Delays Starting Postoperative Radiotherapy Among Head and Neck Cancer Patients: A Systematic Review and Meta-analysis.

OBJECTIVE: Initiating postoperative radiotherapy (PORT) within 6 weeks (42 days) of surgery is the first and only Commission on Cancer (CoC) approved quality metric for head and neck squamous cell carcinoma (HNSCC). No study has systematically reviewed nor synthesized the literature to establish national benchmarks for delays in starting PORT. DATA SOURCES: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we performed a systematic review of PubMed, Scopus, and CINAHL. REVIEW METHODS: Studies that described time-to-PORT or PORT delays in patients with HNSCC treated in the United States after 2003 were included. Meta-analysis of proportions and continuous measures was performed on nonoverlapping datasets to examine the pooled frequency of PORT delays and time-to-PORT. RESULTS: Thirty-six studies were included in the systematic review and 14 in the meta-analysis. Most studies utilized single-institution (n = 17; 47.2%) or cancer registry (n = 16; 44.4%) data. Twenty-five studies (69.4%) defined PORT delay as >6 weeks after surgery (the definition utilized by the CoC and National Comprehensive Cancer Network Guidelines), whereas 4 (11.1%) defined PORT delay as a time interval other than >6 weeks, and 7 (19.4%) characterized time-to-PORT without defining delay. Meta-analysis revealed that 48.6% (95% confidence interval [CI], 41.4-55.9) of patients started PORT > 6 weeks after surgery. Median and mean time-to-PORT were 45.8 (95% CI, 42.4-51.4 days) and 47.4 days (95% CI, 43.4-51.4 days), respectively. CONCLUSION: Delays in initiating guideline-adherent PORT occur in approximately half of patients with HNSCC. These meta-analytic data can be used to set national benchmarks and assess progress in reducing delays.

Persistent ethnicity-associated disparity in anti-tumor effectiveness of immune checkpoint inhibitors despite equal access.

We reviewed response to immune checkpoint inhibitors (ICI) of 207 patients with diagnoses of lung or head and neck cancer treated with chemotherapy/ICI combination therapy and ICI monotherapy between 2015 and 2020 at one of three clinical pavilions associated with the Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine. Two of these pavilions (Harris Health System and the Michael E. DeBakey Veterans Affairs Medical Center) serve large minority populations and provide equal access to care regardless of means. 174 patients had a diagnosis of lung cancer (non-small cell or small cell) and 33 had a diagnosis of head and neck squamous cell carcinoma (HNSCC). 38% self-identified as Black, 45% as non-Hispanic White, and 18% as Hispanic. The objective response rate (ORR) was similar for lung cancer (35.057%) and HNSCC patients (30.3%) (p=0.894). The ORR for Hispanic and Black patients was lower compared to non-Hispanic White patients (H 27.0%, B 32.5%, W 38.7%; H vs. W p=0.209; B vs. W p=0.398). When considering only patients treated with ICI monotherapy, the ORR for Hispanic patients dropped further to 20.7% while the ORR of Black and non-Hispanic White patients remained about the same (B 29.3% and W 35.9%, H vs. W p=0.133; B vs. W p=0.419). Immune related adverse events were the lowest in the Hispanic population occurring in only 30% of patients compared to 40% of patients in the Black cohort and 50% of the non-Hispanic White cohorts.

Demographic and Tumor Characteristic Impact on Laryngeal Cancer Outcomes in a Minority Underserved Patient Population.

OBJECTIVE: Advanced laryngeal squamous cell carcinoma remains associated with approximately 50% mortality at 5 years. Delivery of multimodality treatment remains critical to maximizing survival for this disease, but achieving this at a national level remains a difficult undertaking, particularly in under- and uninsured patients as well as minority patients. We sought to evaluate laryngeal cancer treatment delivery and clinical outcomes in a predominantly minority and underserved cohort of largely under- and uninsured patients in a county hospital. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care county hospital in Houston, Texas. SUBJECTS AND METHODS: Patients (N = 210) with a new diagnosis of laryngeal squamous cell carcinoma treated between 2005 and 2015 were included in a retrospective analysis of patient demographics, tumor and treatment characteristics, and oncologic outcomes. RESULTS: The majority of patients presented with advanced disease (T4 = 43%, N>0 = 45%). Treatment selection was compliant with National Comprehensive Cancer Network guidelines in 81% of cases, but 76% of patients who required adjuvant radiotherapy were unable to start it within 6 weeks postsurgery. Overall survival and disease-free survival were 52% and 63% for the entire cohort, respectively. Supraglottic subsite and nodal metastases were significantly associated with decreased overall survival and disease-free survival. Race/ethnicity and insurance status were not associated with worse oncologic outcomes. CONCLUSION: Under- and uninsured patients often present with advanced laryngeal cancer. Oncologic outcomes in this cohort of patients is similar to that of other published series. Moreover, tumor characteristics rather than demographic variables drive oncologic outcomes for the predominantly minority and underserved patients seeking care in our tertiary care county hospital.

Oropharyngeal squamous cell carcinoma in the veteran population: Association with traditional carcinogen exposure and poor clinical outcomes.

