Awareness of the Harms of Continued Smoking Among Cancer Survivors.

BACKGROUND: Smoking cessation is an integral part of cancer survivorship. To help improve survivorship education, clinicians need an understanding of patient awareness of the harms of continued smoking. METHODS: Cancer survivors from Princess Margaret Cancer Centre (Toronto, ON) were surveyed on their awareness of the harms of continued smoking on cancer-related outcomes. Multivariable logistic regression models assessed factors associated with awareness and whether awareness was associated with subsequent cessation among smokers at diagnosis. RESULTS: Among 1118 patients, 23% were current smokers pre-diagnosis and 54% subsequently quit; 25% had lung and 30% head and neck cancers. Many patients reported being unaware that continued smoking results in greater cancer surgical complications (53%), increased radiation side effects (62%), decreased quality of life during chemotherapy (51%), decreased chemotherapy or radiation efficacy (57%), increased risk of death (40%), and increased development of second primaries (38%). Being a current smoker was associated with greater lack of awareness of some of these smoking harms (aORs = 1.53-2.20, P < 0.001-0.02), as was exposure to any second-hand smoke (aORs = 1.45-1.53, P = 0.006-0.04) and being diagnosed with early stage cancer (aORs = 1.38-2.31, P < 0.001-0.06). Among current smokers, those with fewer pack-years, being treated for cure, or had a non-tobacco-related cancer were more likely unaware. Awareness that continued tobacco use worsen quality of life after chemotherapy was associated with subsequent cessation (aOR = 2.26, P = 0.006). CONCLUSIONS: Many cancer survivors are unaware that continued smoking can negatively impact cancer-related outcomes. The impact of educating patients about the potential harms of continued smoking when discussing treatment plans should be further evaluated.

Impact of neoadjuvant radiation on margins for non-squamous cell carcinoma sinonasal malignancies.

OBJECTIVES/HYPOTHESIS: Treatment of non-squamous cell carcinoma sinonasal malignancies (NSCCSMs) typically involves surgery and radiotherapy (RT), but optimal sequencing remains controversial. STUDY DESIGN: Retrospective chart review. METHODS: Patients with NSCCSM treated with combined surgery and RT between 2000 and 2011 were identified. Margin control, overall survival, disease-free survival, local recurrence-free survival, and regional recurrence-free survival were compared between neoadjuvant and adjuvant RT groups. RESULTS: Eight-four patients were included (23 neoadjuvant and 61 adjuvant RT). A higher proportion of patients receiving neoadjuvant RT achieved negative/close resection margins compared to those receiving adjuvant RT (83% vs. 41%, P = .003). Multivariable analysis also showed that neoadjuvant RT was associated with an 81% decreased odds of positive margins odds ratio: 0.19, 95% confidence interval: 0.05-0.77, P = .02). CONCLUSIONS: Neoadjuvant RT may be associated with improved margin status among patients with NSCCSM treated with surgery and RT. Future prospective studies with larger, more homogeneous populations are needed to clarify optimal treatment strategies. LEVEL OF EVIDENCE: 4 Laryngoscope, 128:2796-2803, 2018.

Effect of Intensity Modulated Radiation Therapy With Concurrent Chemotherapy on Survival for Patients With Cervical Esophageal Carcinoma.

