Patient-Reported Outcomes of Split-Thickness Skin Grafts for Floor of Mouth Cancer Reconstruction.

INTRODUCTION: Patient-reported outcome measures (PROM) on quality of life (QOL) for early-stage floor of mouth carcinoma (FOM-CA) undergoing surgical resection and split-thickness skin graft (STSG) reconstruction have not been established. We have performed a cross-sectional QOL analysis of such patients to define functional postoperative outcomes. METHODS: Patients with pathologic stage T1/T2 FOM-CA who underwent resection and STSG reconstruction at a tertiary academic cancer center reported outcomes with the University of Washington QOL (v4) questionnaire after at least 6 months since surgery. RESULTS: Twenty-four out of 49 eligible patients completed questionnaires with a mean follow-up of 41 months (range: 6-88). Subsites of tumor involvement/resection included the following: (1) lateral FOM (L-FOM) (n = 17), (2) anterior FOM (A-FOM) (n = 4), and (3) alveolar ridge with FOM, all of whom underwent lateral marginal mandibulectomy (MM-FOM) (n = 3). All patients reported swallowing scores of 70 ("I cannot swallow certain solid foods") or better. Ninety-six percent (23/24) reported speech of 70 ("difficulty saying some words, but I can be understood over the phone") or better. A-FOM patients reported worse chewing than L-FOM patients (mean: 50.0 vs. 85.3; p = 0.01). All 4 A-FOM patients reported a low chewing score of 50 ("I can eat soft solids but cannot chew some foods"). Otherwise, there were no significant differences between subsite groups in swallowing, speech, or taste. CONCLUSION: STSG reconstructions for pathologic T1-T2 FOM-CA appear to result in acceptable PROM QOL outcomes with the exception of A-FOM tumors having worse chewing outcomes.

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.

Clinicopathologic characteristics and outcomes of recurrent oropharyngeal squamous cell carcinoma.

PURPOSE: Positive p16 immunohistochemical staining is predictive of improved survival and response to treatment. The purpose of this study is to determine the clinicopathologic characteristics and outcomes of patients with p16+ oropharynx cancer who fail initial treatment. MATERIALS AND METHODS: Case series including all patients with recurrent oropharyngeal squamous cell carcinoma from 2002 to 2014. RESULTS: Forty patients met inclusion criteria. Thirty-one (77.5%) tumors were p16+ and 9 (22.5%) were p16-. There was no difference in T/M stage at diagnosis; more patients with p16+ tumors presented initially with ≥N2 disease (p=0.04). Regional and/or metastatic recurrence was more common in the p16+ group as compared to the p16- group - 71% vs 22.2%, p=0.003. Outcomes for both groups were poor - 67.7% p16+ and 44.4% p16- patients died from disease. CONCLUSIONS: Compared to p16- recurrent tumor patients, p16+ recurrent tumor patients were more likely to experience regional or distant metastatic recurrence. Overall outcomes for both p16+ and p16- recurrent oropharynx tumors were poor.

Prognostic risk factors of buccal squamous cell carcinoma: A case-control study.

OBJECTIVES: To describe the clinicopathologic presentation of buccal squamous cell carcinoma and identify risks factors for recurrence and overall survival. METHODS: This is a retrospective case-control study of patients with oral cavity squamous cell carcinoma (OCSCC) treated at a single tertiary care center between 2010 and 2022. All patients with buccal subsite OCSCC treated during this time frame were included and paired with a randomly selected age and gender matched patient with non-buccal OCSCC. Relevant data was collected via chart review. RESULTS: Seventy-seven patients with buccal SCC were matched with 77 non-buccal OCSCC controls. The median follow-up time was 27 months (IQR 14-61). Median age was 67 years (IQR 57-75) and 53% of the cohort was female. Twenty (26%) buccal SCC patients experienced a recurrence versus 19 (25%) in the controls. Age ≥65-years-old increased odds of all-cause mortality in the buccal SCC group, but not in the control group. Perineural invasion and positive margins increased odds of recurrence in the buccal group only. Overall survival and progression-free survival did not differ between the groups, despite a greater number of T2 buccal tumors and T1 non-buccal tumors. CONCLUSIONS: Buccal SCC presents at a higher T stage than other oral cavity SCC subsite and may exhibit variance in the pathologic risk factors that predict poor outcomes versus non-buccal OCSCC. Despite these relatively minor differences, however, oncologic outcomes between these groups were similar.

