Prevalence and predictive role of p16 and epidermal growth factor receptor in surgically treated oropharyngeal and oral cavity cancer

Background The purpose of this study was to describe the relationship of p16 and epidermal growth factor receptor (EGFR) expression with survival in surgically treated patients who had oropharyngeal or oral cavity squamous cell carcinoma (SCC). Methods Tissue from 36 patients with oropharyngeal SCC and 49 patients with oral cavity SCC treated between 1997 and 2001 was imbedded and immunostained using a tissue microarray. Results The p16 was positive in 57% and 13% of patients with oropharyngeal SCC and oral cavity SCC, respectively. EGFR was positive in 60% and 63% of patients with oropharyngeal SCC and oral cavity SCC, respectively. In patients with oropharyngeal SCC, p16 expression was associated with improved disease‐specific survival (DSS), overall survival (OS), and time to recurrence (TTR) ( p < .01, < .01, and <.01, respectively). EGFR expression was associated with poorer DSS, OS, and TTR ( p < .01, = .01, and < .01, respectively). For oropharyngeal SCC, when examining both p16 and EGFR expression as combined biomarkers, high p16 expression coupled with low EGFR expression was associated with improved DSS ( p p16 = .01; p EGFR = .01). Patients with oral cavity SCC showed no association between biomarker and outcome. Conclusions For patients with oropharyngeal SCC, high p16 and low EGFR were associated with improved outcome, suggesting a predictive role in surgically treated patients. © 2012 Wiley Periodicals, Inc. Head Neck, 2013Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99017/1/23087_ftp.pd

Cost-Effectiveness Analysis of Elective Neck Dissection in Patients With Clinically Node-Negative Oral Cavity Cancer.

Purpose Recently, a large randomized trial found a survival advantage among patients who received elective neck dissection in conjunction with primary surgery for clinically node-negative oral cavity cancer compared with those receiving primary surgery alone. However, elective neck dissection comes with greater upfront cost and patient morbidity. We present a cost-effectiveness analysis of elective neck dissection for the initial surgical management of early-stage oral cavity cancer. Methods We constructed a Markov model to simulate primary, adjuvant, and salvage therapy; disease recurrence; and survival in patients with T1/T2 clinically node-negative oral cavity squamous cell carcinoma. Transition probabilities were derived from clinical trial data; costs (in 2015 US dollars) and health utilities were estimated from the literature. Incremental cost-effectiveness ratios, expressed as dollar per quality-adjusted life-year (QALY), were calculated with incremental cost-effectiveness ratios less than $100,000/QALY considered cost effective. We conducted one-way and probabilistic sensitivity analyses to examine model uncertainty. Results Our base-case model found that over a lifetime the addition of elective neck dissection to primary surgery reduced overall costs by$6,000 and improved effectiveness by 0.42 QALYs compared with primary surgery alone. The decrease in overall cost despite the added neck dissection was a result of less use of salvage therapy. On one-way sensitivity analysis, the model was most sensitive to assumptions about disease recurrence, survival, and the health utility reduction from a neck dissection. Probabilistic sensitivity analysis found that treatment with elective neck dissection was cost effective 76% of the time at a willingness-to-pay threshold of $100,000/QALY. Conclusion Our study found that the addition of elective neck dissection reduces costs and improves health outcomes, making this a cost-effective treatment strategy for patients with early-stage oral cavity cancer

Cost-Effectiveness Analysis of Elective Neck Dissection in Patients With Clinically Node-Negative Oral Cavity Cancer.

