Shayan Cheraghlou

Treatment delay and facility case volume are associated with survival in early‐stage glottic cancer

To identify and compare treatment and system factors associated with survival in early‐stage glottic cancer.

Untreated oral cavity cancer: Long-term survival and factors associated with treatment refusal

Oral cavity cancer is the most common malignant disease of the head and neck. The natural course of the disease is poorly characterized and unavailable for patient consideration during initial treatment planning. Our primary objective was to outline this natural history, with a secondary aim of identifying predictors of treatment refusal.

Salvage Surgery after Radiation Failure in T1/T2 Larynx Cancer: Outcomes following Total versus Conservation Surgery:

Objective After radiation failure for early T-stage larynx cancer, national guidelines recommend salvage surgery. Total laryngectomy and conservation laryngeal surgery with an open or endoscopic approach are both used. Beyond single-institution studies, there is a lack of evidence concerning the outcomes of these procedures. We aim to study whether treatment with conservation laryngeal surgery is associated with poorer outcomes than treatment with total laryngectomy as salvage surgery after radiation failure for T1/T2 larynx cancers. Study Design A retrospective study was conducted of adult squamous cell larynx cancer cases in the National Cancer Database diagnosed from 2004 to 2012. Setting Commission on Cancer cancer programs in the United States. Methods Demographic, facility, tumor, and survival variables were included in the analyses. Multivariate survival regressions as well as univariate Kaplan-Meier analyses were conducted. Results Slightly more than 7% of patients receiving radiotherapy for T1/T2 larynx cancers later received salvage surgery. Salvage with partial laryngectomy was not associated with diminished survival as compared with total laryngectomy. However, positive surgical margins were associated with worse outcomes (hazard ratio, 1.782; P = .001), and a larger percentage of patients receiving partial laryngectomy had positive margins than those receiving total laryngectomy. Facility characteristics were not associated with differences in salvage surgery type or outcomes. Conclusion In recognition of the inherent selection bias, patients who experienced recurrences after radiation for T1/T2 larynx cancer and underwent conservation salvage laryngeal surgery demonstrated clinical outcomes similar to those of patients undergoing salvage total laryngectomy. Increased rates of positive surgical margins were observed among patients undergoing salvage conservation surgery.

Prognostic Value of Lymph Node Yield and Density in Head and Neck Malignancies

Objective Studies have suggested that the lymph node yield and lymph node density from selective or elective neck dissections are predictive of patient outcomes and may be used for patient counseling, treatment planning, or quality measurement. Our objective was to systematically review the literature and conduct a meta-analysis of studies that investigated the prognostic significance of lymph node yield and/or lymph node density after neck dissection for patients with head and neck cancer. Data Sources The Ovid/Medline, Ovid/Embase, and NLM PubMed databases were systematically searched on January 23, 2017, for articles published between January 1, 1946, and January 23, 2017. Review Methods We reviewed English-language original research that included survival analysis of patients undergoing neck dissection for a head and neck malignancy stratified by lymph node yield and/or lymph node density. Study data were extracted by 2 independent researchers (S.C. and M.O.). We utilized the DerSimonian and Laird random effects model to account for heterogeneity of studies. Results Our search yielded 350 nonduplicate articles, with 23 studies included in the final synthesis. Pooled results demonstrated that increased lymph node yield was associated with a significant improvement in survival (hazard ratio, 0.833; 95% CI, 0.790-0.879). Additionally, we found that increased lymph node density was associated with poorer survival (hazard ratio, 1.916; 95% CI, 1.637-2.241). Conclusions Increased nodal yield portends improved outcomes and may be a valuable quality indicator for neck dissections, while increased lymph node density is associated with diminished survival and may be used for postsurgical counseling and planning for adjuvant therapy.

Adjuvant therapy in major salivary gland cancers: Analysis of 8580 patients in the National Cancer Database

BACKGROUND Evidence surrounding the effect of adjuvant treatment in salivary gland cancers is limited. The benefit of adding chemotherapy to adjuvant treatment is also of interest. We investigated the association of these treatments with survival and whether this differed by stage or the presence of adverse features. METHODS A retrospective study of adult salivary gland cancer cases diagnosed from 2004 to 2013 in the National Cancer Data Base (NCDB) was conducted. RESULTS Treatment with adjuvant radiotherapy was associated with improved survival for both patients with early-stage (hazard ratio [HR] 0.744; P = .004) and late-stage (HR 0.688; P < .001) disease with adverse features. Further addition of chemotherapy to the adjuvant treatment of patients with late-stage disease with adverse features was not associated with a survival benefit (HR 1.028; P = .705). CONCLUSION Adjuvant radiotherapy is associated with improved survival for patients with adverse features, regardless of stage. The addition of chemotherapy to the adjuvant treatment of patients with late-stage disease with adverse features is not associated with improved outcomes.

