Oropharyngeal Squamous Cell Cancer Patients Research Articles

Analysis of Swallowing Functional Preservation by Surgical Versus CRT After Induction Chemotherapy for Oropharyngeal Cancer.

Objectives: This retrospective observational study investigated to determine whether surgery or chemoradiation therapy after induction chemotherapy leads to better swallow function for oropharyngeal cancer patients. Methods: We documented the treatment paths and results of 267 patients with oropharyngeal squamous cell cancer (OPSCC). By quantifying nasogastric (NG) tube usage, surgery after induction chemotherapy (IC-surgery), and chemoradiation therapy after induction chemotherapy (IC-CRT) could be compared to determine the effectiveness of each. Cancer stages were also recorded concerning treatment options. The differences in NG tube usage IC-surgery and IC-CRT groups were compared. The NG tube dependence rates were also presented. Results: The prognosis and tube dependence differed significantly between the two groups. The IC-surgery had a better prognosis compared to IC-CRT for oropharyngeal cancer. The findings indicated that NG tube dependence was greater in advanced tumor stage 4 compared to stages 1-3, and NG tube dependence rates were higher for patients who underwent chemoradiation therapy after induction chemotherapy. Swallowing function was better in the IC-surgery group compared to the IC-CRT group. Conclusions: Higher NG tube retention rates and NG dependence are found in OPSCC patients who choose CRT as their treatment and also in the advanced-stage group.

Patterns and distribution of regional nodal involvement and recurrence in a surgically treated oropharyngeal squamous cell carcinoma cohort at a tertiary center

ObjectivesTo investigate and describe the patterns of regional metastases and recurrences after surgical treatment of oropharyngeal squamous cell cancer (OPSCC). Materials and MethodsRetrospective study of patients diagnosed with OPSCC from 2006 to 2021 at a tertiary referral center. Only patients treated with surgery including a neck dissection were included. Patients with unknown human papillomavirus (HPV) status, prior head and neck cancer, distant metastases, or synchronous head and neck cancer were excluded. ResultsA total of 928 patients were included. 89% were males, the average age was 58.6 years (range: 25.2–87.5), 874 (94%) were HPV(+), and 513 (55.3%) had a tonsil cancer. Among cN + patients, the most commonly involved levels at presentation were level II (85.2%), level III (33.3%), and level IV (9.4%). In cN0 patients, metastases were only observed in level II (16.2%) and level III (9.2%). Nodal recurrence occurred in 48 (5.2%) patients after a median time of 1.0 years (interquartile range: 0.6–2.0). Nodal recurrence incidence was similar in HPV(+) and HPV(-) patients (5.0% vs. 7.4%, p = 0.44). The most common levels for regional recurrence were ipsilateral level II (45.8%), contralateral level II (43.8%), and ipsilateral level V (25.0%). Multivariable analysis revealed that pN was a significant predictor for regional recurrence (p = 0.02). ConclusionThere is no difference in the distribution of regional metastases and recurrences in HPV(+) and HPV(-) OPSCC patients. Our findings align with the established understanding that regional metastases predominantly manifest in the ipsilateral level II-IV at presentation. Moreover, the data support the clinical recommendation to restrict elective neck dissection in cN0 patients to ipsilateral levels IIa and III, excluding level IIb. Regional recurrence is significantly associated with pN status.

Value of routine follow-up in oropharyngeal squamous cell cancer patients treated with curative intent.

The major goal of routine follow-up in oropharyngeal squamous cell carcinoma (OPSCC) patients is the asymptomatic detection of new disease in order to improve survival. This study evaluated the effect of routine follow-up on overall survival (OS). A retrospective cohort of 307 consecutive OPSCC patients treated with curative intent between 2006 and 2012 was analyzed. The effectiveness of routine follow-up was studied by comparing treatment-intent and OS in patients with asymptomatically versus symptomatically detected new disease. Three- and five-year risks of new disease were 29% (95% CI: 24-34) and 33% (95% CI: 27-39). Of the 81 patients with locoregional recurrence or second primary head and neck cancer, 8 (10%) were detected asymptomatically with no difference in OS with those detected with symptoms. Asymptomatic detection of new disease during routine visits was not associated with improved OS. The focus of follow-up should be on providing psychosocial care and rehabilitation.

