Treatment outcomes and cost comparisons for older adults with T4 laryngeal squamous cell cancer.

BACKGROUND: To evaluate treatment modalities of T4 larynx cancer in older adults using SEER-Medicare. METHODS: The database was queried for patients aged 66 and older with nonmetastatic T4 laryngeal squamous cell cancer from 2006 to 2015. Treatment modalities compared were surgery plus chemoradiation (SCR), surgery plus radiation (SR), chemoradiation (CR), surgery (S), and radiation (R). Multivariate analysis and Kaplan-Meier methods were used to explore the relationship of treatment modality and survival. Total cancer-related costs were calculated. RESULTS: A total of 438 patients met inclusion criteria. Patients receiving CR or SR had similar CSS to SCR (HR 1.36 and HR 1.24, respectively). Those receiving S (HR 2.00) or R (HR 2.41) had significantly worse CSS. Similar findings were observed for OS. Cancer care-related costs were not significantly different but highest in SCR ($162215) and lowest in R ($121421). CONCLUSION: Older patients with T4 larynx cancer had similar survival rates when treated with CR, SR, and SCR. Average total health care costs were not significantly different between modalities. Patients not eligible for triple-modality could consider these other treatment options.

A phase I/Ib trial and biological correlate analysis of neoadjuvant SBRT with single-dose durvalumab in HPV-unrelated locally advanced HNSCC.

Five-year survival for human papilloma virus-unrelated head and neck squamous cell carcinomas remain below 50%. We assessed the safety of administering combination hypofractionated stereotactic body radiation therapy with single-dose durvalumab (anti-PD-L1) neoadjuvantly (n = 21) ( NCT03635164 ). The primary endpoint of the study was safety, which was met. Secondary endpoints included radiographic, pathologic and objective response; locoregional control; progression-free survival; and overall survival. Among evaluable patients at an early median follow-up of 16 months (448 d or 64 weeks), overall survival was 80.1% with 95% confidence interval (95% CI) (62.0%, 100.0%), locoregional control and progression-free survival were 75.8% with 95% CI (57.5%, 99.8%), and major pathological response or complete response was 75% with 95% exact CI (51.6%, 100.0%). For patients treated with 24 Gy, 89% with 95% CI (57.1%, 100.0%) had MPR or CR. Using high-dimensional multi-omics and spatial data as well as biological correlatives, we show that responders had: (1) an increase in effector T cells; (2) a decrease in immunosuppressive cells; and (3) an increase in antigen presentation post-treatment.

Outcomes between intensity-modulated radiation therapy versus 3D-conformal in early stage glottic cancer.

BACKGROUND: The purpose of this study is to evaluate practice patterns and outcomes between intensity-modulated radiation therapy (IMRT) and 3D-conformal radiation (3D-CRT) in early stage glottic cancer. METHODS: The linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used to identify and compare patient and disease profiles, mortality, and toxicity in patients with T1-2 larynx cancer undergoing definitive radiation (RT). RESULTS: A total of 1520 patients underwent definitive radiation with 3D-CRT (n = 1309) or IMRT (n = 211). Non-white race, those with a Charlson Comorbidity Index ≥2, T2 disease, and those treated at community practices were more likely to undergo IMRT. Rates of IMRT increased from 2006 to 2015, while relative rates of 3D-CRT decreased. Two-year CSS was superior with 3D-CRT (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.22-0.65; p < 0.001). There was no difference in OS between 3D-CRT and IMRT (p = 0.119). CONCLUSIONS: Patients receiving 3D-CRT had improved CSS compared to IMRT with no difference in OS.

Survival impact of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists in head and neck cancer.

BACKGROUND: Preclinical evidence suggests a link between the renin-angiotensin system and oncogenesis. We aimed to explore the impact of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) in head and neck cancer (HNC). METHODS: Over 5000 patients were identified from the Surveillance, Epidemiology, and End Results-Medicare linked dataset and categorized according to ACEi and ARB and diagnoses of chronic kidney disease (CKD) or hypertension (HTN). Overall survival (OS) and cancer-specific survival (CSS) were compared using Cox multivariable regression (MVA), expressed as hazard ratios (HR) with 95% confidence intervals (95%CI). RESULTS: No significant MVA associations for OS or CSS were found for ACEi. Compared to patients with CKD/HTN taking ARB, those with CKD/HTN not taking ARB experienced worse OS (HR 1.28, 95%CI 1.09-1.51, p = 0.003) and CSS (HR 1.23, 95%CI 1.00-1.50, p = 0.050). CONCLUSIONS: ARB usage is associated with improved OS and CSS among HNC patients with CKD or HTN.

