Publications by authors named "Gregory S Weinstein"

127 Publications

Definitive tumor directed therapy confers a survival advantage for metachronous oligometastatic HPV-associated oropharyngeal cancer following trans-oral robotic surgery.

Oral Oncol 2021 Oct 30;121:105509. Epub 2021 Aug 30.

Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA.

Objectives: To assess the prognostic significance of oligometastatic versus polymetastatic disease in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC), and to evaluate the impact of definitive tumor directed therapy on the survival outcomes for patients with oligometastatic disease when compared to systemic therapy.

Materials And Methods: This was a retrospective observational cohort study of patients with HPV-associated OPSCC who developed distant metachronous metastatic disease after undergoing initial primary surgical management from 2008 to 2017. We classified patients based on the extent of metastatic disease [Oligometastatic (≤5 metastases) and polymetastatic (>5 metastases)], and the initial treatment of metastatic disease [definitive tumor directed therapy (all metastases treated with surgery or radiotherapy) versus upfront systemic therapy].

Results: Among 676 patients undergoing primary surgical management for HPV-associated OPSCC, 39 patients (5.8%) developed metastases after a median follow-up of 29.6 months (range 4.5-127.0). Of the 34 metastatic patients who met study criteria, 26 (76.5%) were oligometastatic and 8 (23.5%) were polymetastatic. Oligometastatic patients had improved median overall survival (OS) compared to polymetastatic patients (47.9 vs. 22.7 months, p = 0.036). For oligometastatic patients, definitive tumor directed therapy was associated with an improved median progression free survival (not reached vs 6.13 months, p = 0.001) and median OS (not reached vs 40.7 months, p = 0.004).

Conclusion: In a cohort of patients surgically treated for HPV-associated OPSCC, metachronous metastatic disease was uncommon and, in most cases, considered oligometastatic. Oligometastasis portends a favorable prognosis and definitive tumor directed therapy may be associated with improved overall survival in these patients. Future multi-institutional efforts are warranted to further demonstrate the impact of definitive tumor directed therapy on disease outcomes.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105509DOI Listing
October 2021

Survival and toxicity in patients with human papilloma virus-associated oropharyngeal squamous cell cancer receiving trimodality therapy including transoral robotic surgery.

Head Neck 2021 10 25;43(10):3053-3061. Epub 2021 Jun 25.

Department of Otorhinolaryngology - Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: Patients with oropharyngeal cancer who undergo transoral robotic surgery (TORS) and have high-risk features generally receive adjuvant chemoradiotherapy or trimodality therapy (TMT). The notion that TMT leads to high toxicity is largely based on studies that included human papilloma virus (HPV)-negative cancers and/or nonrobotic surgery; we sought to describe outcomes in HPV-associated oropharyngeal squamous cell cancer (HPV + OPSCC) undergoing TORS-TMT.

Methods: In consecutive patients with HPV + OPSCC receiving TMT at an academic center from 2010 to 2017, survival was estimated using Kaplan-Meier methodology, and toxicities were ascertained via chart review.

Results: In our cohort of 178 patients, 5-year survival was 93.6%. Feeding tube rates were 25.8% at therapy completion and 0.7% at 1 year. Rates of grade ≥ 3 kidney injury, anemia, and neutropenia in cisplatin-treated patients were 2.7%, 3.4%, and 11.0%, respectively.

Conclusions: Patients with HPV + OPSCC who underwent TORS-TMT had excellent survival and low rates of toxicity and feeding tube dependence. These outcomes compare favorably to historical cohorts treated with definitive chemoradiotherapy.
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http://dx.doi.org/10.1002/hed.26797DOI Listing
October 2021

Oncologic outcomes of transoral robotic surgery for HPV-negative oropharyngeal carcinomas.

Head Neck 2021 10 8;43(10):2923-2934. Epub 2021 Jun 8.

Department of Otorhinolaryngology - Head & Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: Patients with human papillomavirus (HPV)-negative oropharyngeal squamous cell carcinoma (OPSCC) continue to experience disappointing outcomes following chemoradiotherapy (CRT) and appreciable morbidity following historical surgical approaches. We aimed to investigate the oncologic outcomes and perioperative morbidity of a transoral robotic surgery (TORS) approach to surgically resectable HPV-negative OPSCC.

Methods: Retrospective analysis HPV-negative OPSCC patients who underwent TORS, neck dissection and pathology-guided adjuvant therapy (2005-2017).

Results: Fifty-six patients (91.1% stage III/IV) were included. Three-year overall survival, locoregional control, and disease-free survival were 85.5%, 84.4%, and 73.6%, respectively (median follow-up 30.6 months, interquartile range 18.4-66.6). Eighteen (32.1%) patients underwent adjuvant radiotherapy and 20 (39.3%) underwent adjuvant CRT. Perioperative mortality occurred in one (1.8%) patient and hemorrhage occurred in two (3.6%) patients. Long-term gastrostomy and tracheostomy rates were 5.4% and 0.0%, respectively.

Conclusion: The TORS approach for resectable HPV-negative OPSCC can achieve encouraging oncologic outcomes with infrequent morbidity.
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http://dx.doi.org/10.1002/hed.26776DOI Listing
October 2021

Locoregional Recurrence in p16-Positive Oropharyngeal Squamous Cell Carcinoma After TORS.

Laryngoscope 2021 Jun 2. Epub 2021 Jun 2.

Department of Otorhinolaryngology: Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.

Objective: To analyze the patterns, risk factors, and salvage outcomes for locoregional recurrences (LRR) after treatment with transoral robotic surgery (TORS) for HPV-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC).

Study Design: Retrospective analysis of HPV+ OPSCC patients completing primary TORS, neck dissection, and NCCN-guideline-compliant adjuvant therapy at a single institution from 2007 to 2017.

Methods: Features associated with LRR, detailed patterns of LRR, and outcomes of salvage therapy were analyzed. Disease-free survival (DFS) and overall survival (OS) were calculated for subgroups of patients receiving distinct adjuvant treatments.

Results: Of 541 patients who completed guideline-indicated therapy, the estimated 5-year LRR rate was 4.5%. There were no identifiable clinical or pathologic features associated with LRR. Compared to patients not receiving adjuvant therapy, those who received indicated adjuvant radiation alone had a lower risk of LRR (HR 0.28, 95% CI [0.09-0.83], P = .023), but there was no difference in DFS (P = .21) and OS (P = .86) between adjuvant therapy groups. The 5-year OS for patients who developed LRR was 67.1% vs. 93.9% for those without LRR (P < .001). Patients who initially received adjuvant chemoradiation and those suffering local, in-field, and/or retropharyngeal node recurrences had decreased disease control after salvage therapy.

