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Established prognostic factors for head and neck squamous cell carcinoma (HNSCC) mostly consist of clinical and tumor features assessed before treatment. We report a novel application of DNA methylation in peripheral blood before and after radiation therapy to further improve outcomes stratification.Peripheral blood samples from patients with nonmetastatic HNSCC were obtained for methylation analysis 1 week before and 1 month after radiation therapy. Patients were randomized 1:1 to a Discovery Cohort or a Validation Cohort. In the Discovery Cohort, associations between genome-wide methylation change (posttreatment minus pretreatment) and recurrence-free survival (RFS) as well as overall survival (OS) were evaluated using Cox regression. A methylation risk score (MRS) was then constructed from methylation levels at the top associated sites, filtered for residing within the regulatory regions of genes expressed in cells of hematopoietic lineage. The prognostic value of MRS was separately assessed in the Discovery and Validation Cohorts.Between December 2013 and September 2018, 115 patients participated in this study. Human papilloma virus negative status, oral cavity cancer, gastrostomy tube insertion, and higher neutrophil count before radiation therapy were associated with shorter RFS and OS (P.05). Genes downstream of the methylation sites comprising MRS are HIF1A, SF1, LGALS9, and FUT5, involved in hypoxia response, blood cell maturation, and immune modulation. High MRS (in the top third) was significantly associated with worse RFS (hazard ratio [HR], 7.1; 95% confidence interval [CI], 1.4-35.5; P = .016) and OS (HR, 15.9; 95% CI, 1.6-153.6; P = .017) in the Discovery Cohort, independent of the aforementioned risk factors. These findings were replicated in the Validation Cohort, for which high MRS also independently predicted worse RFS (HR, 10.2; 95%, CI 2.4-43.4; P = .002) and OS (HR, 3.7; 95% CI, 1.3-10.4; P = .015).We successfully trained and validated a signature of DNA methylation in peripheral blood before and after radiation therapy that stratified outcomes among patients with HNSCC, implicating the potential for genomics-tailored surveillance and consolidation treatment.

Purpose:People living with chronic illness face significant challenges with employment. This study explores the impact of participating in the Career Construction Interview (CCI) on the career exploration of individuals facing a forced career transition due to the onset or exacerbation of a chronic illness.Method:An instrumental multiple case study design was used in this qualitative study. A purposeful, homogeneous sample of three female adults was used to gain multiple perspective of forced career transitions. The participants were within 2 years of their diagnosis or exacerbation of one or more chronic health conditions and had to change their career because of the impact of their condition(s).Results:Eight open codes and five axial codes were discovered through the process of constant comparative analysis. For this study one open code (CCI experience) and five axial codes will be discussed.Conclusions:This study found patterns related to chronic illness and career and that the Career Construction Interview was helpful to the participants in assisting them with making decisions about potential careers and options for employment. Implications for rehabilitation counseling practice and suggestions for future research.

Tobacco cessation is a critical but challenging intervention for cancer patients. Our National Cancer Institute-designated Comprehensive Cancer Center instituted a tobacco cessation program in 2019. This manuscript reports on the first 2 years of our experience.Patients were referred to the program by their care team, and a certified tobacco treatment specialist contacted patients remotely and provided behavioral therapy and coordinated pharmacotherapy. We retrospectively captured data from patients with a cancer diagnosis referred to the tobacco cessation program. Univariate and multivariable logistic regression analyses with the backward elimination approach were performed to determine factors associated with patient acceptance of referral to the tobacco cessation program. Tobacco cessation rates after referral to the program were also captured.Between July 2019 and August 2021, 194 patients were referred to the tobacco cessation program. Of the 194 patients referred, 93 agreed to enroll in the tobacco cessation program (47.9%), of which 84 requested pharmacotherapy (90.3%). Twenty-four were able to cease tobacco use (25.8%). Only 7 patients out of the 101 patients (6.9%) who declined cessation services were successful (p 0.001). On univariate logistic regression, race (p = 0.027) and marital status (p = 0.020) were associated with referral acceptance. On multivariable analysis, single patients (odds ratio [OR] = 0.33) and Caucasian patients (OR = 0.43) were less likely to accept a referral.Access to tobacco cessation services is a critical component of comprehensive cancer care. Our experience highlights the need to understand patient-specific factors associated with engagement with a tobacco cessation program during cancer treatment. The use of pharmacotherapy is also a critical component of successful tobacco cessation.