Oropharyngeal tumor cells induce COX-2 expression in peripheral blood monocytes by secretion of IL-1α.

Oropharyngeal squamous cell cancer (OPC) accounts for 3% of all cancers and greater than 1.5% of all cancer deaths in the United States, with marked treatment-associated morbidity in survivors. More than 80% of OPC is caused by HPV16. Tumors induced by HPV have been linked to impaired immune functions, with most studies focused on the local tumor microenvironment. Fewer studies have characterized the effects of these tumors on systemic responses in OPC, especially innate responses that drive subsequent adaptive responses, potentially creating feed-back loops favorable to the tumor. Here we report that elevated plasma levels of PGE2 are expressed in half of patients with OPC secondary to overexpression of COX-2 by peripheral blood monocytes, and this expression is driven by IL-1α secreted by the tumors. Monocytes from patients are much more sensitive to the stimulation than monocytes from controls, suggesting the possibility of enhanced immune-modulating feed-back loops. Furthermore, control monocytes pre-exposed to PGE2 overexpress COX-2 in response to IL-1α, simulating responses made by monocytes from some OPC patients. Disrupting the PGE2/IL-1α feed-back loop can have potential impact on targeted medical therapies.

Optimized decision support for selection of transoral robotic surgery or (chemo)radiation therapy based on posttreatment swallowing toxicity.

A primary goal in transoral robotic surgery (TORS) for oropharyngeal squamous cell cancer (OPSCC) survivors is to optimize swallowing function. However, the uncertainty in the outcomes of TORS including postoperative residual positive margin (PM) and extranodal extension (ENE), may necessitate adjuvant therapy, which may cause significant swallowing toxicity to survivors. A secondary analysis was performed on a prospective registry data with low- to intermediate-risk human papillomavirus-related OPSCC possibly resectable by TORS. Decision trees were developed to model the uncertainties in TORS compared with definitive radiation therapy (RT) and chemoradiation therapy (CRT). Swallowing toxicities were measured by Dynamic Imaging Grade of Swallowing Toxicity (DIGEST), MD Anderson Dysphagia Inventory (MDADI), and the MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) instruments. The likelihoods of PM/ENE were varied to determine the thresholds within which each therapy remains optimal. Compared with RT, TORS resulted in inferior swallowing function for moderate likelihoods of PM/ENE (>60% in short term for all instruments, >75% in long term for DIGEST and MDASI) leaving RT as the optimal treatment. Compared with CRT, TORS remained the optimal therapy based on MDADI and MDASI but showed inferior swallowing outcomes based on DIGEST for moderate-to-high likelihoods of PM/ENE (>75% for short-term and >40% for long-term outcomes). In the absence of reliable estimation of postoperative PM/ENE concurrent with significant postoperative PM, the overall toxicity level in OPSCC patients undergoing TORS with adjuvant therapy may become more severe compared with patients receiving nonsurgical treatments thus advocating definitive (C)RT protocols.

The effect of human papillomavirus status on prognosis and local treatment strategies of T1-2N0 oropharyngeal squamous cell cancer.

PurposeTo explore the effect of human papillomavirus (HPV) status on prognosis and further investigate whether human papillomavirus (HPV) status has an impact on the local treatment strategies for T1-2N0 oropharyngeal squamous cell cancer (OPSCC) patients.MethodsPatients diagnosed with T1-2N0 OPSCC between 2010 and 2015 were included from the Surveillance, Epidemiology, and End Results database. Data were analyzed using propensity score matching (PSM), Chi-square test, Kaplan-Meier survival analysis, and Cox multivariable analyses.ResultsA total of 1,004 patients were identified, of whom 595 (59.3%) had HPV-related tumors. Of all the patients, 386 (38.4%) and 618 (61.6%) received definitive radiotherapy and radical surgery, respectively. HPV status had no significant effect on local treatment strategies for early-stage OPSCC (P = 0.817). The 3-year cancer-specific survival (CSS) and overall survival (OS) were 89.6 and 80.1%, respectively. Compared to those with HPV-negative diseases, patients with HPV-positive diseases had better CSS and OS. A total of 222 pairs of patients were completely matched after PSM. The results of multivariate Cox regression analysis showed that patients with HPV-positive disease had significantly better CSS (P = 0.001) and OS (P < 0.001) compared to those with HPV-negative tumors. However, local treatment strategy was not associated with survival outcomes after PSM (CSS, P = 0.771; OS, P = 0.440). The subgroup analysis showed comparable CSS and OS between those treated with radical surgery and definitive radiotherapy regardless of HPV status.ConclusionsHPV status is an independent prognostic factor for the survival of stage T1-2N0 OPSCC patients. Local treatment strategies had no significant effect on the survival of early-stage OPSCC regardless of HPV status. Patients with early-stage OPSCC should be informed regarding the pros and cons of definitive radiotherapy or radical surgery.

