancer is associated with fewer 90‐day acute hospitalizations, lower effective dose to immune circulating cells, and less grade 3+ lymphopenia compared with intensity‐modulated radiation therapy. [ABSTRACT FROM AUTHOR]

Objectives: To describe swallowing and feeding‐tube outcomes in patients with high‐risk oropharyngeal cancer treated with trimodality therapy (TMT), including transoral robotic surgery (TORS) and adjuvant chemoradiotherapy. Methods: A chart review was conducted on patients with HPV+ OPSCC receiving TMT with TORS at an academic medical center from March 2010 to March 2021. Data collected included demographics, treatment, feeding tube placement, functional oral intake scale (FOIS) scores, and swallowing‐language pathology (SLP) evaluations. Results: A total of 255 patients met selection criteria (mean age 61 years, 88% male). Following intraoperative nasogastric tube (NG) placement, 31% remained NG tube dependent after 3 weeks. A gastrostomy tube was placed in 19% of patients, and at 1 year after end‐of‐treatment (EOT), 3.5% overall remained tube‐dependent. Mean FOIS scores were 6.9 (SD = 0.3) at pre‐operative visit, 2.6 (1.8) at first post‐operative visit, and 5.5 (1.5) after EOT. In the subset of patients with follow‐up longer than 2 years (n = 118), the mean FOIS was 6.1 (SD = 1.3) at most recent visit. Clinical signs of aspiration/penetration were suspected on SLP evaluation in 18% of patients. These patients were subsequently evaluated with fiberoptic endoscopic evaluation of swallowing (FEES) and/or barium swallow study, which confirmed signs of aspiration in 2.7% of patients overall. Delayed NG tube removal after 3 weeks was predictive of (1) gastrostomy tube requirement and (2) clinical signs of aspiration on an SLP visit after EOT. Conclusions: Favorable functional and feeding‐tube outcomes are demonstrated in patients with HPV‐associated OPSCC undergoing TMT. In this single‐institution study, we found low rates of long‐term feeding tube dependence and high median FOIS following treatment. Review of routine SLP visits provides a detailed and easily accessible means for assessing swallowing function in this cohort. Level of Evidence: 4 Laryngoscope, 133:3013–3020, 2023 [ABSTRACT FROM AUTHOR]

Inherited biallelic pathogenic variants (PVs) in BRCA2 cause Fanconi Anemia complementation group D1 (FA‐D1), a severe pediatric bone marrow failure and high‐risk cancer syndrome. We identified biallelic BRCA2 PVs in a young adult with multiple basal cell carcinomas, adult‐onset colorectal cancer and small cell neuroendocrine carcinoma, without bone marrow failure. No PVs were identified in any other known cancer susceptibility gene, and there was no evidence of reversion mosaicism. The proband's deceased sister had a classic FA‐D1 presentation and was shown to carry the same biallelic BRCA2 PVs. A lymphoblastoid cell line derived from the proband demonstrated hypersensitivity to DNA damaging agents, and bone marrow showed aberrant RAD51 staining. Family expansion demonstrated the presence of BRCA2 related cancers in heterozygous family members. Our data highlight the striking phenotypic differences which can be observed within FA‐D1 families and expands the clinical spectrum of FA‐D1 to include adult presentation with a constellation of solid tumors not previously thought of as characteristic of Fanconi Anemia. Early recognition of this syndrome in a family could prevent further morbidity and mortality by implementation of hereditary breast and ovarian cancer screening and treatment strategies for heterozygous family members. [ABSTRACT FROM AUTHOR]