Higher estimated radiation doses to immune cells (EDIC) have correlated with worse overall survival (OS) in patients with locally-advanced non-small cell lung cancer (NSCLC) prior to the PACIFIC trial, which established consolidative durvalumab as standard-of-care. Here, we examine the prognostic impact of EDIC in the durvalumab era.This single-institution, multi-center study included patients with unresectable stage II/III NSCLC treated with chemoradiation followed by durvalumab. Associations between EDIC [analyzed continuously and categorically (≤6 Gy vs 6 Gy)] and OS, progression-free survival (PFS), and locoregional control (LRC) were evaluated by Kaplan-Meier and Cox proportional methods.100 patients were included with median follow-up of 23.7 months. The EDIC 6 Gy group had a significantly greater percentage of stage IIIB/IIIC disease (76.0 % vs 32.6 %; p 0.001) and larger tumor volumes (170 cc vs 42 cc; p 0.001). There were no differences in early durvalumab discontinuation from toxicity (24.1 % vs 15.2 %; p = 0.27). Median OS was shorter among the EDIC 6 Gy group (29.6 months vs not reached; p 0.001). On multivariate analysis, EDIC 6 Gy correlated with worse OS (HR: 4.15, 95 %CI: 1.52-11.33; p = 0.006), PFS (HR: 3.79; 95 %CI: 1.80-8.0; p 0.001), and LRC (HR: 2.66, 95 %CI: 1.15-6.18; p = 0.023). Analyzed as a continuous variable, higher EDIC was associated with worse OS (HR: 1.34; 95 %CI: 1.16-1.57; p 0.001), PFS (HR: 1.52; 95 %CI: 1.29-1.79; p 0.001), and LRC (HR: 1.34, 95 %CI: 1.13-1.60; p = 0.007).In the immunotherapy era, EDIC is an independent predictor of OS and disease control in locally advanced NSCLC, warranting investigation into techniques to reduce dose to the immune compartment.

ImportanceThymic carcinoma is rare, and its oncologic management is controversial due to a paucity of prospective data. For this reason, multidisciplinary consensus guidelines are crucial to guide oncologic management.ObjectiveTo develop expert multidisciplinary consensus guidelines on the management of common presentations of thymic carcinoma.Evidence ReviewCase variants spanning the spectrum of stage I to IV thymic carcinoma were developed by the 15-member multidisciplinary American Radium Society (ARS) Thoracic Appropriate Use Criteria (AUC) expert panel to address management controversies. A comprehensive review of the English-language medical literature from 1980 to 2021 was performed to inform consensus guidelines. Variants and procedures were evaluated by the panel using modified Delphi methodology. Agreement/consensus was defined as less than or equal to 3 rating points from median. Consensus recommendations were then approved by the ARS Executive Committee and subject to public comment per established ARS procedures.FindingsThe ARS Thoracic AUC panel identified 89 relevant references and obtained consensus for all procedures evaluated for thymic carcinoma. Minimally invasive thymectomy was rated as usually inappropriate (regardless of stage) due to the infiltrative nature of thymic carcinomas. There was consensus that conventionally fractionated radiation (1.8-2 Gy daily) to a dose of 45 to 60 Gy adjuvantly and 60 to 66 Gy in the definitive setting is appropriate and that elective nodal irradiation is inappropriate. For radiation technique, the panel recommended use of intensity-modulated radiation therapy or proton therapy (rather than 3-dimensional conformal radiotherapy) to reduce radiation exposure to the heart and lungs.Conclusions and RelevanceThe ARS Thoracic AUC panel has developed multidisciplinary consensus guidelines for various presentations of thymic carcinoma, perhaps the most well referenced on the topic.

MICROABSTRACT: We evaluated the association of operability status with early post-treatment mortality among patients with early-stage non-small cell lung cancer undergoing stereotactic body radiotherapy. In this cohort study of 80,108 patients from a large US cancer dataset, operable patients undergoing stereotactic body radiotherapy experienced

The treatment for locally advanced non–small-cell lung cancer has changed dramatically over the past several years, with consolidative immunotherapy after concurrent chemoradiation becoming the new standard of care. Five-year survival outcomes have substantially improved with this approach. Despite these advances, further improvements are needed as the majority of patients ultimately develop progression of disease. The next-generation immunotherapy trials are currently being conducted that include approaches such as concurrent immunotherapy and addition of other therapeutic agents in the concurrent and consolidative settings. Specific unmet needs continue to exist for patients who develop disease progression after concurrent chemoradiation and immunotherapy, as well as defining the best treatment for patients with driver mutations. Future directions also include refinement of radiation techniques to reduce toxicities as much as possible, as well as the use of circulating tumor DNA in the surveillance setting. The current scientific landscape shows promising approaches that may further improve outcomes for patients with locally advanced non–small-cell lung cancer.

Introduction: Lung cancer is the leading cause of cancer-related death due to frequent diagnosis at an advanced stage, especially among underserved populations. Given the marked heterogeneity in disease course for metastatic non-small cell lung cancer (mNSCLC), we sought to further explore its distribution of genomic alterations and outcomes across population subgroups. Methods: Clinicogenomics data were downloaded from the MSK-MET cohort study, one of the largest publicly accessible databases of metastatic cancer featuring 25775 patients in the February 2022 release. Tumor mutation burden (TMB) was quantified as number of non-synonymous mutations per megabase (Mb) sequenced. Categorical variables were compared using the χ2-test. Analysis of overall survival (OS) was performed using Cox proportional hazards regression. Results: Between 2013 and 2020, tumor and matched-normal samples from 4710 adult patients (58% female) with mNSCLC (86% adenocarcinoma) were obtained for genomic characterization. Median age at diagnosis was 67 years (IQR 59–73) and median OS was 38 months (95% CI 34–40 months). Smoking status and treatment history were unavailable. Patients self-identified as non-Hispanic white (76%), Asian (10%), Black (5%), Hispanic (4%), Native American (1%), or none of the above (1%). Compared to patients of other races, Hispanic patients were more likely to be diagnosed with mNSCLC prior to age 50 (17% vs. 7%, P Citation Format: David C. Qian, Conor E. Steuer, Sibo Tian, Jennifer W. Carlisle, Ticiana A. Leal, Madhusmita Behera, Jeffrey D. Bradley, Suresh S. Ramalingam, Kristin A. Higgins. Landscape of actionable mutations and outcomes in metastatic non-small cell lung cancer across age, sex, and race [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PR008.

