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Oropharyngeal squamous cell carcinoma (OPSCC), largely fueled by the human papillomavirus (HPV), has a complex biological and immunologic phenotype. Although HPV/p16 status can be used to stratify OPSCC patients as a function of survival, it remains unclear what drives an improved treatment response in HPV-associated OPSCC and whether targetable biomarkers exist that can inform a precision oncology approach. We analyzed OPSCC patients treated between 2000 and 2016 and correlated locoregional control (LRC), disease-free survival (DFS) and overall survival (OS) with conventional clinical parameters, risk parameters generated using deep-learning algorithms trained to quantify tumor-infiltrating lymphocytes (TILs) (OP-TIL) and multinucleated tumor cells (MuNI) and targeted transcriptomics. P16 was a dominant determinant of LRC, DFS and OS, but tobacco exposure, OP-TIL and MuNI risk features correlated with clinical outcomes independent of p16 status and the combination of p16, OP-TIL and MuNI generated a better stratification of OPSCC risk compared to individual parameters. Differential gene expression (DEG) analysis demonstrated overlap between MuNI and OP-TIL and identified genes involved in DNA repair, oxidative stress response and tumor immunity as the most prominent correlates with survival. Alteration of inflammatory/immune pathways correlated strongly with all risk features and oncologic outcomes. This suggests that development of OPSCC consists of an intersection between multiple required and permissive oncogenic and immunologic events which may be mechanistically linked. The strong relationship between tumor immunity and oncologic outcomes in OPSCC regardless of HPV status may provide opportunities for further biomarker development and precision oncology approaches incorporating immune checkpoint inhibitors for maximal anti-tumor efficacy.

Background Immunotherapy agents are used to treat advanced head and neck lesions. We aim to elucidate relationship between immunotherapy and surgical wound complications. Methods Retrospective multi-institutional case series evaluating patients undergoing ablative and flap reconstructive surgery and immunotherapy treatment. Main outcome wound complications. Results Eight-two (62%) patients received preoperative therapy, 89 (67%) postoperative, and 33 (25%) in both settings. Forty-one (31%) patients had recipient site complications, 12 (9%) had donor site. Nineteen (14%) had major recipient site complications, 22 (17%) had minor. There was no statistically significant difference in complications based on patient or tumor-specific variables. Preoperative therapy alone demonstrated increased major complications (odds ratio [OR] 3.7, p = 0.04), and trend to more donor site complications (OR 7.4, p = 0.06), however treatment in both preoperative and postoperative therapy was not. Conclusions Preoperative immunotherapy may be associated with increased wound complications. Controlled studies are necessary to delineate this association and potential risks of therapy.

Scapula tip free flaps (STFFs) have become an increasingly popular option for head and neck reconstruction. The aim of this study is to demonstrate the feasibility of using the STFF in a horizontal orientation to take advantage of the anatomy of the scapular tip bone to re-create a mandibular symphysis. Eight patients underwent oromandibular reconstruction with a horizontally oriented STFF between October 2016 and June 2020. Virtual surgical planning was used to design the bony reconstruction in 6 cases. Primary outcomes, including flap survival, complications, and return to oral diet, were collected. Cephalometric measurements were obtained to compare preoperative and postoperative mandibular projection and width. All flaps survived without compromise, and no fistulas developed postoperatively. Seven patients returned to taking an oral diet. Cephalometric analysis revealed comparable measurements between preoperative and postoperative mandibles and reconstructed mandibles, respectively. STFFs may be oriented horizontally to reconstruct large anterior mandibular defects with satisfactory results.

Background Fibula free flap (FFF) is the preferred osteocutaneous flap for reconstruction of large head and neck composite defects. There is a paucity of data whether FFF can be performed safely in patients with knee replacement (total knee arthroplasty [TKA]). Methods Multi-institutional review of outcomes following FFF in patients who had prior TKA. Results Ten surgeons reported successful FFF in 53 patients with prior TKA. The most common preoperative imaging was a CT angiogram of the bilateral lower extremities. There was no evidence of intraoperative vascular abnormality. Physical therapy began between postoperative day 1 to postoperative day 3. At 1 month postoperatively, 40% of patients were using a cane or walker to ambulate, but by 3 months all had returned to baseline ambulatory status. At >1 year, there were no gait complications. Conclusion FFF appears safe in patients with prior knee replacement without an increased risk of complications compared to baseline.

Distress with self-perceived changes in appearance and function can result in body image disturbance (BID), which is common in head and neck cancer (HNC) survivors and a major source of psychosocial morbidity. To address the lack of psychometrically sound patient-reported outcome measures (PROMs) of HNC-related BID, we aim to create and validate the Inventory to Measure and Assess imaGe disturbancE-HeadNeck (IMAGE-HN).Survey study.Multiple academic centers.Following item development, HNC survivors from 4 academic centers completed the IMAGE-HN. Item responses were psychometrically analyzed using confirmatory factor analysis (CFA) and Rasch analysis.Item development resulted in a 31-item PROM consisting of 5 individual domains and a global domain. In total, 305 HNC survivors of diverse ages, HNC subsites, and reconstructive paradigms completed the initial items. After removal of 3 items for local dependence, CFA confirmed the unidimensionality and local independence (item residual correlations|0.20|) for each domain. Rasch analysis indicated acceptable fit (infit and outfit mean squares2.0), monotonicity of all rating scale categories, and low person misfit (4%). Person separation indices and person reliability were adequate for each domain except appearance concealment, which was removed (4 items). This resulted in the IMAGE-HN, a psychometrically acceptable 24-item PROM of HNC-related BID consisting of a global scale and 4 subscales measuring unique constructs and comprised independent items.IMAGE-HN is a novel, psychometrically sound, multidomain PROM of HNC-related BID for use in clinical and research settings.

Patients on chronic pharmacologic immunosuppressive therapy are at increased risk of wound infection and complications after surgery. There is a paucity of data examining perioperative complications after microvascular free tissue transfer (MVFTT) reconstruction of the head and neck in this patient population.Retrospective cohort study performed at two tertiary referral centers between August 2016 and May 2020.Nine hundred and seventy-nine patients underwent MVFTT during the study period; of these 47 (5%) patients were taking chronic immunosuppressive medications. The most common indications for immunosuppression were solid organ transplant and autoimmune disease. Fourteen (30%) patients had surgical complications within 30 days of surgery: 8 (17%) wound dehiscences, 6 (12%) hematomas, and 2 (4%) surgical site infections. There was one total and one partial flap failure with a 30-day reoperation rate of 4%.MVFTT of the head and neck appears to be safe in patients on chronic pharmacologic immunosuppression.