Objective: To analyze the patterns, risk factors, and salvage outcomes for locoregional recurrences (LRR) after treatment with transoral robotic surgery (TORS) for HPV‐associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC). Study Design: Retrospective analysis of HPV+ OPSCC patients completing primary TORS, neck dissection, and NCCN‐guideline‐compliant adjuvant therapy at a single institution from 2007 to 2017. Methods: Features associated with LRR, detailed patterns of LRR, and outcomes of salvage therapy were analyzed. Disease‐free survival (DFS) and overall survival (OS) were calculated for subgroups of patients receiving distinct adjuvant treatments. Results: Of 541 patients who completed guideline‐indicated therapy, the estimated 5‐year LRR rate was 4.5%. There were no identifiable clinical or pathologic features associated with LRR. Compared to patients not receiving adjuvant therapy, those who received indicated adjuvant radiation alone had a lower risk of LRR (HR 0.28, 95% CI [0.09–0.83], P =.023), but there was no difference in DFS (P =.21) and OS (P =.86) between adjuvant therapy groups. The 5‐year OS for patients who developed LRR was 67.1% vs. 93.9% for those without LRR (P <.001). Patients who initially received adjuvant chemoradiation and those suffering local, in‐field, and/or retropharyngeal node recurrences had decreased disease control after salvage therapy. Conclusion: LRR rates are low for HPV+ OPSCCs completing TORS and guideline‐compliant adjuvant therapy. Patients without indication for adjuvant therapy more often suffer LRR, but these recurrences are generally controllable by salvage therapy. Improved understanding of the patterns of recurrence most amenable to salvage therapy may guide treatment decisions, counseling, and adjuvant therapy de‐escalation trials. Level of Evidence: 3 Laryngoscope, 131:E2865–E2873, 2021 [ABSTRACT FROM AUTHOR]

Background: Patients with oropharyngeal cancer who undergo transoral robotic surgery (TORS) and have high‐risk features generally receive adjuvant chemoradiotherapy or trimodality therapy (TMT). The notion that TMT leads to high toxicity is largely based on studies that included human papilloma virus (HPV)‐negative cancers and/or nonrobotic surgery; we sought to describe outcomes in HPV‐associated oropharyngeal squamous cell cancer (HPV + OPSCC) undergoing TORS‐TMT. Methods: In consecutive patients with HPV + OPSCC receiving TMT at an academic center from 2010 to 2017, survival was estimated using Kaplan–Meier methodology, and toxicities were ascertained via chart review. Results: In our cohort of 178 patients, 5‐year survival was 93.6%. Feeding tube rates were 25.8% at therapy completion and 0.7% at 1 year. Rates of grade ≥ 3 kidney injury, anemia, and neutropenia in cisplatin‐treated patients were 2.7%, 3.4%, and 11.0%, respectively. Conclusions: Patients with HPV + OPSCC who underwent TORS‐TMT had excellent survival and low rates of toxicity and feeding tube dependence. These outcomes compare favorably to historical cohorts treated with definitive chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Background: Patients with human papillomavirus (HPV)‐negative oropharyngeal squamous cell carcinoma (OPSCC) continue to experience disappointing outcomes following chemoradiotherapy (CRT) and appreciable morbidity following historical surgical approaches. We aimed to investigate the oncologic outcomes and perioperative morbidity of a transoral robotic surgery (TORS) approach to surgically resectable HPV‐negative OPSCC. Methods: Retrospective analysis HPV‐negative OPSCC patients who underwent TORS, neck dissection and pathology‐guided adjuvant therapy (2005–2017). Results: Fifty‐six patients (91.1% stage III/IV) were included. Three‐year overall survival, locoregional control, and disease‐free survival were 85.5%, 84.4%, and 73.6%, respectively (median follow‐up 30.6 months, interquartile range 18.4–66.6). Eighteen (32.1%) patients underwent adjuvant radiotherapy and 20 (39.3%) underwent adjuvant CRT. Perioperative mortality occurred in one (1.8%) patient and hemorrhage occurred in two (3.6%) patients. Long‐term gastrostomy and tracheostomy rates were 5.4% and 0.0%, respectively. Conclusion: The TORS approach for resectable HPV‐negative OPSCC can achieve encouraging oncologic outcomes with infrequent morbidity. [ABSTRACT FROM AUTHOR]

With rapid modifications in cancer clinical trial operations necessitated by the global pandemic over the last year, there is now an unprecedented opportunity to reform clinical research permanently and solidify innovative practices that have clearly been effective. On the basis of the authors' experience and recommendations from other institutions, a set of specific proposals for clinical trial reform are identified that can be implemented immediately by sponsors, regulators, and study sites. Improvements in clinical trial processes should include increased leverage of technology to facilitate remote trial activity and electronic documents, more efficient and effective communication of adverse event information, and better study design to optimize inclusion criteria, required research procedures, and data collection. The authors suggest that such reform will preserve patient safety and study integrity, address unnecessary and inefficient pre‐pandemic constraints, improve access to clinical trials for patients, and speed improvements in cancer care. The changes in clinical trial processes required during the COVID‐19 pandemic present an unprecedented opportunity for clinical trial reform. A set of specific proposals is identified that can be implemented immediately to improve trial efficiency and speed improvements in cancer care. [ABSTRACT FROM AUTHOR]