Brain metastases from non-small cell lung cancer often cause neurologic symptoms which lead to initial diagnosis or identification of recurrence. In other patients, they are identified on surveillance imaging or when a patient undergoing treatment develops neurological symptoms. Patients with symptomatic lesions should be started on dexamethasone and evaluated by a neurosurgeon as soon as possible. If feasible, surgery should be offered to decrease intracranial pressure, alleviate symptoms, and prevent irreversible neurological damage. Postoperative stereotactic radiosurgery (SRS) to the resection cavity and any additional brain metastases should follow within 4 weeks of surgery, as early as 2 weeks post-op. Tissue from surgery is used to confirm the diagnosis and test for targetable oncogenic driver mutations. Treatment response and surveillance for development of additional lesions is assessed with MRI of the brain 1 month after SRS and every 3 months thereafter. Patients who are not surgical candidates or who have small, asymptomatic brain metastases should proceed with SRS, the preferred treatment, or sometimes whole-brain radiation therapy (WBRT) if multifocal disease requires more extensive treatment, such as for leptomeningeal spread of disease. The number of brain metastases that warrants use of WBRT over SRS is controversial and a topic of ongoing investigation, and is discussed in this review. When possible, SRS is preferred over WBRT due to reduce morbidity and cognitive side effects. When patients are already on systemic therapy at time of brain metastases diagnosis, systemic therapy should continue, with radiation therapy occurring between cycles. Regarding systemic therapy for new diagnosis at time of brain metastases presentation, molecular testing will guide treatment choice, when available. If there is no neurosurgical intervention, biopsy of another site of disease may provide tissue for molecular testing. If there are no targetable oncogenic driver mutations, concurrent immune checkpoint blockade (ICB) and chemotherapy is preferable for patients who can tolerate it. Single-agent ICB is an alternative option for patients who cannot tolerate chemotherapy. Systemic therapy should start as soon as possible. In some patients with poor performance status, best supportive care may be the most appropriate choice. Treatment decisions should always incorporate patients' goals of care and in many cases should be discussed in a multidisciplinary setting.

Objectives: Patients with head and neck cancer experience neuropsychological symptoms (NPS) (i.e., depression, fatigue, sleep disturbance, pain, and cognitive dysfunction) during radiation therapy (RT) that decrease their functional status and quality of life. The purposes of this study were to examine and visualize the relationships among NPS within networks over time and evaluate demographic and clinical characteristics associated with symptom networks. Methods: A total of 192 patients (mean age 59.5±10.1 years, 75% male, 81% White) completed symptom questionnaires four times, namely, before RT (T1), 1 month (T2), 3 months (T3), and 1 year (T4) after RT. Network analysis was used to explore relationships among the five common NPS. Centrality indices, including strength, closeness, and betweenness, were used to describe the degrees of symptom interconnection. The network comparison test was used to assess the differences between two symptom networks. Results: Depression (reported by 13%-24% of patients) was associated with the other four symptoms, and fatigue (reported by 54%-77% of patients) was associated with the other three symptoms across four times. Based on centrality indices, depression (rstrength=1.1-1.4, rcloseness=0.07-0.08, rbetweeness=4-12) was the most central symptom in all four symptom networks, followed by fatigue (rstrength=0.8-1.0, rcloseness=0.05-0.06, rbetweeness=0-2). Higher levels of stress and no alcohol use were associated with stronger symptom networks in network global strength (low stress: 1.49 vs. moderate to high stress: 1.92; p=0.02; no alcohol use: 2.38 vs. alcohol use: 1.75; p=0.01), but not in network structure or edge strength prior to RT. No significant differences were found in other time points. Conclusions: Network analysis provided a novel approach to gain insights into the relationships of co-occurring NPS and identify central symptoms and associated characteristics. Clinicians can use this information to develop personalized symptom management interventions that target central symptoms and interactions within a network. Citation Format: Yufen Lin, Deborah W. Bruner, Sudeshna Paul, Andrew H. Miller, Nabil F. Saba, Kristin A. Higgins, Dong M. Shin, Wenhui Zhang, Christine Miaskowski, Canhua Xiao. Neuropsychological symptoms in patients with head and neck cancer undergoing radiation therapy: A network analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 500.

