Delayed TS-RT of 50 days or more was associated with worse overall survival. The multidisciplinary care team should focus on shortening TS-RT to improve survival. Unavoidable delays may be an indication for accelerated fractionation or other dose intensification strategies.

Purpose Multiple smaller studies have demonstrated an association between overall survival and lymph node (LN) count from neck dissection in patients with head and neck cancer. This is a large cohort study to examine these associations by using a national cancer database. Patients and Methods The National Cancer Database was used to identify patients who underwent upfront nodal dissection for mucosal head and neck squamous cell carcinoma between 2004 and 2013. Patients were stratified by LN count into those with < 18 nodes and those with ≥ 18 nodes on the basis of prior work. A multivariable Cox proportional hazards regression model was constructed to predict hazard of mortality. Stratified models predicted hazard of mortality both for patients who were both node negative and node positive. Results There were 45,113 patients with ≥ 18 LNs and 18,865 patients with < 18 LNs examined. The < 18 LN group, compared with the ≥ 18 LN group, had more favorable tumor characteristics, with a lower proportion of T3 and T4 lesions (27.9% v 39.8%), fewer patients with positive nodes (46.6% v 60.5%), and lower rates of extracapsular extension (9.3% v 15.1%). Risk-adjusted Cox models predicting hazard of mortality by LN count showed an 18% increased hazard of death for patients with < 18 nodes examined (hazard ratio [HR] 1.18; 95% CI, 1.13 to 1.22). When stratified by clinical nodal stage, there was an increased hazard of death in both groups (node negative: HR, 1.24; 95% CI, 1.17 to 1.32; node positive: HR, 1.12; 95% CI, 1.05 to 1.19). Conclusion The results of our study demonstrate a significant overall survival advantage in both patients who are clinically node negative and node positive when ≥ 18 LNs are examined after neck dissection, which suggests that LN count is a potential quality metric for neck dissection.

For many solid tumors, surgical resection remains the gold standard and tumor-involved margins are associated with poor clinical outcomes. Near-infrared (NIR) fluorescence imaging using molecular agents has shown promise for imaging during resection. However, for cancers with difficult imaging conditions, surgical value may lie in tumor mapping of surgical specimens. We thus evaluated a novel approach for real-time, intraoperative tumor margin assessment. Twenty-one adult patients with biopsy-confirmed squamous cell carcinoma arising from the head and neck (HNSCC) scheduled for standard-of-care surgery were enrolled. Cohort 1 ( = 3) received panitumumab-IRDye800CW at an intravenous microdose of 0.06 mg/kg, cohort 2A ( = 5) received 0.5 mg/kg, cohort 2B ( = 7) received 1 mg/kg, and cohort 3 ( = 6) received 50 mg. Patients were followed 30 days postinfusion and adverse events were recorded. Imaging was performed using several closed- and wide-field devices. Fluorescence was histologically correlated to determine sensitivity and specificity. imaging demonstrated tumor-to-background ratio (TBR) of 2 to 3, compared with specimen imaging TBR of 5 to 6. We obtained clear differentiation between tumor and normal tissue, with a 3-fold signal difference between positive and negative specimens ( < 0.05). We achieved high correlation of fluorescence intensity with tumor location with sensitivities and specificities >89%; fluorescence predicted distance of tumor tissue to the cut surface of the specimen. This novel method of detecting tumor-involved margins in surgical specimens using a cancer-specific agent provides highly sensitive and specific, real-time, intraoperative surgical navigation in resections with complex anatomy, which are otherwise less amenable to image guidance. This study demonstrates that fluorescence can be used as a sensitive and specific method of guiding surgeries for head and neck cancers and potentially other cancers with challenging imaging conditions, increasing the probability of complete resections and improving oncologic outcomes. .

Purpose: To demonstrate the safety and feasibility of leveraging therapeutic antibodies for surgical imaging.Procedures: We conducted two phase I trials for anti-epidermal growth factor receptor antibodies cetuximab-IRDye800CW (n=12) and panitumumab-IRDye800CW (n=15). Adults with biopsy-confirmed head and neck squamous cell carcinoma scheduled for standard-of-care surgery were eligible. For cetuximab-IRDye800CW, cohort 1 was intravenously infused with 2.5 mg/m2, cohort 2 received 25 mg/m2, and cohort 3 received 62.5 mg/m2. For panitumumab-IRDye800CW, cohorts received 0.06 mg/kg, 0.5 mg/kg, and 1 mg/kg, respectively. Electrocardiograms and blood samples were obtained, and patients were followed for 30 days post-study drug infusion.Results: Both fluorescently labeled antibodies had similar pharmacodynamic properties and minimal toxicities. Two infusion reactions occurred with cetuximab and none with panitumumab. There were no grade 2 or higher toxicities attributable to cetuximab-IRDye800CW or panitumumab-IRDye800CW; fifteen grade 1 adverse events occurred with cetuximab-IRDye800CW, and one grade 1 occurred with panitumumab-IRDye800CW. There were no significant differences in QTc prolongation between the two trials (p=0.8).Conclusions: Panitumumab-IRDye800CW and cetuximab-IRDye800CW have toxicity and pharmacodynamic profiles that match the parent compound, suggesting that other therapeutic antibodies may be repurposed as imaging agents with limited preclinical toxicology data.