PURPOSE: We evaluated the effect of consecutive protocols on overall survival (OS) for cervical esophageal carcinoma (CEC). METHODS AND MATERIALS: All CEC cases that received definitive radiation therapy (RT) with or without chemotherapy from 1997 to 2013 in 3 consecutive protocols were reviewed. Protocol 1 (P1) consisted of 2-dimensional RT of 54 Gy in 20 fractions with 5-fluorouracil plus either mitomycin C or cisplatin. Protocol 2 (P2) consisted of 3-dimensional conformal RT (3DRT) of ≥60 Gy in 30 fractions plus elective nodal irradiation plus cisplatin. Protocol 3 (P3) consisted of intensity modulated RT (IMRT) of ≥60 Gy in 30 fractions plus elective nodal irradiation plus cisplatin. Multivariable analyses were used to assess the effect of the treatment protocol, RT technique, and RT dose on OS, separately. RESULTS: Of 81 cases (P1, 21; P2, 23; and P3, 37), 34 local (P1, 11 [52%]; P2, 12 [52%]; and P3, 11 [30%]), 16 regional (P1, 6 [29%]); P2, 3 [13%]; and P3, 7 [19%]), and 34 distant (P1, 10 [48%]; P2, 9 [39%]; and P3, 15 [41%]) failures were identified. After adjusting for age (P=.49) and chemotherapy (any vs none; hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.3-0.9; P=.023), multivariable analysis showed P3 had improved OS compared with P1 (HR 0.4, 95% CI 0.2-0.8; P=.005), with a trend shown for benefit compared with P2 (HR 0.6, 95% CI 0.3-1.0; P=.061). OS between P1 and P2 did not differ (P=.29). Analyzed as a continuous variable, higher RT doses were associated with a borderline improved OS (HR 0.97, 95% CI 0.95-1.0; P=.075). IMRT showed improved OS compared with non-IMRT (HR 0.57, 95% CI 0.3-0.8; P=.008). CONCLUSIONS: The present retrospective consecutive cohort study showed improved OS with our current protocol (P3; high-dose IMRT with concurrent high-dose cisplatin) compared with historical protocols. The outcomes for patients with CEC remain poor, and novel approaches to improve the therapeutic ratio are warranted.

Validation of microRNA pathway polymorphisms in esophageal adenocarcinoma survival.

Polymorphisms in miRNA and miRNA pathway genes have been previously associated with cancer risk and outcome, but have not been studied in esophageal adenocarcinoma outcomes. Here, we evaluate candidate miRNA pathway polymorphisms in esophageal adenocarcinoma prognosis and attempt to validate them in an independent cohort of esophageal adenocarcinoma patients. Among 231 esophageal adenocarcinoma patients of all stages/treatment plans, 38 candidate genetic polymorphisms (17 biogenesis, 9 miRNA targets, 5 pri-miRNA, 7 pre-miRNA) were genotyped and analyzed. Cox proportional hazard models adjusted for sociodemographic and clinicopathological covariates helped assess the association of genetic polymorphisms with overall survival (OS) and progression-free survival (PFS). Significantly associated polymorphisms were then evaluated in an independent cohort of 137 esophageal adenocarcinoma patients. Among the 231 discovery cohort patients, 86% were male, median diagnosis age was 64 years, 34% were metastatic at diagnosis, and median OS and PFS were 20 and 12 months, respectively. GEMIN3 rs197412 (aHR = 1.37, 95%CI: [1.04-1.80]; P = 0.02), hsa-mir-124-1 rs531564 (aHR = 0.60, 95% CI: [0.53-0.90]; P = 0.05), and KIAA0423 rs1053667 (aHR = 0.51, 95% CI: [0.28-0.96]; P = 0.04) were found associated with OS. Furthermore, GEMIN3 rs197412 (aHR = 1.33, 95% CI: [1.03-1.74]; P = 0.03) and KRT81 rs3660 (aHR = 1.29, 95% CI: [1.01-1.64]; P = 0.04) were found associated with PFS. Although none of these polymorphisms were significant in the second cohort, hsa-mir-124-1 rs531564 and KIAA0423 rs1053667 had trends in the same direction; when both cohorts were combined together, GEMIN3 rs197412, hsa-mir-124-1 rs531564, and KIAA0423 rs1053667 remained significantly associated with OS. We demonstrate the association of multiple miRNA pathway polymorphisms with esophageal adenocarcinoma prognosis in a discovery cohort of patients, which did not validate in a separate cohort but had consistent associations in the pooled cohort. Larger studies are required to confirm/validate the prognostic value of these polymorphisms in esophageal adenocarcinoma.

Recursive Partitioning Method on Competing Risk Outcomes.

In some cancer clinical studies, researchers have interests to explore the risk factors associated with competing risk outcomes such as recurrence-free survival. We develop a novel recursive partitioning framework on competing risk data for both prognostic and predictive model constructions. We define specific splitting rules, pruning algorithm, and final tree selection algorithm for the competing risk tree models. This methodology is quite flexible that it can corporate both semiparametric method using Cox proportional hazards model and parametric competing risk model. Both prognostic and predictive tree models are developed to adjust for potential confounding factors. Extensive simulations show that our methods have well-controlled type I error and robust power performance. Finally, we apply both Cox proportional hazards model and flexible parametric model for prognostic tree development on a retrospective clinical study on oropharyngeal cancer patients.