Conclusion: LRR rates are low for HPV+ OPSCCs completing TORS and guideline-compliant adjuvant therapy. Patients without indication for adjuvant therapy more often suffer LRR, but these recurrences are generally controllable by salvage therapy. Improved understanding of the patterns of recurrence most amenable to salvage therapy may guide treatment decisions, counseling, and adjuvant therapy de-escalation trials.

Level Of Evidence: 3 Laryngoscope, 2021.
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http://dx.doi.org/10.1002/lary.29659DOI Listing
June 2021

Oncologic and survival outcomes for resectable locally-advanced HPV-related oropharyngeal cancer treated with transoral robotic surgery.

Oral Oncol 2021 07 28;118:105307. Epub 2021 Apr 28.

Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.

Objectives: To determine whether up-front trans-oral robotic surgery (TORS) for clinically-staged locally-advanced human papillomavirus (HPV)-related oropharyngeal cancer is associated with oncologic and survival outcomes comparable to early-stage (cT1/T2) tumors.

Materials And Methods: Retrospective cohort study of 628 patients with HPV-related oropharyngeal cancer who underwent up-front TORS from 2007 to 2017. Patients were stratified into two cohorts based on early-stage (cT1/2) versus locally-advanced (cT3/4) tumor at presentation.

Results: We identified 589 patients who presented with early-stage tumors, and 39 patients with locally-advanced tumors. Of these, 73% of patients required adjuvant radiation, and 33% required adjuvant chemoradiation. There was no significant difference in the administration of adjuvant radiation or chemoradiation between the two cohorts. Patients in the locally-advanced disease cohort were significantly more likely to have Stage II/III disease by clinical and pathologic criteria by American Joint Committee on Cancer 8th edition criteria (p < 0.001). However, there was no significant difference in 5-year overall survival (OS) or recurrence-free survival (RFS) based on Kaplan-Meier survival estimates between the two cohorts (p = 0.75, 0.6, respectively), with estimated OS of 91% at 5 years, and estimated RFS of 86% at 5 years across the study population.

Conclusions: Up-front TORS offers favorable survival outcomes for appropriately selected locally-advanced cases of HPV-related oropharyngeal cancer. Furthermore, up-front TORS is comparably effective in allowing avoidance of adjuvant therapy, particularly chemotherapy, in both cT1/T2 and locally-advanced HPV-positive oropharyngeal cancer. In the absence of clear technical contraindication to surgery, cT3/T4 classification should not be considered an absolute contraindication to surgery.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105307DOI Listing
July 2021

The microbiome of HPV-positive tonsil squamous cell carcinoma and neck metastasis.

Oral Oncol 2021 06 24;117:105305. Epub 2021 Apr 24.

Department of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA, United States.

Background: Oropharyngeal squamous cell carcinoma (OPSCC) has now surpassed cervical cancer as the most common site of HPV-related cancer in the United States. HPV-positive OPSCCs behave differently from HPV-negative tumors and often present with early lymph node involvement. The bacterial microbiome of HPV-associated OPSCC may contribute to carcinogenesis, and certain bacteria may influence the spread of cancer from the primary site to regional lymphatics.

Objective: To determine the bacterial microbiome in patients with HPV-associated, early tonsil SCC and compare them to benign tonsil specimens.

Method: The microbiome of primary tumor specimens and lymph nodes was compared to benign tonsillectomy specimens with pan-pathogen microarray (PathoChip).

Results: A total of 114 patients were enrolled in the study. Patients with OPSCC had a microbiome that shifted towards more gram-negative. Numerous signatures of bacterial family and species were associated with the primary tumors and lymph nodes of cancer patients, including the urogenital pathogens Proteus mirabilis and Chlamydia trachomatis, Neisseria gonorrhoeae, Shigella dysenteriae, and Orientia tsutsugamushi.

Conclusion: Our results suggest that detection of urogenital pathogens is associated with lymph node metastasis for patients with HPV-positive OPSCCs. Additional studies are necessary to determine the effects of the OPSCC microbiome on disease progression and clinical outcomes.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105305DOI Listing
June 2021

Increased rate of recurrence and high rate of salvage in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma with adverse features treated with primary surgery without recommended adjuvant therapy.

Head Neck 2021 04 16;43(4):1128-1141. Epub 2020 Dec 16.

Department of Otorhinolaryngology - Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: Some patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) do not receive guideline-recommended postoperative radiation therapy (PORT) following primary transoral robotic surgery (TORS).

Methods: Three-hundred and sixty-four patients with treatment-naïve, HPV-associated OPSCC were recommended to receive PORT based on clinicopathological features following TORS. Patients were stratified based on if they received PORT. Oncologic outcomes were compared.

Results: The 3-year locoregional failure (LRF) was 32% in patients who did not receive PORT and 4% in patients who received PORT (P < .001). Despite increased LRF, avoiding PORT was not associated with increased 3-year distant metastasis rates (8% vs 4%, P = .56) or worse 3-year survival (95% vs 98%, P = .34). Recurrences in the surgery alone cohort varied between local and regional sites and were often successfully salvaged.

Conclusions: Patients with HPV-associated OPSCC who do not receive indicated PORT have an increased risk of LRF but similar survival due to high salvage rates.
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http://dx.doi.org/10.1002/hed.26578DOI Listing
April 2021

Revisiting the Recommendation for Contralateral Tonsillectomy in HPV-Associated Tonsillar Carcinoma.

Otolaryngol Head Neck Surg 2021 06 3;164(6):1222-1229. Epub 2020 Nov 3.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Objective: Despite epidemiologic evidence that second primaries occur infrequently in HPV (human papillomavirus)-associated oropharyngeal squamous cell carcinoma, recent recommendations advocate for elective contralateral palatine tonsillectomy. We aimed to study this discordance and define the necessary extent of up-front surgery in a large contemporary cohort with long-term follow-up treated with unilateral transoral robotic surgery. We hypothesized that second primaries are discovered exceedingly rarely during follow-up and that survival outcomes are not compromised with a unilateral surgical approach.

Study Design: Retrospective cohort analysis.

Setting: Tertiary care academic center between 2007 and 2017.

Methods: Records for patients with p16-positive oropharyngeal squamous cell carcinoma of the tonsil and workup suggestive of unilateral disease who underwent ipsilateral transoral robotic surgery were analyzed for timing and distribution of locoregional recurrence, distant metastases, and second primary occurrence as well as survival characteristics.

Results: Among 295 included patients, 21 (7.1%) had a locoregional recurrence; 17 (5.8%) had a distant recurrence; and 3 (1.0%) had a second primary during a median follow-up of 48.0 months (interquartile range, 29.5-62.0). Only 1 (0.3%) had a second primary found in the contralateral tonsil. The 2- and 5-year estimates of overall survival were 95.5% (SE, 1.2%) and 90.1% (SE, 2.2%), respectively, while the 2- and 5-year estimates of disease-free survival were 90.0% (SE, 1.8%) and 84.7% (SE, 2.3%).