Map regional lymph node metastases for lateralized oral cavity squamous cell carcinoma (OCSCC) and evaluate factors associated with regional metastases and recurrence.Retrospective cohort study of 715 patients with lateralized OCSCC surgically treated in 1997-2011. Analysis was performed using log-rank, Kaplan-Meier, and multivariable logistic and Cox regression.Regional metastases were identified in ipsilateral levels IIA (24%), IB (18%), III (13%), V (9%), IV (7%), IA (2%) and IIB (1%) and the contralateral neck (3%). Lymphovascular invasion (LVI) (Hazard Ratio [HR] 2.2, 95% Confidence Interval [CI] 1.2-3.9) and T category (T3 vs. T1: HR 4.1, 95% CI 1.9-9.3; T4 vs. T1: HR 2.3, 95% CI 1.2-4.3) were associated with regional metastases. Most (71%) isolated regional metastatic recurrences were in undissected levels of the neck, including 58% in levels IV and V. Tumors of the hard palate (HR 4.3, 95% CI 1.2-16.1), upper alveolus (HR 3.2, 95% CI 1.0-4.7) or with LVI (HR 2.0, 95% CI 1.0-3.9) were associated with isolated regional recurrence. For upper alveolar/hard palate tumors, depth of invasion (DOI) ≥4 mm (P = .003) and LVI (P = .04) were associated with regional metastases.For lateralized OCSCC, elective neck dissection of level IIB or the contralateral neck may rarely be needed, but additional surgical or radiation treatment of levels IV and V may be considered based on patient risk factors, including T category 3-4 or LVI. For upper alveolar/hard palate tumors, DOI ≥4 mm is an appropriate threshold for elective neck dissection.

IMPORTANCE: Surveillance imaging and visits are costly and have not been shown to improve oncologic outcomes for patients with head and neck cancer (HNC). However, the benefit of surveillance visits may extend beyond recurrence detection. To better understand surveillance and potentially develop protocols to tailor current surveillance paradigms, it is important to elicit the perspectives of the clinicians who care for patients with HNC. OBJECTIVE: To characterize current surveillance practices and explore clinician attitudes and beliefs on deintensifying surveillance for patients with HNC. DESIGN, SETTING, AND PARTICIPANTS: This qualitative study was performed from January to March 2021. Guided by an interpretive description approach, interviews were analyzed to produce a thematic description. Data analysis was performed from March to April 2021. Otolaryngologists and radiation oncologists were recruited using purposive and snowball sampling strategies. MAIN OUTCOMES AND MEASURES: The main outcomes were current practice, attitudes, and beliefs about deintensifying surveillance and survivorship as well as patients’ values and perspectives collected from interviews of participating physicians. RESULTS: Twenty-one physicians (17 [81%] men) were interviewed, including 13 otolaryngologists and 8 radiation oncologists with a median of 8 years (IQR, 5-20 years) in practice. Twelve participants (57%) stated their practice comprised more than 75% of patients with HNC. Participants expressed that there was substantial variation in the interpretation of the surveillance guidelines. Participants were open to the potential for deintensification of surveillance or incorporating symptom-based surveillance protocols but had concerns that deintensification may increase patient anxiety and shift some of the burden of recurrence monitoring to patients. Patient and physician peace of mind, the importance of maintaining the patient-physician relationship, and the need for adequate survivorship and management of treatment-associated toxic effects were reported to be important barriers to deintensifying surveillance. CONCLUSIONS AND RELEVANCE: In this qualitative study, clinicians revealed a willingness to consider altering cancer surveillance but expressed a need to maintain patient and clinician peace of mind, maintain the patient-clinician relationship, and ensure adequate monitoring of treatment-associated toxic effects and other survivorship concerns. These findings may be useful in future research on the management of posttreatment surveillance.

INTRODUCTION: Osteocutaneous microvascular free tissue transfer (OMFTT) is the current standard in reconstruction of large bony defects of the oral cavity. Although being able to swallow ranks as a top priority for patients undergoing OMFTT, factors associated with achieving an oral diet following surgery remain unclear. We sought to describe the rate of total oral diet achievement, and to identify possible pre-, intra-, and post-operative factors associated with achievement in patients undergoing OMFTT. METHODS: Retrospective review between January 1, 2010 and March 31, 2018 at two tertiary academic centers. RESULTS: 249 patients (67% male, mean age 58 years) met inclusion criteria, with a median follow up of 15 months. Overall, 142 (57%) of patients achieved a total PO diet post-operatively, with median time to achievement of 3.2 months. Multivariate analysis identified that lack of concurrent glossectomy (SHR 1.72 [1.09-2.70], p=0.02), N0/1 disease (SHR 1.92 [1.16-3.13], p=0.011), avoidance of post-operative fistula formation (SHR 1.96 [1.22-3.23], p=0.005), preoperative G-tube independence (SHR 3.33 [1.69-6.25], p

Objectives Multiple population studies have shown racial discrepancies in head and neck cancer treatment and outcomes. We sought to characterize the impact of race on clinical outcomes for patients with early glottic squamous cell carcinoma (SCC) in a tertiary institution which provides equivalent access to care. Methods We retrospectively reviewed all early glottic (T1-T2) squamous cell carcinoma at a single institution, the Michael E. DeBakey Veterans' Administration Medical Center (MEDVAMC). Data collected included demographic information, primary and adjuvant treatment modalities, time to diagnosis, time to treatment, recurrences, recurrence treatment modality, secondary malignancies, recurrence-free survival (RFS), and overall survival (OS). Results One hundred seventeen patients with a primary diagnosis of T1-T2 glottic squamous cell carcinoma were included. Black and white patients demonstrated equivalent rates of recurrence, RFS, and OS. There was no significant difference in treatment delivery by race for all recorded parameters. T1b tumors were associated with an increased risk of recurrence which did not translate into a statistically significant decrease in RFS or OS. Surgical treatment was associated with increased recurrence but similar RFS and OS compared to radiation-based treatment. Secondary malignancies were common; 12% of patients were diagnosed with a second primary lung cancer during the study period. Conclusion At our institution, race did not impact survival when access to care, treatment selection, and delivery are equivalent for early glottic SCC. Secondary lung cancer is a critical risk factor for mortality in this patient group and requires long-term surveillance and monitoring. Level of evidence 4 Laryngoscope, 130:1733-1739, 2020.