The neutrophil-to-lymphocyte ratio in salivary gland cancers treated with pembrolizumab.

BACKGROUND: A minority of patients with recurrent/metastatic (R/M) salivary gland cancers (SGCs) benefit from immune checkpoint inhibitors (ICIs), necessitating reliable biomarkers for ICI response prediction. METHODS: Retrospective observational study of R/M SGC patients treated with pembrolizumab between 2016 and 2022, with a primary outcome of 6-month progression-free survival (PFS) and secondary outcome of 2-year overall survival (OS). Univariate and multivariable Cox proportional hazards models were employed. RESULTS: Twenty R/M SGC patients were included. After adjustment, NLR as a continuous variable was independently associated with 6-month PFS (HR 1.30, 95% CI 1.10-1.54, p = 0.002) and 2-year OS (HR 1.33, 95% CI 1.07-1.66, p = 0.010). Similarly, NLR ≥ 5 was associated with higher hazards of progression at 6 months (HR 12.85, 95% CI 2.17-76.16, p = 0.005) and death at 2 years (HR 11.25, 95% CI 1.67-75.77, p = 0.013). CONCLUSIONS: Higher pretreatment NLR was independently associated with inferior 6-month PFS and 2-year OS in pembrolizumab-treated R/M SGC patients.

Endoscopic surgery for tuberculum sellae meningiomas: a systematic review and meta-analysis.

Recent reports of surgical resection of tuberculum sellae meningiomas through an endoscopic endonasal approach (EEA) have provided an alternative to transcranial approaches in selected cases. However, these published reports have been limited by small sample size from single institutions. We performed a systematic review and meta-analysis to gain insight into potential limitations and benefits of EEA for tuberculum sellae meningiomas. We performed a systematic review of the literature and analyzed pooled data for descriptive statistics on short-term morbidity and outcomes. We compared EEA to transcranial approaches reported during the same time-frame. Six studies (49 patients) met inclusion criteria for EEA. A pooled analysis of transcranial results reported during a similar time period yielded 11 studies (412 patients). There were no differences in rate of gross total resection or peri-operative complications between the two groups. Although the EEA group was associated with higher rates of CSF leak (p < 0.05; OR 3.9; 95 % CI 1.15, 15.75), EEA were also associated with significantly higher rates of post-operative visual improvement compared to transcranial approaches (p < 0.05; OR 1.5; 95 % CI 1.18, 1.82). A systematic review of the small series of EEA for tuberculum sellae meningiomas published to date revealed similar extent of resection and morbidity, but increased post-operative visual improvement compared to transcranial approaches during a similar time period. Long-term follow-up will be needed to define recurrence rates of EEA as compared to transcranial approaches. Cautious use of EEA for the removal of smaller tuberculum sellae meningiomas after formal endoscopic training may be warranted.

Patterns of Postoperative Trismus Following Mandibulectomy and Fibula Free Flap Reconstruction.

The factors that contribute to postoperative trismus after mandibulectomy and fibula free flap reconstruction (FFFR) are undefined. We retrospectively assessed postoperative trismus (defined as a maximum interincisal opening ≤35 mm) in 106 patients undergoing mandibulectomy with FFFR, employing logistic regression to identify risk factors associated with this sequela. The surgical indication was primary ablation in 64%, salvage for recurrence in 24%, and osteonecrosis in 12%. Forty-five percent of patients had existing preoperative trismus, and 58% of patients received adjuvant radiation/chemoradiation following surgery. The overall rates of postoperative trismus were 76% in the early postoperative period (≤3 months after surgery) and 67% in the late postoperative period (>6 months after surgery). Late postoperative trismus occurred more frequently in patients with ramus-involving vs. ramus-preserving posterior mandibulotomies (82% vs. 46%, p = 0.004). A ramus-involving mandibulotomy was the only variable significantly associated with trismus >6 months postoperatively on multivariable logistic regression (OR, 7.94; 95% CI, 1.85−33.97; p = 0.005). This work demonstrates that trismus is common after mandibulectomy and FFFR, and suggests that posterior mandibulotomies that involve or remove the ramus may predispose to a higher risk of persistent postoperative trismus.