BACKGROUND: A significant fraction of oropharyngeal squamous cell carcinoma (SCC) cases is associated with traditional carcinogens; in these patients, treatment response and clinical outcomes remain poor. METHODS: We evaluated patient, tumor, and treatment characteristics for 200 veterans with oropharyngeal SCC treated at the Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) between 2000 and 2012. RESULTS: Most patients (77%) were white and heavy smokers. Twenty-seven patients required tracheostomy and 63 required gastrostomy placement during treatment. Overall survival (OS) at 5 years was 40%. Survival was impacted by T classification, treatment intensity, completion of treatment, and p16 tumor status. Almost 30% of patients were unable to complete a treatment regimen consistent with National Comprehensive Cancer Network (NCCN) guidelines. CONCLUSION: Oropharyngeal SCC in veterans is associated with traditional carcinogens and poor clinical outcomes. Despite heavy smoking exposure, p16 tumor status significantly impacts survival. Careful consideration must be given to improving treatment paradigms for this cohort given their limited tolerance for treatment escalation.

Management of obstructive sleep apnea in the indigent population: a deviation of standard of care?

Comprehensive management of patients with obstructive sleep apnea (OSA) typically is managed best via a multidisciplinary approach, involving otolaryngologists, sleep psychologists/psychiatrists, pulmonologists, neurologists, oral surgeons, and sleep trained dentists. By utilizing these resources, one could fashion a treatment individualized to the patient, giving rise to the holistic phrase of "personalized medicine." Unfortunately, in situations and environments with limited resources, the treatment options in an otolaryngologist's armamentarium are restricted--typically to continuous positive airway pressure (CPAP) versus sleep surgery. However, a recent patient encounter highlighted here shows how a hospital's reimbursement policy effectively dictated a patient's medical management to sleep surgery. This occurred although the current gold standard for the initial treatment of OSA is CPAP. Changing the course of medical/surgical management by selectively restricting funding is a cause of concern, especially when it promotes patients to choose a treatment option that is not considered the current standard of care.

Impact of race/ethnicity on laryngeal cancer in patients treated at a Veterans Affairs Medical Center.

OBJECTIVES/HYPOTHESIS: Black patients generally present with advanced head and neck cancer resulting in decreased survival. The objective of this study was to determine whether equal access to laryngeal cancer care in a tertiary care Veterans Affairs (VA) Medical Center would result in similar survival for white and black patients. STUDY DESIGN: Retrospective chart review. METHODS: Patient and tumor characteristics, compliance with National Comprehensive Cancer Network (NCCN) guidelines, and survival outcomes were collected for 205 male patients with squamous cell carcinoma of the larynx treated between 2000 and 2012 at the Michael E. DeBakey Veterans Affairs Medical Center. RESULTS: Black patients constituted 33% of the entire cohort, were older (mean age, 65.1 vs. 62.1 years), and consumed less tobacco (46.6 vs. 65.8 mean pack-years) than white patients. Disease stage and compliance with NCCN guidelines were not affected by race. Mean follow up time was 3.6 years. A higher recurrence rate was noted among white patients (24% vs. 15%, P < .05). Neither disease-free survival (DFS) nor overall survival (OS) was significantly different between black and white patients (DFS 69% vs. 68%, P = .7; OS 68% vs. 77%, P = .1). CONCLUSIONS: Utilization of a multidisciplinary approach to laryngeal cancer care at the VA medical center allows for high compliance with NCCN guidelines and excellent oncologic outcomes. Ethnicity did not impact stage at presentation, treatment selection, or treatment intensity in this patient cohort. Our data suggest that cancer care at a VA medical center results in clinical outcomes that do not significantly vary based on patient race.

Prostaglandin E2 inhibition of keloid fibroblast migration, contraction, and transforming growth factor (TGF)-beta1-induced collagen synthesis.

Keloid formation has been linked to aberrant fibroblast activity, exacerbated by growth factors and inflammatory mediators. Prostaglandin E2 (PGE2), synthesized from arachidonic acid by cyclooxygenases (COX) and synthases (PGES), acts as both an inflammatory mediator and fibroblast modulator. Although PGE2 has known antifibrotic effects in the lower airway, its role in dermal fibrosis in general, and keloid formation in particular, remains unclear. This study focused on: (1) the effects of PGE2 on keloid fibroblast migration, contraction, and collagen synthesis and (2) endogenous PGE2 synthesis in response interleukin-1beta. PGE2 decreased keloid fibroblast migration and contraction via an EP2/EP4-cAMP mechanism that disrupted actin cytoskeletal dynamics and reversed transforming growth factor-beta1-induced collagen I and III synthesis. Impaired fibroblast PGE2 production has been linked to lower airway fibrosis and recently to keloid formation. Here, we showed that interleukin-1beta stimulation leads to nuclear factor-kappaB translocation to the nucleus, resulting in up-regulation of COX-2 and microsomal PGE2 synthase 1. Up-regulation of COX-2 in, and secretion of PGE2 by keloid fibroblasts are diminished compared with their normal fibroblast counterparts. We suggest that the antifibrotic effects of PGE2 during keloid formation are potentially diminished due to aberrant paracrine fibroblast signaling. Exogenous PGE2 may supplement decreased endogenous levels and inhibit keloid formation or progression.