Faculty Bibliography

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Non-squamous cell carcinoma (SCC) malignancies are rare, but well described laryngeal pathologies. However, the epidemiology and clinical behavior of these tumors is not well studied. STUDY DESIGN/METHODS:Retrospective cohort study. METHODS:Patients diagnosed with non-squamous cell larynx cancer from 2004 to 2017 in the National Cancer Database were selected. Demographic, clinicopathologic factors, treatments, and survival were analyzed. Univariable and multivariable cox regression were performed. Survival was compared with a propensity score-matched (PSM) population of laryngeal SCC patients. RESULTS:A total of 136,235 cases of larynx cancer were identified. After excluding SCC variants, 2,172 (1.6%) patients met inclusion criteria. The most common histology was chondrosarcoma (374, 17.2%), followed by small cell (345, 15.9%), and spindle cell carcinoma (268, 12.3%). The most common treatment was surgery (683, 31.4%) followed by chemoradiation (409, 18.8%) and surgery and adjuvant radiation (288, 13.3%). Overall, 3- and 5-year survival was 67.9% and 59.4%, respectively. In multivariate analysis controlling for age, stage, comorbidity, histology, and treatment modality; chondrosarcoma had the best survival (hazard ratio [HR] 0.11, confidence interval [CI] 0.07-0.19, P < .001). In a PSM population, matched for age, stage, comorbidity, and treatments; non-SCC patients had significantly lower survival (51.5% vs. 59.9%, P < .001). CONCLUSION/CONCLUSIONS:A diverse range of non-squamous cell malignancies occur in the larynx. In general, these tumors have poor survival, with few exceptions such as chondrosarcoma. While the majority of these histologies undergo surgical-based treatments in other sites, only 53% of patients underwent surgical-based treatment in the larynx. These data could guide clinicians in determining the outcome of treatment in these patients. LEVEL OF EVIDENCE/METHODS:4 Laryngoscope, 2022.

BACKGROUND:Medullary thyroid carcinoma (MTC) is a rare malignancy with high incidence of cervical lymph node (CLN) metastasis. We investigated the impact of nodal disease burden on survival. METHODS:We searched the National Cancer Database for MTC patients treated surgically. Impact of nodal metastasis on survival was analyzed using Cox univariable and multivariable regression. RESULTS:We identified 2627 patients from 2004 to 2015. Positive CLNs were identified in 1433 (54.5%), and 542 (20.6%) had >10 CLN+. Overall survival was 94.5% and 89.6% at 3 and 5 years. Patients with 11 to 20 CLN+ had significantly worse survival than patients with 1 to 10 CLN+ in univariable and multivariable analyses (HR = 3.56 (2.31-5.50) vs 2.26 (1.60-3.20); P < .0001). The ratio of positive to dissected CLN was associated with overall survival. CONCLUSIONS:Higher burden of nodal disease is associated with worse survival in MTC. The number of positive nodes could be a valuable prognosticator in addition to the current staging system.