Importance Body image–related distress (BID) is common among head and neck cancer (HNC) survivors and associated with significant morbidity. Risk factors for HNC-related BID remain poorly characterized because prior research has used outcome measures that fail to fully capture BID as experienced by HNC survivors. Objective To assess the association of demographic and oncologic characteristics with HNC-related BID using the Inventory to Measure and Assess imaGe disturbancE-Head & Neck (IMAGE-HN), a validated, multidomain, patient-reported outcome measure of HNC-related BID. Design, Setting, and Participants This cross-sectional study assessed 301 adult survivors of surgically managed HNC at 4 academic medical centers. Main Outcomes and Measures The primary outcome measure was IMAGE-HN scores, for which higher scores reflect more severe HNC-related BID. Multivariable linear regression analyses were performed to evaluate the association of patient characteristics with IMAGE-HN global and 4 subdomain (other-oriented appearance concerns, personal dissatisfaction with appearance, distress with functional impairments, and social avoidance) scores. Results Of the 301 participants (212 [70.4%] male; mean [SD] age, 65.3 [11.7] years), 181 (60.1%) underwent free flap reconstruction. Graduation from college (β = −9.6; 95% CI, −17.5 to −1.7) or graduate school (β = −12.6; 95% CI, −21.2 to −3.8) was associated with lower IMAGE-HN social avoidance scores compared with less than a high school education. Compared with paid work, unemployment was associated with higher IMAGE-HN other-oriented appearance (β = 10.7; 95% CI, 2.0-19.3), personal dissatisfaction with appearance (β = 12.5; 95% CI, 1.2-23.7), and global (β = 8.0; 95% CI, 0.6-15.4) scores. Compared with no reconstruction, free flap reconstruction was associated with higher IMAGE-HN global scores (β = 11.5; 95% CI, 7.9-15.0) and all subdomain scores (other-oriented appearance: β = 13.1; 95% CI, 8.6-17.6; personal dissatisfaction with appearance: β = 15.4; 95% CI, 10.0-20.7; distress with functional impairment: β = 12.8; 95% CI, 8.1-17.4; and social avoidance and isolation: β = 10.2; 95% CI, 5.8-14.6). Higher IMAGE-HN distress with functional impairment scores were found in those who received surgery and adjuvant radiation (β = 7.8; 95% CI, 2.9-12.7) or chemoradiotherapy (β = 6.5; 95% CI, 1.8-11.3) compared with surgery alone. The multivariable regression model accounted for a modest proportion of variance in IMAGE-HN global (R2 = 0.18) and subdomain scores (R2 = 0.20 for other-oriented appearance, 0.14 for personal dissatisfaction with appearance, 0.21 for distress with functional impairment, and 0.13 for social avoidance and isolation). Conclusions and Relevance In this cross-sectional study, factors associated with risk of HNC-related BID included free flap reconstruction, lower educational attainment, unemployment, and multiple treatment modalities. These characteristics explain a modest proportion of variance in IMAGE-HN scores, suggesting that other characteristics may be the major risk factors for HNC-related BID and should be explored in future studies.

BACKGROUND Wide anterolateral thigh (ALT) flap donor site defects may make primary closure difficult or impossible, with split thickness skin grafting and/or negative pressure therapy often used instead. Here, we describe a technique using propeller flaps based on varying thigh perforating vasculature in donor site reconstruction for these larger deformities. METHODS Case series RESULTS: Three patients are described that had perforator-based propeller flap reconstruction of large ALT donor site wounds that were not amenable to primary closure. Two propeller flaps were supplied by perforators of the transverse branch of the lateral circumflex femoral artery and one by a perforator of the deep femoral system. One patient experienced partial loss of the propeller flap, but completely healed with local wound care. CONCLUSION The propeller flap is a safe method to reconstruct large ALT donor sites not amenable to primary closure.

To characterize pharyngocutaneous fistula (PCF) rates and functional outcomes following microvascular free tissue transfer (MVFTT) reconstruction of salvage total laryngectomy (STL) with a review of two different flap inset techniques and a review of the literature.Retrospective review.Review of the literature revealed 887 patients who underwent STL MVFTT from 14 references. Ninety-six STL MVFTTs were performed by the authors, with 36 (38%) patients undergoing multilayer fascial underlay (MLFU) closure and 60 (62%) a standard single layer closure (SLC). One (3%) PCF occurred in the MLFU group compared to 12 (20%) in the SLC cohort (P = .03). Postoperative gastrostomy (G)-tube dependence was lower following MLFU closure compared to SLC (25% vs. 57%, P .01), whereas pharyngoesophageal stricture (PES) (28% vs. 38%), tracheoesophageal puncture (TEP) placement (42% vs. 42%), and TEP usage (87% vs. 88%) did not significantly differ (P .05). Compared to pooled rates from the literature, patients who underwent a MLFU MVFTT inset technique demonstrated significantly lower PCF incidence (3% vs. 23%, P .01) without significant differences in PES (28% vs 23%, P = .55), G-tube dependence (25% vs. 23%, P = .25), or TEP placement (42% vs. 59%, P = .09).Despite MVFTT reconstruction after STL, G-tube dependence, PCF formation, and limitations of speaking rehabilitation (TEP) remain a significant issue. Modification of MVFTT inset may provide an opportunity to reduce PCF incidence without affecting other functional outcomes.4 Laryngoscope, 131:E875-E881, 2021.

Background Following salvage total laryngectomy (STL) with microvascular-free tissue transfer (MFTT), patients are at high risk for swallowing dysfunction, but risk factors for persistent gastrostomy tube (G-tube) dependence are unknown. Methods Retrospective review of 33 patients who underwent STL with MFTT. Results A total oral diet was achieved by 81% of patients with ≥6 months of postoperative follow-up. Approximately 27% of patients were G-tube dependent preoperatively with 67% achieving a total oral diet postoperatively. Factors associated with persistent G-tube dependence included pT4 tumor, pN2+ status, more extensive pharyngectomy, and re-irradiation. Strictures occurred in 30% of patients and were associated with more extensive pharyngectomy and tubed reconstruction. Conclusions For patients undergoing STL with MFTT, the majority of patients achieve a total oral diet regardless of their preoperative swallowing function. Advanced-stage recurrent tumors and increased extent of pharyngectomy contribute to poorer swallowing outcomes.