Conclusion: Second primary occurrence in the contralateral tonsil was infrequent, and survival outcomes were encouraging with unilateral surgery. This provides a rationale for not routinely performing elective contralateral tonsillectomy in patients whose workup suggests unilateral disease.
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http://dx.doi.org/10.1177/0194599820968800DOI Listing
June 2021

Oncologic Outcomes Following Transoral Robotic Surgery for Human Papillomavirus-Associated Oropharyngeal Carcinoma in Older Patients.

JAMA Otolaryngol Head Neck Surg 2020 12;146(12):1167-1175

Department of Otorhinolaryngology-Head & Neck Surgery, University of Pennsylvania, Philadelphia.

Importance: While early epidemiologic studies ascribed increases in the incidence of human papillomavirus-associated oropharyngeal cancers to middle-aged patients, recent analyses have demonstrated an increasing median age of diagnosis. Treatment of patients older than 70 years is controversial as their inclusion in the practice-defining clinical trials has been limited and the survival benefit conferred by chemotherapy may be outweighed by treatment toxic effects.

Objective: To assess the oncologic outcomes of older adults with human papillomavirus-associated oropharyngeal cancer who underwent upfront transoral robotic surgery and pathologic characteristics-guided adjuvant therapy in a large cohort of patients with close follow-up.

Design, Setting, And Participants: A retrospective cohort analysis was conducted in a tertiary care academic medical center between January 1, 2010, and December 30, 2017. Patients aged 70 years or older at time of diagnosis with biopsy-proven and surgically resectable p16-positive oropharyngeal cancers were included. Data analysis was conducted from March 1 to June 1, 2020.

Exposures: Transoral robotic surgery oropharyngeal resection and neck dissection with pathologic characteristic-guided adjuvant therapy.

Main Outcomes And Measures: Three-year estimates of disease-specific survival, overall survival, and disease-free survival, as well as rates of adjuvant therapy (radiotherapy and chemoradiotherapy) and perioperative complications.

Results: Seventy-seven patients were included (median age, 73.0; interquartile range, 71.0-76.0; range, 70-89 years); of these, 58 were men (75.3%). Perioperative mortality was 1.3% and the rate of oropharyngeal hemorrhage was 2.6%. Twenty-seven patients (35.1%) underwent postoperative radiotherapy and 20 patients (26.0%) underwent postoperative chemoradiotherapy. The median length of follow-up was 39.6 (range, 0.1-96.2) months, and the 3-year estimates of survival were 92.4% (95% CI, 82.4%-96.9%) for disease-specific survival, 90.0% (95% CI, 79.4%-95.0%) for overall survival, and 84.3% (95% CI, 73.4%-91.0%) for disease-free survival.

Conclusions And Relevance: The findings of this cohort study suggest that transoral robotic surgery and pathologic characteristic-guided adjuvant therapy can provide beneficial survival outcomes, infrequent perioperative mortality, and, for most carefully selected older adults, obviate the need for chemotherapy.
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http://dx.doi.org/10.1001/jamaoto.2020.3787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596684PMC
December 2020

Predictors of Nodal Metastasis in Mucoepidermoid Carcinoma of the Oral Cavity and Oropharynx.

ORL J Otorhinolaryngol Relat Spec 2020;82(6):327-334. Epub 2020 Aug 18.

Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA,

Introduction: Mucoepidermoid carcinoma (MEC) of the upper aerodigestive tract (UADT) is an uncommon malignancy, with limited literature available on its clinical and pathologic characteristics. Here, we describe the behavior of MEC of the UADT including pathologic characteristics and predictors of nodal metastasis.

Methods: Retrospective cohort study of patients with MEC of the UADT treated at an academic medical center from January 2008 to May 2018. Data was collected about demographics and tumor characteristics including clinical and histological data. The two-tailed Student t test and χ2 analysis were performed to assess for predictors of nodal metastasis.

Results: We identified 44 patients with minor salivary gland MEC of the oral cavity (OC) and oropharynx (OP). All patients were treated with primary site surgery. The primary site was the OC in 25 patients (57%) and OP in 19 (43%). Low-grade histology was seen in 27 specimens (61.4%), intermediate histology in 9 specimens (20.5%), and high-grade histology in 8 specimens (18.2%). Perineural invasion was noted in 10 specimens (22.7%). Neck dissection was performed in 17 patients (39%), with pathologically positive nodes found in 9 (20.5%). Notably, 5 of the 9 positive nodal specimens were found in clinically node-negative necks. Pathologically positive cervical lymph nodes were significantly associated with the OP as the primary site (p = 0.0005), perineural invasion (p = 0.012), lymphovascular invasion (p < 0.001), and high-grade histology (p = 0.004) in the primary specimen.

Discussion: MEC of the UADT is an uncommon malignancy. Our findings suggest elective neck dissection should be considered with perineural and lymphovascular invasion, high-grade tumor, and the OP as the primary site.
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http://dx.doi.org/10.1159/000509142DOI Listing
March 2021

Impact of Lymph Node Yield on Survival in Surgically Treated Oropharyngeal Squamous Cell Carcinoma.

Otolaryngol Head Neck Surg 2021 01 21;164(1):146-156. Epub 2020 Jul 21.

University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA.

Objectives: (1) To estimate the association between neck dissection lymph node yield (LNY) and survival among patients with surgically treated human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). (2) To identify a clinically relevant quality metric for surgical treatment of HPV-related OPSCC.

Study Design: Retrospective cohort study.

Setting: National Cancer Database.

Subjects And Methods: From the National Cancer Database, 4130 patients were identified with HPV-associated OPSCC treated with primary surgery from 2010 to 2016. Based on prior literature, an adequate neck dissection LNY was defined as ≥18 lymph nodes. To determine whether LNY is associated with survival, univariable and multivariable Cox proportional hazards regression was performed. Analysis was stratified by adjuvant therapy regimen.

Results: A total of 2113 patients (51.2%) underwent surgery with or without adjuvant radiation (S ± RT), and 2017 patients (48.8%) underwent surgery with adjuvant chemoradiation. LNY ≥18 was associated with a 5-year survival benefit of 7.15% (91.7% for LNY ≥18, 84.5% for LNY <18, = .004) for the S ± RT cohort on unadjusted survival analysis. For the S ± RT group, LNY ≥18 was associated with decreased hazard of death (hazard ratio, 0.45; 95% CI, 0.29-0.70; < .001) after adjustment for patient characteristics, TNM staging, surgical margins, extranodal extension, and treating facility characteristics. For surgery with adjuvant chemoradiation, the adjusted hazard ratio estimate for LNY ≥18 was 0.64 (95% CI, 0.41-1.00), but the result was not statistically significant ( = .052).