As cochlear implant (CI) candidacy has expanded, commercial payers in the United States have varied in their adoption of new indications, potentially confusing providers' knowledge about appropriate patients for referral. We reviewed how third-party payers classify the medical necessity of cochlear implants for a variety of indications across the lifespan. We compared policies of the six largest commercial payers in our region, focusing on clinical scenarios for which many centers experience difficulty obtaining pre-authorization. These include: (1) CI in children under 12 months, (2) audiometric and speech perception criteria in children, (3) sequential bilateral CI, (4) electro-acoustic stimulation, (5) impending cochlear ossification, and (6) single-sided deafness (SSD). Of the more notable findings for the clinical scenarios half of commercial payers have a pediatric age requirement of greater than 12 months. Generally, audiologic and speech perception criteria are more stringent for children than adults across all policies. SSD is considered investigational by most policies. Third-party payers employ variable criteria regarding the medical necessity of CI, many of which are not contemporaneous with clinical knowledge and best practices. This may impact referral patterns among audiologists. More methodologically rigorous clinical trials may help shift such restrictive policies to benefit a greater number of patients.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Advances in cancer treatment have increased survival for many patients, prompting a need for greater recognition of the long-term complications of treatment. Chemotherapy agents have the potential to induce carcinogenesis and can increase the risk of secondary malignancy. Pegylated liposomal doxorubicin (PLD) used for maintenance treatment of recurrent high-grade serous cancers has been associated with the development of oral cavity squamous cell carcinoma (SCC). STUDY DESIGN/METHODS:Retrospective review. METHODS:Cases of oral cavity SCC in patients with recurrent high-grade serous cancer treated with PLD between 1997 and 2017 at a single institution were reviewed. RESULTS:). Seven patients tested positive for BRCA mutations (four BRCA 1+, three BRCA 2+). No patients had a history of alcohol or tobacco use. All had early-stage oral cavity disease; five were T1N0, two were T2N0, and one had carcinoma in situ. All patients underwent surgery, and two received adjuvant radiation. Four developed locoregional recurrence requiring additional treatment. Of these, one patient died from complications of oral SCC, one developed recurrent ovarian cancer, and two had no evidence of disease of the oral cavity or ovarian cancer at the last follow-up. CONCLUSIONS:Long-term PLD therapy may be associated with the development of oral cavity SCC. A high index of suspicion and routine head and neck examination should be included in follow-up for exposed patients. LEVEL OF EVIDENCE/METHODS:4 Laryngoscope, 2019.

OBJECTIVE:To investigate differences in epidemiology of oropharyngeal squamous cell carcinoma (OPSCC) with regards to human papillomavirus (HPV), race, and socioeconomic status (SES) using the National Cancer Database (NCDB). STUDY DESIGN/METHODS:Population-based cohort study. SETTING/METHODS:Racial and socioeconomic disparities in survival of OPSCC have been previously acknowledged. However, the distribution of HPV-related cancers and its influence on survival in conjunction with race and SES remain unclear. SUBJECTS AND METHODS/METHODS:All patients with OPSCC in the NCDB with known HPV status from 2010 to 2016 were included. Differences in presentation, HPV status, treatment, and outcomes were compared along racial and socioeconomic lines. Univariable and multivariable Cox regression survival analyses were performed. RESULTS:< .001) were associated with worse survival. CONCLUSION/CONCLUSIONS:Significant differences in HPV status exist between socioeconomic and racial groups, with HPV-negative disease more common among blacks and lower SES. When controlling for HPV status, race and SES still influence outcomes in oropharyngeal cancers.

BACKGROUND:Postoperative complications (POCs) can negatively impact survival after oncologic resection. POCs may also decrease the rate of adjuvant therapy completion. We evaluated the impact of complications on gastric cancer survival and analyzed the combined effect of complications and adjuvant therapy on survival. METHODS:We analyzed 824 patients from 7 institutions of the U.S. Gastric Cancer Collaborative who underwent curative resection for gastric adenocarcinoma between 2000 and 2012. POC were graded using the modified Clavien-Dindo system. Survival probabilities were estimated using the method of Kaplan and Meier and analyzed using multivariate Cox regression. RESULTS:Median follow-up was 35 months. The overall complication rate was 41 %. The 5-year overall survival (OS) and recurrence-free survival (RFS) of patients who experienced complications were 27 and 23 %, respectively, compared with 43 and 40 % in patients who did not have complications (p < 0.0001 for OS and RFS). On multivariate analysis, POC remained an independent predictor for decreased OS and RFS (HR 1.3, 95 % CI 1.1-1.6, p = 0.03 for OS; HR 1.3, 95 % CI 1.01-1.6, p = 0.03 for RFS). Patients who experienced POC were less likely to receive adjuvant therapy (OR 0.5, 95 % CI 0.3-0.7, p < 0.001). The interaction of complications and failure to receive adjuvant therapy significantly increased the hazard of death compared with patients who had neither complications nor adjuvant therapy (HR 2.3, 95 % CI 1.6-3.2, p < 0.001). CONCLUSIONS:Postoperative complications adversely affect long-term outcomes after gastrectomy for gastric cancer. Not receiving adjuvant therapy in the face of POC portends an especially poor prognosis following gastrectomy for gastric cancer.