Impact of Smoking and Primary Tumor Subsite on Recurrence in HPV-Associated Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVE: To describe risk of recurrence and recurrence characteristics between ever- and never-smoking patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) when stratified by primary tumor subsite. STUDY DESIGN: Retrospective observational study. SETTING: Tertiary care center. METHODS: Retrospective chart review of 171 patients with HPV+ OPSCC with primary treatment between 2008 and 2019. Five-year recurrence-free survival and risk of recurrence were evaluated through Kaplan-Meier curves with log-rank test and Cox proportional hazards models, respectively. RESULTS: Of 171 patients with HPV+ OPSCC, 81.9% were male, and the average age was 63.9 years. Eighty patients (46.8%) had a smoking history (average, 17.7 pack-years), including 4 current smokers. Recurrence occurred in 31 patients (18.1%), 19 of whom were ever smokers. The recurrence rate for ever smokers with primary base of tongue (BOT) cancer was 41.7%, while 5.1% of never smokers with BOT primaries had recurrence. For primary tonsillar disease, 9.1% of ever smokers had recurrence versus 19.2% of never smokers. Five-year recurrence-free survival for BOT primaries was lower in ever smokers than never smokers (P = .001) but did not differ between ever and never smokers for tonsillar primaries (P = .215). In multivariable analysis across this period, ever-smoking status was associated with higher risk of recurrence than never-smoking status in BOT primaries (adjusted hazard ratio, 7.36; 95% CI, 1.61-33.68; P = .010) but with lower risk of recurrence after tonsillar primaries (adjusted hazard ratio, 0.23; 95% CI, 0.06-0.89; P = .033). CONCLUSION: Smoking may uniquely interact with tumor subsites within the oropharynx to influence recurrence risk. Understanding the association between smoking and HPV+ OPSCC recurrence could lead to personalized, evidence-based treatments to improve oncologic outcomes.

Should Sentinel Lymph Node Biopsy Status Guide Adjuvant Radiation Therapy in Patients With Merkel Cell Carcinoma?

PURPOSE: Radiation of the draining lymph node basin remains controversial for Merkel cell carcinoma, particularly in the era of sentinel lymph node biopsy (SLNB). METHODS AND MATERIALS: Based on a 20-year experience using SLNB-guided adjuvant radiation therapy (RT), we conducted a retrospective review of clinically node-negative patients testing 2 hypotheses: (1) whether nodal RT could be safely omitted in SLNB-negative Merkel cell carcinoma and (2) whether the excised primary site should always be radiated. Clinically node-positive patients were excluded. RESULTS: Among 57 clinically node-negative patients who underwent SLNB and wide local excision (WLE), 42 (74%) had a negative SLNB, and 15 (26%) had a positive SLNB. At a median follow-up of 43 months (range, 5-182), SLNB-negative patients irradiated to the primary site had improved 4-year disease-specific survival (100% vs 65%, P = .008), local recurrence-free survival (100% vs 76%, P = .009), and distant recurrence-free survival (100% vs 75%, P = .008), but not overall survival (87.5% vs 57.7%, P = .164) compared with SLNB-positive patients receiving comprehensive RT. Among SLNB-negative patients treated with WLE only, 67% (6/9) had a disease relapse, half of which were local relapses (33%). CONCLUSIONS: In this single-institution retrospective review, after negative SLNB and WLE, RT given only to the primary site provided 100% disease control without a need for nodal RT. Among SLNB-negative patients who had WLE, omission of postoperative primary-site RT was associated with 67% cancer relapse, of which half was local.

Patient-Reported Quality of Life After Resection With Primary Closure for Oral Tongue Carcinoma.