Prophylactic versus reactive percutaneous endoscopic gastrostomy in oropharyngeal squamous cell carcinoma patients undergoing radical radiotherapy.

Radiotherapy (RT) for oropharyngeal squamous cell cancer (OPSCC) is associated with malnutrition due to treatment-related mucositis and dysphagia. While percutaneous endoscopic gastrostomy (PEG) feeding can improve nutrition, it has acute and late complications, including dependence on PEG feeding. We retrospectively evaluated patient outcomes by whether gastrostomy placement was prophylactic (P-G) or reactive to RT complications (R-G). Retrospective analysis of OPSCC patients undergoing curative-intent RT at Waikato Hospital between 2010 and 2015. Of 103 OPSCC patients treated with RT (+/- chemotherapy) 21 had P-G, 15 had R-G and 67 had none (No-G). P-G patients were significantly more likely to be female, older, have higher tumour stage and receive bilateral RT (all p< 0.05). P-G and No-G patients had similar rates and duration of hospital admission for complications during treatment, but both were significantly less than in R-G patients (admission rates 52.3%, 49.3% and 86.7%, and mean length of stay 3.5, 3.3 and 11.9 days, respectively; p< 0.001). R-G patients also had greater RT treatment delays than P-G or No-G patients (mean 1.1, 0.7 and 0.4 days, respectively, p< 0.05). No significant differences were noted between groups in PEG dependence or weight change during, or 1, 3 or 6months after, RT. Weight loss was not significantly different with P-G than R-G despite more frequent use of bilateral RT fields in the former group. P-G placement affords shorter and less frequent hospital admissions than R-G during RT for OPSCC, with no increased complications or gastrostomy-dependence rates.

The decreased mean platelet volume is associated with poor prognosis in patients with oropharyngeal cancer treated with radiotherapy

BackgroundThere is considerable evidence that platelets contribute to cancer growth and metastatic dissemination. In recent studies, altered mean platelet volume (MPV) has been associated with prognosis in different types of cancer. However, the prognostic role of the MPV in head and neck squamous cell cancer (HNSCC) is currently discussed controversially. The present study was performed to analyze and further elucidate the prognostic significance of the MPV in HNSCC.MethodsA total of 319 oropharyngeal squamous cell cancer (OPSCC) patients treated with radiotherapy at a tertiary academic center were enrolled in the present study. Kaplan–Meier method as well as uni- and multivariate Cox proportional hazards were used to evaluate the impact of MPV on cancer-specific survival (CSS), locoregional control (LC) and recurrence-free survival (RFS).ResultsThe median MPV was 10.30 fL (mean 10.26 ± 1.17fL). Univariate analyses showed a significant association of the MPV with CSS (HR 0.85, 95% CI 0.74–0.98, p = 0.025), LC (HR 0.86, 95% CI 0.74–0.99, p = 0.034) and RFS (HR 0.87, 95% CI 0.76–0.996; p = 0.043). In multivariate analysis, the MPV remained an independent prognostic factor for CSS (HR 0.77, 95% CI 0.63–0.93, p = 0.008), LC (HR 0.80, 95% CI 0.65–0.98, p = 0.030), and RFS (HR 0.83, 95% CI 0.685–0.999, p = 0.049).ConclusionsOur findings indicate that the MPV is a prognostic marker in OPSCC patients and may contribute to future individual risk assessment.

Radiotherapy in Metastatic Oropharyngeal Cancer.

