Faculty Bibliography

OBJECTIVES/HYPOTHESIS/OBJECTIVE:To assess patterns of care and outcomes with the use of neoadjuvant chemotherapy followed by definitive radiation in local-regionally advanced nasopharyngeal carcinoma. STUDY DESIGN/METHODS:Retrospective database analysis. METHODS:We queried the National Cancer Database for patients with T3-4N2 or T1-4N3 nasopharyngeal carcinoma who received concurrent chemoradiotherapy or neoadjuvant chemotherapy followed by radiation. Overall survival (OS) was analyzed using the Kaplan-Meier method, propensity-score matching, and a Cox proportional hazards model adjusting for demographic and disease-specific prognostic factors. RESULTS:P = .001). At a median follow-up of 36.6 months, patients had 3-year OS of 66% in the neoadjuvant group compared with 70% in those who received concurrent chemoradiotherapy (log rank P = .29). On subgroup analysis by histology, T stage, and N stage, there remained no differences in OS between the two groups. On multivariable analysis, there was no significant survival difference associated with neoadjuvant chemotherapy (adjusted hazard ratio [HR]: 1.05, 95% confidence interval [CI]: 0.89-1.25, P = .54). In a propensity score-matched population of 1,008 patients (504 with neoadjuvant therapy and 504 without), there was no significant survival difference associated with neoadjuvant chemotherapy (H: 1.13, 95% CI: 0.93-1.38, P = .22). CONCLUSIONS:Neoadjuvant chemotherapy was used in over 25% of patients, and its use is increasing. However, neoadjuvant chemotherapy was not associated with any differences in survival compared to concurrent chemoradiotherapy. LEVEL OF EVIDENCE/METHODS:4 Laryngoscope, 2018.

Purpose or Objective Definitive chemoradiotherapy is the upfront treatment of choice in anal squamous cell carcinoma while surgery is reserved to refractory cases. Anterior peroneal resection (APR) of anal cancers often necessitates life-long a lifelong ostomy, leading to lower quality of life for the patient. High risk human papillomavirus HPV subtypes have been shown to have improved outcomes in head and neck cancer. We analyze data from a large hospital based database to evaluate the impact of high risk HPV status on APR in patients with anal cancer. Material and Methods The National Cancer Database (NC

BACKGROUND:Recent data support the use of post-mastectomy radiation therapy (PMRT) in women with one to three positive lymph nodes; however, the benefit of PMRT in patients with micrometastatic nodal disease (N1mi) is unknown. We evaluated the survival impact of PMRT in patients with N1mi within the National Cancer Database. METHODS:The pattern of care and survival benefit of PMRT was examined in women with pT1-2N1mi breast cancer who underwent mastectomy without neoadjuvant chemotherapy. Univariable and multivariable Cox proportional hazard models were employed for survival analysis, and subanalyses of high-risk patients and a propensity score-matched (PSM) cohort were completed. RESULTS:From 2004 to 2014, we identified 14,019 patients who fitted the study criteria. PMRT was delivered in 18.5% of patients and its use increased over the study period. Patients treated with PMRT were younger, had better performance status and larger primaries, were estrogen receptor (ER)-negative, had higher grade, lymphovascular invasion and positive surgical margins, and more often received systemic therapy. PMRT was significantly associated with overall survival (OS) in univariable analysis (hazard ratio [HR] 0.75 [0.64-0.89]), but was not significant in multivariable analysis (adjusted HR 1.01 [0.84-1.20]). There was no survival benefit to PMRT in ER-negative, high-grade, and/or young patients. There were 2 (0.9%) death events in the sentinel lymph node biopsy (SLNB) + PMRT group versus 21 (2.9%) in the SLNB-alone group (log-rank p = 0.053), and 8 (3.9%) death events in the axillary lymph node biopsy (ALNB) + PMRT group versus 27 (3.6%) in the axillary lymph node dissection-alone group (p = 0.82). There was no significant association between PMRT and OS within the PSM subgroup. CONCLUSION/CONCLUSIONS:In this largest reported retrospective study, no OS differences were associated with PMRT, which suggests that PMRT may not benefit every patient with microscopic nodal disease.

PURPOSE/OBJECTIVE:Hypofractionated whole-breast radiation therapy (RT) has proved to be equivalent to conventionally fractionated RT in multiple randomized trials. There is controversy regarding its use in younger women because of their underrepresentation in trials and the concern for late toxicity. We evaluated disease control and cosmetic outcomes in patients aged <50 years treated with hypofractionated RT in 4 prospective single-institutional trials. METHODS AND MATERIALS/METHODS:From 2003 to 2015, 1313 patients were enrolled in 4 prospective protocols investigating the use of adjuvant hypofractionated RT after breast-conserving surgery with a daily or weekly concomitant boost. We identified the records of 348 patients aged <50 years at consultation for this analysis. Overall survival, disease-free survival, and local recurrence-free survival were estimated using the Kaplan-Meier method by study and across studies using meta-analytic methods. The late effects of RT, clinician-rated cosmesis, and patient-rated cosmesis were also evaluated. RESULTS:With a median follow-up period of 66.9 months, the overall survival rate was 99.6%, the disease-free survival rate was 96.3%, and the local recurrence-free survival rate was 97.7% at 3 years. Clinician-rated cosmesis (n = 242) was excellent or good in 93.4% of cases and fair or poor in 6.6%. Patient-rated cosmesis (n = 259) was excellent or good in 86.1% and fair or poor in 13.9%. When patients rated themselves differently than their physicians, patients more often rated themselves poorly compared with their physicians (P = .0044, Cochran-Mantel-Haenszel test). CONCLUSIONS:At a median follow-up of 5 years, an analysis of patients aged <50 years demonstrated that hypofractionated RT was safe and effective, with good to excellent cosmesis as assessed by both clinicians and patients.