OBJECTIVES/HYPOTHESIS: For early-stage oral tongue carcinoma and carcinoma in situ (ESOTCCIS), we evaluated patient-reported quality-of-life (QOL) outcomes following resection with primary closure (R-PC). STUDY DESIGN: Retrospective review at an academic cancer center. METHODS: Thirty-nine ESOTCCIS patients (Tis, T1, T2) who underwent R-PC without radiation completed the University of Washington Quality of Life Questionnaire Version 4 (UW-QOL) at least 6 months since R-PC (mean = 2.39 years; range = 0.5-6.7 years). We compared UW-QOL scores for pain, swallowing, chewing, speech, and taste to established normative population scores. Multivariable regression analysis evaluated factors associated with QOL impairment. RESULTS: ESOTCCIS patients who underwent R-PC in comparison to the normative population reported significantly worse mean speech (87.7 vs. 98, P < .001) and taste (85.6 vs. 95, P = .002) scores and no significant differences in mean pain (91.7 vs. 86, P = .96), swallowing (100 vs. 98, P = .98), chewing (97.4 vs. 94, P = .98) scores. For speech and taste, 59% (23/39) reported no postoperative change from baseline, whereas 41% (16/39) and 35.9% (14/39) reported mild impairment, respectively. Overall, postoperative QOL was reported as good, very good, or outstanding by 87.2% (34/39). Higher American Society of Anesthesiologists class, cT1 compared to CIS, and ventral tongue involvement were independently associated with worse speech. Age < 60 years was independently associated with worse taste. CONCLUSIONS: ESOTCCIS patients who undergo R-PC without radiation can expect long-term swallowing, chewing, and pain to be in the normative range. Although a majority of patients can expect to achieve normative speech and taste outcomes, R-PC carries the risks of mild speech and/or taste impairments. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:312-318, 2021.

Head and neck surgery during the coronavirus-19 pandemic: The University of California San Francisco experience.

BACKGROUND: Guidelines regarding head and neck surgical care have evolved during the coronavirus-19 (COVID-19) pandemic. Data on operative management have been limited. METHODS: We compared two cohorts of patients undergoing head and neck or reconstructive surgery between March 16, 2019 and April 16, 2019 (pre-COVID-19) and March 16, 2020 and April 16, 2020 (COVID-19) at an academic center. Perioperative, intraoperative, and postoperative outcomes were recorded. RESULTS: There were 63 operations during COVID-19 and 84 operations during pre-COVID-19. During COVID-19, a smaller proportion of patients had benign pathology (12% vs 20%, respectively) and underwent thyroid procedures (2% vs 23%) while a greater proportion of patients underwent microvascular reconstruction±ablation (24% vs 12%,). Operative times increased, especially among patients undergoing microvascular reconstruction±ablation (687 ± 112 vs 596 ± 91 minutes, P = .04). Complication rates and length of stay were similar. CONCLUSIONS: During COVID-19, perioperative outcomes were similar, operative time increased, and there were no recorded transmissions to staff or patients. Continued surgical management of head and neck cancer patients can be provided safely.

Modified technique of submandibular gland transfer followed by intensity modulated radiotherapy to reduce xerostomia in head and neck cancer patients.

BACKGROUND: Xerostomia is one of the most common long-term adverse effects of radiotherapy for head and neck cancer patients. Contralateral submandibular gland transfer (SMG-T) before radiotherapy was shown to reduce xerostomia compared to pilocarpine. We sought to evaluate a modification of this surgery preserving the ipsilateral facial artery and vein to simplify the SMG-T. METHODS: Eighteen patients planned for head and neck intensity modulated radiotherapy to both necks were reviewed. Surgical complications were recorded. The grade of xerostomia was assessed after treatment completion. RESULTS: There were no minor or major complications resulting from the modified SMG-T. At 24.5-months follow up, the incidence of post-treatment moderate to severe xerostomia was 16.7%. No locoregional recurrence occurred. Only one patient had distant solitary lung metastasis. CONCLUSION: The modified SMG-T technique is a practical and effective method to reduce the dose of radiation to the contralateral SMG and limit post-treatment xerostomia.

Treatment modality impact on quality of life for human papillomavirus-associated oropharynx cancer.