The role of locoregional radiotherapy for metastatic oropharyngeal squamous cell cancer (OPSCC) is unclear. We investigated the impact of head and neck radiotherapy on survival in de novo metastatic OPSCC patients who received systemic therapy. We queried the NCDB from 2004-2015 for metastatic OPSCC patients at diagnosis with known HPV-status who received systemic therapy. The association of head and neck radiotherapy with overall survival was analyzed using the Kaplan-Meier method, Cox proportional hazards model, and propensity score-matched analysis adjusting for demographic and disease-specific prognostic factors. Of the 2,139 patients with metastatic OPSCC who presented with metastases and received systemic treatment, we identified 556 patients with known HPV-status. Among these 556 patients, 49% were HPV-positive and 56% received head and neck radiotherapy. With a median follow-up of 17.5 months (IQR 6.0-163.4 months), radiotherapy was associated with significantly improved 1-year OS (67% vs 58%, log-rank P < .001) which remained significant on MVA (HR 0.78 95% CI 0.62-0.97 P = .029). In HPV-status subgroup analysis, a survival benefit was identified in HPV-positive patients (1-year OS 77% vs 67%, log-rank P < .001) but not in HPV-negative patients. Results were consistent on a propensity score-matched analysis of 212 HPV-positive matched patients (HR 0.66, 95% CI 0.49-0.83, P < .001). The survival of metastatic OPSCC remains limited. In this large series of patients with known HPV-status, head and neck radiotherapy was associated with longer survival in those with HPV-associated disease. These data could guide management of this challenging group of patients for head and neck cancer practitioners. 3 Laryngoscope, 131:E1847-E1853, 2021.

Treatment decision-making among patients with oropharyngeal squamous cell cancer: A qualitative study.

Oropharyngeal squamous cell cancer (OPSCC) is now the most common site of head and neck squamous cell cancer. Despite the focus on treatment deintensification in clinical trials, little is known about the preferences, experiences and needs of patients with OPSCC when deciding between surgery and radiation therapy as primary treatment with curative intent. In this qualitative study, pre-treatment and post-treatment oropharyngeal cancer patients were recruited to take part in one-on-one interviews (n=11 pre-treatment) and focus group discussions (n=15 post-treatment) about treatment decision-making. Recordings were transcribed and assessed for emergent themes using framework analysis. From the one-on-one interviews and focus group discussions with OPSCC patients, fourteen themes were identified. Participants expressed alarm at diagnosis, decisional conflict, and a variety of roles in decision-making (physician-controlled, shared, and autonomous). Decisions were driven by the perceived recommendation of the treatment team, a desire for physical (surgical) tumor removal, fear of adverse effects of treatment, and patient-specific values. Although participants felt well-informed by their treating physicians, they identified a need for additional patient-centered information. Participants were critical of the poor quality of information available on the internet, and acknowledged the advantage of hearing the experiences of post-treatment patients. The experiences identified herein may be used to guide patient-centered communication during patient counseling and to inform interventions designed to support patients' needs at diagnosis, ultimately helping to implement high-quality, patient-centered care.

HPV-driven oropharyngeal squamous cell cancer in Croatia - Demography and survival.

ObjectivesHead and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Main HNSCC risk factors are tobacco, alcohol, and high-risk human papillomavirus (HPV). HPV+ oropharyngeal squamous cell cancer (OPSCC) usually have different etiology, increasing incidence and often show an improved survival when compared to HPV-negative cases. The objective of the current study was to retrospectively examine the influence of HPV on the survival of OPSCC patients in a non-Western population setting.Materials and methodsWe determined the presence of HPV DNA and/or RNA in 99 formalin-fixed paraffin embedded (FFPE) tissue samples of OPSCC patients treated between 2002 and 2015. Patients were compared based on laboratory, demographic, clinical, life style characteristics and survival.ResultsHPV RNA was found in 29.3% cases. However, groups based on HPV data (either RNA, DNA or retrospectively collected p16 staining) did not show significant differences. Overall, 5-year survival was 30% with minimal influence of the HPV positivity.ConclusionsThe HPV influence on survival of OPSCC patients is not identical between populations probably due to other factors overshadowing the HPV effect. This should be taken into account when treatment or policy decisions are made in each particular setting.

De-intensified adjuvant (chemo)radiotherapy versus standard adjuvant chemoradiotherapy post transoral minimally invasive surgery for resectable HPV-positive oropharyngeal carcinoma.

