Dataset Information

A benchmark for oncologic outcomes and model for lethal recurrence risk after transoral robotic resection of HPV-related oropharyngeal cancers.

ABSTRACT:

Objectives

Increasing use of transoral robotic surgery (TORS) is likely to impact outcomes for HPV+ oropharyngeal squamous cell carcinomas (OPSCCs). We aimed to describe oncologic outcomes for a large HPV+ OPSCC cohort after TORS and develop a risk prediction model for recurrence under this treatment paradigm.

Materials and methods

634 HPV+ OPSCC patients receiving TORS-based therapy at a single institution were reviewed retrospectively to describe survival across the entire cohort and for patients suffering recurrence. Risks for distant metastatic recurrence (DMR) and locoregional recurrence (LRR) were modeled using multivariate logistic regression analyses of case-control sub-cohorts.

Results

5-year overall and recurrence-free survival were 91.2% and 86.1%, respectively. 5-year overall survival was 52.5% following DMR and 83.3% after isolated LRR (P = .01). In case-control analyses, positive surgical margins were associated with DMR (adjusted OR 5.8, CI 2.1-16.0, P = .001), but not isolated LRR, and increased DMR risk 4.2 fold in patients with early clinical stage disease. By contrast, LRR was associated with not receiving recommended adjuvant therapy (OR 13.4, CI 6.3-28.5, P < .001).

Conclusions

This study sets a benchmark for oncologic outcomes from HPV+ OPSCC after TORS-based therapy. Under this treatment paradigm, margins are relevant for assessing lethal recurrence risk during clinical trial design and post-treatment surveillance.

SUBMITTER: Brody RM

PROVIDER: S-EPMC9288202 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

A benchmark for oncologic outcomes and model for lethal recurrence risk after transoral robotic resection of HPV-related oropharyngeal cancers.

Brody Robert M RM Shimunov David D Cohen Roger B RB Lin Alexander A Lukens John N JN Hartner Lee L Aggarwal Charu C Duvvuri Umamaheswar U Montone Kathleen T KT Jalaly Jalal B JB LiVolsi Virginia A VA Carey Ryan M RM Shanti Rabie M RM Rajasekaran Karthik K Chalian Ara A AA Rassekh Christopher H CH Cannady Steven B SB Newman Jason G JG O'Malley Bert W BW Weinstein Gregory S GS Gimotty Phyllis A PA Basu Devraj D

Oral oncology 20220301

<h4>Objectives</h4>Increasing use of transoral robotic surgery (TORS) is likely to impact outcomes for HPV+ oropharyngeal squamous cell carcinomas (OPSCCs). We aimed to describe oncologic outcomes for a large HPV+ OPSCC cohort after TORS and develop a risk prediction model for recurrence under this treatment paradigm.<h4>Materials and methods</h4>634 HPV+ OPSCC patients receiving TORS-based therapy at a single institution were reviewed retrospectively to describe survival across the entire cohor ...[more]

