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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. 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. 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). 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.

Highlights • Tissue segmentation can be achieved using a spatially registered cytokeratin mask. • Automated and manual cell counts and stain intensities were highly correlated. • Smokers had significantly stronger PD-L1 stain intensity and higher numbers TILs. • After radiotherapy, greater CD8+ TILs was associated with inferior survival., Oral tongue squamous cell carcinoma (OTSCC) displays variable levels of immune cells within the tumor microenvironment. The quantity and localization of tumor infiltrating lymphocytes (TILs), specific functional TIL subsets (e.g., CD8+), and biomarker-expressing cells (e.g., PD-L1+) may have prognostic and predictive value. The purpose of this study was to evaluate the robustness and utility of computer-assisted image analysis tools to quantify and localize immunohistochemistry-based biomarkers within the tumor microenvironment on a tissue microarray (TMA). We stained a 91-patient OTSCC TMA with antibodies targeting CD3, CD4, CD8, FOXP3, IDO, and PD-L1. Cell populations were segmented into epithelial (tumor) or stromal compartments according to a mask derived from a pan-cytokeratin stain. Definiens Tissue Studio was used to enumerate marker-positive cells or to quantify the staining intensity. Automated methods were validated against manual tissue segmentation, cell count, and stain intensity quantification. Univariate associations of cell count and stain intensity with smoking status, stage, overall survival (OS), and disease-free survival (DFS) were determined. Our results revealed that the accuracy of automated tissue segmentation was dependent on the distance of the tissue section from the cytokeratin mask and the proportion of the tissue containing tumor vs. stroma. Automated and manual cell counts and stain intensities were highly correlated (Pearson coefficient range: 0.46–0.90; p

Objective To identify any association between type 2 diabetes mellitus (T2DM) and survival outcomes for mucosal squamous cell carcinoma of the head and neck. An association has been demonstrated between T2DM and cancer outcomes at numerous sites, but data for the head and neck are limited. Improving our understanding of the impact that diabetes has on head and neck cancer survival is relevant for making treatment decisions and counseling patients regarding prognosis. Study Design Retrospective cohort study. Setting Academic tertiary referral head and neck cancer center. Subjects and Methods By accessing data retrospectively from prospectively collected databases at the Princess Margaret Cancer Centre, patients were studied who were treated for mucosal head and neck squamous cell cancer between January 2005 and December 2011. Collection of clinical, pathologic, and survival data was completed with an emphasis on T2DM. Results Of 2498 patients identified in the study period, 319 (12.8%) had T2DM. Five-year overall survival was not different between the diabetic (64%, 95% CI = 58%-71%) and nondiabetic (67%, 95% CI = 65%-69%; P = .078) groups. Furthermore, cause-specific survival did not demonstrate a statistically significant difference between groups (diabetic: 84%, 95% CI = 79%-88%, vs nondiabetic: 84%, 95% CI = 82%-86%; P = .67). Conclusion Despite contradictory evidence at other cancer sites, the presence of T2DM alone does not appear to adversely affect cancer survival outcomes in head and neck squamous cell cancer. This is encouraging for the diabetic patients with head and neck squamous cell cancer, and it provides guidance for the multidisciplinary team that treats them.

Aim The aim is to evaluate the impact of cisplatin dose modification on outcomes of human papillomavirus (HPV)-related (HPV+) and HPV-unrelated (HPV−) locally advanced head and neck cancer (LAHNC) treated with chemoradiotherapy (CRT). Patients and methods A pooled analysis was conducted of stage III/IV oropharyngeal cancer (OPC), carcinoma of unknown primary (CUP) and laryngo-hypopharyngeal cancer (LHC) patients treated with single-agent cisplatin CRT in 2000–2012 from two tertiary academic cancer centres. HPV status was determined by p16 staining and/or in situ hybridisation. LHC was assumed to be HPV−. Unknown HPV status OPC/CUPs were excluded. Overall survival (OS) was calculated. Multivariable analysis (MVA) evaluated the impact of cisplatin dose intensity on survival for HPV+ and HPV− cohorts separately. Results A total of 404 HPV+ and 255 HPV− LAHNC (481 OPC, 18 CUP, 160 LHC) patients were included. Median follow-up was 4.3 (0.5–11.9) years. Three-year OS for cisplatin 200 mg/m 2 subgroups were 52%, 60%, and 72% ( P = 0.001) for the HPV− and 91%, 90%, and 91% ( P = 0.30) for the HPV+ patients. MVA confirmed a survival benefit with cisplatin >200 mg/m 2 for the HPV− (hazard ratio [HR] 0.5, 95% confidence interval [CI]: 0.3–0.7, P P = 0.104). There was a superior OS trend in the HPV+ T4 or N3 high-risk subset ( N = 107) with cisplatin >200 mg/m 2 (HR 0.5, 95% CI: 0.2–1.1, P = 0.07). Conclusions A survival benefit of cisplatin dose >200 mg/m 2 is evident for HPV− LAHNC patients, but not for HPV+ cohort overall, although the T4 or N3 subset may benefit from a higher cumulative cisplatin dose.

