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.

Predicting treatment Response based on Dual assessment of magnetic resonance Imaging kinetics and Circulating Tumor cells in patients with Head and Neck cancer (PREDICT-HN): matching 'liquid biopsy' and quantitative tumor modeling.

BACKGROUND: Magnetic resonance imaging (MRI) has improved capacity to visualize tumor and soft tissue involvement in head and neck cancers. Using advanced MRI, we can interrogate cell density using diffusion weighted imaging, a quantitative imaging that can be used during radiotherapy, when diffuse inflammatory reaction precludes PET imaging, and can assist with target delineation as well. Correlation of circulating tumor cells (CTCs) measurements with 3D quantitative tumor characterization could potentially allow selective, patient-specific response-adapted escalation or de-escalation of local therapy, and improve the therapeutic ratio, curing the greatest number of patients with the least toxicity. METHODS: The proposed study is designed as a prospective observational study and will collect pretreatment CT, MRI and PET/CT images, weekly serial MR imaging during RT and post treatment CT, MRI and PET/CT images. In addition, blood sample will be collected for biomarker analysis at those time intervals. CTC assessments will be performed on the CellSave tube using the FDA-approved CellSearch® Circulating Tumor Cell Kit (Janssen Diagnostics), and plasma from the EDTA blood samples will be collected, labeled with a de-identifying number, and stored at - 80 °C for future analyses. DISCUSSION: The primary objective of the study is to evaluate the prognostic value and correlation of weekly tumor response kinetics (gross tumor volume and MR signal changes) and circulating tumor cells of mucosal head and neck cancers during radiation therapy using MRI in predicting treatment response and clinical outcomes. This study will provide landmark information as to the utility of CTCs ('liquid biopsy) and tumor-specific functional quantitative imaging changes during treatment to guide personalization of treatment for future patients. Combining the biological information from CTCs and the structural information from MRI may provide more information than either modality alone. In addition, this study could potentially allow us to determine the optimal time to obtain MR imaging and/ or CTCs during radiotherapy to assess tumor response and provide guidance for patient selection and stratification for future dose escalation or de-escalation strategies. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT03491176 ). Date of registration: 9th April 2018. (retrospectively registered). Date of enrolment of the first participant: 30th May 2017.

Influence of induction chemotherapy in trimodality therapy-eligible oesophageal cancer patients: secondary analysis of a randomised trial.

BACKGROUND: A randomised phase 2 trial of trimodality with or without induction chemotherapy (IC) in oesophageal cancer (EC) patients showed no advantage in overall survival (OS) or pathologic complete response rate. To identify subsets that might benefit from IC, a secondary analysis was done. METHODS: The trial had accrued 126 patients (NCT 00525915). Recursive partitioning and proportional hazards regression with interactions were performed. RESULTS: The median follow-up of surviving patients was 6.7 years and the median OS duration was 3.8 years (95% confidence interval (CI), 2.6-5.8 years). OS was associated with tumour length (P=0.03), cT (P=0.02), cN (P=0.04), clinical stage (P=0.01), and tumour grade (P<0.001). The effect of IC differed according to tumour grade. Among patients with well or moderately differentiated (WMD) ECs (n=59), the 5-year survival rate was 74% with IC and 50% without IC, P=0.001. IC had no effect on OS of patients with poorly differentiated (PD) ECs (31% and 28%, respectively; interaction, P=0.04; IC, P=0.03). In the multivariate reduced model, WMD with IC was an independent prognosticator for better OS (HR=0.41, 95% CI, 0.25-0.67; P=<0.001). The following four EC phenotypes emerged for OS: (1) very high risk (PD, cN2/N3), (2) high risk (PD, cN0/N1, stage cIII), (3) moderate risk (PD, cN0/N1, stage cI/II or WMD without IC), and (4) low risk (WMD with IC). The 5-year survival rates were 11%, 27%, 48%, and 74%, respectively (P<0.001). CONCLUSIONS: Our data show that IC significantly prolonged OS of WMD EC patients who undergo trimodality; prospective evaluation is needed.

Nuclear expression of Gli-1 is predictive of pathologic complete response to chemoradiation in trimodality treated oesophageal cancer patients.

BACKGROUND: Predictive biomarkers or signature(s) for oesophageal cancer (OC) patients undergoing preoperative therapy could help administration of effective therapy, avoidance of ineffective ones, and establishment new strategies. Since the hedgehog pathway is often upregulated in OC, we examined its transcriptional factor, Gli-1, which confers therapy resistance, we wanted to assess Gli-1 as a predictive biomarker for chemoradiation response and validate it. METHODS: Untreated OC tissues from patients who underwent chemoradiation and surgery were assessed for nuclear Gli-1 by immunohistochemistry and labelling indices (LIs) were correlated with pathologic complete response (pathCR) or

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.

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.