PMID: 35245888

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Project description:ImportanceLarge patient cohorts are necessary to validate the efficacy of transoral robotic surgery (TORS) in the management of head and neck cancer.ObjectivesTo review oncologic outcomes of TORS from a large multi-institutional collaboration and to identify predictors of disease recurrence and disease-specific mortality.Design, setting, and participantsA retrospective review of records from 410 patients undergoing TORS for laryngeal and pharyngeal cancers from January 1, 2007, through December 31, 2012, was performed. Pertinent data were obtained from 11 participating medical institutions.InterventionsSelect patients received radiation therapy and/or chemotherapy before or after TORS.Main outcomes and measuresLocoregional control, disease-specific survival, and overall survival were calculated. We used Kaplan-Meier survival analysis with log-rank testing to evaluate individual variable association with these outcomes, followed by multivariate analysis with Cox proportional hazards regression modeling to identify independent predictors.ResultsOf the 410 patients treated with TORS in this study, 364 (88.8%) had oropharyngeal cancer. Of these 364 patients, information about post-operative adjuvant therapy was known about 338: 106 (31.3) received radiation therapy alone, and 72 (21.3%) received radiation therapy with concurrent chemotherapy. Neck dissection was performed in 323 patients (78.8%). Mean follow-up time was 20 months. Local, regional, and distant recurrence occurred in 18 (4.4%), 15 (3.7%), and 10 (2.4%) of 410 patients, respectively. Seventeen (4.1%) died of disease, and 13 (3.2%) died of other causes. The 2-year locoregional control rate was 91.8% (95% CI, 87.6%-94.7%), disease-specific survival 94.5% (95% CI, 90.6%-96.8%), and overall survival 91% (95% CI, 86.5%-94.0%). Multivariate analysis identified improved survival among women (P = .05) and for patients with tumors arising in tonsil (P = .01). Smoking was associated with worse overall all-cause mortality (P = .01). Although advanced age and tobacco use were associated with locoregional recurrence and disease-specific survival, they, as well as tumor stage and other adverse histopathologic features, did not remain significant on multivariate analysis.Conclusions and relevanceThis large, multi-institutional study supports the role of TORS within the multidisciplinary treatment paradigm for the treatment of head and neck cancer, especially for patients with oropharyngeal cancer. Favorable oncologic outcomes have been found across institutions. Ongoing comparative clinical trials funded by the National Cancer Institute will further evaluate the role of robotic surgery for patients with head and neck cancers.

Project description:ObjectivesTo compare taste changes after transoral robotic surgery (TORS) to taste changes in healthy controls.MethodsOropharyngeal cancer patients receiving TORS and healthy controls were recruited. Participants underwent posterolateral and whole-mouth psychophysical taste testing (identification, intensity, and hedonics) at baseline and at 2 weeks postoperatively (patients) or follow-up (controls). Surgeons reported suspension time and glossopharyngeal nerve injury (GNI) based on the identification and sacrifice of the nerve. A Clinical Global Impression (CGI) of taste symptoms was completed at each session ("My sense of taste bothers me" on a 5-point scale from Never [1] to Always [5]). A taste disorder (TD) was a CGI of 3 (Sometimes) or worse. Within-subject changes in CGI and psychophysical scores were computed. "Worsened taste" was a CGI increase by ≥1 point at follow-up.ResultsOf 69 participants, most (33/37 tumor, 31/32 controls) had normal baseline taste (CGI < 3). 14/33 (42%) TORS patients and no controls developed new TDs at follow-up. More smokers (7/9) had worsened taste than nonsmokers (19/60, difference = 46% [95% CI 16%-76%]). More patients without GNI (6/22) than with GNI (0/15) had postoperative phantogeusia (difference = 27% [95% CI 9-45%]). Tumor-ipsilateral taste identification (TI) decreased more in patients (-11.3%) than controls (0.8%, difference = 12.2% [95% CI 5.0-19.3%]). Suspension time was not associated with worsened taste symptoms or psychophysical changes.ConclusionsPatient-reported taste changes after TORS are frequent. Compared to healthy controls, TORS patients have decreased tumor-ipsilateral TI. Suspension time and GNI are unlikely to cause symptomatic TDs. Further investigations of the etiology and long-term symptom burden of TORS-associated TDs will aid in the management of oropharyngeal cancer patients.Level of evidence3 (non-randomized controlled cohort study) Laryngoscope, 133:3520-3528, 2023.