Elderly Black Non-Hispanic Patients With Head and Neck Squamous Cell Cancer Have the Worst Survival Outcomes.

BACKGROUND: In this population study, we compared head and neck cancer (HNC) prognosis and risk factors in 2 underserved minority groups (Hispanic and Black non-Hispanic patients) with those in other racial/ethnicity groups. METHODS: In this SEER-Medicare database study in patients with HNC diagnosed in 2006 through 2015, we evaluated cancer-specific survival (CSS) between different racial/ethnic cohorts as the main outcome. Patient demographics, tumor factors, socioeconomic status, and treatments were analyzed in relation to the primary outcomes between racial/ethnic groups. RESULTS: Black non-Hispanic patients had significantly worse CSS than all other racial/ethnic groups, including Hispanic patients, in unadjusted univariate analysis (Black non-Hispanic patients: hazard ratio, 1.48; 95% CI, 1.33-1.65; Hispanic patients: hazard ratio, 1.12; 95% CI, 0.99-1.28). To investigate the association of several variables with CSS, data were stratified for multivariate analysis using forward Cox regression. This identified socioeconomic status, cancer stage, and receipt of treatment as predictive factors for the survival differences. Black non-Hispanic patients were most likely to present at a later stage (odds ratio, 1.62; 95% CI, 1.38-1.90) and to receive less treatment (odds ratio, 0.67; 95% CI, 0.55-0.81). Unmarried status, high poverty areas, increased emergency department visits, and receipt of healthcare at non-NCI/nonteaching hospitals also significantly impacted stage and treatment. CONCLUSIONS: Black non-Hispanic patients have a worse HNC prognosis than patients in all other racial/ethnic groups, including Hispanic patients. Modifiable risk factors include access to nonemergent care and prevention measures, such as tobacco cessation; presence of social support; communication barriers; and access to tertiary centers for appropriate treatment of their cancers.

Epidemiology of Head and Neck Squamous Cell Carcinomas: Impact on Staging and Prevention Strategies.

OPINION STATEMENT: The epidemiology of head and neck squamous cell carcinoma (HNSCC) has shifted dramatically over the last 50 years, as smoking-related HNSCCs decrease in incidence while human papillomavirus (HPV)-related cancers rise. The shift in HNSCC risk factors has changed patient demographics, the distribution of affected anatomical subsites, and prognosis of this illness. As such, the medical community has responded by devising novel staging systems and prevention strategies. The medical community will require continued vigilance in reducing HNSCC traditional risks factors for HNSCC, such as cigarette use, and emerging risk like HPV infection.

Short- and Long-term Opioid Use in Patients with Oral and Oropharynx Cancer.

OBJECTIVE: Opioid use and abuse is a national health care crisis, yet opioids remain the cornerstone of pain management in cancer. We sought to determine the risk of acute and chronic opioid use with head and neck squamous cell cancer (HNSCC) treatment. STUDY DESIGN: Retrospective population-based study. SETTING: Surveillance, Epidemiology and End Results (SEER)-Medicare database from 2008 to 2011. SUBJECTS AND METHODS: In total, 976 nondistant metastatic oral cavity and oropharynx patients undergoing cancer-directed treatment enrolled in Medicare were included. Opiate use was the primary end point. Univariate and multivariable logistic analyses were completed to determine risk factors. RESULTS: Of the patients, 811 (83.1%) received an opioid prescription during the treatment period, and 150 patients (15.4%) had continued opioid prescriptions at 3 months and 68 (7.0%) at 6 months. Opioid use during treatment was associated with prescriptions prior to treatment (odds ratio [OR], 3.28; 95% confidence interval [CI], 2.11-5.12) and was least likely to be associated with radiation treatment alone (OR, 0.35; 95% CI, 0.18-0.68). Risk factors for continued opioid use at both 3 and 6 months included tobacco use (OR, 2.23; 95% CI, 1.05-4.71 and OR, 3.84; 95% CI, 1.44-10.24) and opioids prescribed prior to treatment (OR, 3.84; 95% CI, 2.45-5.91 and OR, 3.56; 95% CI, 1.95-6.50). Oxycodone prescribed as the first opioid was the least likely to lead to ongoing use at 3 and 6 months (OR, 0.33; 95% CI, 0.17-0.62 and OR, 0.26; 95% CI, 0.10-0.67). CONCLUSION: Patients with oral/oropharyngeal cancer are at a very high risk for receiving opioids as part of symptom management during treatment, and a significant portion continues use at 3 and 6 months after treatment completion.