A 62-year-old man with an extensive smoking history is diagnosed with oral cavity squamous cell carcinoma. After consultation, he is scheduled for radical resection with free flap reconstruction. The patient continues to smoke and is strongly advised to quit. When he returns for follow-up prior to his scheduled operation, the patient reluctantly discloses to his care team that he has not quit smoking. The surgeon considers withholding the operation until the patient has been tobacco-free for 4 weeks, consistent with evidence showing a significant decrease in surgical complications. Would it be ethically defensible to do so?

PURPOSE: High-risk oropharyngeal squamous cell carcinoma (OPSCC) associated with tobacco exposure remains difficult to treat due to high rates of locoregional recurrence similar to oral cavity squamous cell carcinoma (OCSCC). Current NCCN guidelines allow for surgical management of this disease, but oncologic and functional data in the modern era remain scarce. We sought to compare and contrast oncologic and functional considerations for surgical management of OPSCC and OCSCC in a cohort of Veterans. MATERIALS AND METHODS: We conducted a retrospective review of patients treated at the Michael E. DeBakey Veterans Affairs Medical Center between 2017 and 2020, treated using a homogenous, multi-modality algorithm. RESULTS: OPSCC tumors presented with a higher rate of perineural invasion (p < 0.05) and extranodal extension (p = 0.02) compared to OCSCC tumors. Compliance with NCCN guidelines for adjuvant treatment were lower for OPSCC patients primarily due to a higher rate of previous irradiation; re-irradiation could be delivered in 75% of patients when recommended by NCCN guidelines. Total glossectomy was accompanied by concomitant total laryngectomy in 100% of OPSCC patients and 0% of OCSCC. CONCLUSION: Surgical resection and free flap reconstruction of high-risk OPSCC generates oncologic outcomes comparable to OCSCC with comparable complication rates but a lower overall functional status. Reconstruction focused on rapid healing allows for high-rates of re-irradiation and minimal treatment delays. Level of evidence: level 4.

Importance Data regarding outcomes after major head and neck ablation and reconstruction in the growing geriatric population (specifically ≥80 years of age) are limited. Such information would be extremely valuable in preoperative discussions with elderly patients about their surgical risks and expected functional outcomes. Objectives To identify patient and surgical factors associated with 30-day postoperative complications, 90-day mortality, and 90-day functional decline; to explore whether an association exists between the type of reconstructive procedure and outcome; and to create a preoperative risk stratification system for these outcomes. Design, Setting, and Participants This retrospective, multi-institutional cohort study included patients 80 years or older undergoing pedicle or free-flap reconstruction after an ablative head and neck surgery from January 1, 2015, to December 31, 2017, at 17 academic centers. Data were analyzed from February 1 through April 20, 2019. Main Outcomes and Measures Thirty-day serious complication rate, 90-day mortality, and 90-day decline in functional status. Preoperative comorbidity and frailty were assessed using the American Society of Anesthesiologists classification, Adult Comorbidity Evaluation–27 score, and Modified Frailty Index. Multivariable clustered logistic regressions were performed. Conjunctive consolidation was used to create a risk stratification system. Results Among 376 patients included in the analysis (253 [67.3%] men), 281 (74.7%) underwent free-flap reconstruction. The median age was 83 years (range, 80-98 years). A total of 193 patients (51.3%) had 30-day serious complications, 30 (8.0%) died within 90 days, and 36 of those not dependent at baseline declined to dependent status (11.0%). Type of flap (free vs pedicle, bone vs no bone) was not associated with these outcomes. Variables associated with worse outcomes were age of at least 85 years (odds ratio [OR] for 90-day mortality, 1.19 [95% CI 1.14-1.26]), moderate or severe comorbidities (OR for 30-day complications, 1.80 [95% CI, 1.34-2.41]; OR for 90-day mortality, 3.33 [95% CI, 1.29-8.60]), body mass index (BMI) of less than 25 (OR for 30-day complications, 0.95 [95% CI, 0.91-0.99]), high frailty (OR for 30-day complications, 1.72 [95% CI, 1.10-2.67]), duration of surgery (OR for 90-day functional decline, 2.94 [95% CI, 1.81-4.79]), flap failure (OR for 90-day mortality, 3.56 [95% CI, 1.47-8.62]), additional operations (OR for 30-day complications, 5.40 [95% CI, 3.09-9.43]; OR for 90-day functional decline, 2.94 [95% CI, 1.81-4.79]), and surgery of the maxilla, oral cavity, or oropharynx (OR for 90-day functional decline, 2.51 [95% CI, 1.30-4.85]). Age, BMI, comorbidity, and frailty were consolidated into a novel 3-tier risk classification system. Conclusions and Relevance Important demographic, clinical, and surgical characteristics were found to be associated with postoperative complications, mortality, and functional decline in patients 80 years or older undergoing major head and neck surgery. Free flap and bony reconstruction were not independently associated with worse outcomes. A novel risk stratification system is presented.

Background To describe the types of research being conducted and the availability of research ethics training and research ethics review in Thailand and Vietnam. Methods An English survey with four major domains, Research Area, Societal Conditions, Research Ethics, and Basic Information was translated into Thai and Vietnamese by native training partners from the NIH Fogarty Research Ethics Training Program. Setting/Participants The survey was administered in two modes - an online survey distributed via an email link in Thailand, and an onsite paper survey in Vietnam. Participants were Thai and Vietnamese trainees and investigators from prestigious universities. Results In Thailand, there were 363 respondents (9.3% online response rate); in Vietnam there were 117 survey participants. Among those who conduct research, 81% in Thailand and 92% percent in Vietnam reported that their research involves human subjects. Among human subject researchers, 83% in Thailand reported having ethics training, and among these, only 44% reported having formal training. In Vietnam, 66% reported having research ethics training; among them, 72% had formal training. Human subject research reported include clinical observations (26% from Thailand and 26% from Vietnam) and clinical interventions (29% from Thailand and 26% from Vietnam). Significant proportion of respondents reported that their institutions have guidelines (97% in Thailand; 89% from Vietnam) and have established Institutional Review Boards (92% in Thailand; 77% in Vietnam). 76% and 79% of respondents in Thailand and Vietnam respectively reported no experience in teaching research ethics. Lack of trained research ethics teachers (38% in Thailand and 59% in Vietnam), training materials (34% in Thailand; 43% in Vietnam), and an adequate curricular “delivery platform” (58% in Thailand; 49% in Vietnam) are most pressing issues. Conclusions We identified gaps in research ethics training in these two South East Asian countries undergoing rapid socioeconomic transition and identified future curricular focus opportunities.