OBJECTIVES/HYPOTHESIS: Compare treatment-related quality of life (QOL) impact for early-stage human papillomavirus-associated oropharynx squamous cell carcinoma (HPV+ OPSCC) patients. STUDY DESIGN: Retrospective cohort at a tertiary center. METHODS: Stage I (T0-2/N0-1) HPV+ OPSCC patients (n = 76) with pretreatment Karnofsky scores ≥80 reported QOL after surgery alone (n = 17, 22%), surgery with adjuvant radiation ± chemotherapy (S-a[C]XRT) (n = 23, 30%), or definitive radiation ± chemotherapy (d[C]XRT) (n = 36, 47%) with the University of Washington QOL version 4 (UW-QOL); European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core Module (EORTC QLQ-C30) and Head and Neck Module (EORTC QLQ-HN35); University of Michigan Xerostomia, and Neck Dissection Impairment Index questionnaires (median follow-up = 2.2 years, interquartile range = 1.0-4.2 years). Treatment adverse events and gastrostomy tube rates were assessed. RESULTS: Over 87% of each treatment group reported good or better overall QOL. Each group had low gastrostomy tube and treatment-specific complication rates. S-a(C)XRT and d(C)XRT patients had similar mean scores with wide ranges for most individual and all composite categories. S-a(C)XRT compared to d(C)XRT patients reported significantly fewer dental problems (EORTC QLQ-C30/HN35 means = 10.1 vs. 34.3, P = .007), worse appearance (UW-QOL means = 72.8 vs. 82.6, P = .02), and worse coughing (EORTC QLQ-C30/HN35 means = 31.9 vs. 15.7, P = .007). Surgery alone compared to d(C)XRT and S-a(C)XRT patients reported significantly better salivary/taste/oral functions and less pain, financial, oral/dental, and sexual problems. CONCLUSIONS: For early-stage HPV+ OPSCC, patients usually achieve acceptable QOL regardless of treatment. S-a(C)XRT and d(C)XRT patients report generally similar QOL including neck/shoulder pain/function, but with a wide range in a limited patient sample. Surgery alone should be considered, when oncologically and functionally safe, given the better associated QOL. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:E48-E56, 2020.

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.

Socioeconomic disparities in a population of patients undergoing total thyroidectomy for benign disease.

BACKGROUND: This study examines the effect of insurance status (as a measure of socioeconomic status) on patient with benign thyroid disease. METHODS: A retrospective review was performed among 60 patients undergoing total thyroidectomy for benign thyroid disease. Univariate and multivariable analyses examined the relationship between insurance status and thyroid volume (sum of the left and right lobe volumes). RESULTS: Twenty-eight (47%) patients were considered of underinsured/uninsured status, and 32 (53%) patients were considered of private/government/military insurance status. Median pathologic whole thyroid volume was 66 mL (range, 2-855). After multivariable linear regression, underinsured/uninsured status was the only significant predictor of larger volume (correlation coefficient [r] = 118; 95% CI, 42 to 194; P = .003), after adjusting for age, sex, body mass index, and presence of concomitant thyroid disease and compressive symptoms. CONCLUSION: Patients of underinsured/uninsured status suffered more severe disease presentations at time of thyroidectomy, as measured by larger thyroid volumes.

Defining cancer cachexia in head and neck squamous cell carcinoma.

PURPOSE: Cancer cachexia is a devastating and understudied illness in patients with head and neck squamous cell carcinoma (HNSCC). The primary objective was to identify clinical characteristics and serum levels of cytokines and cachexia-related factors in patients with HNSCC. The secondary objective was to detect the occurrence of cytokine and cachexia-related factor gene expression in HNSCC tumors. EXPERIMENTAL DESIGN: For the primary objective, cross-sectional data were obtained from prospectively recruited patients identified as cachexia cases and matching cachexia-free controls. For the secondary objective, a retrospective cohort design with matched controls was used. RESULTS: Clinical characteristics associated with cancer cachexia in HNSCC were T(4) status (P = 0.01), increased C-reactive protein (P = 0.01), and decreased hemoglobin (P < 0.01). Exploratory multiplex analysis of serum cytokine levels found increased interleukin (IL)-6 (P = 0.04). A highly sensitive ELISA confirmed the multiplex result for increased IL-6 in cachectic patients (P = 0.02). Quality of life was substantially reduced in patients with cachexia compared with noncachectic patients (P < 0.01). All tumors of HNSCC patients both with and without cachexia expressed RNA for each cytokine tested and the cachexia factor lipid-mobilizing factor. There were no statistically significant differences between the cytokine and cachexia factor RNA expression of cachectic and noncachectic patients (each P > 0.05). No tumors expressed the cachexia factor proteolysis-inducing factor. CONCLUSION: We have identified clinical characteristics and pathophysiologic mechanisms associated with cancer cachexia in a carefully defined population of patients with HNSCC. The data suggest that the acute-phase response and elevated IL-6 are associated with this complex disease state. We therefore hypothesize that IL-6 may represent an important therapeutic target for HNSCC patients with cancer cachexia.