Comparing outcomes of concurrent chemotherapy regimens in patients 65 years old or older with locally advanced oropharyngeal carcinoma.

BACKGROUND: The comparative efficacy of cisplatin (CDDP), carboplatin, and cetuximab (CTX) delivered concurrently with radiation for locally advanced oropharyngeal squamous cell carcinoma continues to be evaluated. METHODS: The linked Surveillance, Epidemiology, and End Results-Medicare database was used to identify and compare patient and disease profiles, mortality, toxicity, and overall cost for patients with oropharynx cancer undergoing definitive concurrent chemoradiation with CDDP, carboplatin, or CTX between 2006 and 2011. The human papillomavirus status was unknown. The primary outcome was 2-year overall survival (OS). RESULTS: Four hundred nine patients receiving concurrent CDDP (n = 167), carboplatin (n = 69), or CTX (n = 173) were included. Those who were older, those who were nonwhite, and those with a Charlson Comorbidity Index ≥ 2 were less likely to receive CDDP. Two-year OS was inferior with CTX (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.08-2.60; P = .020) and no different with carboplatin (HR, 1.31; 95% CI, 0.73-2.35; P = .362) in a Cox proportional hazards model (reference CDDP). There was no statistically significant difference between carboplatin and CTX (HR, 1.28; 95% CI, 0.77-2.14; P = .891). Rates of antiemetic use and hospital visits for nausea/emesis/diarrhea or dehydration were statistically higher with CDDP. Pneumonia rates were higher with carboplatin. In the multivariate model, the corrected mean per-patient spending was significantly higher for CTX and carboplatin than CDDP ($61,133 and $65,721 vs $48,709). CONCLUSIONS: Patients who received CDDP had improved OS. CDDP was also associated with slightly lower overall costs and higher antiemetic usage and hospital visit rates, although a strong selection bias was observed because those receiving CTX and carboplatin were older and had higher comorbidity scores.

Survival impact and toxicity of metformin in head and neck cancer: An analysis of the SEER-Medicare dataset.

OBJECTIVES: Recent preclinical research has renewed interest in the interplay between glucose dysregulation and cancer. Metformin holds promise as an adjunctive antineoplastic agent in head and neck cancer (HNC). We aimed to explore the impact of metformin in HNC patients from a population-based dataset. PATIENTS & METHODS: Patients diagnosed with HNC from 2008 to 2011 were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked dataset and categorized into three groups: non-diabetics (nD), diabetics not taking metformin (DnM), and diabetics taking metformin (D + M). Overall survival (OS) and cancer-specific survival (CSS) were compared between groups using Kaplan-Meier and Cox regression controlling for sociodemographic, clinical, and treatment covariates. The incidence of toxicities associated with HNC therapy was compared among groups using χ2 analysis. RESULTS: Among 1646 patients, there were 1144 nD, 378 DnM, and 124 D + M. 2-year OS rates was 65.6% for nD, 57.7% for DnM, and 73.4% for D + M by Kaplan-Meier (p < 0.01), and corresponding rates of 2-year CSS were 73.7%, 66.1%, and 88.8% (p < 0.01), respectively. On Cox multivariable analysis, OS among the three groups did not significantly differ; however, CSS was significantly worse among both nD versus DnM as compared to D + M. Toxicity rates were not significantly increased among D + M. CONCLUSION: HNC patients with diabetes taking metformin experience improved CSS. Prospective investigation of the addition of metformin to standard-of-care HNC therapy is warranted.

Survival impact of pre-treatment neutrophils on oropharyngeal and laryngeal cancer patients undergoing definitive radiotherapy.