More than 400,000 cases of oropharyngeal squamous cell cancer (OPSCC) are diagnosed every year worldwide and this is rising. Much of the increase has been attributed to human papillomavirus (HPV). HPV-positive OPSCC patients are often younger and have significantly improved survival relative to HPV-negative patients. Traditional management of OPSCC has been with radiotherapy with or without chemotherapy, as this was shown to have similar survival to open surgery but with significantly lower morbidity. Techniques have evolved, however, with the development of computerised planning and intensity-modulated radiotherapy, and of minimally invasive surgical techniques. Acute and late toxicities associated with chemoradiotherapy are a significant burden for OPSCC patients and with an ever-younger cohort, any strategies that could decrease treatment-associated morbidity should be investigated. To assess the effects of de-intensified adjuvant (chemo)radiotherapy in comparison to standard adjuvant (chemo)radiotherapy in patients treated with minimally invasive transoral surgery (transoral robotic surgery or transoral laser microsurgery) for resectable HPV-positive oropharyngeal squamous cell carcinoma. The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 26 April 2018. Randomised controlled trials (RCTs) in patients with carcinoma of the oropharynx (as defined by the World Health Organization classification C09, C10). Cancers included were primary HPV-positive squamous cell tumours originating from the oropharyngeal mucosa. Tumours were classified as T1-4a with or without nodal spread and with no evidence of distant metastatic spread. The intervention was minimally invasive transoral surgery followed by de-intensified adjuvant therapy (either omission of chemotherapy or reduced-dose radiotherapy). The comparator was minimally invasive transoral surgery followed by standard concurrent chemoradiotherapy or standard-dose radiotherapy. The treatments received were of curative intent and patients had not undergone any prior intervention, other than diagnostic biopsy. We used the standard methodological procedures expected by Cochrane. Our primary outcomes were overall survival (disease-related survival was to be studied where possible) and disease-free survival, measured at one, two, three and five years. Our secondary outcomes included assessment of swallowing ability and voice, measured at one, six, 12 and 24 months. We planned to use GRADE to assess the quality of evidence for each outcome. We did not identify any completed RCTs that met our inclusion criteria. However, three eligible studies are in progress:ADEPT is a phase III trial comparing postoperative radiotherapy with or without cisplatin in HPV-positive T1-4a OPSCC patients. Included patients must have received minimally invasive surgery and demonstrated extra-capsular spread from disease in the neck.ECOG-E3311 is a phase II trial of treatment for HPV-positive locally advanced OPSCC (stages III-IVa + IVb without distant metastasis). Patients are stratified after minimally invasive surgery. Medium-risk patients are randomised to either standard or reduced-dose radiotherapy.PATHOS is a phase III trial of treatment for HPV-positive OPSCC (T1-3, N0-2b). Patients are stratified after minimally invasive surgery. Medium-risk patients are randomised to either standard or reduced-dose radiotherapy. High-risk patients are randomised to radiotherapy with or without concurrent cisplatin. This review highlights the current lack of high-quality randomised controlled trials studying treatment de-escalation after minimally invasive surgery in patients with HPV-positive OPSCC. However, trials that will meet the inclusion criteria for this review are in progress with results expected between 2021 and 2023.

EP-2292: CD44, EGFR and p16 expressions in oropharyngeal squamous cell cancer patients treated by IMRT

The aim of this study was to analyse the expression of epidermal growth factor receptor (EGFR), cluster of differentiation- 44 (CD44) and p16 in patients with oropharyngeal squamous cell carcinoma (OSCC) and correlate the expression profiles with radiation treatment outcomes.

Impact of Time to Treatment Initiation in Patients with Human Papillomavirus-positive and -negative Oropharyngeal Squamous Cell Carcinoma