Conclusion: An adequate LNY from a neck dissection may affect survival when HPV-related OPSCC is treated with up-front surgery.
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http://dx.doi.org/10.1177/0194599820936637DOI Listing
January 2021

A novel surgeon credentialing and quality assurance process using transoral surgery for oropharyngeal cancer in ECOG-ACRIN Cancer Research Group Trial E3311.

Oral Oncol 2020 11 14;110:104797. Epub 2020 Jul 14.

Winship Cancer Institute at Emory University, Atlanta, GA, United States.

Purpose: Understanding the role of transoral surgery in oropharyngeal cancer (OPC) requires prospective, randomized multi-institutional data. Meticulous evaluation of surgeon expertise and surgical quality assurance (QA) will be critical to the validity of such trials. We describe a novel surgeon credentialing and QA process developed to support the ECOG-ACRIN Cancer Research Group E3311 (E3311) and report outcomes related to QA.

Patients And Methods: E3311 was a phase II randomized clinical trial of transoral surgery followed by low- or standard-dose, risk-adjusted post-operative therapy with stage III-IVa (AJCC 7th edition) HPV-associated OPC. In order to be credentialed to accrue to this trial, surgeons were required to demonstrate active hospital credentials and technique-specific surgical expertise with ≥20 cases of transoral resection for OPC. In addition, 10 paired operative and surgical pathology reports from the preceding 24 months were reviewed by an expert panel. Ongoing QA required <10% rate of positive margins, low oropharyngeal bleeding rates, and accrual of at least one patient per 12 months. Otherwise surgeons were placed on hold and not permitted to accrue until re-credentialed using a new series of transoral resections.

Results: 120 surgeons trained in transoral minimally invasive surgery applied for credentialing for E3311 and after peer-review, 87 (73%) were approved from 59 centers. During QA on E3311, positive final pathologic margins were reported in 19 (3.8%) patients. Grade III/IV and grade V oropharyngeal bleeding was reported in 29 (5.9%) and 1 (0.2%) of patients.

Conclusions: We provide proof of concept that a comprehensive credentialing process can support multicenter transoral head and neck surgical oncology trials, with low incidence of positive margins and *grade III/V oropharyngeal bleeding.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771718PMC
November 2020

Retropharyngeal Internal Carotid Artery Management in TORS Using Microvascular Reconstruction.

Laryngoscope 2021 03 4;131(3):E821-E827. Epub 2020 Jul 4.

Department of Otorhinolaryngology - Head & Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.

Objectives: Guidelines for transoral robotic surgery (TORS) have generally regarded patients with retropharyngeal carotid arteries as contraindicated for surgery due to a theoretical risk of intraoperative vascular injury and/or perioperative cerebrovascular accident. We aimed to demonstrate that careful TORS-assisted resection and free flap coverage could not only avoid intraoperative injury and provide a physical barrier for vessel coverage but also achieve adequate margin control.

Study Design: Retrospective cohort analysis.

Methods: Retrospective review of patients with oropharyngeal malignancies and radiologically confirmed retropharyngeal carotid arteries who underwent TORS, concurrent neck dissection, and free flap reconstruction between 2015 and 2019.

Results: Twenty patients were included, 19 (95.0%) with tonsillar tumors and one (5.0%) with a tongue base tumor with significant tonsillar extension. Eighteen patients (90.0%) received a radial artery forearm flap, one (5.0%) an ulnar artery forearm flap, and one (5.0%) an anteromedial thigh flap. All 20 (100%) flaps were inset through combined transcervical and transoral approaches without mandibulotomy. There were no perioperative mortalities, carotid injuries, oropharyngeal bleeds, cervical hematomas, or cerebrovascular accidents. One patient (5.0%) had a free flap failure requiring explant. All patients underwent decannulation and resumed a full oral diet. The mean length of hospitalization was 6.8 (standard deviation 1.2) days. One (5.0%) patient had a positive margin.

Conclusion: In this analysis, 20 patients with oropharyngeal malignancy and retropharyngeal carotid arteries underwent TORS, neck dissection, and microvascular reconstruction without serious complication (perioperative mortality, vascular injury, or neurologic sequalae) with an acceptable negative margin rate. These results may lead to a reconsideration of a commonly held contraindication to TORS.

Level Of Evidence: 3 Laryngoscope, 131:E821-E827, 2021.
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http://dx.doi.org/10.1002/lary.28876DOI Listing
March 2021

Penn Medicine Head and Neck Cancer Service Line COVID-19 management guidelines.

Head Neck 2020 Jul 25;42(7):1507-1515. Epub 2020 Jun 25.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Introduction: The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus has altered the health care environment for the management of head and neck cancers. The purpose of these guidelines is to provide direction during the pandemic for rational Head and Neck Cancer management in order to achieve a medically and ethically appropriate balance of risks and benefits.

Methods: Creation of consensus document.

Results: The process yielded a consensus statement among a wide range of practitioners involved in the management of patients with head and neck cancer in a multihospital tertiary care health system.

Conclusions: These guidelines support an ethical approach for the management of head and neck cancers during the COVID-19 epidemic consistent with both the local standard of care as well as the head and neck oncological literature.
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http://dx.doi.org/10.1002/hed.26318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362039PMC
July 2020

Identifying predictors of HPV-related head and neck squamous cell carcinoma progression and survival through patient-derived models.

Int J Cancer 2020 12 6;147(11):3236-3249. Epub 2020 Jul 6.

Department of Otorhinolaryngology, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Therapeutic innovation for human papilloma virus-related (HPV+) head and neck squamous cell carcinomas (HNSCCs) is impaired by inadequate preclinical models and the absence of accurate biomarkers. Our study establishes the first well-characterized panel of patient-derived xenografts (PDXs) and organoids from HPV+ HNSCCs while determining fidelity of the models to the distinguishing genetic features of this cancer type. Despite low engraftment rates, whole exome sequencing showed that PDXs retain multiple distinguishing features of HPV+ HNSCC lost in existing cell lines, including PIK3CA mutations, TRAF3 deletion and the absence of EGFR amplifications. Engrafted HPV+ tumors frequently contained NOTCH1 mutations, thus providing new models for a negatively prognostic alteration in this disease. Genotype-phenotype associations in the models were then tested for prediction of tumor progression and survival in published clinical cohorts. Observation of high tumor mutational burdens (TMBs) in the faster-growing models facilitated identification of a novel association between TMB and local progression in both HPV+ and HPV- patients that was prognostic in HPV- cases. In addition, reduced E7 and p16 levels found in a PDX from an outlier case with lethal outcome led to detection of similar profiles among recurrent HPV+ HNSCCs. Transcriptional data from the Cancer Genome Atlas was used to demonstrate that the lower E2F target gene expression predicted by reduced E7 levels has potential as a biomarker of disease recurrence risk. Our findings bridge a critical gap in preclinical models for HPV+ HNSCCs and simultaneously reveal novel potential applications of quantifying mutational burden and viral oncogene functions for biomarker development.
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http://dx.doi.org/10.1002/ijc.33125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554059PMC
December 2020

Considerations in the evaluation and management of oral potentially malignant disorders during the COVID-19 pandemic.