BACKGROUND: Squamous cell carcinoma of the head and neck (HNSCC) represents an array of disease processes with a generally unfavorable prognosis. Inflammation plays an important role in tumor development and response to therapy. We performed a retrospective analysis of HNSCC patients to explore the relationship of the lymphocyte and neutrophil counts, the neutrophil-to-lymphocyte ratio (NLR) overall survival (OS), cancer-specific survival (CSS), local control (LC) and distant control (DC). MATERIALS/METHODS: All patients received definitive treatment for cancers of the oropharynx or larynx between 2006-2015. Neutrophil and lymphocyte counts were collected pre-, during-, and post-treatment. The correlations of patient, tumor, and biological factors to OS, CSS, LC and DC were assessed. RESULTS: 196 patients met our inclusion criteria; 171 patients were Stage III or IV. Median follow-up was 2.7 years. A higher neutrophil count at all treatment time points was predictive of poor OS with the pre-treatment neutrophil count and overall neutrophil nadir additionally predictive of DC. Higher pre-treatment and overall NLR correlated to worse OS and DC, respectively. CONCLUSION: A higher pre-treatment neutrophil count correlates to poor OS, CSS and DC. Lymphocyte counts were not found to impact survival or tumor control. Higher pre-treatment NLR is prognostic of poor OS.

A comparison of concurrent cisplatin versus cetuximab with radiotherapy in locally-advanced head and neck cancer: A bi-institutional analysis.

AIM: To present our experience comparing cisplatin- and cetuximab-based radiotherapy for locally-advanced head and neck squamous cell carcinoma. BACKGROUND: The comparative effectiveness of cisplatin-based chemoradiotherapy (CRT) versus cetuximab-based bioradiotherapy (BRT) for locally-advanced head and neck squamous cell carcinoma (LAHNSCC) continues to be explored. MATERIALS AND METHODS: Outcomes of LAHNSCC patients treated with CRT (125) or BRT (34) at two institutions were compared retrospectively, with attention to overall survival (OS), cancer-specific survival (CSS), locoregional control (LRC), and distant control (DC). Univariate analysis (UVA) using Cox regression was performed to explore the association of intervention with survival and disease control, and multivariate (MVA) Cox regression was then performed to assess the association of intervention with survival. RESULTS: There were significant baseline differences between the CRT and BRT groups with respect to age, race, performance status, N-classification, tobacco history, and human papillomavirus status. UVA demonstrated inferiority of BRT versus CRT with respect to both OS (hazard ratio [HR] 2.19, 95% confidence interval [95%CI] 1.03-4.63, p = 0.04) and CSS (HR 3.33, 95%CI 1.42-7.78, p < 0.01), but non-significantly different outcomes in LRC (HR 0.99, 95%CI 0.37-2.61, p = 0.98) and DC (HR 2.01, 95%CI 0.78-5.37, p = 0.14). On MVA, there was no significant OS difference between interventions (HR 1.19, 95%CI 0.42-3.35, p = 0.74); there were too few events for the other outcomes to draw meaningful conclusions with MVA. CONCLUSIONS: In our retrospective analysis, patients undergoing CRT experienced improved OS and CSS over those receiving BRT; however, disease control did not significantly differ. These findings may inform management of LAHNSCC patients.

A comprehensive comparative analysis of treatment modalities for sinonasal malignancies.

BACKGROUND: Sinonasal malignancies are a rare and heterogeneous group of tumors for which there is a paucity of robust data with which to guide management decisions. The authors used the National Cancer Data Base to better understand the presenting characteristics of these tumors and to compare outcomes by treatment modality. METHODS: The National Cancer Data Base was queried for sinonasal malignancies diagnosed between 2004 and 2012. Overall survival was assessed using multivariate analyses and propensity score matching. RESULTS: A total of 11,160 patients were identified for the initial analysis. The majority were male, aged 40 to 69 years, with tumors of the nasal cavity or maxillary sinus. Squamous cell histology was most common. The majority of patients presented with advanced tumor stage but without locoregional lymph node or distant metastases. Treatment modalities were compared for squamous cell carcinomas. In multivariate analysis, compared with surgery alone, patients who received adjuvant radiotherapy (hazard ratio [HR], 0.658 [P<.001]), adjuvant chemoradiotherapy (HR, 0.696 [P = .002]), or neoadjuvant therapy (HR, 0.656 [P = .007]) had improved overall survival. Patients who received radiotherapy alone (HR, 1.294 [P = .001]) or chemotherapy alone (HR, 1.834 [P<.001]) had worse outcomes. These findings were validated in propensity score matching. It is important to note that neoadjuvant chemoradiotherapy was associated with achieving a negative surgical margin (odds ratio, 2.641 [P = .045]). CONCLUSIONS: Surgery is the mainstay of therapy for patients with sinonasal malignancies, but multimodality therapy is associated with improved overall survival. Cancer 2017;123:3040-49. © 2017 American Cancer Society.