8513 Background: In advanced non-small cell lung cancer (NSCLC), high Programmed-Death-1 Ligand (PD-L1) (>50%) expression demonstrate superior response and survival with immune checkpoint inhibitors compared to chemotherapy. We hypothesize that it is safe and feasible to substitute durvalumab instead of chemotherapy concurrently with radiotherapy (RT) in patients with Locally Advanced-NSCLC (LA-NSCLC) and high PD-L1. Methods: NRG-LU004 (NCT03801902) is a Phase I study for patients with stage II-III unresectable or inoperable, LA-NSCLC with PD-L1> 50% (Dako 22C3 or Ventana SP263) expression. There were safety and expansion phases with a primary endpoint of safety. Patients started with 1500 mg durvalumab Q4 weeks and thoracic RT within 2 weeks from 1st infusion. Durvalumab continued once a month up to 1 year. In the safety cohort, 6 patients in cohort 1 were treated with accelerated fractionated RT (ACRT) to 60 Gy in 15 fractions, followed by a required safety hold for 90 days. During cohort 1 safety hold, cohort 2 patients were treated with conventional RT 60 Gy in 30 fractions (CONV) followed by a 60-day safety hold. A cohort advanced to the expansion phase to enroll 6 more patients if safety criteria (0-1 patients with a dose limiting toxicity [DLT]) were met. If both cohorts were deemed safe, patients would be randomized 1:1 to ACRT or CONV with safety defined as < 4 of 12 evaluable patients per arm experiencing a DLT. Feasibility was defined as at least 80% of patients in each arm receiving at least 80% of the planned dose of durvalumab during the first 8 weeks. Results: 24 evaluable patients enrolled between January 2019 and June 2021. No DLTs were reported in cohort 1, and 1 (unrelated bronchopulmonary hemorrhage leading to discontinuation of durvalumab) in cohort 2. Both safety cohorts advanced to the expansion phase. All but one patient (CONV) received RT per protocol/with an acceptable variation. At the time of analysis, 24% had received all 13 cycles of durvalumab. For the ACRT cohort, there were 4 grade 3, 1 grade 4 (lymphopenia), and 1 grade 5 AE (lung infection, assessed as unrelated to therapy). For CONV, there were 8 grade 3, 0 grade 4, and 1 grade 5 AE (respiratory failure, unrelated to therapy). For feasibility, 10 of 12 (85%) patients in the ACRT cohort received the second dose of durvalumab (2 not received due to shingles and unrelated death), while 9 of 12 (75%) of the CONV cohort received the second dose (reasons for not receiving: viral hepatitis, bronchopulmonary hemorrhage, and respiratory failure, all assessed as unrelated to therapy). Conclusions: Chemotherapy-free thoracic RT approaches (ACRT or CONV RT) are safe, when given with concurrent durvalumab in patients with PD-L1 high LA-NSCLC. A trial to compare immunoradiotherapy and consolidation durvalumab to standard chemoradiation and consolidation durvalumab is planned. Clinical trial information: NCT03801902.

9128 Background: Precision medicine has resulted in improved outcomes for non-small cell lung cancer (NSCLC); while molecular testing is considered critical for guiding treatment decisions for advanced stage NSCLC, adoption of testing in routine practice is variable. We analyzed the factors contributing to molecular testing and treatment patterns in patients with lung cancer. Methods: The ASCO CancerLinQ Discovery dataset was queried to identify patients diagnosed with lung cancer between the years 2010-2018. Data on demographics, tumor stage, histology and treatments were extracted, and receipt of molecular testing was investigated as the primary outcome. Univariate association of each clinicopathological variable with molecular testing outcome was performed using chi-square test for categorical variables and ANOVA test for numerical variables. A multivariable logistic regression analysis with backward selection at an alpha of 0.05 was reported. All analyses were conducted using SAS 9.4. Results: A total of 37,925 NSCLC patients with stage IV disease were analyzed. Patient characteristics: median age 65 years, 51% male, 68% white, 33.5% adenocarcinoma. Approximately 22% of all NSCLC patients had molecular testing results. In adenocarcinoma patients, 49% had molecular testing results available. In the stage IV group, 47% were treated with chemotherapy, 16% with immunotherapy and 3% with targeted therapy. On multivariable analysis, females were more likely to have molecular testing compared to males [(OR: 1.29 (1.22-1.37); p < 0.001]. Compared to White patients, Black patients were less likely to have molecular testing [OR: 0.89 (0.81-0.97); p = 0.009] and Asians were more likely to undergo testing [OR: 2.22 (1.79-2.75); p < 0.001]. Hispanic patients were more likely to undergo molecular testing compared to non-Hispanics [OR:1.24 (1.02-1.52); p = 0.03]. Additionally, treatment with immunotherapy [OR: 1.86 (1.72-2.01); p < 0.001] and targeted therapy [OR: 2.29 (2.00-2.64); p < 0.001] were associated with significantly higher likelihood of having molecular testing. These results were also confirmed on a subgroup analysis of adenocarcinoma patients. Conclusions: In this analysis of a US-based real-world dataset of stage IV NSCLC patients, White race and female sex are associated with higher likelihood of having molecular test performed. The percentage of patients undergoing testing remains sub-optimal.