Head Neck 2020 Jul 16;42(7):1497-1502. Epub 2020 May 16.

Department of Oral Medicine, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Aim: The COVID-19 pandemic has resulted in society experiencing unprecedented challenges for health care practitioners and facilities serving at the frontlines of this pandemic. With regard to oral cancer, there is a complete absence of literature regarding the long-term impact of pandemics on patients with oral potentially malignant disorders (OPMDs). The objective of this article is to put forth an institutional multidisciplinary approach for the evaluation and management of OPMDs.

Methods: A multidisciplinary approach was put formalized within our institution to risk stratify patients based on need for in-person assessment vs telehealth assessment during the COVID-19 pandemic.

Results: With judicious risk stratification of patients based on clinical features of their OPMD and with consideration of ongoing mitigation efforts and regional pandemic impact, providers are able to safely care for their patients.

Conclusions: The COVID-19 pandemic has required health care practitioners to make novel decisions that are new to us with development of creative pathways of care that focused on patient safety, mitigation efforts, and clinical management of disease processes. The care of patients with OPMDs requires special considerations especially as patients at high risk for severe COVID-19 illness are also higher risk for the development of OPMDs.
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http://dx.doi.org/10.1002/hed.26258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276902PMC
July 2020

Lymph node yield and lymph node ratio in oral cavity and oropharyngeal carcinoma: Preliminary results from a prospective, multicenter, international cohort.

Oral Oncol 2020 08 4;107:104740. Epub 2020 May 4.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA.

Objectives: Recently, Lymph Node Yield (LNY) and Lymph Node Ratio (LNR) have emerged as prognostic indicators in head and neck cancer. However, there is a lack of data regarding the LNY and LNR values in the specific neck levels dissected and regarding the factors that influence these values.

Materials And Methods: Preliminary results of the NCT03534778 trial are reported. LNY and LNR values were estimated for 100 patients with oral or oropharynx carcinoma, from November 1, 2018 to September 30, 2019.

Results: Overall, the mean number of lymph nodes retrieved was 34.4 (95% confidence interval [CI] 31.6-37.3). LNY means and CI per single neck level were as follows: level I 5.5 lymph nodes harvested (95% CI 3.5-7.5), level II 15.4 (95% CI 10.6-20.2), level III 8.0 (95% CI 4.6-11.3), level IV 6.3 (95% CI 3.4-9.15), level V 6.3 (95% CI 3.6-9.0). cN+ patients had a higher number of lymph nodes retrieved, odds ratio (OR) 1.2 (95% CI 1.05-1.36). Smokers had less lymph nodes harvested, OR 0.78 (95% CI, 0.71-0.87). Mean LNR was 0.063 (95% CI 0.047-0.078). A multiple regression analysis showed that anatomic site, pN, smoking status and LNY statistically significantly predicted the LNR (p < 0.05) CONCLUSIONS: The LNY and LNR values are influenced by various demographic and pathological characteristics of the patient, such as the number of dissected levels, primary site, cN positivity, and smoking status.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104740DOI Listing
August 2020

Topical preparations to reduce SARS-CoV-2 aerosolization in head and neck mucosal surgery.

Head Neck 2020 06 25;42(6):1268-1272. Epub 2020 Apr 25.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Aim: The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has put health care workers at risk when exposed to aerosolized viral particles during upper airway mucosal surgery. The objective of this review was to discuss topical preparations that could be utilized preoperatively to help to decrease viral load and potentially reduce the risks of viral transmission.

Methods: A PubMed/MEDLINE database review of articles was performed querying topical preparations with virucidal activity against coronaviruses.

Results: Povidone-iodine (PVP-I) solutions ranging from 0.23% to 7% have been found to demonstrate highly effective virucidal activity against a broad range of viruses including several coronaviruses responsible for recent epidemics including SARS-CoV-1 and MERS-CoV.

Conclusions: While specific evidence regarding SARS-CoV-2 is lacking, PVP-I-based preparations have been successfully demonstrated to reduce viral loads of coronaviruses. They are relatively safe to use in the upper airway and may reduce risk of SARS-CoV-2 aerosolization during upper airway mucosal surgery.
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http://dx.doi.org/10.1002/hed.26200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267296PMC
June 2020

Management of the difficult airway in the COVID-19 pandemic: Illustrative complex head and neck cancer scenario.

Head Neck 2020 06 22;42(6):1273-1277. Epub 2020 Apr 22.

Department of Otorhinolaryngology-Head and Neck Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: This case highlights challenges in the assessment and management of the "difficult airway" patient in the SARS-CoV-2 (COVID-19) pandemic era.

Methods: A 60-year-old male with history of recent transoral robotic surgery resection, free flap reconstruction, and tracheostomy for p16+ squamous cell carcinoma presented with stridor and dyspnea 1 month after decannulation. Careful planning by a multidisciplinary team allowed for appropriate staffing and personal protective equipment, preparations for emergency airway management, evaluation via nasopharyngolaryngoscopy, and COVID testing. The patient was found to be COVID negative and underwent imaging which revealed new pulmonary nodules and a tracheal lesion.

Results: The patient was safely transorally intubated in the operating room. The tracheal lesion was removed endoscopically and tracheostomy was avoided.

Conclusions: This case highlights the importance of careful and collaborative decision making for the management of head and neck cancer and other "difficult airway" patients during the COVID-19 epidemic.
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http://dx.doi.org/10.1002/hed.26175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262249PMC
June 2020

The virome of HPV-positive tonsil squamous cell carcinoma and neck metastasis.

Oncotarget 2020 Jan 21;11(3):282-293. Epub 2020 Jan 21.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.