Background: Some patients with human papillomavirus (HPV)–associated oropharyngeal squamous cell carcinoma (OPSCC) do not receive guideline‐recommended postoperative radiation therapy (PORT) following primary transoral robotic surgery (TORS). Methods: Three‐hundred and sixty‐four patients with treatment‐naïve, HPV‐associated OPSCC were recommended to receive PORT based on clinicopathological features following TORS. Patients were stratified based on if they received PORT. Oncologic outcomes were compared. Results: The 3‐year locoregional failure (LRF) was 32% in patients who did not receive PORT and 4% in patients who received PORT (P <.001). Despite increased LRF, avoiding PORT was not associated with increased 3‐year distant metastasis rates (8% vs 4%, P =.56) or worse 3‐year survival (95% vs 98%, P =.34). Recurrences in the surgery alone cohort varied between local and regional sites and were often successfully salvaged. Conclusions: Patients with HPV‐associated OPSCC who do not receive indicated PORT have an increased risk of LRF but similar survival due to high salvage rates. [ABSTRACT FROM AUTHOR]

Therapeutic innovation for human papilloma virus‐related (HPV+) head and neck squamous cell carcinomas (HNSCCs) is impaired by inadequate preclinical models and the absence of accurate biomarkers. Our study establishes the first well‐characterized panel of patient‐derived xenografts (PDXs) and organoids from HPV+ HNSCCs while determining fidelity of the models to the distinguishing genetic features of this cancer type. Despite low engraftment rates, whole exome sequencing showed that PDXs retain multiple distinguishing features of HPV+ HNSCC lost in existing cell lines, including PIK3CA mutations, TRAF3 deletion and the absence of EGFR amplifications. Engrafted HPV+ tumors frequently contained NOTCH1 mutations, thus providing new models for a negatively prognostic alteration in this disease. Genotype‐phenotype associations in the models were then tested for prediction of tumor progression and survival in published clinical cohorts. Observation of high tumor mutational burdens (TMBs) in the faster‐growing models facilitated identification of a novel association between TMB and local progression in both HPV+ and HPV− patients that was prognostic in HPV− cases. In addition, reduced E7 and p16INK4A levels found in a PDX from an outlier case with lethal outcome led to detection of similar profiles among recurrent HPV+ HNSCCs. Transcriptional data from the Cancer Genome Atlas was used to demonstrate that the lower E2F target gene expression predicted by reduced E7 levels has potential as a biomarker of disease recurrence risk. Our findings bridge a critical gap in preclinical models for HPV+ HNSCCs and simultaneously reveal novel potential applications of quantifying mutational burden and viral oncogene functions for biomarker development. What's new?: While the incidence of human papillomavirus (HPV)‐related head and neck squamous cell carcinoma (HNSCC) is increasing, therapeutic development has been slow to progress, due in part to insufficient biomarkers and lack of experimental models. Here, the authors present detailed characterization of HPV‐positive patient‐derived xenograft (PDX) and organoid models generated from HPV‐positive HNSCCs, which typically grow poorly outside the human body. The models retained genetic hallmarks frequently lost in HPV‐positive HNSCC cell lines. In addition, fast growing PDX and organoid models were found to harbor a high tumor mutational burden, which predicted tumor progression and survival when tested in patient cohorts. [ABSTRACT FROM AUTHOR]