Radiotherapy for human papillomavirus-positive oropharyngeal cancers in the National Cancer Data Base: Correspondence

We read with great interest the article published by Garden et al comparing outcomes for patients with phenotypically human papillomavirus (HPV)-positive oropharyngeal cancers who are treated with radiotherapy with and without chemotherapy. We were curious to learn whether the results could be replicated in a different, multiinstitutional cohort and therefore performed a similar analysis using the National Cancer Data Base, a nationwide clinical surveillance resource data set that includes approximately 70% of all newly diagnosed malignancies in the United States from >1500 cancer programs. We examined patients with American Joint Commission on Cancer stage III/IVA (T1-T3, N1-N2b, and T3N0) squamous cell primary oropharyngeal cancers with confirmed high-risk HPV in the National Cancer Data Base between 2004 and 2013. There were 707 cases treated with chemoradiotherapy compared with 51 cases that were treated with radiotherapy alone for a total of 758 cases. The 2-year cumulative survival rate for the group treated with chemoradiotherapy was 94.2% and that for those treated with radiotherapy was 79.9%. There were significant differences noted in the Kaplan-Meier curves between the 2 groups, with a log-rank P<.001 (Fig. 1). In a multivariate Cox regression analysis adjusting for age, sex, race, comorbidity, and American Joint Committee on Cancer T/N classification, radiotherapy was found to have a significantly worse hazard ratio compared with chemoradiotherapy (hazard ratio, 4.73; 95% confidence interval, 2.51-8.94 [P<.001]). These findings were limited by the small number of patients in the radiotherapy cohort, but in this database, outcomes did not appear to be comparable for radiotherapy with and without systemic therapy. It is interesting to note that when we performed separate subgroup analysis for stage III and stage IVA cases, there were more comparable survival outcomes noted between chemoradiotherapy and radiotherapy in the stage III subset compared with the stage IVA subset. Thus, there still may be a population of HPV-positive patients for whom deintensification of therapy is appropriate. Although we commend Garden et al on their article, we recommend caution regarding the generalizability of applying deintensified therapy to all patients with stage III/IVA disease.

Restricting Symptoms Before and After Admission to Hospice

BACKGROUND Prior work has shown that symptoms leading to restrictions in daily activities are common at the end of life. Hospice is a Medicare benefit designed to alleviate distressing symptoms in the last 6 months of life. The effect of hospice on the burden of such symptoms is uncertain. METHODS From an ongoing cohort study of 754 community-dwelling older persons, aged ≥70 years, we evaluated 241 participants who were admitted to hospice from March 1998 to December 2013. A set of 15 physical and psychological symptoms leading to restricted activity (ie, cut down on usual activities or spend at least half the day in bed) were ascertained during monthly telephone interviews in the year before and 3 months after hospice admission. RESULTS The prevalence and mean number of restricting symptoms increased progressively until about 2 months before hospice admission, before increasing precipitously to a peak around the time of hospice admission. After the start of hospice, both the prevalence and the mean number of restricting symptoms dropped markedly. For several symptoms deemed most amenable to hospice treatment, including depression and anxiety, the prevalence dropped to levels comparable to or lower than those observed 12 months before the start of hospice. The trends observed in symptom prevalence and mean number of symptoms before and after hospice did not differ appreciably according to hospice admission diagnosis or sex. The median duration of hospice (before death) was only 15 days. CONCLUSION The burden of restricting symptoms increases progressively several months before the start of hospice, peaks around the time of hospice admission, and decreases substantially after the start of hospice. These results, coupled with the short duration of hospice, suggest that earlier referral to hospice may help to alleviate the burden of distressing symptoms at the end of life.