Oropharyngeal squamous cell carcinoma (OPSCC) represents the most common HPV-related malignancy in the United States with increasing incidence. There is heterogeneity between the behavior and response to treatment of HPV-positive oropharyngeal squamous cell carcinoma that may be linked to the tumor virome. In this prospective study, a pan-pathogen microarray (PathoChip) was used to determine the virome of early stage, p16-positive OPSCC and neck metastasis treated with transoral robotic surgery (TORS) and neck dissection. The virome findings of primary tumors and neck lymph nodes were correlated with clinical data to determine if specific organisms were associated with clinical outcomes. A total of 114 patients were enrolled in the study. Double-stranded DNA viruses, specifically Papillomaviridae, showed the highest hybridization signal (viral copies) across all viral families in the primary and positive lymph node samples. High hybridization signals were also detected for signatures of Baculoviridae, Reoviridae, Siphoviridae, Myoviridae, and Polydnaviridae in most of the cancer specimens, including the lymph nodes without cancer present. Across all HPV signatures, HPV16 and 18 had the highest average hybridization signal index and prevalence. To our knowledge, this is the first study that has identified the viral signatures of OPSCC tumors. This will serve as a foundation for future research investigating the role of the virome in OPSCC. Further investigation into the OPSCC microbiome and its variations may allow for improved appreciation of the impact of microbial dysbiosis on risk stratification, oncologic outcomes, and treatment response which has been shown in other cancer sites.
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http://dx.doi.org/10.18632/oncotarget.27436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980631PMC
January 2020

Potentially malignant disorders of the oral cavity and oral dysplasia: A systematic review and meta-analysis of malignant transformation rate by subtype.

Head Neck 2020 03 5;42(3):539-555. Epub 2019 Dec 5.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania Health System, Philadelphia, Pennsylvania.

Importance: Potentially malignant disorders of the oral cavity (OPMD) are a heterogeneous group of lesions associated with a variable risk of malignant transformation (MT) to invasive cancer. Leukoplakia (LE), lichen planus (LP), oral lichenoid lesions (OLL), oral erythroplakia (OE), oral submucous fibrosis (OSF), and proliferative verrucous leukoplakia (PVL) are among the most common of these lesions. Oral dysplasia is a mucosal area characterized by cellular and architectural derangement, which may be associated with OPMDs or not.

Objective: To define the MT rate of OPMDs and the risk of development into cancer of mild vs moderate/severe oral dysplasia. This in order to implement adequate follow-up strategies and treatment decisions.

Study Design: We performed a systematic review and meta-analysis on studies reporting the MT rates of OPMDs and oral dysplasia. Ninety-two studies were included for the analysis. Cumulative rates were reported for OPMDs overall and as a subgroup, a comparison was made of mild vs moderate/severe dysplasia. Meta-regression on OPMD and year of publication was also performed.

Main Outcome And Measures: Overall MT rates of OPMDs and odds ratio of MT of mild vs moderate/severe dysplasia.

Results: Overall MT rate across all OPMD groups was 7.9% (99% confidence interval [CI] 4.9%-11.5%). MT rates of the specific OPMD subgroups were as follows: LP 1.4% (99% CI 0.9%-1.9%), LE 9.5 (5.9%-14.00%), OLL 3.8% (99% CI 1.6%-7.00%), OSF 5.2% (99% CI 2.9%-8.00%), OE 33.1% (99% CI 13.6%-56.1%), and PVL 49.5% (99% CI 26.7%-72.4%). Regarding the dysplasia grades comparison, the meta-analysis showed that moderate/severe dysplasia is meaningfully associated to a much greater risk of MT compared to mild dysplasia with an odds ratio of 2.4 (95% CI 1.5-3.8) [Correction added on 27 December 2019, after first online publication: CI updated from 99% to 95%.]. Heterogeneity was not significant. Annual MT rates were approximated based on the average follow-up as reported in the various subgroups. Lichen planus had an annual MT of 0.28%, OLL of 0.57%, leukoplakia of 1.56%, PVL of 9.3%, and OSF of 0.98%. Mild dysplasia had an annual MT of 1.7%, while severe dysplasia of 3.57%. Meta-regression showed a significant negative correlation of PVL MT rate and year of the study (P value <.001).

Conclusions And Relevance: OPMDs and oral dysplasia are relatively common conditions that general practitioners, head and neck, and oral medicine specialists, face in their everyday practice. Our analysis confirms the significant risk of MT of these lesions, although variable among the subgroups. Moderate/severe dysplasia bears a much higher risk of cancer evolution than mild dysplasia. It is important to raise public health awareness on the MT rates of these conditions, at the same time efficacious communication with the patient is of utmost importance. This, coupled with strict follow-up measures and optimal treatment strategies, would help in reducing the transformation of these oral conditions into invasive cancer.
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http://dx.doi.org/10.1002/hed.26006DOI Listing
March 2020

Voice Restoration after Radiation and Supracricoid Partial Laryngectomy by Injection Augmentation of the Arytenoid.

J Voice 2021 May 29;35(3):483-486. Epub 2019 Nov 29.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Supracricoid partial laryngectomy (SCPL) is an organ-preserving surgical technique intended to achieve oncologic control of laryngeal cancer while maintaining laryngeal functions. Most patients who undergo SCPL achieve a serviceable voice. However, several factors can affect the function of the neoglottis after SCPL. We report the case of a 53-year-old male referred for near aphonia after undergoing SCPL for recurrent laryngeal carcinoma initially treated with radiation. Calcium hydroxylapatite injection augmentation of the right arytenoid was performed to assist neoglottic closure. Flexible laryngoscopy demonstrated greatly improved neoglottic closure postoperatively, and the patient's voice was successfully restored. This case demonstrates a novel technique for voice restoration in patients who have undergone partial laryngectomy.
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http://dx.doi.org/10.1016/j.jvoice.2019.11.002DOI Listing
May 2021

Quality of Life of Postoperative Photon versus Proton Radiation Therapy for Oropharynx Cancer.

Int J Part Ther 2018 30;5(2):11-17. Epub 2018 Nov 30.

Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA.

Purpose: Quality of life (QOL) for patients with oropharyngeal squamous cell cancer is negatively affected by conventional radiation (RT) owing to radiation exposure to normal tissues. Proton therapy, via pencil beam scanning (PBS), can better spare many of these tissues, and may thereby improve QOL.

Patients And Methods: Patient-reported outcomes were prospectively collected from patients treated from April 2013 to April 2015. Patients were treated with PBS or intensity-modulated radiation therapy (IMRT) via volumetric arc therapy after transoral robotic surgery. Validated QOL questionnaires were collected before RT, and 3, 6, and 12 months post RT.

Results: Sixty-four patients were treated with adjuvant RT after transoral robotic surgery, 33 (52%) with volumetric arc therapy, and 31 (48%) with PBS. Both groups were similar in terms of age, site, stage, and dose delivered. Patients receiving PBS had significantly less dose to many normal structures than those receiving IMRT. These dosimetric advantages with PBS were reflected in higher scores in head and neck specific, as well as general, QOL measures. Most notable was significantly less xerostomia with PBS, on multiple patient-reported outcomes at multiple timepoints (6 and 12 months).