Metastatic nasopharyngeal carcinoma: Patterns of care and survival for patients receiving chemotherapy with and without local radiotherapy.

BACKGROUND AND PURPOSE: Radiotherapy (RT) to the primary nasopharyngeal tumor is frequently offered to patients with metastatic nasopharyngeal carcinoma (mNPC). However, only limited data exist to support RT in this setting. We used the National Cancer Database (NCDB) to evaluate outcomes for mNPC patients receiving chemotherapy with and without local RT. METHODS: The NCDB was queried for patients with mNPC with synchronous metastatic disease at diagnosis who received chemotherapy. Overall survival (OS) was analyzed using the Kaplan-Meier method, Cox proportional hazards models, and propensity score-matched analyses. RESULTS: From 2004 to 2013, 718 cases were identified (39% chemotherapy-alone, 61% chemotherapy+RT). At a median follow-up of 4.4years, RT was associated with improved survival on univariate analysis (median OS 21.4 vs 15.5months; 5-year OS 28% vs 10%; p<0.001) and multivariate analyses (HR, 0.61; CI, 0.51-0.74; p<0.001). Propensity score analysis with matched baseline characteristics demonstrated a similar OS advantage with RT (HR, 0.68; CI, 0.55-0.84; p<0.001). The benefits of RT remained consistent in models controlling for single vs multi-organ metastases and anatomic sites of metastatic involvement. RT dose was an independent prognostic factor as both a continuous and categorical variable, with OS benefits observed among patients receiving ≥50Gy. Long-term survival of >10years was only observed in the RT cohort. CONCLUSIONS: This analysis supports strategies incorporating local RT with chemotherapy for mNPC. Prospective trials evaluating RT integration for mNPC are warranted.

Survival impact of induction chemotherapy in advanced head and neck cancer: A National Cancer Database analysis.

BACKGROUND: Adding induction chemotherapy to concurrent chemotherapy and radiotherapy (RT) has generally not improved the overall survival (OS) in randomized trials of patients with head and neck cancer. This failure may stem from inadequate power or inappropriate patient selection, prompting this National Cancer Data Base analysis. METHODS: 8031 patients with T4 or N2b to N3 disease undergoing RT and chemotherapy were divided into induction chemotherapy and concurrent chemotherapy cohorts. Multivariate analysis was used to explore the association of treatment with survival and to identify predictors of radiation dose. RESULTS: On multivariate analysis incorporating sociodemographic and clinical variables, survival of the induction chemotherapy cohort was not significantly different from that of the concurrent cohort (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.88-1.05; p = .35), nor on subgroup analyses of advanced disease. Multivariate analysis demonstrated increased odds of receiving <66 Gy among the patients in the induction chemotherapy cohort (p < .01). CONCLUSION: Induction chemotherapy subjects experienced no survival advantage over concurrent chemotherapy subjects but were more likely to receive lower RT doses. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1113-1121, 2017.

A comparison of overall survival for patients with T4 larynx cancer treated with surgical versus organ-preservation approaches: A National Cancer Data Base analysis.

