Jonathan R. George

Association of TERT Promoter Mutation, But Not BRAF Mutation, With Increased Mortality in PTC

CONTEXT Papillary thyroid carcinoma (PTC) carrying the BRAF mutation has been reported to be associated with high recurrence and potentially increased mortality. PTC carrying the TERT promoter mutation has been associated with older age, recurrence, and aggressive disease. OBJECTIVE The objective of this study was to determine the association of BRAF and TERT promoter gene alterations with recurrence and survival in a high-risk population. DESIGN Genomic DNA was analyzed for the BRAF mutation from 256 persistent/recurrent PTC (p/rPTC; 202 new, 54 previously reported) and for the TERT promoter mutation and polymorphism (242 p/rPTC). Two-tailed Fisher exact tests or the Pearson χ(2) test were performed for the associations between mutations and other variables. Overall and disease-free survivals were compared by log rank tests on Kaplan-Meier plots and by Cox regression analysis. TERT promoter constructs were tested in PTC cell lines to determine their activities in these cells. RESULTS BRAF V600E mutation was identified in 235 of 256 (91.8%), TERT promoter mutation at -124 was detected in 77 of 242 (31.8%), and TERT promoter polymorphism at -245 was found in 113 of 242 (46.7%) p/rPTC patients. A significant difference in survival was found in p/rPTC patients with the TERT promoter mutation, which also displayed increased activity in vitro as compared to the nonmutated promoter sequence. No association was noted between the BRAF mutation or TERT promoter polymorphism and recurrence or survival. A drawback of our study could be the limited number of patients with nonmutated BRAF (21 of 256 [8.2%]). CONCLUSIONS Mutation in the TERT promoter, but not in BRAF, was associated with decreased survival in 19 (24.7%) p/rPTC patients who died of disease and in 38 (49.4%) p/rPTC patients who died at last contact. The presence or absence of the BRAF mutation and TERT promoter polymorphism, however, was not significantly correlated with survival.

Comparison of drug‐induced sleep endoscopy and lateral cephalometry in obstructive sleep apnea

To evaluate the association between findings from drug‐induced sleep endoscopy (DISE) and lateral cephalometry in obstructive sleep apnea (OSA)

Cancer cachexia update in head and neck cancer: Definitions and diagnostic features.

Cachexia is a profoundly debilitating wasting syndrome that affects patients with head and neck cancer and often contributes to their demise. A comprehensive literature search was performed up to April 2013 using PubMed, the Cochrane Library, CINAHL, and the Google search engine. For the meta‐analyses, pooled prevalence estimates were calculated with a confidence interval of 95% (95% CI) by using random effects modeling. In this review, we outlined the unique challenges of cancer cachexia among patients with head and neck cancer by reviewing its impacts on quality of life (QOL), morbidity, and mortality. We explored the prevalence of different clinical markers of cachexia at the time of diagnosis and before and after treatment. Finally, we present updates regarding the diagnosis of cancer cachexia and recent findings, such as cardiac dysfunction that warrant clinical attention to more carefully identify patients at risk and potentially lead to better outcomes.

Improved outcomes in adjuvant radiotherapy for oral cavity carcinoma at an academic center: A matched‐pair analysis

Our objective was to evaluate for outcomes differences for patients with oral cavity squamous cell carcinoma (OCSCC) who underwent primary surgical resection at an academic center (AC), followed by postoperative radiation therapy either at the AC or at a nonacademic radiation treatment center (non‐AC).

Combined modality treatment outcomes for head and neck cancer: comparison of postoperative radiation therapy at academic vs nonacademic medical centers.