Background: Despite a protracted disease course and multiple available therapies, patients with well-differentiated neuroendocrine tumors (NETs) inevitably experience disease progression. Programmed death-ligand 1 (PD-L1) has been associated with NET progression and prognosis. The multicohort, phase 1 KEYNOTE-028 study (ClinicalTrials.gov identifier NCT02054806) evaluated the activity and safety of the anti-programmed cell death protein 1 immunotherapy pembrolizumab in patients with well-differentiated or moderately-differentiated NETs.Methods: Patients with PD-L1-positive, locally advanced or metastatic carcinoid or well-differentiated or moderately-differentiated pancreatic NETs (pNETs) were enrolled into separate cohorts and received pembrolizumab at a dose of 10 mg/kg every 2 weeks for up to 2 years. The objective response rate was the primary endpoint (as per Response Evaluation Criteria in Solid Tumors version 1.1, by investigator review). Safety was a secondary endpoint.Results: Of 170 and 106 patients, respectively, who had evaluable samples among those screened for the carcinoid and pNET cohorts, 21% and 25%, respectively, had PD-L1-positive tumors; of these, 25 and 16 patients, respectively, were eligible and treated. The median follow-up was 20 months (range, 2-35 months) and 21 months (range, 5-32 months), respectively. The objective response rate was 12.0% (95% CI, 2.5%-31.2%) and 6.3% (95% CI, 0.2%-30.2%), respectively; 3 partial responses occurred among the carcinoid cohort and 1 among the pNET cohort. The median duration of response in the carcinoid cohort was 9.2 months (range, 6.9-11.1 months), and was not reached in the pNET cohort. No complete responses occurred. Treatment-related adverse events occurred in 68% and 69% of patients, respectively, most often diarrhea (7 patients in the carcinoid cohort and 4 patients in the pNET cohort) and fatigue (6 patients in each cohort). Hypothyroidism was the most common immune-mediated adverse event (5 patients in the carcinoid cohort and 2 patients in the pNET cohort).Conclusions: Pembrolizumab demonstrated antitumor activity in a subset of patients with NETs and was well-tolerated. [ABSTRACT FROM AUTHOR]

Introduction: The COVID‐19 pandemic caused by the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) virus has altered the health care environment for the management of head and neck cancers. The purpose of these guidelines is to provide direction during the pandemic for rational Head and Neck Cancer management in order to achieve a medically and ethically appropriate balance of risks and benefits. Methods: Creation of consensus document. Results: The process yielded a consensus statement among a wide range of practitioners involved in the management of patients with head and neck cancer in a multihospital tertiary care health system. Conclusions: These guidelines support an ethical approach for the management of head and neck cancers during the COVID‐19 epidemic consistent with both the local standard of care as well as the head and neck oncological literature. [ABSTRACT FROM AUTHOR]

The article presents the highlights of an online conference held by the Middle East Policy Council on April 17, 2020. Columnist Roger Cohen claims that U.S. President Donald Trump has destroyed significant progress made by the U.S. in the Middle East due to his ignorance to the region's history. Senior advisor on the Middle East and North Africa Mona Yacoubian mentions three dynamics that characterize the current situation in the region.

Background and Methods: There is an added level of complexity in the management of head and neck cancer patients with underlying immunosuppressive disorders during the COVID‐19 pandemic. Head and neck oncologists are tasked with balancing the dual risks of cancer progression in the setting of impaired tumor immunity and increased susceptibility to life‐threatening complications from exposure to viral infection for patients and providers. Through two cases of immunocompromised patients with newly diagnosed head and neck malignancies, we aim to provide guidance to clinicians struggling with how to best counsel and manage this unique subset of patients under these difficult circumstances. Results: After careful consideration of the options, we took different approaches in the care of these two patients. Conclusions: Ultimately, there is no uniform set of rules to apply to this heterogeneous group of immunocompromised patients. We provide some general principles to help guide patient management during the current pandemic. [ABSTRACT FROM AUTHOR]

Background: For patients with head and neck squamous cell carcinoma (SCC) undergoing surgery followed by postoperative radiotherapy (PORT), time from surgery to completion of adjuvant therapy, "package time" impacts locoregional control (LRC). However, the significance of package time in HPV+ oropharyngeal SCC (OPSCC) is unknown. Methods: We examined patients undergoing TORS resection with PORT for HPV+ OPSCC from January 2010 to December 2015 with ≥18 months follow‐up (n = 267). A cutoff of 15 weeks was used to delineate patients into short and long package time groups. LRC loss was defined as any recurrence after surgery. Results: Prolonged package time >15 weeks was associated with inferior LRC in this HPV+ OPSCC cohort, driven primarily by interval from surgery to PORT initiation. Multivariate analysis showed that package time and T classification are both independently associated with LRC. Conclusions: Among HPV+ OPSCC, prolongation of package time appears to compromise LRC, but not survival. [ABSTRACT FROM AUTHOR]