BACKGROUND: Although laryngectomy is the treatment of choice for patients with T4 larynx cancer, many patients are unable or unwilling to undergo laryngectomy and instead pursue larynx-preservation strategies combining radiotherapy (RT) and chemotherapy. Herein, the authors analyzed the National Cancer Data Base to evaluate overall survival (OS) between patients treated with surgical and organ-preserving modalities. METHODS: The National Cancer Data Base was queried for patients diagnosed from 2004 through 2012 with T4M0 laryngeal cancer who underwent either laryngectomy (surgery) with adjuvant RT (SRT), chemotherapy starting concurrently within 7 days of RT (CCRT), or multiagent induction chemotherapy starting 43 to 98 days before RT (ICRT). Multivariate analysis and propensity score matching were used to explore the association between the intervention and OS. Recursive partitioning analysis was performed to identify groups benefiting from particular modalities. RESULTS: A total of 1559 patients who underwent SRT, 1597 patients who underwent CCRT, and 386 patients who underwent ICRT were included. Adjusting for covariates, CCRT was found to be associated with inferior OS compared with SRT (hazard ratio [HR], 1.55; 95% confidence interval [95% CI], 1.41-1.70 [P<.01]) and with ICRT (HR, 1.25; 95% CI, 1.07-1.45 [P<.01]). OS among the patients treated with SRT did not appear to differ significantly from that of the ICRT cohort (HR, 0.87; 95% CI, 0.73-1.03 [P = 0.10]), a finding confirmed with propensity score matching. Recursive partitioning analysis identified no subset of patients that derived an OS benefit from either approach over the other. CONCLUSIONS: OS among patients undergoing SRT was found to be superior to that of patients treated with CCRT but did not significantly differ from that of those undergoing ICRT. Because these intriguing findings require validation, SRT should remain the standard of care for patients with this disease. However, organ preservation with ICRT may be a reasonable alternative in certain patients. Cancer 2017;123:600-608. © 2016 American Cancer Society.

Association of Adjuvant Chemoradiotherapy vs Radiotherapy Alone With Survival in Patients With Resected Major Salivary Gland Carcinoma: Data From the National Cancer Data Base.

Importance: Data on adjuvant concurrent chemoradiotherapy (CRT) after resection of salivary gland carcinomas (SGCs) are limited. Objective: To examine overall survival (OS) outcomes of patients who receive CRT vs radiotherapy (RT) alone after resection of SGCs. Design, Setting, and Participants: The National Cancer Data Base (NCDB), a hospital-based registry that represents 70% of all cancer cases in the United States, was queried for patients who underwent resection of major SGCs with at least 1 high-risk feature (T3-T4 stage, N1-N3 stage, or positive margins). Included patients had histologic findings for malignant SGC with grades 2 to 3 disease and at least 1 high-risk feature. All patients underwent resection with postoperative CRT or RT alone. Patients were treated from 1998 to 2011. Data were analyzed from January to March 2016. Exposures: Patients received CRT, defined as chemotherapy start within 14 days of RT initiation, or RT alone. Main Outcomes and Measures: Univariate, multivariate, and propensity score-matched analyses were performed to compare OS for patients undergoing CRT vs RT alone. Results: Analyses included 2210 eligible patients (1372 men [62.1%] and 838 women [37.9%]; median age [range], 63 [18-90] years); of these, 1842 (83.3%) received RT alone and 368 (16.7%) received CRT. Median follow-up was 39 (range, 2-188) months. Most of the resected major SGCs occurred at the parotid gland (1852 [83.8%]), followed by the submandibular gland (276 [12.5%]), major gland not otherwise specified (66 [3.0%]), and sublingual gland (16 [0.7%]). Unadjusted 2-year OS was worse with adjuvant CRT vs RT alone (71.3% vs 80.2%), as was 5-year OS (38.5% vs 54.2%) (hazard ratio [HR], 1.51; 95% CI, 1.29-1.76; P < .001). Overall survival was inferior with adjuvant CRT on multivariate analysis (HR, 1.22; 95% CI, 1.03-1.44; P = .02) and propensity score-matched analysis (HR, 1.20; 95% CI, 0.98-1.47; P = .08) compared with RT alone. Subgroup analyses by age, comorbidity score, primary site, histologic type, grade, T stage, N stage, margin status, and chemotherapy (single agent vs multiagent) demonstrated equivalent or shorter OS with the addition of chemotherapy to RT. Conclusions and Relevance: This large analysis compared survival outcomes between postoperative CRT and RT alone in patients undergoing resection of high-risk major SGCs using a nationally representative database. The addition of concurrent chemotherapy to RT in patients with high-risk major SGCs did not offer an advantage in OS.