This article summarizes the current use of patient-specific implants in oral and maxillofacial surgery.

Objective The use of microvascular free tissue transfer (MVFTT) for defects of the scalp and lateral temporal bone in patients with cochlear implants (CI) is uncommon. Herein, we report our experience with the utility, indications, and outcomes for MVFTT in patients with cochlear implants. Methods A retrospective review of patients at our institution from September 2016 to December 2017 identified subjects with coexistent cochlear implant and ipsilateral MVFTT of the lateral temporal bone or scalp. Information including demographics, indication for MVFTT, timing of CI and MVFTT, donor site, and previous radiation to the head and neck was collected. To assess the current literature on MVFTT in CI patients, a MEDLINE search was performed using key search terms. Results Two patients with cochlear implants and MVFTT of the ipsilateral temporal bone or scalp were identified. One patient underwent MVFTT for advanced device extrusion with stable audiometric parameters rather than locoregional reconstruction or device explantation. The second patient had primary cochlear implantation at oncologic lateral temporal bone resection (LTBR) and MVFTT for locally advanced squamous cell carcinoma and concurrent profound sensorineural hearing loss (SNHL). A literature review identifies MVFTT as an option for advanced device extrusion, treatment of osteoradionecrosis, and reconstruction after primary oncologic surgery. Conclusion MVFTT is an important reconstructive tool for patients with functional, exposed cochlear implants. Cochlear implantation for severe to profound SNHL should be considered at the time of primary oncologic surgery and MVFTT of the lateral temporal bone or scalp. Level of evidence IV Laryngoscope, 130:1552-1557, 2020.

Objective Oropharyngeal squamous cell carcinoma (OPSCC) incidence is rapidly increasing, as are survival rates, in large part due to the human papillomavirus (HPV). Treatment intensity, however, has remained unchanged, making treatment-related toxicity (i.e., dysphagia) a critical problem for an increasing number of patients. The primary objective of this study was to determine whether pretreatment objective swallowing measures can predict percutaneous fluoroscopic guided gastrostomy tube (PFG) utilization during OPSCC treatment. Methods Forty-one newly diagnosed OPSCC patients treated with radiation underwent evaluation of swallow function with modified barium swallow study (MBSS) prior to and at completion of radiation treatment using the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST); a subset of patients were evaluated using the MD Anderson Dysphagia Inventory (MDADI). Results Patients were male (100%), primarily Caucasian (85.4%) and p16 positive (85.4%) with mean age of 65.7 years. PFG were placed in 70.7% patients (n = 29) and used by 63.4% (n = 26). Pre- and post-treatment DIGEST scores were associated with T-classification (t = -2.9, p = .001, t = -2.7, p = .01) and indicated deteriorating swallow function during treatment (mean change = 0.46 [t = -2.7, p = .01]). DIGEST and MDADI scores were generally not associated with patient PFG utilization. DIGEST and MDADI scores were significantly correlated prior to, but not following completion of treatment. Conclusion Pre-treatment DIGEST and patient reported swallowing outcomes (MDADI) can be useful in identifying patients with unsafe and/or grossly inefficient swallowing function. However, objectively measured swallow function was not associated with PFG utilization. Development of PFG placement algorithms (reactive vs. prophylactic) therefore require additional inputs/metrics. Level of evidence 4 Laryngoscope, 130:2153-2159, 2020.

Objective Primary surgery followed by adjuvant therapy is the current standard of care in the multidisciplinary management of squamous cell carcinoma (SCC) of the oral tongue. Additionally, salvage glossectomy is used to treat recurrent base of tongue SCC. Microvascular free tissue transfer reconstruction (MVFTT) is utilized to maximize functional outcomes such as swallowing. We sought to identify prognostic factors related to achievement of a total oral diet in patients that underwent glossectomy with MVFTT. Methods Retrospective review at a tertiary care center from 2010 to 2015. Results 200 patients (69% male, mean age 60 years) met inclusion criteria. Extent of glossectomy was categorized as partial or hemiglossectomy (39%), tongue base resection with or without hemi-oral glossectomy (23%), composite resection with mandibulectomy (18%), and subtotal or total glossectomy (21%). Flap success rate was 96%. Median follow-up time was 14 months. A total oral diet was achieved by 49% of patients with median time to achievement of 31 days (IQR 9-209). Multivariate analysis identified body mass index Conclusion Swallowing dysfunction represents a significant morbidity following glossectomy in the treatment of SCC. High BMI, smaller resection fields, and absence of prior radiation therapy or adjuvant chemoradiotherapy correlated with improved likelihood of obtaining a total oral diet. Patients should be appropriately counseled of this risk with emphasis placed on aggressive swallow rehabilitation in the post- treatment setting.