Conclusion: Pencil beam scanning, when compared to IMRT, confers a significant dosimetric advantage to many normal organs at risk, with a corresponding benefit in multiple patient-reported QOL parameters in patients receiving adjuvant RT for oropharyngeal squamous cell cancer.
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http://dx.doi.org/10.14338/IJPT-18-00032.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874189PMC
November 2018

Risk of post-operative, pre-radiotherapy contralateral neck recurrence in patients treated with surgery followed by adjuvant radiotherapy for human papilloma virus-associated tonsil cancer.

Br J Radiol 2019 Dec 15;92(1104):20190466. Epub 2019 Oct 15.

Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Objective: One approach to reduce treatment-related morbidity for human papilloma virus (HPV)-associated tonsil cancer is omitting radiotherapy to the contralateral neck. Pathologic risk factors for early contralateral neck disease, however, are poorly understood. We report on the risk contralateral neck failures from the time of pre-operative diagnostic imaging to time of planning for adjuvant radiation in a single institution series of HPV-associated tonsillar cancer patients undergoing surgery followed by radiotherapy (RT).

Methods: Retrospective analysis of 123 patients with T1T3 HPV-positive tonsillar squamous cell carcinoma treated between 2010 and 2016 with transoral robotic surgery and selective ipsilateral neck dissection followed by adjuvant RT. Contralateral neck recurrence was classified as the detection of a pathologic node in the contralateral neck prior to initiation of adjuvant RT.

Results: Seven patients (5.7%) developed contralateral neck disease/failure between the time of pre-operative diagnostic neck imaging and time of planning of adjuvant radiation. Increased ratio of positive/resected nodes [odds ratio (OR) 1.073, = 0.005] was significantly associated with increased risk of contralateral neck recurrence, with a trend found for close/positive margins (OR 5.355, = 0.06), tumor size (OR 2.046, = 0.09), and total number of nodes positive (OR 1.179, = 0.062).

Conclusions: Patients who develop very early contralateral neck disease, between completion of ipsilateral neck dissection and the initiation of radiotherapy, have a higher ratio of positive nodes to total nodes resected in the ipsilateral neck. These findings suggest that proper selection of patients for omission of treatment of the contralateral, node-negative neck should be made with this in mind, with future studies needed to document the impact on toxicity and disease outcomes from such an approach.

Advances In Knowledge: Pathologic risk factors in the dissected, ipsilateral neck in patients with tonsil cancer may inform the risk of contralateral neck failure. Patient selection for future, prospective efforts to examine sparing of the contralateral neck need to be based with these risk factors in mind.
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http://dx.doi.org/10.1259/bjr.20190466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913358PMC
December 2019

A Next-Generation Single-Port Robotic Surgical System for Transoral Robotic Surgery: Results From Prospective Nonrandomized Clinical Trials.

JAMA Otolaryngol Head Neck Surg 2019 Nov;145(11):1027-1034

Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, Minnesota.

Importance: Transoral endoscopic head and neck surgery now plays an important role in the multidisciplinary management of oropharyngeal carcinoma. Previous generations of robotic surgical systems used a multiport system with a rigid stereo-endoscope and 2 wristed instruments that facilitated transoral robotic surgery.

Objective: To evaluate a new single-port robotic surgical system in head and neck surgery prospectively through concurrent nonrandomized clinical trials.

Design, Setting, And Participants: Two prospective clinical trials were conducted from December 16, 2016, to December 26, 2017, to assess the safety, feasibility, and performance of a flexible single-port robotic surgical system in 4 institutions, including 3 in the United States and 1 in Hong Kong. A total of 47 patients with tumors of the oropharynx were enrolled and underwent surgery. All patients were classified as having American Society of Anesthesiologists class I to III status and Eastern Cooperative Oncology Group status 0 to 1. An initial cohort of 7 patients underwent staging and endoscopic procedures for benign disease. The remaining 40 patients all had malignant tumors of the oropharynx.

Main Outcomes And Measures: Safety was measured by the incidence of device-related serious adverse events. Feasibility and performance were measured by the conversion rate from the use of the single-port robotic surgical system to either open surgery or the use of any other transoral technology required to complete the planned procedure. Secondary end points of swallowing function and surgical margins were also measured.

Results: All 47 patients (8 women and 39 men; mean [SD] age, 61 [8] years) safely underwent transoral resection with the single-port robotic surgical system without conversion to open surgery, laser surgery, or multiport robotic surgery. There were no intraoperative complications or device-related serious adverse events. Mean (SD) estimated intraoperative blood loss per procedure was 15.4 (23.9) mL; no patients received a transfusion. Two patients underwent a planned tracheotomy owing to medical comorbidity (previous chemoradiotherapy; obesity and severe sleep apnea). Two patients (4%) had grade III or IV postoperative hemorrhage, requiring a return to the operating room; however, both patients had medical comorbidities requiring the use of antithrombotic medication. The incidence of positive margins for patients with oropharyngeal malignancy was 3% (1 of 40). Within 30 days, 45 patients (96%) were eating by mouth and without the need for a percutaneous endoscopic gastrostomy tube.

Conclusions And Relevance: This study describes the results of phase 2 clinical testing of a next-generation, robotic surgical system using a single-port architecture. The use of the device appears to be feasible, safe, and effective for transoral robotic surgery of oropharyngeal tumors.

Trial Registration: ClinicalTrials.gov identifiers: NCT03010813 and NCT03049280.
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http://dx.doi.org/10.1001/jamaoto.2019.2654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902126PMC
November 2019

Pharyngeal-sparing radiation for head and neck carcinoma of unknown primary following TORS assisted work-up.

Laryngoscope 2020 03 14;130(3):691-697. Epub 2019 Aug 14.

Department of Radiation Oncology, Philadelphia, Pennsylvania, U.S.A.

Objective: In patients with head and neck carcinoma of unknown primary (HNCUP;pT0) following TORS-assisted workup, we have adopted a pharyngeal-sparing radiation therapy (PSRT) approach targeting only the at-risk neck and omitting treatment of the pharynx. We report outcomes following PSRT, and compare to institutional historical control subjects who received pharyngeal-targeted RT (PRT).

Methods: Between 2009 and 2018, 172 patients underwent TORS-assisted endoscopy as part of their workup for HNCUP. Following TORS, 54 patients had pT0 disease, of which 45 received RT. Forty-nine percent received PSRT and 51% received PRT.