BACKGROUND: The Hedgehog (Hh) signaling pathway is active in esophageal adenocarcinoma (EAC). We used a patient-derived murine xenograft (PDX) model of EAC to evaluate tumour response to conventional treatment with radiation/chemoradiation with or without Hh inhibition. Our goal was to determine the potential radioresistance effects of Hh signaling and radiosensitization by Hh inhibitors.METHODS: PDX models were treated with radiation, chemotherapy or combined chemoradiation. Tumour response was measured by growth delay. Hh transcript levels (qRT-PCR) were compared among frozen tumours from treated and control mice. 5E1, a monoclonal SHH antibody, or LDE225, a clinical SMO inhibitor (Novartis®) inhibited Hh signaling.RESULTS: Precision irradiation significantly delayed xenograft tumour growth in all 7 PDX models. Combined chemoradiation further delayed growth relative to either modality alone in three of six PDX models. Following irradiation, two of three PDX models demonstrated sustained up-regulation of Hh transcripts. Combined LDE225 and radiation, and 5E1 alone delayed growth relative to either treatment alone in a Hh-responsive PDX model, but not in a non-responsive model.CONCLUSION: Hh signaling mediates the radiation response in some EAC PDX models, and inhibition of this pathway may augment the efficacy of radiation in tumours that are Hh dependent.

Purpose: Continued smoking after a cancer diagnosis leads to poorer treatment outcomes, survival, and quality of life. We evaluated the perceptions of the effects of continued smoking on quality of life, survival, and fatigue among patients with cancer after a cancer diagnosis and the effects of these perceptions on smoking cessation. Patients and Methods: Patients with cancer from all disease subsites from Princess Margaret Cancer Centre (Toronto, Ontario) were surveyed between April 2014 and May 2016 for sociodemographic variables, smoking history, and perceptions of continued smoking on quality of life, survival, and fatigue. Multivariable regression models evaluated the association between patients’ perceptions and smoking cessation and the factors influencing patients’ perceptions of smoking. Results: Among 1,121 patients, 277 (23%) were smoking cigarettes up to 1 year before diagnosis, and 54% subsequently quit; 23% had lung cancer, and 27% had head and neck cancers. The majority felt that continued smoking after a cancer diagnosis negatively affected quality of life (83%), survival (86%), and fatigue (82%). Current smokers during the peridiagnosis period were less likely to perceive that continued smoking was harmful when compared with ex-smokers and never-smokers ( P < .01). Among current smokers, perceiving that smoking negatively affected quality of life (adjusted odds ratio [aOR], 2.68 [95% CI, 1.26 to 5.72]; P = .011), survival (aOR, 5.00 [95% CI, 2.19 to 11.43]; P < .001), and fatigue (aOR, 3.57 [95% CI, 1.69 to 7.54]; P < .001) were each strongly associated with smoking cessation. Among all patients, those with a greater smoking history were less likely to believe that smoking was harmful in terms of quality of life (aOR, 0.98 [95% CI, 0.98 to 0.99]; P < .001), survival (aOR, 0.98 [95% CI, 0.98 to 0.99]; P < .001), and fatigue (aOR, 0.99 [95% CI, 0.98 to 0.99]; P < .001). Conclusion: The perceptions of continued smoking after a cancer diagnosis among patients with cancer are strongly associated with smoking cessation. Counseling about the harms of continued smoking in patients with cancer, and in particular among those who have lower risk perceptions, should be considered when developing a smoking cessation program.