Background Parotid adenocarcinoma not otherwise specified (PANOS) is a common parotid cancer, but studies specifically on this subject are limited. Methods We conducted a retrospective review of the National Cancer Database. Results Ten percent of all parotid cancers were PANOS (n = 3155). Median age was 67 years. Most patients were men (62.8%) with high-grade histology (67.2%). Regional metastasis was common (35.9%), whereas occult nodal metastasis (20.2% overall) was less frequent in non-high-grade lesions (8.5% vs 31.6%; p < .001). Distant metastasis was rare (7.9%). Five-year overall survival (OS) was 47%. In multivariate analysis, age, regional metastasis, distant metastasis, high-grade, and T classification were predictors of lower survival. Patients with stage III to IV disease receiving surgery and radiotherapy had a better OS than those receiving surgery alone (51% vs 41%; p < .001). Conclusion PANOS is an aggressive disease with frequent regional metastasis and low survival. Numerous variables are associated with worse survival. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

Objective To describe swallowing outcomes in elderly patients undergoing microvascular reconstruction of the upper aerodigestive tract and identify risk factors for poor postoperative swallowing function. Study Design Case series with chart review. Setting Academic medical center. Subjects and Methods Sixty-six patients aged ≥70 years underwent microvascular reconstruction of the upper aerodigestive tract. The primary outcome measure was the Functional Oral Intake Scale (FOIS); preoperative and postoperative scores were dichotomized to define "good swallowing" and "poor swallowing." Logistic regression was performed to identify risk factors for poor postoperative swallowing function. Results In total, 91% of reconstructions were performed for oncologic defects. The most common defect site was the oral cavity (67%), and the anterolateral thigh (29%) was the most frequently used donor site. At 3-year follow up, 75% of patients had good swallowing function with 95% of patients who achieved good swallowing function doing so within 6 months of surgery. On multivariable analysis, patients with pT4 tumors (odds ratio [OR], 5.2; 95% confidence interval [CI], 1.0-25.6) and those undergoing at least partial glossectomy (OR, 4.7; 95% CI, 1.1-20.7) were more likely to experience poor swallowing function at 6-month follow-up. Conclusion Approximately half of elderly patients achieve good swallowing function within 6 months following microvascular reconstruction of the upper aerodigestive tract. Elderly patients with pT4 tumors and those requiring glossectomy are at highest risk for poor swallowing outcomes. These data can be used to inform preoperative patient counseling and design interventions aimed at improving swallowing function in those at high risk for poor outcomes.

PURPOSE FDG PET that has been used is good for diagnosing asymptomatic colorectal cancer (CRC) recurrence in patients with elevated serum carcinoembryonic antigen (CEA) level. However, there is no reference level of CEA rise that would universally suggest the necessity of a PET study. The purpose of this retrospective study was to identify the high-risk group of CRC recurrence through an examination of the dynamics of the CEA level rise as a recurrence indicator. PATIENTS AND METHODS Between July 2002 and May 2010, 112 patients (59 men, 53 women; age, 18-87 years) had FDG PET for suspicious CRC recurrence indicated by elevated CEA level. We reviewed the PET results and the medical records for recurrence verification and calculated the ratio of increase and the velocity of change in CEA levels for risk stratification. RESULTS The patient-based sensitivity, specificity, and accuracy of PET are 96.6%, 91.3%, and 95.5%, respectively. The probability of recurrence positively correlated with the CEA level rise and the newly diagnosed disease stage. Carcinoembryonic antigen level greater than 13 ng/mL indicated significantly higher risks of recurrence. In patients with CEA level rise of 13 ng/mL or less, an increase over 3.34 times the individualized baseline also indicated high risks of recurrence. CONCLUSIONS A posttreatment CEA level rise to greater than 13 ng/mL is suggestive of the optimal use of FDG PET, and so is a mild increase below 13 ng/mL at an increase rate over 3.34.

BACKGROUND Characteristics of 30-day unplanned readmissions after head and neck microvascular reconstruction remain poorly understood. METHODS We conducted a retrospective cohort of patients who underwent head and neck microvascular reconstruction between 2010 and 2015. RESULTS The 30-day unplanned readmission rate was 13.0% (64/493). The most common readmission diagnoses were dehiscence, surgical site infection, or fistula (45.3%; n = 29). Of the readmissions, 46.9% (30/64) occurred within 7 days of discharge from the hospital. Risk factors for readmission on multivariable analysis included body mass index (BMI)

Nodal disease predicts survival in oral cavity squamous cell carcinoma (SCC). Currently, no large studies on predictors of occult nodal disease in cT1N0 oral cavity SCC exist.The National Cancer Database (NCDB) review for cT1N0 oral cavity SCC with surgical resection and elective neck dissection (END).The number of patients found with occult nodal disease was 2623 (15.1%). In multivariable regression, female sex and tumor differentiation predict occult nodal disease. Occult nodal disease incidence was 5.9% in well-differentiated tumors, 17.4% in moderately differentiated tumors, and 28.5% in poorly differentiated tumor (P.001). Women with oral tongue tumors had higher occult nodal disease (19.1%) than men (12%; P = .001). Adjusted odds ratios (aORs) for occult nodal disease in women were: aOR 1.26; 95% confidence interval (CI) 1.01-1.59; P = .045; moderately differentiated aOR 3.52; 95% CI 2.47-5.01; P.001; and poorly differentiated aOR 6.25; 95% CI 4.17-9.38; P.001.Sex and tumor differentiation significantly predict occult nodal disease. END is recommended for all moderately and poorly differentiated cT1N0 oral cavity SCC, regardless of the depth of invasion. One can consider not performing END in well-differentiated tumors.

Sarcoidosis is a systemic inflammatory disease that can affect virtually every organ system, leading to a wide variety of clinical manifestations. Central nervous system involvement producing neurologic symptoms can occur in patients with sarcoidosis, yet rarely are these symptoms the initial manifestations of the disease. Here we present the case of a 38-year-old man who presented with a history of chronic facial pain, blurred vision, increased lacrimation, and periodontal abscesses. Physical examination revealed no evidence of infection or neoplasm. Magnetic resonance imaging revealed space-occupying lesions in Meckel cave bilaterally, with soft-tissue density extending into the left sphenoid and posterior ethmoid sinuses. Endoscopic biopsy of sinus mucosa demonstrated the presence of noncaseating granulomas and the absence of organisms, findings suggestive of neurosarcoidosis. The diagnosis was further supported by chest radiography, which demonstrated bilateral hilar adenopathy. The patient was treated with corticosteroids, and his facial pain improved markedly. In this article we discuss neurosarcoidosis and its manifestations, diagnosis, and clinical course.