National treatment times in oropharyngeal cancer treated with primary radiation or chemoradiation

OBJECTIVE To characterize treatment delays in oropharyngeal cancer treated with radiation in a national sample, identify factors associated with delays, and associate treatment delays with survival. MATERIALS AND METHODS We included adults in the National Cancer Database treated for oropharyngeal cancer with primary radiation or chemoradiation 2010-2013. We characterized diagnosis-to-treatment initiation, radiation treatment duration, and diagnosis-to-treatment end intervals as medians. We examined delays for association with patient, tumor, and treatment characteristics and with overall survival with multivariable logistic and Cox proportional hazards regression, respectively. RESULTS 4089 patients were included; 12% received radiation alone and 88% chemoradiation. The incidence of human papilloma virus-associated tumors was 64%. Median durations of diagnosis-to-treatment initiation, radiation duration, and diagnosis-to-treatment end were 35, 50, and 87 days, respectively. Human papilloma virus-positive tumors were linked to decreased delays in radiation treatment duration and diagnosis-to-treatment end (OR = 0.72 (0.60-0.85), p < 0.001 and OR = 0.79 (0.66-0.95), p = 0.010, respectively). Delays in radiation treatment duration and diagnosis-to-treatment end were negatively associated with overall survival (HR = 1.23 (1.03-1.47), p = 0.024 and 1.24 (1.04-1.48), p = 0.017, respectively). When examined separately, radiation duration remained associated with decreased overall survival in patients with human papilloma virus-negative (HR = 1.29 (1.03-1.63), p = 0.030) but not human papilloma virus-positive tumors (HR = 1.17 (0.89-1.54), p = 0.257). CONCLUSION These median durations can serve as national benchmarks. Diagnosis-to-treatment end interval is associated with overall survival in all patients, and radiation treatment duration in patients with human papilloma virus-negative tumors. These intervals could be considered quality indicators for oropharyngeal squamous cell carcinoma treated with primary radiation or chemoradiation.

Treatment Delays in Primarily Resected Oropharyngeal Squamous Cell Carcinoma: National Benchmarks and Survival Associations

Objective To characterize treatment delays in surgically treated oropharyngeal cancer, identify factors associated with delays, and associate delays with survival. Study Design Retrospective cross-sectional analysis. Setting Commission on Cancer–accredited institutions. Subjects and Methods We identified patients in the National Cancer Database with surgically treated oropharyngeal cancer. We characterized the durations of diagnosis-to-treatment initiation, surgery-to-radiation treatment, radiation treatment duration, total treatment package, and diagnosis-to-treatment end intervals as medians. We associated delays with patient, tumor, and treatment factors via multivariable logistic regression analysis and with overall survival by Cox proportional hazards regression. Results In total, 3708 patients met inclusion criteria. Median durations of diagnosis-to-treatment initiation, surgery-to-radiation treatment, radiation treatment duration, total treatment package, and diagnosis-to-treatment end intervals were 27, 42, 47, 90, and 106 days, respectively. Medicaid and human papillomavirus (HPV) negativity were associated with delays. Delayed total treatment package and diagnosis-to-treatment end intervals were associated with decreased survival (hazard ratio [HR] = 1.81 [1.29-2.54], P = .001 and HR = 1.97 [1.39-2.78], P < .001, respectively); this was maintained following HPV stratification. Delays in the surgery-to-radiation treatment interval were associated with decreased overall survival in HPV-negative but not HPV-positive patients (HR = 2.05 [1.19-3.52], P = .010 and HR = 1.15 [0.74-1.80], P = .535, respectively). Diagnosis-to-treatment initiation and radiation treatment duration were not associated with overall survival in the overall cohort (HR = 1.21 [0.86-1.72], P = .280 and HR = 1.40 [0.99-1.99], P = .061, respectively); however, following stratification, delayed radiation treatment duration approached significance in HPV-negative but not HPV-positive patients (HR = 1.60 [0.96-2.68], P = .072 and HR = 1.35 [0.84-2.18], P = .220). Conclusion Treatment durations identified here can serve as national benchmarks and for institutions to compare quality to their peers. Distinct benchmarks should be applied to HPV-negative and HPV-positive patients.

Adjuvant Chemotherapy Is Associated With Improved Survival for Late-Stage Salivary Squamous Cell Carcinoma: Chemotherapy for Squamous Salivary Malignancies

Salivary squamous cell carcinomas (SCCs) represent a unique disease entity because many are thought to represent metastases from primary cutaneous malignancies. Nevertheless, they represent a significant proportion of parotid gland cancers and have a notably poor prognosis. Recently, there has been controversy regarding the utility of adjuvant chemotherapy in the treatment of these malignancies, with most studies concluding that there is no survival benefit. We aim to determine the outcomes associated with the use of adjuvant radiotherapy and chemoradiotherapy in the treatment of early‐ and late‐stage salivary SCC.