AIM:To evaluate the factors involved in the impairment of health-related quality of life (HRQOL) in patients with celiac disease. METHODS:A multicenter, cross-sectional prospective study was performed in patients with celiac disease w h o c o m p l e t e d t w o H R Q O L q u e s t i o n n a i re s : t h e gastrointestinal quality of life index (GIQLI) and the EuroQol-5D (EQ). RESULTS:Three hundred and forty patients (163 controlled with a gluten-free diet, and 177 newly diagnosed with a normal diet) were included. The GIQLI score was significantly better in patients on a glutenfree diet (GFD) than in non-treated patients on their usual diet, both in terms of the overall score (3.3 vs 2.7, respectively; P < 0.001), as well as on the individual questionnaire dimensions. Both the preference value of the EQ as the visual analogue scale were significantly better in treated than in non-treated patients (0.93 vs 0.72 P < 0.001 and 80 vs 70 P < 0.001, respectively).Variables significantly associated with a worse HRQOL score were female gender, failure to adhere to a GFD, and symptomatic status. CONCLUSION:In untreated celiac disease, the most important factors that influence patient perception of www.wjgnet.com health are the presence of symptoms and a normal diet. HRQOL improves to levels similar to those described in the general population in celiac disease patients well controlled with a GFD.

Objective The National Cancer Center Network recommends starting radiation therapy within 6 weeks after surgery for oral cavity squamous cell carcinoma (OCSCC), but there is limited evidence of the importance of the total time from surgery to completion of radiation therapy (package time). We set out to determine if there was an association between package time and survival in OCSCC and to evaluate the impact of treatment location on outcomes. Study Design Retrospective cohort study. Setting Tertiary academic medical center. Subjects and Methods We reviewed the records of patients with OCSCC who completed postoperative radiation therapy at an academic medical center from 2008 to 2016. The primary endpoints were overall survival and recurrence-free survival. Statistical analysis included χ tests and Cox proportional hazards regressions. Results We identified 132 patients with an average package time of 12.6 weeks. On multivariate analysis, package time >11 weeks was independently associated with decreased overall survival (hazard ratio, 6.68; 95% CI, 1.42-31.44) and recurrence-free survival (hazard ratio, 2.94; 95% CI, 1.20-7.18). Patients who received radiation therapy at outside facilities were more likely to have treatment delays (90.2% vs 62.9%, P = .001). Conclusions Prolonged package times are associated with decreased overall and recurrence-free survival among patients with OCSCC. Patients who received radiation therapy at outside facilities are more likely to have prolonged package times.

Objective Subpopulations of highly tumorigenic cells, which have the unique capacity to self-renew and produce differentiated progeny, have been identified in multiple malignancies. In head and neck squamous cell carcinoma (HNSCC), this subpopulation of cells, termed cancer stem cells (CSCs) are contained within the population with high CD44 expression. It has been postulated that CSCs play a role in invasion and metastasis; however, there is little evidence to support this theory. We designed in vitro and in vivo models of metastasis to study the behavior of CSCs in HNSCC. Design Cells were sorted for CD44 expression using flow cytometry. Sorted cells were used in an in vitro invasion assay. For in vivo studies, CSCs and non-CSCs were injected into the tail veins of mice, and lungs were either harvested or imaged to evaluate for metastases. Results In vitro, CD44high cells were more motile but less invasive than CD44low cells. In vivo, 4/5 mice injected with CD44high cells and 0/5 mice injected with CD44low cells formed lung metastases. Two of the metastases arose from CSCs from a primary tumor and three from CSCs from HNSCC cell lines. Conclusions In vitro, CSCs do not have an increased ability to invade through basement membrane, but they do migrate more efficiently through a porous barrier. In contrast, CSCs formed metastases quite efficiently in vivo, whereas non-CSCs did not form metastases at all. This phenomenon could be due to enhanced migratory capacity of CSCs, which may be more important than basement membrane degradation in vivo.

Background Prospective quality metrics for neck dissection have not been established for patients with head and neck squamous cell carcinoma. The purpose of this study is to investigate the association between lymph node counts from neck dissection, local-regional recurrence, and overall survival. Methods The number of lymph nodes counted from neck dissection in patients treated on NRG Oncology RTOG trials 9501 and 0234 was evaluated for its prognostic impact on overall survival using a multivariate Cox model adjusted for demographic, tumor, and lymph node data, and stratified by postoperative treatment group. Results 572 patients were analyzed at median follow-up of eight years. 98% of patients were pathologically N+. Median number of lymph nodes recorded on the left and right sides were 24 and 25. Fewer than 18 nodes identified was associated with worse overall survival relative to ≥18 nodes (hazard ratio 1.38, 95%CI 1.09–1.74, p=0.007). The difference appeared to be driven by local-regional failure (HR 1.46, 95%CI 1.02–2.08, p=0.04) but not distant metastases (HR 1.08, 95%CI 0.77–1.53, p=0.65). When analysis was limited to NRG Oncology RTOG 0234 patients, adding p16 status to the model did not affect the hazard ratio for dissected nodes and the effect of nodes was not different by p16 status. Conclusion The removal and identification of 18 or more lymph nodes was associated with improved overall survival and lower rates of local-regional failure, and should be further evaluated as a measure of quality in neck dissections for mucosal squamous cell carcinoma.