Treatment for advanced lung adenocarcinoma (AC) has become increasingly personalized based on molecular results. However, for patients with AC brain metastases (BMs), intracranial outcomes based on molecular subtype and the frequency of molecular aberrations are less well defined. This study sought to report targeted next-generation sequencing results and investigate molecularly based outcomes for patients with AC-BMs treated with radiotherapy.The records of 132 patients with AC-BMs treated at Emory University from September 2008 to August 2016 with successful next-generation sequencing were reviewed. Rates of local disease recurrence, distant brain failure (DBF), and salvage whole-brain radiotherapy (WBRT) were estimated using cumulative incidence with competing risk analysis. Univariate and multivariate analyses were performed.The most common aberrations included tumor protein 53 (TP53) (60%), KRAS (29%), epidermal growth factor receptor (EGFR) (20.5%), phosphatase and tensin homolog (PTEN) loss (15.5%), and MET amplification (13%). The majority of patients (62%) were treated with stereotactic radiosurgery alone. In these patients, KRAS mutation, anaplastic lymphoma kinase (ALK) rearrangement, and having ≥ 6 BMs were associated with an increased risk of salvage WBRT (P .05). KRAS mutation remained significant for an increased risk of salvage WBRT when compared with EGFR/ALK/KRAS-negative patients (hazard ratio, 5.17; P .05), despite a similar risk of DBF. PTEN loss was associated with increased risk of DBF (P .05), whereas EGFR and ALK aberrations were associated with a decreased risk of local disease recurrence (P .05).The results of the current study quantified the frequency of genetic aberrations in patients with AC-BMs and demonstrated their association with intracranial outcomes. In particular, a cohort of patients with KRAS mutations and ≥6 BMs were identified to be at high risk of requiring salvage WBRT after undergoing upfront stereotactic radiosurgery.

To the authors' knowledge, the practice patterns for patients aged more than 80 years with stage III non-small cell lung cancer (NSCLC) is not well known. The purpose of the current study was to investigate factors predictive of and the impact on overall survival (OS) after concurrent chemoradiation (CRT) among patients aged ≥80 years with American Joint Committee on Cancer stage III NSCLC in the National Cancer Data Base (NCDB).In the NCDB, patients aged ≥80 years who were diagnosed with stage III NSCLC from 2004 to 2013 with complete treatment records were identified. Multivariable logistic regression and Cox proportional hazard models were generated and propensity score-matched analysis was used.A total of 12,641 patients met the entry criteria: 6018 (47.6%) had stage IIIA disease and 6623 (52.4%) had stage IIIB disease. The median age at the time of diagnosis was 83.0 years (range, 80-91 years). A total of 7921 patients (62.7%) received no therapy. Black race (odds ratio [OR], 1.23; 95% confidence interval [95% CI], 1.06-1.43) and living in a lower educated census tract of residence (OR, 1.20; 95% CI, 1.03-1.40) were found to be associated with not receiving care, whereas treatment at an academic center (OR, 0.80; 95% CI, 0.70-0.92) was associated with receiving cancer-directed therapy. Receipt of no treatment (hazard ratio [HR], 2.69; 95% CI, 2.57-2.82) or definitive radiation alone (HR, 1.15; 95% CI, 1.07-1.24) compared with CRT was associated with worse OS. On propensity score matching, not receiving CRT was found to be associated with worse OS (HR, 1.58; 95% CI, 1.44-1.72).In this NCDB analysis, approximately 62.7% of patients aged ≥80 years with stage III NSCLC received no cancer-directed care. Black race and living in a lower educated census tract were associated with not receiving cancer-directed care. OS was found to be improved in patients receiving CRT. Cancer 2018;124:775-84. © 2018 American Cancer Society.

Genetic aberrations are well characterized in lung adenocarcinomas (LACs) and clinical outcomes have been influenced by targeted therapies in the advanced setting. Stereotactic body radiotherapy (SBRT) is the standard-of-care therapy for patients with nonoperable, early-stage LAC, but to the authors' knowledge, no information is available regarding the impact of genomic changes in these patients. The current study sought to determine the frequency and clinical impact of genetic aberrations in this population.Under an Institutional Review Board-approved protocol, the records of 242 consecutive patients with early-stage lung cancers were reviewed; inclusion criteria included LAC histology with an adequate tumor sample for the successful use of next-generation sequencing and fluorescence in situ hybridization testing. Univariate analysis was performed to identify factors associated with clinical outcomes.LAC samples from 98 of the 242 patients were reviewed (40.5%), of whom 45 patients (46.0%) had genetic testing. The following mutations were noted: KRAS in 20.0% of samples, BRAF in 2.2% of samples, SMAD family member 4 (SMAD4) in 4.4% of samples, epidermal growth factor receptor (EGFR) in 15.6% of samples, STK1 in 2.2% of samples, tumor protein 53 (TP53) in 15.6% of samples, and phosphatase and tensin homolog (PTEN) in 2.2% of samples. The following gene rearrangements were observed: anaplastic lymphoma kinase (ALK) in 8.9% of samples, RET in 2.2% of samples, and MET amplification in 17.8% of samples. The median total delivered SBRT dose was 50 grays (range, 48-60 grays) over a median of 5 fractions (range, 3-8 fractions). The KRAS mutation was associated with worse local control (odds ratio [OR], 3.64; P.05). MET amplification was associated with worse regional (OR, 4.64; P.05) and distant (OR, 3.73; P.05) disease control.To the authors' knowledge, the current series is the first to quantify genetic mutations and their association with clinical outcomes in patients with early-stage LAC treated with SBRT. KRAS mutations were associated with worse local control and MET amplification was associated with worse regional and distant disease control, findings that need to be validated in a prospective setting. Cancer 2017;123:3681-3690. © 2017 American Cancer Society.