Background: The addition of cisplatin or cetuximab to radiation therapy (RT) improves outcomes in comparison with RT alone in the nonoperative management of head and neck squamous cell carcinoma (HNSCC), but limited data exist for comparing these approaches. Using Veterans Health Affairs data, this study compared the outcomes of patients treated with RT plus cisplatin or cetuximab.Methods: Patients with stage III to IVb HNSCC who had been treated nonsurgically with RT and cisplatin or cetuximab from 2000 to 2016 within the Veterans Health Affairs system were identified. Patients were analyzed by the drug used in the first treatment cycle (intent to treat). Overall survival (OS) was compared by treatment group with Cox regression models, and propensity score (PS) methods were used to account for a treatment allocation bias. The risk of toxicities was determined, with logistic regression models fit into propensity-matched cohorts.Results: A total of 4520 patients were included in the analysis with a median follow-up of 3 years: 83% received cisplatin. Cisplatin patients were younger (P < .001) and had fewer comorbidities (P < .001). In an unmatched analysis, cetuximab was associated with inferior OS (P < .001). After PS matching, cetuximab treatment remained statistically significantly associated with inferior OS (1.7 vs 4.1 years; hazard ratio, 1.61; 95% confidence interval, 1.44-1.79; P < .001). These differences remained significant across all primary HNSCC subsites and in comparison with low- and high-dose cisplatin.Conclusions: Cetuximab with RT yields inferior OS in comparison with cisplatin for the nonoperative management of stage III to IVb HNSCC. According to this study, cisplatin may be the most appropriate partner for RT in this setting. [ABSTRACT FROM AUTHOR]