AimsThe distinct difference in disease phenotype of human papillomavirus-positive (HPV+) and -negative (HPV–) oropharyngeal squamous cell cancer (OPSCC) patients might also be apparent when assessing the effect of time to treatment initiation (TTI). We assessed the overall survival and progression-free survival (PFS) effect from increasing TTI for HPV+ and HPV– OPSCC patients. Materials and methodsWe examined patients who received curative-intended therapy for OPSCC in eastern Denmark between 2000 and 2014. TTI was the number of days from diagnosis to the initiation of curative treatment. Overall survival and PFS were measured from the start of treatment and estimated with the Kaplan–Meier estimator. Hazard ratios and 95% confidence intervals were estimated with Cox proportional hazard regression. ResultsAt a median follow-up of 3.6 years (interquartile range 1.86–6.07 years), 1177 patients were included (59% HPV+). In the adjusted analysis for the HPV+ and HPV– patient population, TTI influenced overall survival and PFS, most evident in the HPV– group, where TTI >60 days statistically significantly influenced overall survival but not PFS (overall survival: hazard ratio 1.60; 95% confidence interval 1.04–2.45; PFS: hazard ratio 1.46; 95% confidence interval 0.96–2.22). For patients with a TTI >60 days in the HPV+ group, TTI affected overall survival and PFS similarly, with slightly lower hazard ratio estimates of 1.44 (95% confidence interval 0.83–2.51) and 1.15 (95% confidence interval 0.70–1.88), respectively. ConclusionFor patients treated for a HPV+ or HPV– OPSCC, TTI affects outcome, with the strongest effect for overall survival among HPV– patients. Reducing TTI is an important tool to improve the prognosis.

Quality indicators of oropharyngeal cancer care in the elderly.

To examine associations between quality of care, survival, and costs in elderly patients treated for oropharyngeal squamous cell cancer (OPSCC). Retrospective analysis of Surveillance, Epidemiology, and End Results-Medicare data. We evaluated 666 patients diagnosed with OPSCC from 2004 to 2007 using multivariate regression and survival analysis. Using quality indicators derived from guidelines for recommended care, summary measures of quality were calculated for diagnosis, initial treatment, surveillance, treatment for recurrence, end-of-life care, performance, and an overall summary measure of quality. Higher-quality care was associated with significant differences in survival for initial treatment (hazard ratio [HR] = 0.55 [0.41 to 0.73]), surveillance (HR = 0.32 [0.22 to 0.48]), treatment of recurrence (HR = 2.37 [1.56 to 3.60]), performance measures (HR = 0.50 [0.36 to 0.69]), and the overall summary measure of quality (HR = 0.53 [0.39 to 0.71]). Higher-quality salvage surgery was associated with improved survival (HR = 0.16 [0.04 to 0.54]), whereas higher-quality chemotherapy given for recurrence was associated with worse survival (HR = 5.70 [1.92 to 16.94]). Overall, higher-quality care was not associated with differences in costs. Higher-quality care was associated with significantly lower mean incremental costs for treatment of recurrence and end-of-life care, and higher costs for diagnosis and surveillance. Higher-quality OPSCC care in elderly patients was associated with improved survival; however, higher-quality care was not associated with reduced costs, and higher-quality care for treatment of recurrence was associated with poorer survival, primarily due to poorer survival in patients treated with palliative chemotherapy. These data demonstrate a complex relationship between quality and costs in elderly OPSCC patients, which can be used to frame discussions of value and guide disease-specific quality-measure development. 2c. Laryngoscope, 128:2312-2319, 2018.

Treatment, survival, and costs of oropharyngeal cancer care in the elderly.

To examine associations between treatment, survival, and costs in elderly patients with oropharyngeal squamous cell cancer (OPSCC). Retrospective cross-sectional analysis of Surveillance, Epidemiology, and End Results-Medicare data. We evaluated 666 patients diagnosed with OPSCC from 2004 to 2007 using cross-tabulations, multivariate logistic and generalized linear regression modeling, and survival analysis. The majority of patients were nonsmokers (79%), had advanced-stage disease (59%), and received chemoradiation (38%) or radiation (28%). Surgery with postoperative radiation (hazard ratio [HR]: 0.33 [95% CI: 0.20-0.53]) and chemoradiation (HR: 0.45 [95% CI: 0.29-0.71]) were associated with improved survival, whereas stage IV disease was associated with poorer survival (HR: 1.95 [95% CI: 1.13-3.38]). Additional cancer-directed treatment after primary treatment was more likely following chemoradiation (odds ratio [OR]: 3.44 [95% CI: 1.78-6.63]). Salvage surgery was performed in 25% of patients undergoing subsequent additional cancer-directed treatment, and was associated with high-volume hospitals (OR: 2.81 [95% CI: 1.07-7.74]). Additional radiation (HR: 0.47 [95% CI: 0.31-0.72]) and salvage surgery (HR: 0.61 [95% CI: 0.38-0.99]) were associated with improved overall survival when performed >6 months following initial treatment, whereas salvage neck dissection alone was not significantly associated with survival after controlling for time to salvage (HR: 0.38 [95% CI: 0.05-2.78]). Treatment and 5-year overall costs were highest for chemoradiation, surgery with postoperative radiation, and additional cancer-directed treatment. Multimodality treatment in elderly OPSCC patients was associated with improved survival and increased costs. Chemoradiation was associated with an increased likelihood of additional cancer-directed treatment. Salvage surgery was centralized at high-volume hospitals, and was associated with improved survival when performed >6 months after last initial treatment date, but was performed in <20% of patients undergoing additional treatment. 2c. Laryngoscope, 128:1103-1112, 2018.