Purpose This study is designed to validate a previously developed locoregional recurrence risk (LRR) scoring system and further define which groups of patients with breast cancer would benefit from postmastectomy radiation therapy (PMRT). Methods and Materials An LRR risk scoring system was developed previously at our institution using breast cancer patients initially treated with modified radical mastectomy between 1990 and 2001. The LRR score comprised 4 factors: patient age, lymphovascular invasion, estrogen receptor negativity, and number of involved lymph nodes. We sought to validate the original study by examining a new dataset of 1545 patients treated between 2002 and 2007. Results The 1545 patients were scored according to the previously developed criteria: 920 (59.6%) were low risk (score 0-1), 493 (31.9%) intermediate risk (score 2-3), and 132 (8.5%) were high risk (score ≥4). The 5-year locoregional control rates with and without PMRT in low-risk, intermediate-risk, and high-risk groups were 98% versus 97% ( P =.41), 97% versus 91% ( P =.0005), and 89% versus 50% ( P =.0002) respectively. Conclusions This analysis of an additional 1545 patients treated between 2002 and 2007 validates our previously reported LRR scoring system and suggests appropriate patients for whom PMRT will be beneficial. Independent validation of this scoring system by other institutions is recommended.

Value-driven payment system reform is a potential tool for aligning economic incentives with the improvement of quality and efficiency of health care and containment of cost. Such a payment system has not been researched satisfactorily in full-cycle cancer care.To examine the association of outcomes and medical expenditures with a bundled-payment pay-for-performance program for breast cancer in Taiwan compared with a fee-for-service (FFS) program.Data were obtained from the Taiwan Cancer Database, National Health Insurance Claims Data, the National Death Registry, and the bundled-payment enrollment file. Women with newly diagnosed breast cancer and a documented first cancer treatment from January 1, 2004, to December 31, 2008, were selected from the Taiwan Cancer Database and followed up for 5 years, with the last follow-up data available on December 31, 2013. Patients in the bundled-payment program were matched at a ratio of 1:3 with control individuals in an FFS program using a propensity score method. The final sample of 17 940 patients included 4485 (25%) in the bundled-payment group and 13 455 (75%) in the FFS group.Rates of adherence to quality indicators, survival rates, and medical payments (excluding bonuses paid in the bundled-payment group). The Kaplan-Meier method was used to calculate 5-year overall and event-free survival rates by cancer stage, and the Cox proportional hazards regression model was used to examine the effect of the bundled-payment program on overall and event-free survival. Sensitivity analysis for bonus payments in the bundled-payment group was also performed.The study population included 17 940 women (mean [SD] age, 52.2 [10.3] years). In the bundled-payment group, 1473 of 4215 patients (34.9%) with applicable quality indicators had full (100%) adherence to quality indicators compared with 3438 of 12 506 patients (27.5%) with applicable quality indicators in the FFS group (P .001). The 5-year event-free survival rates for patients with stages 0 to III breast cancer were 84.48% for the bundled-payment group and 80.88% for the FFS group (P .01). Although the 5-year medical payments of the bundled-payment group remained stable, the cumulative medical payments for the FFS group steadily increased from $16 000 to $19 230 and exceeded pay-for-performance bundled payments starting in 2008.In Taiwan, compared with the regular FFS program, bundled payment may lead to better adherence to quality indicators, better outcomes, and more effective cost-control over time.

Objectives/Hypothesis: To describe the authors' experience with an extended deep-plane cervicofacial (EDPCF) advancement flap, a modification of the deep-plane cervicofacial flap, for reconstruction of large forehead and temple soft-tissue defects. Study Design: Case series at a tertiary referral medical center. Methods: The charts of 11 consecutive patients who underwent EDPCF flap surgery for reconstruction of forehead and temple skin cancer defects were reviewed for demographics, smoking status, defect size, length of surgery and hospitalization, American Society of Anesthesiologists Physical Status Classification (ASA) grade, and postoperative complications. Results: All patients had reconstruction of large forehead and temple defects following either primary resection or Mohs micrographic surgery for skin cancer. No skin grafting was required for secondary defects. The average defect size was 52.2 cm2. Patient ages averaged 74 years with a median ASA grade of 3. Thirty-six percent of patients admitted to smoking. Average operative time was 100 minutes, with 82% of patients treated on an outpatient basis. There were no complications of ectropion or facial nerve injury encountered. Partial distal flap necrosis occurred in one patient who admitted to smoking and resolved with conservative management. Conclusions: The EDCPF flap is a robust flap with a dual arterial supply and both rotation and advancement components. It is ideal in frail patients with good soft-tissue laxity and provides an immediate one-stage reconstruction with ideal skin color, texture, and thickness matches for large forehead and temple defects.

Klebsiella pneumoniae causes serious, life-threatening infections in humans in endemic and epidemic settings. The objective of this study was to determine whether the incidence of K. pneumoniae bloodstream infection (BSI) was higher during warm months.We analyzed surveillance data from 2001-2006 at 4 hospitals located on 4 continents. Incidence rates (IRs) and IR ratios (IRRs) were determined using multivariable Poisson regression.In total, 1189 cases of K. pneumonia BSIs occurred during 6,671,337 patient-days. The IR of K. pneumoniae BSI during the 4 warmest months of the year was 2.23/10,000 patient-days, whereas the IR of K. pneumoniae BSI for the other 8 months was 1.55/10,000 patient-days (IRR, 1.46 [95% confidence interval, 1.04-2.06]; P= .03). In contrast, no seasonal variation was identified in rates of BSI due to Enterobacter or Serratia species. Using Poisson regression, we showed that temperature (P.0001) and dew point (a marker for relative humidity; P.0001) were both linearly predictive of increasing rates of K. pneumoniae BSI.Environmental pressures may lead to an increase in the IR of K. pneumoniae BSI during the warmest months of the year.

Parotid adenocarcinoma not otherwise specified (PANOS) is a common parotid cancer, but studies specifically on this subject are limited.We conducted a retrospective review of the National Cancer Database.Ten percent of all parotid cancers were PANOS (n = 3155). Median age was 67 years. Most patients were men (62.8%) with high-grade histology (67.2%). Regional metastasis was common (35.9%), whereas occult nodal metastasis (20.2% overall) was less frequent in non-high-grade lesions (8.5% vs 31.6%; p.001). Distant metastasis was rare (7.9%). Five-year overall survival (OS) was 47%. In multivariate analysis, age, regional metastasis, distant metastasis, high-grade, and T classification were predictors of lower survival. Patients with stage III to IV disease receiving surgery and radiotherapy had a better OS than those receiving surgery alone (51% vs 41%; p.001).PANOS is an aggressive disease with frequent regional metastasis and low survival. Numerous variables are associated with worse survival. © 2016 Wiley Periodicals, Inc. Head Neck 38:1208-1212, 2016.