Background: Existing data supporting the use of proton-beam therapy (PBT) for limited-stage small cell lung cancer (LS-SCLC) are limited to a single 6-patient case series. This is the first prospective study to evaluate clinical outcomes and toxicities of PBT for LS-SCLC.Methods: This study prospectively analyzed patients with primary, nonrecurrent LS-SCLC definitively treated with PBT and concurrent chemotherapy from 2011 to 2016. Clinical backup intensity-modulated radiotherapy (IMRT) plans were generated for each patient and were compared with PBT plans. Outcome measures included local control (LC), recurrence-free survival (RFS), and overall survival (OS) rates and toxicities.Results: Thirty consecutive patients were enrolled and evaluated. The median dose was 63.9 cobalt gray equivalents (range, 45-66.6 cobalt gray equivalents) in 33 to 37 fractions delivered daily (n = 18 [60.0%]) or twice daily (n = 12 [40.0%]). The concurrent chemotherapy was cisplatin/etoposide (n = 21 [70.0%]) or carboplatin/etoposide (n = 9 [30.0%]). In comparison with the backup IMRT plans, PBT allowed statistically significant reductions in the cord, heart, and lung mean doses and the volume receiving at least 5 Gy but not in the esophagus mean dose or the lung volume receiving at least 20 Gy. At a median follow-up of 14 months, the 1-/2-year LC and RFS rates were 85%/69% and 63%/42%, respectively. The median OS was 28.2 months, and the 1-/2-year OS rates were 72%/58%. There was 1 case each (3.3%) of grade 3 or higher esophagitis, pneumonitis, anorexia, and pericardial effusion. Grade 2 pneumonitis and esophagitis were seen in 10.0% and 43.3% of patients, respectively.Conclusions: In the first prospective registry study and largest analysis to date of PBT for LS-SCLC, PBT was found to be safe with a limited incidence of high-grade toxicities. Cancer 2017;123:4244-4251. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Patients with platinum-refractory, recurrent or metastatic squamous cell carcinoma of the head and neck (RM-SCCHN) have limited options. Activin receptor-like kinase 1 (ALK1) is a type I receptor of the transforming growth factor β superfamily expressed on activated endothelial cells. Dalantercept is an ALK1 receptor fusion protein that acts as a ligand trap to block signaling through ALK1 and inhibits stages of angiogenesis involved in blood vessel maturation and stabilization. In a phase 1 study, dalantercept demonstrated clinical activity in patients with RM-SCCHN. The objective of the current study was to evaluate the activity of dalantercept in RM-SCCHN.Methods: Forty-six patients received dalantercept at doses of 80 mg (n = 2), 0.6 mg/kg (n = 13), or 1.2 mg/kg (n = 31) subcutaneously every 3 weeks. The primary endpoint was the overall response rate according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). Secondary endpoints included progression-free survival and overall survival, safety and tolerability, and pharmacokinetic and pharmacodynamic assessments.Results: Forty patients were evaluable for response (13 who received dalantercept 0.6 mg/kg and 27 who received dalantercept 1.2 mg/kg). The overall response rate was 5% (n = 2), and 35% of patients had stable disease; 44% of patients who received 1.2 mg/kg and 30.8% of those who received 0.6 mg/kg achieved disease control (partial response or stable disease). The median progression-fee survival was 1.4 months (95% confidence interval, 1.3-2.2 months), and the median overall survival was 7.1 months (95% confidence interval, 5.5-11.1 months). Drug-related adverse events (>15%) were anemia, fatigue, peripheral edema, headache, and hyponatremia.Conclusions: In an unselected, heavily pretreated population of patients with RM-SCCHN, dalantercept monotherapy resulted in a favorable safety profile but only modest dose-dependent activity, and it did not meet the primary efficacy objective of the study. Cancer 2016;122:3641-9. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The combination of cisplatin, 5-fluorouracil, and cetuximab is a standard treatment for patients with recurrent/metastatic head and neck cancer, with a high rate of toxicity. Identifying less toxic, equally effective regimens is imperative. Therefore, in the current study, the authors investigated first-line treatment with an all-oral regimen of capecitabine and lapatinib.Methods: Patients were required to have incurable head and neck cancer of any primary site other than the nasopharynx, an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 2, and no prior exposure to capecitabine or lapatinib. Subjects were treated with capecitabine at a dose of 1000 mg/m(2) twice daily and lapatinib at a dose of 1250 mg daily. Capecitabine was administered for 14 days of each 21-day cycle for 4 cycles. Lapatinib was administered daily until disease progression. The primary outcome was overall survival.Results: A total of 44 subjects were accrued between November 13, 2009 and April 29, 2014. Approximately 38.6% of the sample had an ECOG PS of 0, 52.3% had an ECOG PS of 1, and 9.1% had an ECOG PS of 2. Approximately 81.8% were male and the median age of the patients was 62 years. Prior attempts at curative treatment with chemotherapy had been used in 68.2% of patients (platinum was used in 55.8%). There was no grade 5 toxicity noted (toxicity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]). The most common adverse events were diarrhea (18.2% of patients with grade 3) and rash (13.6% of patients with grade 3). The primary objective was met; the median overall survival was 10.7 months (90% confidence interval [90% CI], 8.7-12.9 months). The overall response rate was 25% (90% CI, 15%-38%). The median progression-free survival was 4.2 months (90% CI, 3.6-5.1 months). The results were not substantially different when subdivided by p16 status. Only 2 patients were positive for human epidermal growth factor receptor 2 by immunohistochemistry.Conclusions: The current study met its primary objective of survival comparable to the combination of cisplatin, 5-FU and cetuximab regimen, and the toxicity of this all-oral regimen was tolerable. Cancer 2016;122:2350-2355. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background. The purpose of this study was to determine clinical factors that predict locoregional recurrence or distant metastasis in patients with human papillomavirus (HPV)-positive oropharyngeal cancer treated with surgery and guideline-indicated adjuvant therapy. Methods. We identified all presumed HPV-positive patients with oropharyngeal cancer in our health system from January 2010 to August 2012 treated with surgery and guideline-indicated adjuvant therapy. Statistical analysis was performed to identify clinical predictors associated with treatment failure. Results. One hundred fourteen p16+ oropharyngeal cancers managed with initial surgical resection were identified. Median follow-up was 17 months. Two-year locoregional failure was 3.3% and distant failure was 8.4%. Statistical analysis found that conventional poor prognostic features did not predict treatment failure. Conclusion. Locoregional recurrence and development of distant metastatic disease are uncommon in patients who are appropriately selected for surgical management of p16+ oropharyngeal cancer regardless of the presence or absence of conventional poor prognostic features. [ABSTRACT FROM AUTHOR]