Relapse Rates with Surgery Alone in HPV-Related Intermediate- and High-Risk-Group Oropharynx Squamous Cell Cancer: A Multi-Institutional Review

Indications for adjuvant therapy including radiation therapy (RT) and chemotherapy after surgery for oropharyngeal squamous cell cancer (OPSCC) were defined prior to the predominance of human papilloma virus-related (HPV+) disease. Risk factors for relapse were likewise determined prior to the development of minimally invasive surgeries (MIS) such as transoral robotic surgery and transoral laser microsurgery. This study aimed to evaluate whether historic risk categories and indications for adjuvant therapy in the pre-HPV and pre-MIS era were associated with clinically significant relapse rates in HPV+ OPSCC patients undergoing MIS. A multi-institutional retrospective review of intermediate and high risk HPV+ OPSCC patients not receiving adjuvant therapy after MIS was performed. Perineural invasion (PNI), lymphovascular invasion (LVI), T3-T4, or >=N2 disease were considered to be intermediate risk factors and extracapsular extension (ECE) or positive margins were considered to be high risk features based on established risk categories. Histopathologic review evaluated LVSI, PNI, and/or ECE for patients whose initial pathology reports did not comment specifically on the presence or absence of these parameters, when available. Univariate Cox Proportional Hazards models were used to assess clinical and pathologic risk factors for all relapses. Median follow-up was 42.9 months. Among all 53 patients, the three year cumulative incidence of relapse was 26.0%. The three year cumulative incidence was 11.8% in the 37 intermediate risk patients and 52.4% in the 16 high risk patients. LVI was missing for 17 patients and PNI for 18 patients. On univariate analysis, only high risk status was significantly associated with an increased risk of relapse, HR=3.9 (p=0.018). The salvage rate for relapse was 77%, with 10 of 13 patients undergoing salvage therapy. With a median post-salvage follow-up of 20.6 months for these 10 patients, none of the patients had experienced a second relapse at time of last follow up. Risk category was associated with clinically significant relapse rates after MIS alone in HPV+ oropharyngeal cancer, comparable to historical data and traditional indications for adjuvant therapy for all oropharyngeal cancer. ECE had the highest association with relapse. Most intermediate risk category patients had 1 intermediate risk factor. Missing LVI and PNI data are limitations of this analysis. Like HPV- patients, HPV+ patients with traditional intermediate and high risk features should be offered adjuvant therapy. However, given the potential for salvage therapy and relatively low risk for relapse in intermediate risk patients, de-escalation of adjuvant treatment remains an open consideration best answered by a prospective, randomized trial.

Survival Outcomes Among Human Papillomavirus-Associated Oropharyngeal Squamous Cell Cancer Patients Treated with Upfront Surgery Versus Definitive Chemoradiation Therapy