IMPORTANCE Patients with head and neck squamous cell carcinoma (HNSCC) who undergo surgical resection in an academic medical center (AC) often receive postoperative adjuvant external beam radiation therapy (RT) at non-ACs closer to home. Few data exist to compare outcomes of these populations. OBJECTIVE To evaluate treatment metrics and outcomes in patients with HNSCC who underwent surgical resection at an AC and then received postoperative adjuvant external beam RT at an AC vs a non-AC. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study in 1 AC and several community RT non-ACs of patient with primary HNSCC treated with surgery at an AC followed by adjuvant therapy at an AC or a non-AC from January 1, 2002, to January 1, 2012. INTERVENTIONS We evaluated for between-groups differences in demographics, RT metrics, and survival outcomes. Subgroup analysis by tumor site was then performed. MAIN OUTCOMES AND MEASURES Overall survival, disease-specific survival, and locoregional control rates. RESULTS A total of 286 patients underwent surgery at the University of California, San Francisco, followed by adjuvant therapy. A total of 214 patients were analyzed. Significant differences in demographic and oncologic variables emerged, including important differences in RT metrics. Patients treated at a non-AC received a lower total RT dose, lower fractional dose, more delays in RT initiation, more breaks in RT, and more early termination of RT. Adjuvant treatment at an AC was associated with improved survival on univariate but not multivariate analysis. Subgroup analysis by SCC tumor site normalized many of the differences between groups, yet still revealed persistent differences in RT metrics. On multivariate analysis, AC treatment was not an independent predictor of survival for any tumor site. CONCLUSIONS AND RELEVANCE Better oncologic outcomes were seen in the AC group on univariate analysis, but these improved outcomes were not found on multivariate analysis. Important differences in RT metrics were noted for non-AC treatment sites compared with AC sites. Subgroup analysis by tumor site demonstrated persistent differences in treatment metrics. Standardization of adjuvant HNSCC treatment according to national guidelines should be prioritized at non-AC treatment facilities.

Cancer cachexia update in head and neck cancer: Pathophysiology and treatment

The pathophysiology of cancer cachexia remains complex. A comprehensive literature search was performed up to April 2013 using PubMed, the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, and the Google search engine. In this review, we focus on the different mediators of impaired anabolism and upregulated catabolism that alter the skeletal muscle homeostasis resulting in the wasting of cancer cachexia. We present recent evidence of targeted treatment modalities from clinical trials along with their potential mechanisms of action. We also report on the most current evidence from randomized clinical trials using multimodal treatments in patients with cancer cachexia, but also the evidence from head and neck cancer‐specific trials. A more complete understanding of the pathophysiology of the syndrome may lead to more effective targeted therapies and improved outcomes for patients.

Comparison of Output Volume Thresholds for Drain Removal After Selective Lateral Neck Dissection: A Randomized Clinical Trial

Importance Limited evidence is available to guide drain removal after selective lateral neck dissection (SLND). Patients may have drains left in longer than necessary, leading to patient discomfort, longer hospitalizations, and increased costs. Objective To compare 2 output volume thresholds for drain removal after SLND. Design, Setting, and Participants This single-blind randomized clinical trial included a consecutive sample of all adult patients undergoing unilateral or bilateral SLND of levels I to III, I to IV, II to III, or II to IV from March 1, 2015, to December 1, 2016, at a tertiary academic medical center. Eligible patients had at least 30 days of follow-up. Patients undergoing a parotidectomy, a level V lymphadenectomy, or an SLND that communicated with the upper aerodigestive tract or who had a suspected chylous fistula on the first postoperative day were excluded from enrollment. Sixty-five patients were offered enrollment and 12 refused. Fifty-three patients who underwent 67 SLNDs were included in the final analysis, with no patients lost to follow-up. Analysis was based on intention to treat. Interventions On the first postoperative day, patients were randomized to either a drain removal threshold of less than 30 mL or less than 100 mL during a 24-hour period. Main Outcomes and Measures Duration of drain use, hospital length of stay, and wound complications for both groups. Results Among the 53 patients with 67 SLNDs included in the analysis (45 men [85%] and 8 women [15%]; mean age, 58.5 years [95% CI, 53.2-64.5 years]), 32 SLNDs were randomized to the 100-mL group and 35 were randomized to the 30-mL group. No meaningful differences in preoperative characteristics were noted between groups. Two seromas occurred in the 100-mL group (2 of 32 [6.3%; 95% CI, 0%-13.5%]) and in the 30-mL group (2 of 35 [5.7%; 95% CI, 0%-14.6%]). No hematomas, chylous fistulas, or wound infections occurred. The 100-mL group had a 1.87-day reduction in mean hospital length of stay (95% CI, 0.66-3.10 days). Conclusions and Relevance A volume threshold for drain removal of 100 mL during a 24-hour period after SLNDs appears to be safe and may significantly reduce duration of drain use and hospital length of stay. Trial Registration clinicaltrials.gov Identifier: NCT03113526

Human Papillomavirus–Associated Oropharyngeal Cancer: Patterns of Nodal Disease:

Objective To characterize patterns of neck lymph node (LN) metastases in human papillomavirus (HPV)–associated oropharyngeal squamous cell carcinoma, represented by p16 positivity (p16+OPSCC). Study Design Case series with chart review. Setting Tertiary care center. Subjects and Methods Neck dissection (ND) specimens of nonirradiated p16+OPSCC patients were analyzed for frequencies of clinically evident and occult LNs by neck level. Local, regional, and distant recurrences were reviewed. Results Seventy p16+OPSCC patients underwent primary site transoral robotic surgery and 82 NDs of varying levels. Metastatic pathologic LNs were found at the following frequencies: 0% (0/28) in level I, 75.6% (62/82) in level II with 57.4% (35/61) in level IIA and 13.1% (8/61) in level IIB, 22.0% (18/82) in level III, 7.0% (5/71) in level IV, and 6.3% (1/16) in level V. The level V LN was clinically evident preoperatively. Five of 21 (23.8%) elective NDs contained occult LNs, all of which were in level II and without extranodal extension. Twenty-seven (38.6%) patients underwent adjuvant radiation; 19 (27.1%) patients underwent adjuvant chemoradiation. With a mean follow-up of 29 months, 3 patients had developed recurrences, with all but 1 patient still alive. All patients who recurred had refused at least a component of indicated adjuvant treatment. Conclusions For p16+OPSCC, therapeutic NDs should encompass any levels bearing suspicious LNs and levels IIA-B, III, and IV, while elective NDs should be performed and encompass at least levels IIA-B and III. These selective ND plans, followed by indicated adjuvant treatment, are associated with a low nodal recurrence rate.

Major prognostic factors for recurrence and survival independent of the American Joint Committee on Cancer eighth edition staging system in patients with cutaneous squamous cell carcinoma treated with multimodality therapy

BACKGROUND The purpose of this study was to assess changes resulting from the American Joint Committee on Cancer (AJCC) eighth edition for cutaneous squamous cell carcinoma (SCC) and evaluate pertinent excluded factors. METHODS In 101 patients receiving surgery and postoperative radiation, recurrence and survival were estimated by cumulative incidence and Kaplan-Meier method. Time-to-event analysis was performed using Cox proportional hazards and Fine-Gray competing risks regression models. RESULTS The 2-year locoregional recurrence, overall survival (OS), and cause-specific mortality rates were 25%, 72%, and 13%, respectively. The AJCC eighth edition upstaged T classification in 50% of patients and overall stage in 39%. In multivariate analysis, immunosuppression and in-transit metastasis were associated with locoregional recurrence. Older age and in-transit metastasis were associated with worse OS. In univariate analysis (limited by number of events), cause-specific mortality was associated with positive margin, in-transit metastasis, and the seventh edition dichotomized T classification and overall stage. CONCLUSION In-transit metastasis was significantly associated with locoregional recurrence, OS, and cause-specific mortality. Efforts should be made to define in-transit metastasis in the staging system.

Shorter interval between radiation therapy and salvage laryngopharyngeal surgery increases complication rates following microvascular free tissue transfer

PURPOSE To evaluate how the interval between radiation and salvage surgery for advanced laryngeal cancer with free tissue transfer reconstruction influences complication rates. MATERIALS AND METHODS This is a retrospective series of 26 patients who underwent salvage laryngectomy or laryngopharyngectomy with vascularized free tissue reconstruction (anterolateral thigh or radial forearm) following radiation or chemoradiation between 2012 and 2017 at a single academic center. The primary outcome was incidence of postoperative complications, including pharyngocutaneous fistula. Secondary outcomes included the need for a second procedure, time to resumption of oral feeding, feeding tube dependence, and hospital length of stay. RESULTS Salvage surgery was performed for persistence (7/26, 27%), recurrence/new primary (12/26, 46%), and dysfunctional larynges (7/26, 27%). Twenty-two (85%) defects were reconstructed with an anterolateral thigh free flap and 4/26 with a radial forearm free flap (15%). There were no flap failures. There were significantly more complications in patients undergoing surgery within 12 months of completion of radiation therapy (7/12, 58%) versus those undergoing surgery after 12 months (1/14, 7%; p = .02). Patients experiencing complications more often required a second procedure (4/7 vs. 0/1; p = .02), experienced a longer delay to initiation of oral diet (61 vs. 21 days; p = .04), and stayed in the hospital longer (28 vs. 9 days; p = .01). CONCLUSIONS Shorter intervals between definitive radiation and salvage laryngopharyngeal surgery with free tissue reconstruction increases postoperative complications, hospital length of stay, and the likelihood of feeding tube dependence. Reconstructive surgeons can use these findings to help guide preoperative patient counseling and assess postoperative risk.