Project description:Background/Objective: The incidence of oropharyngeal cancer (OPC) remains significant, with a rising prevalence of HPV-positive (HPV+) cases, underscoring the growing importance of appropriate treatment approaches for this condition. While HPV+ OPC typically exhibits a more favorable prognosis than HPV-negative (HPV-) OPC, certain HPV+ OPC patients still face adverse outcomes. This study aimed to assess the effectiveness of TORS versus traditional surgery in treating OPC patients and investigate the prognostic implications of specific variants in the HPV genome. Methods: The clinical information, including pathological features, treatments, and outcomes (death), of 135 OPC patients treated with traditional surgery from 2008 to 2018 (the non-TORS group) and 130 OPC patients treated with TORS from 2017 to 2021 (the TORS group) were obtained from Sun Yat-sen University Cancer Center (SYSUCC). A comparative analysis of 3-year overall survival (OS) was performed between these two groups. Furthermore, we conducted next-generation sequencing for the HPV16 genome of the 68 HPV+ OPC cases to characterize single-nucleotide variations (SNVs) in the HPV16 genome and evaluate its association with HPV+ OPC patient survival. Results: The comparative analysis of 3-year OS between the two groups (TORS vs. non-TORS) revealed a significant prognostic improvement in the TORS group for OPC patients with a T1-T2 classification (89.3% vs. 72.0%; p = 1.1 × 10-2), stages I-II (92.1% vs. 82.2%; p = 4.6 × 10-2), and stages III-IV (82.8% vs. 62.2%; p = 5.7 × 10-2) and for HPV- patients (85.5% vs. 33.3%; p < 1.0 × 10-6). Furthermore, three SNVs (SNV1339A>G, SNV1950A>C, and SNV4298A>G) in the HPV16 genome were identified as being associated with worse survival. These SNVs could alter protein interactions and weaken the binding affinity for MHC-II, promoting viral amplification and immune evasion. Conclusions: TORS exhibited a superior prognosis to traditional surgery in OPC patients. Additionally, identifying specific SNVs within the HPV16 genome provided potential prognostic markers for HPV+ OPC. These significant findings hold clinical relevance for treatment decision-making and prognostic assessment in patients with OPC.

Project description:The global rise of HPV(+) oropharyngeal squamous cell carcinoma (OPSCC) has generated considerable interest underlying its etiology and management. Despite an overall decline in head and neck malignancies, the incidence in OPSCC has by contrast sharply risen, with HPV(+) subtypes now comprising 80% of all OPSCC.1,2 Relative to HPV(-) OPSCC, HPV(+) patients are more responsive to chemoradiation and harbor a 52% risk-of-death reduction.3 Despite this distinct outcome, treatment regimens remain the same for all OPSCC subtypes (smoking-driven and virus-driven), rather than an adaptive approach to what most consider distinct diseases. The short-term effects (e.g., mucositis, odynophagia) and long-term toxicities (e.g., xerostomia, dysphagia, ototoxicity) from treatment substantially affect quality of life, and rival the impact of the cancer itself. Recently published as well as ongoing trials are actively examining deintensification approaches2,4-9, with the goal of diminishing treatment sequelae for HPV(+) subtypes. While deintensification may decrease chemoradiation-related toxicities, it nonetheless may also undertreat a meaningful percentage of HPV(+) patients who may then recur. In examining national trials, 19% of HPV(+) patients had disease progression after therapy, with a two-year survival rate of 60%.10 Current methods to ascertain HPV status involve p16 staining. However, on comparison with gold standard E6/E7 expression by qPCR, p16 harbored a 15% false positivity rate11, suggesting limited utility as a sole biomarker for deintensification. Improved molecular stratification would greatly enhance the clinician’s ability to precisely tailor treatment while minimizing the risk of jeopardizing outcomes. One approach encompasses in-depth proteomic profiling of HPV(+) OPSCC to reveal distinct protein expression profiles and delineate clinically relevant upstream pathways. In turn, these proteomic differences may distinguish higher-risk disease (cases predisposed to recurrence that may benefit from treatment intensification) from lower-risk phenotypes (cases whose treatment response is sufficiently robust to warrant deintensification). Here, two HPV(+) OPSCC cohorts stratified by treatment response are compared via a hybrid data dependent acquisition/data independent acquisition (DDA/DIA) approach via mass spectrometry. We focused on detection of low-abundance proteins to highlight proteomic signatures that can be potentially exploited for treatment stratification.

Dataset Information

A benchmark for oncologic outcomes and model for lethal recurrence risk after transoral robotic resection of HPV-related oropharyngeal cancers.

Objectives

Materials and methods

Results

Conclusions

Publications

A benchmark for oncologic outcomes and model for lethal recurrence risk after transoral robotic resection of HPV-related oropharyngeal cancers.

Similar Datasets

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