Background: Cancer patients and their oncologists often report differing perceptions of consultation discussions and discordant expectations regarding treatment outcomes. CONNECT, a computer-based communication aid, was developed to improve communication between patients and oncologists.Methods: CONNECT includes assessment of patient values, goals, and communication preferences; patient communication skills training; and a preconsultation physician summary report. CONNECT was tested in a 3-arm, prospective, randomized clinical trial. Prior to the initial medical oncology consultation, adult patients with advanced cancer were randomized to the following arms: 1) control; 2) CONNECT with physician summary; or 3) CONNECT without physician summary. Outcomes were assessed with postconsultation surveys.Results: Of 743 patients randomized, 629 completed postconsultation surveys. Patients in the intervention arms (versus control) felt that the CONNECT program made treatment decisions easier to reach (P = .003) and helped them to be more satisfied with these decisions (P < .001). In addition, patients in the intervention arms reported higher levels of satisfaction with physician communication format (P = .026) and discussion regarding support services (P = .029) and quality of life concerns (P = .042). The physician summary did not impact outcomes. Patients with higher levels of education and poorer physical functioning experienced greater benefit from CONNECT.Conclusions: This prospective randomized clinical trial demonstrates that computer-based communication skills training can positively affect patient satisfaction with communication and decision-making. Measurable patient characteristics may be used to identify subgroups most likely to benefit from an intervention such as CONNECT. [ABSTRACT FROM AUTHOR]

BACKGROUND: The high prevalence of v-raf murine sarcoma viral oncogene homolog B1 ( BRAF) and neuroblastoma v- ras oncogene homolog ( NRAS) mutations in melanoma provides a strong rationale to test the clinical efficacy of mitogen-activated protein kinase kinase (MEK) inhibition in this disease. The authors hypothesized that the presence of BRAF or NRAS mutations would correlate with clinical benefit among patients who received treatment with combination regimens that included the MEK inhibitor selumetinib. METHODS: BRAF and NRAS mutation status was determined retrospectively in available tissue specimens from patients with melanoma who were enrolled in a phase 1 trial of selumetinib in combination with 1 of 4 drugs (dacarbazine, docetaxel, temsirolimus, or erlotinib). The clinical response rate and the time to progression (TTP) were assessed as a function of BRAF and NRAS mutation status. RESULTS: Among 18 patients analyzed, 9 patients (50%) harbored a BRAF mutation (8 had a valine-to-glutamic acid substitution at residue 600 [V600E]; 1 had an arginine nonsense mutation at residue 603 [R603]), 4 patients (22%) harbored an NRAS mutation (2 had a glutamine-to-arginine substitution at residue 61 [Q61R], 1 had a glutamine-to-lysine substitution at residue 61 [Q61K], and 1 had a glycine-to-lysine substitution at residue 12 [G12S]), and 5 patient (28%) had the wild type of both genes. These mutations were mutually exclusive. Among the 9 patients who had BRAF mutations, 5 patients (56%) achieved a partial response, and 4 patients (44%) achieved stable disease for at least 6 weeks. No patient with the wild-type BRAF gene achieved a clinical response ( P = .01 vs patients with BRAF mutations). The presence of an NRAS mutation did not correlate with the clinical response rate. The presence of a BRAF mutation was correlated significantly with the TTP in a multivariate model (hazard ratio, 0.22; P = .02 vs wild-type BRAF). CONCLUSIONS: Higher response rates and longer TTP were observed with selumetinib-containing regimens in patients who had tumors that harbored a BRAF mutation compared with patients who had wild-type BRAF. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background. Oropharyngeal, laryngeal, and hypopharyngeal cancer treatment has changed at our institution, but survival outcomes have not been evaluated. Methods. We approached the evaluation by a retrospective single-institution cohort study. Results. Review of 180 patient records from 1993 to 2004 revealed that the number of patients with oropharyngeal cancer treated nearly doubled, whereas the number of patients with laryngeal and hypopharyngeal cancers declined ( p = .006). Since 2000, concurrent chemotherapeutic regimens rather than radiation alone became the dominant treatment approach, with associated improvements in recurrence-free and overall survival ( p = .009 and p = .006, respectively). Stratification by tumor site, however, revealed the survival of patients with oropharyngeal cancer improved markedly, whereas the survival of patients with laryngeal cancer did not change. In the multivariate analysis, T classification ( p = .0001) and chemotherapy use ( p = .0001) were associated with improved survival. The recurrence-free survival of nonsmokers was better than that for former or current smokers ( p = .01), but was accounted for by earlier T classification on presentation in the multivariate analysis ( p = .0001). The predominant initial site of failure remained at the primary site for oropharyngeal cancer (14 of 17 relapses or 82%), but not laryngeal cancer (3 of 7 relapses or 42%). As a result, an increasing number of patients with recurrent oropharyngeal cancer, and a decreasing number of recurrent laryngeal cancer patients were evaluated for salvage surgery. Patients with oropharyngeal recurrences, however, were less likely to undergo surgery with curative intent ( p = .02) and were less likely to achieve locoregional control after disease recurrence. Conclusions. The survival of patients with oropharyngeal and hypopharyngeal cancers treated at our institution has improved over the last 15 years, which is likely related to changes in treatment and tumor biology. The improvement was not observed in patients with laryngeal cancer. A subset of patients with oropharyngeal cancer remain subject to local failure and disease-related death. © 2010 Wiley Periodicals, Inc. Head Neck 33:1433-1440, 2010 [ABSTRACT FROM AUTHOR]