Profiling of 149 Salivary Duct Carcinomas, Carcinoma Ex Pleomorphic Adenomas, and Adenocarcinomas, Not Otherwise Specified Reveals Actionable Genomic Alterations.

PURPOSE: We sought to identify genomic alterations (GA) in salivary gland adenocarcinomas, not otherwise specified (NOS), salivary duct carcinomas (SDC), carcinoma ex pleomorphic adenoma (ca ex PA), and salivary carcinoma, NOS. EXPERIMENTAL DESIGN: DNA was extracted from 149 tumors. Comprehensive genomic profiling (CGP) was performed on hybridization-captured adaptor ligation-based libraries of 182 or 315 cancer-related genes plus introns from 14 or 28 genes frequently rearranged for cancer and evaluated for all classes of GAs. RESULTS: A total of 590 GAs were found in 157 unique genes (mean 3.9/tumor). GAs in the PI3K/AKT/mTOR pathway were more common in SDC (53.6%) than other histologies (P = 0.019) Cyclin-dependent kinase GAs varied among all histotypes: adenocarcinoma, NOS (34.6%); SDC (12.2%); ca ex PA (16.7%); carcinoma, NOS (31.2%; P = 0.043). RAS GAs were observed: adenocarcinoma, NOS (17.3%); SDC (26.8%); ca ex PA (4.2%); and carcinoma, NOS (9.4%; P = 0.054). ERBB2 GAs, including amplifications and mutations, were common: adenocarcinoma, NOS (13.5%); SDC (26.8%); ca ex PA (29.2%); carcinoma, NOS (18.8; P = 0.249). Other notable GAs include TP53 in >45% of each histotype; NOTCH1: adenocarcinoma, NOS (7.7%), ca ex PA (8.3%), carcinoma, NOS (21.6%); NF1: adenocarcinoma, NOS (9.6%), SDC (17.1%), carcinoma, NOS (18.8%). RET fusions were identified in one adenocarcinoma, NOS (CCDC6-RET) and two SDCs (NCOA4-RET). Clinical responses were observed in patients treated with anti-HER2 and anti-RET-targeted therapies. CONCLUSIONS: CGP of salivary adenocarcinoma, NOS, SDCs, ca ex PA, and carcinoma, NOS revealed diverse GAs that may lead to novel treatment options. Clin Cancer Res; 22(24); 6061-8. ©2016 AACR.

Predictors of overall survival in human papillomavirus-associated oropharyngeal cancer using the National Cancer Data Base.

OBJECTIVES: This study identifies clinical characteristics associated with HPV-positive oropharynx squamous cell carcinoma (OPSCC) and evaluates predictors of overall survival (OS) in HPV-positive patients undergoing definitive treatment within the National Cancer Data Base (NCDB). MATERIAL AND METHODS: The NCDB was queried for patients ⩾18years old with OPSCC and known HPV status who underwent definitive treatment: surgery, radiation (RT), chemotherapy-RT (CRT), surgery+RT, surgery+CRT (S-CRT). Cox proportional hazards model was used for multivariate analysis (MVA) to evaluate predictors of OS by HPV status. RESULTS: 3952 patients were included: 2454 (62%) were HPV-positive. Median follow up was 23.7months (range, 1.0-54.5). Unadjusted 2-year OS rates for HPV-positive vs. negative were 93.1% vs. 77.8% (p<0.001) with an adjusted hazard ratio of 0.44 (95% CI, 0.36-0.53; p<0.001). MVA identified multimodality treatment including CRT (HR, 0.42; p=0.024) and S-RT (HR, 0.30; p=0.024), but not S-CRT (HR, 0.51; p=0.086), as predictors for improved OS in HPV-positive stage III-IVB disease. Multimodality treatment including S-CRT was associated with longer OS in HPV-negative OPSCC. Nodal stage was poorly associated with OS in HPV-positive cancers. The presence of positive margins and/or extracapsular extension was associated with worse OS in HPV-negative (HR, 2.11; p=0.008) but not HPV positive OPSCC (HR, 1.61; p=0.154). CONCLUSION: The established demographic and clinical features of HPV-positive OPSCC were corroborated in the NCDB. Population analysis suggests that AJCC staging is poorly associated with OS in HPV-positive cancer, and traditional high-risk features may be less impactful. Bimodality therapy appears beneficial in HPV-positive HNSCC.