Accumulating evidence indicates that although the enrollment of students with psychiatric disabilities in U.S. postsec- ondary institutions is on the rise, these students are not persisting to degree completion at the same rate as their peers without psychiatric disabilities. However, a national investigation of the persistence rates and characteristics of students with disabilities has yet to be conducted. This research study summarizes descriptive data from the Beginning Postsecondary Students Longitu- dinal Study (BPS: 04/09) data set on the characteristics and persistence rates of students with psychiatric disabilities (N = 350) enrolled in U.S. postsecondary institutions. The first-to-second year persistence rate of these students was 76.6% while the three year cumulative persistence and persistence to degree completion rates were 61% and 54.7%, respectively. The demographic and background characteristics of the participants resembled those of typical at-risk students in postsecondary education. Although their academic and social integration into their institutions was limited, chi-square analyses did reveal a significant association between first-to-second year persistence and how often students met with their academic advisors in their first year. These analy- ses also demonstrated a significant relationship between first-to-second year persistence and all three social integration variables examined in the study.

Background: To evaluate the effect of diabetes mellitus (DM) on clinical outcomes in patients managed surgically for non-small cell lung cancer (NSCLC). Methods: Patients who underwent surgery for pathological I-IIIA NSCLC at Duke University from 1995–2005 were analyzed. Postoperative mortality was defined as any death occurring within 30 days of resection or during the initial hospitalization after surgery. Disease recurrence at the surgical margin, ipsilateral hilum, and/or mediastinum was considered a local/regional recurrence (LRR). Survival and LRR rates were estimated using the Kaplan-Meier method and compared using a log rank test. A multivariate regression analysis assessed the association between candidate factors, including DM, and disease recurrence and survival. Results: Of 957 patients, DM was present in 122 (13%). DM was associated with an increased risk of postoperative mortality (7.4% vs. 3.2%, P= 0.04). However, the proportion of patients undergoing sublobar resections, mediastinal lymph node dissection, and receiving adjuvant chemotherapy, was no different among patients with or without DM. Five-year LRR rates were 27% in patients with DM, versus 21% in patients without DM (P= 0.23). Survival at five years was 43% for patients with DM, and 47% for patients without DM (P= 0.10). On multivariate analysis, DM was not independently associated with a higher risk of LRR (hazard ratio [HR] 1.33, P= 0.34), distant recurrence (HR 0.86, P= 0.58), or overall survival (HR 1.08, P= 0.63). Conclusions: Although a higher risk of postoperative mortality was noted in patients with DM, a detriment in local or distant disease control or overall survival was not observed.

Answer questions and earn CME/CNE Laryngeal cancer remains one of the most common tumors of the respiratory tract. Fortunately, significant advancements have been made over the past decade in the treatment of laryngeal cancer. Although surgery has been the historical mainstay for localized disease and still is an integral part of treatment, nonsurgical options like radiation and systemic therapy have emerged as viable options. In addition, in the metastatic setting, novel agents are showing promise for this patient population. The care for patients with laryngeal cancer continues to evolve and truly requires a multidisciplinary team-based approach. Unique morbidities, such as loss of natural voice, respiration, and airway protection during swallowing, are observed with this disease and require special consideration. CA Cancer J Clin 2017;67:31-50. © 2016 American Cancer Society.

Group work can be an effective means of counseling at-risk students. As such, the American School Counselors Association (ASCA) has endorsed group work as an important component of school counseling (ASCA, 2005). Groups can help students learn to solve problems in an efficient and effective manner and is an ideal method for meeting the needs of at-risk populations (Akos & Milsom, 2007). Group counseling allows students to develop connections while at the same time exploring factors that may affect their achievement (Kayler & Sherman, 2009). Groups are used to address such issues as social skills (Bostick & Anderson, 2009), bolstering students’ self-perceptions (Eppler, Olsen, & Hidano 2009), preventing problem behavior (Todd, Campbell, Meyer, & Horner, 2008), increasing academic success (Brigman, Webb, & Campbell, 2007), and reducing school-wide bullying (Allen, 2010). Further, Quinn, Kavale, Mathur, Rutherford, and Forness (1999) conducted a meta-analysis (35 studies) of social skills interventions used with children exhibiting problem or emotional behaviors. Results revealed several important issues. First, it appears that there is a wide range of presenting deficits in children’s social skills. Second, social skills training is widely used as a mechanism to address problem behavior in children; however, it may not be as effective at addressing problem behaviors when used in isolation. The purpose of this study is to compare the effectiveness of two psychosocial intervention programs, Psychosocial Educational Groups for Students (PEGS) and the At-Risk Kids Groups (ARK) and to assess the impact of each program. The PEGS and ARK Programs are designed to help elementary school students in the following areas: social skills development, problem behaviors, bullying, and self-esteem.

The purpose of this study was to evaluate the outcome of a new psychosocial intervention program, Psychosocial Educational Groups for Students (PEGS). The PEGS program is designed to help students ...