The epidemiology of cancer pain and the outcomes associated with pain treatments were investigated through a retrospective survey of 772 patients with advanced cancer. The cumulative prevalence of pain was 87%, including all types of cancer. Mean duration of pain was 6.9+/-8.1 months. The prevalence of pain was 28%, 46%, 67%, 75%, and 79% at 6 months, 3 months, 1 month, 1 week, and 1 day before the time of death, respectively. The so-called "strong" opioids had been used in 85% of the 669 patients with pain. Seventy-nine percent of patients with pain received nonsurgical antineoplastic treatment for pain control. No more than 11% of patients ultimately experienced substantial pain in the last 6 months of life (defined as pain score 5-10 on a 0-10 numeric rating scale). We conclude that the application of a multidisciplinary approach to pain management offers effective pain control for most patients with advanced cancer.

Purpose: This study established a prognostic scoring system for nasopharyngeal carcinoma (NPC), which estimates the probability of locoregional (LR) control following definitive conformal radiotherapy. Methods and Materials: Patients with nondisseminated NPC at initial presentation ( n = 630) were enrolled in this study. All patients had magnetic resonance imaging of the head and neck and were treated with conformal radiotherapy. Among them, 93% had concurrent chemotherapy, and 76% had postradiation chemotherapy. The extent of the primary tumor, age at diagnosis, primary tumor size, tumor and nodal classification, histology, and serum lactate dehydrogenase (LDH) level before treatment were included in the analysis for building a prognostic scoring system. The end point for this study was LR control. Results: The prognostic score was defined as the number of adverse prognostic factors present at diagnosis. Four factors had similarly independent prognostic effects (hazard ratio, 2.0–2.6): age >40 years, histologic WHO type I-II, serum LDH level ≥410 U/L, and involvement of two or more sites of the following anatomic structures, i.e., sphenoid floor, clivus marrow, clivus cortex, prevertebral muscles, and petrous bone. The score predicted the 5-year probability of LR control as follows: 0 (15% of the patients), 100%; 1 (42% of the patients), 93%; 2 (29% of the patients), 83%; 3 or higher (13% of the patients), 71%. Conclusion: This scoring system is useful in the decision-making for individual patients and the design of clinical trials to improve LR control for advanced-stage NPC.

The purpose of this study is to evaluate the prevalence and prognostic significance of prevertebral muscle involvement in patients with nasopharyngeal carcinoma (NPC).Between July 1990 and December 2001, 521 newly diagnosed patients with NPC treated at Koo Foundation Sun Yat-Sen Cancer Center (KF-SYSCC) were examined with magnetic resonance imaging (MRI) for evidence of prevertebral muscle involvement before treatment. Patients were staged according to the 1997 American Joint Committee on Cancer staging classification of NPC based on the physical exams and MRI findings. All patients received radiotherapy with or without chemotherapy. The association between clinical prevertebral muscle involvement and posttreatment outcomes (overall survival, locoregional recurrence, and distant metastasis) were evaluated using Cox regression model to adjust for other prognostic factors.Of 521 patients treated at KF-SYSCC, 181 (35%) patients were found to have prevertebral muscle involvement, one-third in those with Stage II/III tumors and two-thirds in those with Stage IV tumor. In multivariate analysis accounting for all previously known prognostic factors, prevertebral muscle invasion was associated with an increased risk for any recurrence (adjusted relative risk, 2.01; p0.001), locoregional recurrence (adjusted relative risk, 2.69; p0.001), and distant metastasis (adjusted relative risk, 2.25; p0.001), and with a borderline significant increased risk for overall survival (adjusted relative risk, 1.44; p=0.10).Prevertebral muscle involvement is an independent prognostic factor for NPC recurrence.

Numerous recent studies have demonstrated the use of genomic data, particularly gene expression signatures, as clinical prognostic factors in cancer and other complex diseases. Such studies herald the future of genomic medicine and the opportunity for personalized prognosis in a variety of clinical contexts that utilizes genome-scale molecular information. The scale, complexity, and information content of high-throughput gene expression data, as one example of complex genomic information, is often under-appreciated as many analyses continue to focus on defining individual rather than multiplex biomarkers for patient stratification. Indeed, this complexity of genomic data is often—rather paradoxically—viewed as a barrier to its utility. To the contrary, the complexity and scale of global genomic data, as representing the many dimensions of biology, must be embraced for the development of more precise clinical prognostics. The need is for integrated analyses—approaches that embrace the complexity of genomic data, including multiple forms of genomic data, and aim to explore and understand multiple, interacting, and potentially conflicting predictors of risk, rather than continuing on the current and traditional path that oversimplifies and ignores the information content in the complexity. All forms of potentially relevant data should be examined, with particular emphasis on understanding the interactions, complementarities, and possible conflicts among gene expression, genetic, and clinical markers of risk.

To develop clinical prediction models for local regional recurrence (LRR) of breast carcinoma after mastectomy that will be superior to the conventional measures of tumor size and nodal status.Clinical information from 1,010 invasive breast cancer patients who had primary modified radical mastectomy formed the database of the training and testing of clinical prognostic and prediction models of LRR. Cox proportional hazards analysis and Bayesian tree analysis were the core methodologies from which these models were built. To generate a prognostic index model, 15 clinical variables were examined for their impact on LRR. Patients were stratified by lymph node involvement (4 vs.or =4) and local regional status (recurrent vs. control) and then, within strata, randomly split into training and test data sets of equal size. To establish prediction tree models, 255 patients were selected by the criteria of having had LRR (53 patients) or no evidence of LRR without postmastectomy radiotherapy (PMRT) (202 patients).With these models, patients can be divided into low-, intermediate-, and high-risk groups on the basis of axillary nodal status, estrogen receptor status, lymphovascular invasion, and age at diagnosis. In the low-risk group, there is no influence of PMRT on either LRR or survival. For intermediate-risk patients, PMRT improves LR control but not metastases-free or overall survival. For the high-risk patients, however, PMRT improves both LR control and metastasis-free and overall survival.The prognostic score and predictive index are useful methods to estimate the risk of LRR in breast cancer patients after mastectomy and for estimating the potential benefits of PMRT. These models provide additional information criteria for selection of patients for PMRT, compared with the traditional selection criteria of nodal status and tumor size.