BACKGROUND: The association of postoperative complications with long-term oncologic outcomes remains unclear. We sought to determine the incidence of complications among patients who underwent surgery for adrenocortical carcinoma (ACC) and define the relationship of morbidity with long-term survival. METHODS: Patients who underwent surgery for ACC between 1993 and 2014 were identified from 13 academic institutions participating in the US ACC group study. The incidence and type of the postoperative complications, the factors associated with them as well their association with long-term survival were analyzed. RESULTS: A total of 265 patients with median age of 52 years (IQR 44-63) were identified; at surgery, the majority of patients underwent an open abdominal procedure (n = 169, 66.8 %). A postoperative complication occurred in 99 patients for a morbidity of 37.4 %; five patients (1.9 %) died in hospital. Factors associated with morbidity included a thoraco-abdominal operative approach (reference: open abdominal; OR 2.85, 95 % CI 1.00-8.18), and a hormonally functional tumor (OR 3.56, 95 % CI 1.65-7.69) (all P < 0.05). Presence of any complication was associated with a worse long-term outcome (median survival: no complication, 58.9 months vs. any complication, 25.1 months; P = 0.009). In multivariate analysis, after adjusting for patient- and disease-related factors postoperative infectious complications independently predicted shorter overall survival (hazard ratio (HR) 5.56, 95 % CI 2.24-13.80; P < 0.001). CONCLUSION: Postoperative complications were independently associated with decreased long-term survival after resection for ACC. The prevention of complications may be important from an oncologic perspective.

OBJECTIVES/OBJECTIVE:To determine pathologic features associated with recurrence and survival in patients with lymph node-negative gastric adenocarcinoma. STUDY DESIGN/METHODS:Multi-institutional retrospective analysis. BACKGROUND:Lymph node status is among the most important predictors of recurrence after gastrectomy for gastric adenocarcinoma. Pathologic features predictive of recurrence in patients with node-negative disease are less well established. METHODS:Patients who underwent curative resection for gastric adenocarcinoma between 2000 and 2012 from 7 institutions of the US Gastric Cancer Collaborative were analyzed, excluding 30-day mortalities and stage IV disease. Competing risks regression and multivariate Cox regression were used to determine pathologic features associated with time to recurrence and overall survival. Differences in cumulative incidence of recurrence were assessed using the Gray method (for univariate nonparametric analyses) and the Fine and Gray method (for multivariate analyses) and shown as subhazard ratios (SHRs) and adjusted subhazard ratios (aSHRs), respectively. RESULTS:Of 805 patients who met inclusion criteria, 317 (39%) had node-negative disease, of which 54 (17%) recurred. By 2 and 5 years, 66% and 88% of patients, respectively, experienced recurrence. On multivariate competing risks regression, only T-stage 3 or higher was associated with shorter time to recurrence [aSHR = 2.7; 95% confidence interval (CI), 1.5-5.2]. Multivariate Cox regression showed T-stage 3 or higher [hazard ratio (HR) = 1.8; 95% CI, 1.2-2.8], lymphovascular invasion (HR = 2.2; 95% CI, 1.4-3.4), and signet ring histology (HR = 2.1; 95% CI, 1.2-3.6) to be associated with decreased overall survival. CONCLUSIONS:Despite absence of lymph node involvement, patients with T-stage 3 or higher have a significantly shorter time to recurrence. These patients may benefit from more aggressive adjuvant therapy and postoperative surveillance regimens.