The authors review previous examinations of the American Counseling Association's (ACA) Journal of Counseling & Development (JCD), consider various editors' policies that shaped the Journal, and update L. W. Harmon and H. E. Harker's (1989) analysis of special interest topics featured in JCD. Studying the flagship professional journal of ACA provides insight into the evolution and development of the profession of counseling.

Regional recurrence of differentiated thyroid cancer (DTC) is often salvaged with neck dissection without survival penalty. It is unknown whether recurrence may be associated with inferior survival in older patients.Surveillance, Epidemiology, and End Results (SEER) and Medicare data were linked to identify patients age ≥65 with nonmetastatic DTC. Patients undergoing neck dissection6 months after their initial diagnosis were considered to have regional recurrent disease. We compared overall survival (OS) and cause-specific survival (CSS) for patients with recurrent disease versus a matched cohort of patients with non-recurrent DTC.Of 6235 patients, 143 had treatment-defined recurrent disease. Patients with recurrent disease had inferior OS (p.01) and CSS (p.01). Multivariate analysis demonstrated that recurrent disease was independently associated with inferior 10-year OS (hazard ratio [HR] = 1.75; p.01) and CSS (HR = 3.05; p.01).Regional recurrence of DTC may negatively impact OS and CSS in patients ≥65 years old. © 2016 Wiley Periodicals, Inc. Head Neck 38: 919-924, 2016.

The treatment of patients with advanced stage laryngeal cancer includes surgery or concurrent chemoradiation (CRT). Although CRT has become more common in recent years, to the authors' knowledge, the effectiveness of complete CRT in improving survival over surgery has not been studied.The authors examined patients in the Surveillance, Epidemiology, and End Results (SEER)-Medicare claims-linked data set with locoregional laryngeal cancer who were diagnosed between 1997 and 2007. Multivariate Cox proportional hazard analyses were conducted to compare overall and cause-specific 5-year survival rates between treatment modalities, adjusting for patient sociodemographic and clinical characteristics. A propensity score-matched subcohort also was used to compare survival.Of the 3212 patients in the study cohort, 42% underwent surgery and 18% underwent CRT. Only approximately one-quarter of patients who were treated with CRT completed the courses. In adjusted analyses, the authors were unable to reject the null hypothesis of no difference in 5-year all-cause or cause-specific mortality risk between patients treated with surgery and patients undergoing complete CRT (hazards ratio, 1.25 [95% confidence interval, 0.91-1.71; P = .16] and hazard ratio, 1.41 [95% confidence interval, 0.9-2.2; P = .14], respectively). Older age, not currently married, Medicaid eligibility, and prior cancer history were found to be associated with a higher risk of mortality (P.05).Patients with advanced laryngeal cancer who underwent complete CRT were found to have overall and cause-specific survival rates similar to those of patients undergoing surgery. However, a substantial percentage of patients who initiated CRT did not complete the course. Although CRT provides organ preservation, the benefits and trade-offs of CRT and total laryngectomy should be discussed fully with patients. The importance of completing the full course of CRT should be emphasized. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2845-2856. © 2016 American Cancer Society.

Stereotactic body radiation therapy (SBRT) has demonstrated high rates of local control with low morbidity and has now emerged as the standard of care for medically inoperable, early stage non-small cell lung cancer (NSCLC). However, the impact of lung SBRT on survival in the elderly population is less clear given competing comorbid conditions. An analysis of the National Cancer Data Base (NCDB) was undertaken to determine whether definitive SBRT improves survival relative to observation alone patients ages 70 years and older.The NCDB, a retrospective national database that captures approximately 70% of all patients treated for cancer, was queried for patients aged 70 years or older with early stage (T1-T3N0M0) NSCLC from 2003 to 2006. Overall survival was compared between patients who received stereotactic body radiotherapy alone and those who received no treatment. An extended Cox proportional hazards model was applied to estimate the treatment effect of SBRT.In total, 3147 patients met the selection criteria for this analysis. SBRT was delivered to 258 patients (8.2%), and 2889 patients (91.8%) received no treatment. There was no significant difference in the distribution of Charlson/Deyo comorbidity index scores between the 2 groups (P = .076). Multivariable analysis revealed improved overall survival with SBRT compared with observation for the entire cohort (hazard ratio, 0.64; P .001).SBRT is associated with improved survival in elderly patients with early stage NSCLC who have concurrent comorbid conditions compared with observation alone. The current data support the use of SBRT for the treatment of elderly patients with early stage NSCLC who have limiting comorbid conditions.

The benefit of combined chemoradiation in elderly patients with human papillomavirus (HPV)-positive locally advanced oropharyngeal squamous cell carcinoma (SCC) must be balanced with the potential for higher toxicity rates. We performed a retrospective review of our institutional experience.Patients 70 years or older with p16-positive oropharyngeal SCC treated with definitive chemoradiation from 2005 to 2013 were evaluated. Overall survival (OS), disease-free survival (DFS), and locoregional failure-free survival were calculated.Twenty-one eligible patients had a follow-up of 22.4 months. Estimated 5-year OS, DFS, and locoregional failure-free survival were 76.0%, 40%, and 95%, respectively. There was 1 death from acute toxicity, and 50% had unplanned hospitalizations. Sixty percent had late toxicity, and 6-month feeding tube dependence was 25%.Elderly patients with HPV-positive locally advanced SCC of the oropharynx treated with definitive chemoradiation had good OS but high rates of acute and long-term toxicity. © 2015 Wiley Periodicals, Inc. Head Neck 38: 846-851, 2015.