Background. The impact of posttreatment neck dissection on prolonged feeding tube dependence in patients with head and neck squamous cell cancer (HNSCC) treated with primary radiation or chemoradiation remains unknown. Methods. We conducted a retrospective cohort study using propensity score adjustment to investigate the effect of neck dissection on prolonged feeding tube dependence. Results. A review of 67 patients with node-positive HNSCC (T1-4N1-3), treated with primary radiation or chemoradiation, with no evidence of tumor recurrence and follow-up of at least 24 months, was performed. Following adjustment for covariates, the relative risk (RR) of feeding tube dependence at 18 months was significantly increased in patients treated with posttreatment neck dissection (RR 4.74, 95% confidence interval [CI] 2.07-10.89). At 24 months, the relative risk of feeding tube dependence in the patients having undergone neck dissection increased further (RR 7.66, 95% CI 2.07-10.89). Of patients with feeding tubes 2 years after completing treatment, 75% remained feeding tube dependent. Conclusion Neck dissection may contribute to chronic oropharyngeal dysphagia in HNSCC patients treated with primary radiation or chemoradiation. © 2009 Wiley Periodicals, Inc. Head Neck, 2010 [ABSTRACT FROM AUTHOR]

Background. Gene amplification status of the epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor 2 (HER2) were analyzed and correlated with clinical outcome in patients with progressive malignant salivary glands tumors (MSGT) treated with the dual EGFR/Her2 tyrosine kinase inhibitor lapatinib. Methods. Fluorescence in situ hybridization (FISH) analysis for both EGFR and HER2 gene amplification was performed successfully in the archival tumor specimens of 20 patients with adenoid cystic carcinomas (ACC) and 17 patients with non-ACC, all treated with lapatinib. Results. For ACC, no EGFR or HER2 amplifications were detected. For non-ACC, no EGFR gene amplifications were detected but 3 patients (18%) were HER2 amplified and all had stained 3+ for both EGFR and HER2 by immunohistochemistry (IHC) in their archival specimens. Two of these patients had time-to-progression (TTP) durations of 8.3 months and 18.4 months, respectively. Interestingly, patients with low and high HER2/chromosome-specific centromeric enumeration probe (CEP) 17 ratio had a prolonged TTP than those with moderate ratios for both ACC and non-AAC subtypes. Conclusions. HER2 to CEP17 FISH ratio may predict which patients with MSGT have an increased likelihood to benefit from lapatinib. The finding of HER2:CEP17 ratio as a predictive marker of efficacy to lapatinib warrants further investigation. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [ABSTRACT FROM AUTHOR]

This essay will evaluate the factors that have contributed to the increase in the usage and status of the English language in Mongolia since the country's democratic revolution in 1990. The issue of language spread will first be addressed through a description of the economic, social and educational influences that other foreign languages, particularly Russian, have had in Mongolia in the twentieth century. The reasons for the spread of English will then be displayed by discussing the effects of globalism in the mid-1990s and by analyzing a study on the importance of learning English conducted among university students. The various functions that English now serves among the general population will then be categorized according to Kachru's framework of four linguistic functions (instrumental, regulative, interpersonal, imaginative). Lastly, the issue of nativization will be addressed through a brief examination of the lexical and syntactical modifications propagated by Mongolian English users. [ABSTRACT FROM AUTHOR]