Purpose Recently, a large randomized trial found a survival advantage among patients who received elective neck dissection in conjunction with primary surgery for clinically node-negative oral cavity cancer compared with those receiving primary surgery alone. However, elective neck dissection comes with greater upfront cost and patient morbidity. We present a cost-effectiveness analysis of elective neck dissection for the initial surgical management of early-stage oral cavity cancer. Methods We constructed a Markov model to simulate primary, adjuvant, and salvage therapy; disease recurrence; and survival in patients with T1/T2 clinically node-negative oral cavity squamous cell carcinoma. Transition probabilities were derived from clinical trial data; costs (in 2015 US dollars) and health utilities were estimated from the literature. Incremental cost-effectiveness ratios, expressed as dollar per quality-adjusted life-year (QALY), were calculated with incremental cost-effectiveness ratios less than $100,000/QALY considered cost effective. We conducted one-way and probabilistic sensitivity analyses to examine model uncertainty. Results Our base-case model found that over a lifetime the addition of elective neck dissection to primary surgery reduced overall costs by$6,000 and improved effectiveness by 0.42 QALYs compared with primary surgery alone. The decrease in overall cost despite the added neck dissection was a result of less use of salvage therapy. On one-way sensitivity analysis, the model was most sensitive to assumptions about disease recurrence, survival, and the health utility reduction from a neck dissection. Probabilistic sensitivity analysis found that treatment with elective neck dissection was cost effective 76% of the time at a willingness-to-pay threshold of $100,000/QALY. Conclusion Our study found that the addition of elective neck dissection reduces costs and improves health outcomes, making this a cost-effective treatment strategy for patients with early-stage oral cavity cancer

Hypermutated Circulating Tumor DNA: Correlation with Response to Checkpoint Inhibitor–Based Immunotherapy

Purpose: Tumor mutational burden detected by tissue next-generation sequencing (NGS) correlates with checkpoint inhibitor response. However, tissue biopsy may be costly and invasive. We sought to investigate the association between hypermutated blood-derived circulating tumor DNA (ctDNA) and checkpoint inhibitor response.Experimental Design: We assessed 69 patients with diverse malignancies who received checkpoint inhibitor-based immunotherapy and blood-derived ctDNA NGS testing (54-70 genes). Rates of stable disease (SD) ≥6 months, partial and complete response (PR, CR), progression-free survival (PFS), and overall survival (OS) were assessed based on total and VUS alterations.Results: Statistically significant improvement in PFS was associated with high versus low alteration number in variants of unknown significance (VUS, &gt;3 alterations versus VUS ≤3 alterations), SD ≥6 months/PR/CR 45% versus 15%, respectively; P = 0.014. Similar results were seen with high versus low total alteration number (characterized plus VUS, ≥6 vs. &lt;6). Statistically significant OS improvement was also associated with high VUS alteration status. Two-month landmark analysis showed that responders versus nonresponders with VUS &gt;3 had a median PFS of 23 versus 2.3 months (P = 0.0004).Conclusions: Given the association of alteration number on liquid biopsy and checkpoint inhibitor-based immunotherapy outcomes, further investigation of hypermutated ctDNA as a predictive biomarker is warranted. Clin Cancer Res; 23(19); 5729-36. ©2017 AACR

Hypermutated Circulating Tumor DNA: Correlation with Response to Checkpoint Inhibitor–Based Immunotherapy

Purpose: Tumor mutational burden detected by tissue next-generation sequencing (NGS) correlates with checkpoint inhibitor response. However, tissue biopsy may be costly and invasive. We sought to investigate the association between hypermutated blood-derived circulating tumor DNA (ctDNA) and checkpoint inhibitor response.Experimental Design: We assessed 69 patients with diverse malignancies who received checkpoint inhibitor-based immunotherapy and blood-derived ctDNA NGS testing (54-70 genes). Rates of stable disease (SD) ≥6 months, partial and complete response (PR, CR), progression-free survival (PFS), and overall survival (OS) were assessed based on total and VUS alterations.Results: Statistically significant improvement in PFS was associated with high versus low alteration number in variants of unknown significance (VUS, &gt;3 alterations versus VUS ≤3 alterations), SD ≥6 months/PR/CR 45% versus 15%, respectively; P = 0.014. Similar results were seen with high versus low total alteration number (characterized plus VUS, ≥6 vs. &lt;6). Statistically significant OS improvement was also associated with high VUS alteration status. Two-month landmark analysis showed that responders versus nonresponders with VUS &gt;3 had a median PFS of 23 versus 2.3 months (P = 0.0004).Conclusions: Given the association of alteration number on liquid biopsy and checkpoint inhibitor-based immunotherapy outcomes, further investigation of hypermutated ctDNA as a predictive biomarker is warranted. Clin Cancer Res; 23(19); 5729-36. ©2017 AACR