Transoral robotic surgery (TORS) is associated with decreased morbidity compared to open surgery for early-stage oropharynx cancer. However, there is no prospective data comparing oncologic outcomes of primary surgery vs. definitive concurrent chemoradiation (CRT) in the management of human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV-A OPC). We therefore assessed the outcomes of both treatment strategies in presumed TORS-eligible patients in a large national sample. The National Cancer Database was used to identify patients diagnosed with cT2 N1 or cT1-2 N2a-2b HPV-A OPC from 2010-2013 who underwent treatment with either CRT or primary surgery +/- adjuvant therapy. Demographic and clinicopathologic predictors of treatment were analyzed by the chi-square test and logistic regression. Overall survival (OS) was evaluated using the Kaplan-Meier, log-rank test, multivariable Cox proportional hazard regression, and propensity score-matched analysis. We identified 3,168 patients, among whom 1,576 (49.8%) received CRT and 1,592 (50.2%) underwent primary surgery. Median follow-up was 32 months. Nine hundred seventy-two (61.0%) surgical patients received adjuvant CRT. On multivariable logistic regression, female sex, younger age, academic treatment facility, higher comorbidity index, and lower clinical T and N stages were associated with higher odds of receiving primary surgery. Three-year OS in the CRT cohort was 90.8% vs. 92.5% in patients receiving primary surgery (log-rank P = .92). On multivariable Cox regression, upfront surgery was not associated with improved OS when compared with CRT (hazard ratio [HR] 1.10, 95% confidence interval [CI] 0.84-1.43, P = .48). Increasing clinical T and N stage, older age, and non-private insurance were significantly associated with inferior OS. Lack of OS benefit with upfront surgery persisted in a subset analysis of patients with margin-negative resection, with a 3-year OS of 90.1% in patients undergoing CRT vs. 93.5% in primary surgery patients (log-rank P = .14). Propensity score-matching identified a cohort of 2,618 patients and redemonstrated similar OS (HR, 1.11; 95% CI 0.83-1.49; P = 0.49). Upfront surgery was not associated with improved OS compared to CRT in this patient cohort. The majority of surgical patients received trimodal therapy with adjuvant CRT. Efforts to improve patient selection in order to minimize the need for trimodal therapy are justified given the lack of observed survival benefit with surgery.

Relapse Rates With Surgery Alone in Human Papillomavirus–Related Intermediate- and High-Risk Group Oropharynx Squamous Cell Cancer: A Multi-Institutional Review

Toevaluate whether historic risk categories and indications for adjuvant therapy in the pre-human papillomavirus (HPV) and pre-transoral surgery (TOS) era were associated with clinically significant relapse rates in HPV+oropharyngeal squamous cell cancer patients undergoing TOS. A multi-institutional retrospective review of intermediate- and high-risk HPV+oropharyngeal squamous cell cancer patients not receiving adjuvant therapy after TOS was performed. Perineural invasion, lymphovascular invasion, T3-T4, or≥N2 disease were considered to be intermediate-risk factors, and extracapsular extension or positive margins were considered to be high-risk features, according to established risk categories. Median follow-up was 42.9months. Among all 53 patients, the 3-year cumulative incidence of relapse was 26.0%. The 3-year cumulative incidence was 11.8% in the 37 intermediate-risk patients and 52.4% in the 16 high-risk patients. On univariate analysis only high-risk status was significantly associated with an increased risk of relapse (hazard ratio 3.9; P=.018). The salvage rate for relapse was 77%, with 10 of 13 patients undergoing salvage therapy. Risk category was associated with clinically significant relapse ratesafter TOS alone in HPV+oropharyngeal cancer, comparable to historical dataandtraditional indications for adjuvant therapy for all oropharyngeal cancer.

Swallowing outcomes for patients with oropharyngeal squamous cell carcinoma treated with primary (chemo)radiation therapy receiving either prophylactic gastrostomy or reactive nasogastric tube: A prospective cohort study.

There is currently no consensus on the optimal feeding route for an oropharyngeal squamous cell cancer (OPSCC) patient without pre-existing dysphagia undergoing chemoradiotherapy. This study aimed to compare the swallowing outcomes for OPSCC patients fed via either prophylactic RIG (pRIG) or reactive nasogastric tube (rNGT). A prospective cohort study. Four head and neck cancer centres in the North of England Cancer Network. Fifty-three participants with OPSCC, on a normal diet pre-(chemo) radiotherapy. Swallowing outcomes for patients with rNGT and pRIG were compared using the following outcome measures administered prospectively at pre-treatment, three and 12 months post-treatment: MD Anderson Dysphagia Inventory (MDADI), Performance Status Scales (Normalcy of Diet), timed water swallow test. Twenty-three patients received pRIG while 30 were planned for a rNGT. No differences in demographics were found between the groups. The rNGT group had a clinically significant higher score on MDADI at 12 months post-treatment. No significant difference was found on a timed water swallow test or diet texture scale. There is no statistical difference for swallowing outcomes in either group. However, patients' in the rNGT group reported a clinically meaningful difference at 1 year, with a trend for them to do better across all measures. Neither group returned to their baseline swallowing function. Further research with a larger sample size is indicated.