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.

The effect of altered Toll-like receptor 4 signaling on cancer cachexia.

OBJECTIVE: To determine whether mice unable to mount an intact inflammatory response because of a Toll-like receptor (TLR) pathway defect will develop less severe cancer cachexia. DESIGN: Prospective animal study. SETTING: Academic research center. SUBJECTS: Six- to eight-week-old, female C3H/HeJ mice (17-18 g) and age-, weight-, and sex-matched wild-type C3H/HeN mice, differing in that the HeJ mice have nonfunctional TLR4 due to a TLR4 double mutation (TLR4(d/d)). INTERVENTION: The mice were inoculated with equal numbers of SCCF-VII cells and housed in individual cages. MAIN OUTCOME MEASURES: Food intake, body weight, pretumor and posttumor body composition, circulating cytokines, and levels of a marker of muscle atrophy were analyzed. RESULTS: The wild-type HeN mice weighed less on average than the TLR4(d/d) mice (2.6 g vs 4.9 g) (P = .01). They consumed more food, had smaller tumors, and had less lean body mass and fat mass than the TLR4(d/d) mice. Interleukin 1beta level was significantly elevated in the tumor-bearing HeN mice (mean gain of 259 pg/mL) but not in the TLR4(d/d) mice (P = .03). Both mouse strains had evidence of muscle atrophy. CONCLUSIONS: In spite of increased food intake and smaller tumors, the wild-type HeN mice had more severe cachexia than the TLR4(d/d) mice. The impaired ability to secrete proinflammatory cytokines such as interleukin 1beta may protect these animals from developing severe cancer cachexia. This animal model represents a novel system in which the host contributions to cachexia may be further studied.

Does radiation dose matter in thyroid cancer?: Patterns of local-regional failure in recurrent and metastatic well-differentiated thyroid cancers treated with dose-painted intensity-modulated radiation therapy.

INTRODUCTION: Due to complex multimodal treatments and a lengthy natural history of disease, the impact of radiation therapy for well-differentiated thyroid cancer (WDTC) is challenging to evaluate. We analysed the effect of dose escalation, as enabled by intensity-modulated radiation therapy (IMRT), on preventing local-regional failure (LRF) of microscopic and macroscopic WDTC. METHOD: We performed a retrospective review of WDTC patients treated with IMRT from 1998-2011. Diagnostic imaging demonstrating first LRF was registered to the simulation CT containing the treated radiation isodose volumes. Areas of disease progression were contoured and the relationships of LRFs with isodose volumes were recorded. RESULTS: Thirty patients had a median follow-up of 56 months (range = 1-139). Seventeen (57%) had gross residual, five (17%) had microscopic residual and eight (27%) had clear margins at the time of IMRT. Nine patients (30%) developed LRF, at a median time of 44 months (range = 0-116). Of these, six (67%) had been radiated to gross disease and one (11%) had microscopic residual. In the seven analysable cases, only one (14%) LRF occurred within the 70 Gy isodose volume. Marginal LRFs were: four (57%) outside 70 Gy, one (14%) outside 60 Gy and one (14%) outside 50 Gy. All but one recurrence (86%) occurred in the perioesophageal region. CONCLUSIONS: Local-regional failure was seen most in patients who had gross disease at the time of IMRT, almost always occurred outside of the 70 Gy volume and was frequently in the area of oesophageal sparing. Meticulous surgical dissection, especially in the perioesophageal region, should be prioritised to prevent long-term LRF.

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.