Results: No statistically significant differences existed between the PSRT and PRT groups with respect to overall nodal distribution, p16 positivity (55% vs. 43%, P = .12), neck dissection rates (77% vs. 65%, P = .51), and administration of chemotherapy (55% vs. 65%, P = .55). Median follow-up for PSRT and PRT groups were 24 and 28 months, respectively (P = .04). Two-year RFS was 86% and 74% for PSRT and PRT patients, respectively (log-rank P = .30). Three and six patients recurred after PSRT and PRT, respectively. Two-year OS for PSRT and PRT patients was 91% and 74%, respectively (log-rank P = .31). Compared to PRT, PSRT was associated with statistically significantly less: grade 2+ mucositis (18% vs. 91%, P < .01), new opioid requirement (27% vs. 91%, P < .01), mean weight loss during RT (6.2 lbs vs. 17.4 lbs, P < .01), feeding tube placement during RT (5% vs. 43%, P < .01), and treatment-related unplanned hospitalizations (9% vs. 39%, P = .04).

Conclusion: Following TORS-assisted management of patients with pT0 HNCUP, we observed reduced toxicity following PSRT compared to PRT without apparent compromise of disease cure.

Level Of Evidence: Level 3 evidence, retrospective review comparing cases and controls Laryngoscope, 130:691-697, 2020.
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http://dx.doi.org/10.1002/lary.28200DOI Listing
March 2020

The impact of treatment package time on locoregional control for HPV+ oropharyngeal squamous cell carcinoma treated with surgery and postoperative (chemo)radiation.

Head Neck 2019 11 14;41(11):3858-3868. Epub 2019 Aug 14.

Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Background: For patients with head and neck squamous cell carcinoma (SCC) undergoing surgery followed by postoperative radiotherapy (PORT), time from surgery to completion of adjuvant therapy, "package time" impacts locoregional control (LRC). However, the significance of package time in HPV+ oropharyngeal SCC (OPSCC) is unknown.

Methods: We examined patients undergoing TORS resection with PORT for HPV+ OPSCC from January 2010 to December 2015 with ≥18 months follow-up (n = 267). A cutoff of 15 weeks was used to delineate patients into short and long package time groups. LRC loss was defined as any recurrence after surgery.

Results: Prolonged package time >15 weeks was associated with inferior LRC in this HPV+ OPSCC cohort, driven primarily by interval from surgery to PORT initiation. Multivariate analysis showed that package time and T classification are both independently associated with LRC.

Conclusions: Among HPV+ OPSCC, prolongation of package time appears to compromise LRC, but not survival.
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http://dx.doi.org/10.1002/hed.25914DOI Listing
November 2019

A novel transpalatal-transoral robotic surgery approach to clival chordomas extending into the nasopharynx.

Head Neck 2019 08 10;41(8):E133-E140. Epub 2019 Apr 10.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania Health System, Philadelphia, Pennsylvania.

Background: In this paper, we present three cases where a novel transoral robotic surgery (TORS) approach was used to resect clival chordomas extending into the nasopharynx to demonstrate progress in the evolution of robotic surgery of the head and neck.

Methods: The first patient had a history of metastatic chordoma resection and presented with trismus and dysphagia; the second and third patients had first presentation with nasal congestion and facial numbness, respectively. All patients underwent a novel transpalatal-TORS resection.

Results: Total resection was achieved in the first patient and near-total resections were achieved in the second and third patients. All patients had minimal postoperative morbidity and no patients experienced significant adverse events.

Conclusion: Clival chordomas are rare, potentially dangerous lesions with a high rate of recurrence. The novel transpalatal-TORS approach to these tumors presented in this series represents advancement in the realm of minimally invasive surgery of the head and neck. This approach offers patients total or near-total control of these lesions with minimal intraoperative and postoperative side effects.
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http://dx.doi.org/10.1002/hed.25747DOI Listing
August 2019

Techniques for developing and viewing stereoscopic three-dimensional teaching videos for transoral robotic surgery (TORS).

J Robot Surg 2019 Aug 3;13(4):581-584. Epub 2019 Apr 3.

Department of Otorhinolaryngology, Head and Neck Surgery, Hospital of the University of Pennsylvania, 5th Floor Ravdin, 3400 Spruce Street, Philadelphia, PA, 19104, USA.

Advances in three-dimensional (3D) video recording and playback have expanded the availability of stereoscopic videos for consumption with specialized televisions, computer monitors, and virtual reality (VR) headsets. The built-in stereoscopic vision of the da vinci surgical system (Intuitive Surgical, Sunnyvale, CA) enables the recording of both camera views. However, medical-grade devices for direct stereoscopic video recording can be cost-prohibitive. We describe methods of producing and viewing 3D videos in transoral robotic surgery (TORS) without acquisition of dedicated 3D recording equipment. The video output from the left and right cameras of the da Vinci Si endoscope were recorded during a TORS radical tonsillectomy using non-stereoscopic media devices. Raw video was processed using commercially available video-editing software to create stereoscopic videos clips. 3D videos were successfully observed using a low-cost mobile phone VR headset. 3D stereoscopic surgical videos were successfully developed using widely available software, applications, computer peripherals, and mobile devices. The methods described confer significant cost savings when compared to the purchase of specialized recording equipment despite the requirements of time and intermediate computer skills. Future studies will investigate the utility of stereoscopic videos in medical student and resident education.
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http://dx.doi.org/10.1007/s11701-019-00952-zDOI Listing
August 2019

Sinonasal Undifferentiated Carcinoma: A 15-Year Single Institution Experience.

J Neurol Surg B Skull Base 2019 Feb 16;80(1):88-95. Epub 2018 Aug 16.

Department of Otorhinolaryngology - Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, United States.

 Sinonasal undifferentiated carcinoma (SNUC) is an aggressive neoplasm, with conflicting existing literature regarding prognosis and treatment due to the rarity of disease. Characterization of optimal SNUC management is necessary for improved outcomes.  Case series with planned data collection and analysis.  Hospital of the University of Pennsylvania and Pennsylvania Hospital.  Patients with pathologically confirmed SNUC treated within a 15-year period were identified, and records were obtained and evaluated for several demographic characteristics.  Disease-specific survival from diagnosis was the primary endpoint, while disease recurrence was a secondary endpoint of the study.  Twenty-seven patients with established SNUC were included in this cohort, with a median age of 55 years. Eighty-five percent of patients were surgically treated, and 85% of patients presented with stage IV disease. Two-year disease-specific survival was 66% and 5-year disease-specific survival was 46%. Ninety-six percent of patients received both chemotherapy and radiation as adjuvant treatment. Nodal disease at presentation and disease recurrence both significantly decreased patient survival (  < 0.05).  The majority of patients at this institution presented with clinically advanced disease, and most were managed with a multimodal approach of surgical resection, chemotherapy, and radiation. Extent of disease at presentation and progression of disease following treatment are poor prognostic signs and may merit a more aggressive approach, while early detection and treatment may improve survival and decrease patient morbidity.
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http://dx.doi.org/10.1055/s-0038-1668537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365239PMC
February 2019
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