Molecular mechanisms that provide for cGMP activation of cGMP-dependent protein kinase (PKG) are unknown. PKGs are dimeric; each monomer contains a regulatory (R) and catalytic (C) domain. In this study, isolated recombinant R domains of PKGIalpha-(Delta349-670) and PKGIbeta-(Delta364-685) containing the dimerization and autoinhibitory subdomains and two allosteric cGMP-binding sites were expressed in Sf9 cells. Both R domains were dimers with elongated conformations (Stokes radii of 44 and 51 A, respectively, and frictional coefficients of 1.6 and 1.8, respectively). Exchange dissociation kinetics and K(D) values for cGMP were similar for each holoenzyme and its isolated R domain, indicating that under these conditions the C domain does not appreciably alter cGMP-binding functions of the R domain. As determined by gel filtration chromatography, cGMP binding caused elongation of the PKGIalpha-isolated R domain and contraction of the PKGIbeta-isolated R domain. Cyclic GMP-bound forms of the isoforms have similar physical dimensions that may reflect a common conformation of active isoforms. Elongation of the PKGIbeta holoenzyme associated with cGMP binding and PKG activation cannot be explained solely by conformational change in its R domain, but elongation of the PKGIalpha R domain may partially account for the elongation of wild type PKGIalpha associated with cGMP binding. The cGMP-induced conformational changes in the respective R domains are likely to be critical for kinase activation.

This investigation was conducted 10 estimate the reliability and validity of scores on the Riso-Hudson Enneagram Type Indicator (D. R. Riso di R. Hudson. 1999a). Results of 2H7 participants were an...

The purpose of this study was to determine if lymph node ratio is associated with locoregional recurrence for patients with oral cavity or laryngeal cancer treated with initial surgical management.The study included 350 patients with oral cavity (73%) or laryngeal cancer (27%) who underwent initial surgery. All analyses were multivariable, adjusting for primary site, pathologic prognostic factors, and adjuvant therapy.Lymph node ratio was significantly associated with locoregional recurrence, in which each 1% increase in lymph node ratio had an adjusted hazard ratio (HR) for locoregional recurrence of 1.02 (95% confidence interval [CI], 1.002-1.042; p = .05). Lymph node ratio was also associated with OS, in which each 1% increase in lymph node ratio had an adjusted HR for death of 1.028 (95% CI, 1.012-1.045; p = .001).Adjusting for pathologic factors and adjuvant therapy, lymph node ratio was found to be an independent prognostic factor for locoregional recurrence and overall survival (OS). Patients with lymph node ratio ≥20% are at high risk of locoregional recurrence and death, and may be considered for adjuvant chemoradiation.

Prophylactic cranial irradiation (PCI) improves survival in patients with limited-stage small cell lung cancer (SCLC) who have a complete response to chemotherapy and radiotherapy, yet to the best of the authors' knowledge, data specific to the elderly population are lacking.Using the Surveillance, Epidemiology, and End Results (SEER) database, the authors identified 1926 patients aged ≥ 70 years who were diagnosed with limited-stage SCLC between 1988 and 1997. Overall survival (OS) for patients who received PCI versus those who did not were estimated using the Kaplan-Meier method and compared with the log-rank test. A Cox proportional hazards model was further fitted to estimate the effect of PCI on OS after adjusting for age, race, sex, tumor size, lymph node status, stage of disease, and receipt of thoracic radiotherapy and surgery.The median age of the patients was 75 years (range, 70 years-94 years) and 138 patients (7.2 %) received PCI. The 2-year and 5-year OS rates were 33.3% (95% confidence interval [95% CI], 25.6%-41.2%) and 11.6% (95% CI, 6.9%-17.6%), respectively, among patients who received PCI versus 23.1% (95% CI, 21.2%-25.1%) and 8.6% (95% CI, 7.3%-9.9%), respectively, among patients who did not receive PCI (P = .028). On multivariable analysis, PCI was found to be an independent predictor of OS (hazards ratio, 0.72; 95% CI, 0.54-0.97 [P = .032]). On subgroup analysis, PCI remained an independent predictor of OS among patients aged ≥ 75 years, but not among patients aged ≥ 80 years.The receipt of PCI is associated with improved OS in patients aged ≥ 70 years with SCLC, suggesting that the benefit of PCI is maintained in the elderly population.

Asperger Syndrome (AS) is a pervasive developmental disorder characterized by underdeveloped social and communication skills. Despite the fact that most individuals with AS have average to above average cognitive abilities, characteristics of the disorder can cause extreme difficulties in these two domains. While increased attention has been given to the developmental characteristics and educational support needs of children with AS, few studies have focused on the psychosocial and vocational characteristics of emerging adults with AS and the supports they need to succeed in the workplace. This article examines the school-to-work transition of individuals with AS. Psychosocial and vocational characteristics of AS are identified and potential work challenges for these individuals are discussed. The article concludes with specific recommendations for facilitating successful school-to-work transitions for consumers with AS.