A phase II study evaluating axitinib in patients with unresectable, recurrent or metastatic head and neck cancer

BACKGROUND: Axitinib is an oral, potent, small molecule tyrosine kinase inhibitor with selective inhibition of VEGFR 1,2, 3, as well as inhibition of potential downstream effectors of the EGFR pathway. Given the upregulation of EGFR and VEGFR in head and neck squamous cell carcinoma, treatment with axitinib holds promise as a rational targeted therapy. PATIENTS AND METHODS: Patients with unresectable, recurrent or metastatic head and neck squamous cell carcinoma were included in this open label, single arm, phase II trial. Primary endpoint was 6 month progression free survival. All patients received single agent axitinib with planned dose escalation based on tolerability. A planned interim efficacy analysis was performed after enrollment of 30 patients. RESULTS: Forty-two patients were registered, 30 were evaluable. While treatment was well-tolerated with no severe bleeding events, only 19 patients were able to achieve full planned dose. The best overall response rate was 6.7% (two partial responses) with a disease control rate of 76.7%. Median progression free survival was 3.7 months (95% Confidence Interval (CI): 3.5-5.7) and overall survival was 10.9 months (95% CI: 6.4-17.8). Exploratory analysis demonstrated that patients with a smaller sum of diameter of target lesions experienced improved response rates, and better progression-free and overall survival. CONCLUSION: Treatment with single agent axitinib should be considered due to acceptable toxicity profile and favorable median overall survival compared to standard therapies

Chronic Opioid Use Following Surgery for Oral Cavity Cancer.

IMPORTANCE: Opioid misuse and overuse has become an epidemic. Chronic opioid use among oral cavity cancer patients after surgery has not been described. OBJECTIVES: To assess the prevalence of chronic opioid use in patients undergoing surgery for oral cavity cancer, and evaluate possible associated clinical factors; and the association between opioid use and survival. DESIGN, SETTING, AND PARTICIPANTS: For this retrospective cohort study of patients undergoing surgery for oral cavity cancer a consecutive sample of 99 patients between January 1, 2011, and September 30, 2016, were identified through the institutional cancer registry from a single academic center. EXPOSURES: Surgery for oral cavity cancer. MAIN OUTCOMES AND MEASURES: Chronic opioid use, defined as more than 90 days from surgery. Factors associated with chronic opioid use were investigated by univariable and multivariable logistic regression. The Kaplan-Meier method and Cox proportional hazards model were used to assess overall survival and disease-free survival. RESULTS: The mean (SD) patient age was 62.6 (14.3) years; 60 patients (60%) were male. Chronic opioid use was observed in 41 patients (41%). On multivariable logistic regression, preoperative opioid use (odds ratio [OR], 5.6; 95% CI, 2.2-14.3), tobacco use (OR, 2.8; 95% CI, 1.0-8.0), and development of persistence, recurrence, or a second primary tumor (OR, 2.8; 95% CI, 1.0-7.4) were associated with chronic opioid use. Among preoperative opioid users, estimated overall survival (hazard ratio [HR], 3.2; 95% CI, 1.4-7.1) was decreased, and chronic opioid use was associated with decreased disease-free survival (HR, 2.7; 95% CI, 1.1-6.6). CONCLUSIONS AND RELEVANCE: In patients undergoing surgery for oral cavity tumors, the prevalence of chronic opioid use was considerable. Preoperative opioid use, tobacco use, and development of persistence, recurrence, or a second primary tumor were associated with chronic opioid use after surgery, and both preoperative and chronic opioid use were associated with decreased survival