Objective To analyze the patterns of care and survival for pT1-2N1M0 head and neck cancer based on receipt of surgery alone, surgery + postoperative radiotherapy (S + RT), or surgery + postoperative chemoradiotherapy (S + CRT). Study Design Retrospective analysis. Setting National Cancer Database. Subjects and Methods We queried the database for patients with stage pT1-2N1M0 squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx between 2004 and 2012 who were treated with surgery with negative margins and no extracapsular extension. Logistic regression was used to assess predictors of receipt of postoperative treatment. Overall survival was assessed by the Kaplan-Meier method, and Cox regression analysis identified covariates that affected it. Results There were 1598 patients included in this study: 566 (35.4%) received surgery alone; 726 (45.4%), S + RT; and 306 (19.1%), S + CRT. The 5-year overall survival was 68.8%, 74.0%, and 87.8%, respectively ( P = .009 comparing S + RT and surgery alone, P < .001 for all other comparisons). On multivariable logistic regression, academic centers were associated with a decreased likelihood of S + RT (odds ratio = 0.71) and S + CRT (odds ratio = 0.66). Multivariable Cox regression demonstrated no difference in survival for S + RT over surgery alone (hazard ratio = 0.88, 95% CI = 0.70-1.09, P = .24); however, there was a survival benefit associated with S + CRT (hazard ratio = 0.57, 95% CI = 0.39-0.81, P = .002). Conclusion Nearly 65% of patients with pT1-2N1 head and neck cancer with negative margins and no extracapsular extension received S + RT or S + CRT. Improvement in survival was noted only for patients who received S + CRT.

BACKGROUND:Delays in postoperative head and neck (HN) radiotherapy have been associated with decreased overall survival; however, the impact of delays in postoperative HN chemoradiotherapy remains undefined. METHODS:All patients with nonmetastatic HN cancer (oral cavity, oropharynx, larynx, hypopharynx) who underwent curative intent surgery and received adjuvant chemoradiotherapy were identified from the National Cancer Database (2005-2012). Overall treatment time (OTT) was defined as the time from surgery to the end of radiation therapy. Statistical methods included Cox proportional hazards modeling, which adjusted for clinicopathologic, demographic, and socioeconomic factors. Recursive partitioning analysis (RPA) identified the optimal threshold of OTT via conditional inference trees to estimate the greatest differences in overall survival (OS) on the basis of randomly selected training and validation sets. RESULTS:A total of 16,733 patients were included, with a median follow-up of 37 months. Median OS for OTT in a predefined threshold of ≤ 13 weeks was 10.1 years (95% confidence interval [CI], 9.8 years; not reached) compared with 8.7 years (95% CI, 8.2-9.2 years) in > 13 weeks. On multivariate analysis, OTT of > 13 weeks versus ≤ 13 weeks independently increased mortality risk (hazard ratio, 1.10; 95% CI, 1.04-1.17; P = < 0.001). RPA identified an optimal OTT threshold of 97 days (interquartile range: 96-98 days). The OTT threshold of 97 days was confirmed in a full Cox regression model estimating the risk of death according to overall treatment time as a continuous variable. CONCLUSION/CONCLUSIONS:In this large hospital-based national data, an OTT of greater than approximately 14 weeks most consistently increased the risk of death. LEVEL OF EVIDENCE/METHODS:4. Laryngoscope, 2018.

Stereotactic radiosurgery (SRS) can be used as part of multimodality management for patients with primary central nervous system lymphoma (PCNSL). The objective of this study is to evaluate outcomes of SRS for this disease. The International Gamma Knife Research Foundation identified 23 PCNSL patients who underwent SRS for either relapsed (intracerebral in-field or out-of-field tumor recurrences) or refractory disease from 1995-2014. All 23 patients presented with RPA Class I or II PCNSL, and were initially treated with a median of 7 cycles of methotrexate-based chemotherapy regimens (range, 3-26 cycles). Ten received prior whole brain radiation (WBRT) to a median dose of 43 Gy (range, 24-55 Gy). Sixteen presented with relapsed PCNSL, and seven presented with refractory disease. Twenty-three received 26 procedures of SRS. The median tumor volume was 4 cm3 (range, 0.1-26 cm3), and the median margin dose was 15 Gy (range, 8-20 Gy). Median follow-up from SRS was 11 months (interquartile range, 5.7-33.2 months). Twenty presented with treatment response to twenty-three tumors (12 complete, 11 partial). Fourteen patients relapsed or were refractory to salvage SRS, and local control was 95%, 91%, and 75% at 3, 6, and 12 months post SRS. Intracranial (in-field and out-of-field) and distant (systemic) PFS was 86%, 81%, and 55% at 3, 6, and 12 months post SRS. Toxicity of SRS was low, with one developing an adverse radiation effect requiring no additional intervention. Although methotrexate-based chemotherapy regimens with or without WBRT is the first-line management option for PCNSL, SRS may be used as an alternative option in properly selected patients with smaller relapsed or refractory PCNSL tumors.