To explore the impact of tumor human papillomavirus (HPV) status, comorbidity, polypharmacy, and treatment intensity on overall survival (OS) of elderly oropharyngeal cancer (OPC) patients.All elderly (70 years) OPC patients receiving definitive (chemo-) radiation therapy in 2000 to 2013 were reviewed. Charlson comorbidity index (CCI, comorbidity alone) and the comorbidity-polypharmacy score (CPS, comorbidity and medication) were calculated. Overall survival was compared between HPV-positive (HPV+) and HPV-negative (HPV-) cohorts. Multivariable analyses (MVA) incorporating either the CCI (MVA-CCI) or the CPS (MVA-CPS) identified survival predictors.Among 231 of 287 patients (80%) with p16 staining, 117 were HPV+ and 114 HPV-. Systemic treatments were administered in 48 patients (21%) (chemotherapy 17; epidermal growth factor receptor inhibitor 31). The distribution of CCI (P=.59), CPS (P=.23), and age (P=.50) were similar between HPV+ versus HPV- cohorts. Median follow-up was 4.3 years. The HPV+ patients had better 5-year OS (57% vs 32%, P.001) versus HPV- patients. Multivariable analysis adjusted for T-/N-category confirmed that HPV+ status (MVA-CCI: hazard ratio [HR] 0.58, P=.01; MVA-CPS: HR 0.60, P=.02), Zubrod scale score (0-1) (MVA-CCI: HR 0.44, P.001; MVA-CPS: HR 0.43, P.001), and higher radiation therapy dose (MVA-CCI: HR 0.97, P=.001; MVA-CPS: HR 0.96, P.001) were correlated with higher OS. A marginal inverse correlation between CPS and OS was observed in the entire cohort (HR 1.05, P=.05) and was stronger for the HPV+ cohort (HR 1.11, P=.02). Nonsignificant higher OS was also found with ≤20 pack-years of smoking (MVA-CCI: P=.10; MVA-CPS: P=.15) and with systemic treatments (MVA-CCI: P=.13; MVA-CPS: P=.19). No association with OS was found for CCI (P=.46).Elderly HPV+ OPC patients have longer survival than their HPV- counterparts. Lower Zubrod scale score and higher radiation therapy dose are associated with longer OS, whereas fewer smoking pack-years and systemic agents have nonsignificant associations. Comorbidity-polypharmacy score, but not CCI, is correlated with OS, especially in HPV+ patients, suggesting the potential importance of assessing polypharmacy in addition to comorbidity burden in this population.

Improved cancer screening and treatment have led to a greater focus on cancer survivorship care. Older cancer survivors may be a unique population. We evaluated whether older cancer survivors (age ≥ 65 years) had lifestyle behaviors, attitudes, and knowledge distinct from younger survivors.Adult cancer survivors with diverse cancer subtypes were recruited from Princess Margaret Cancer Centre (Toronto, Ontario, Canada). Multivariable models evaluated the effect of age on smoking, alcohol, and physical activity habits, attitudes toward and knowledge of these habits on cancer outcomes, and lifestyle information and recommendations received from health care providers, adjusted for sociodemographic and clinicopathologic covariates.Among the 616 survivors recruited, 23% (n = 139) were older. Median follow-up since diagnosis was 24 months. Older survivors were more likely ex-smokers and less likely current smokers than younger survivors, but they were less likely to know that smoking could affect cancer treatment (adjusted odds ratio [OR], 0.53; P = .007) or prognosis (adjusted OR, 0.53; P = .008). Older survivors were more likely to perceive alcohol as improving overall survival (adjusted OR, 2.39; P = .02). Rates of meeting moderate-to-vigorous physical activity guidelines 1 year before diagnosis (adjusted OR, 0.55; P = .02) and maintaining and improving their exercise levels to meet these guidelines after diagnosis (adjusted OR, 0.48; P = .02) were lower in older survivors. Older and younger cancer survivors reported similar rates of receiving lifestyle behavior information from health care providers (P = .36 to .98).Older cancer survivors reported being less aware of the impact of smoking on their overall health, more likely perceived alcohol as beneficial to survival, and were less likely to meet exercise goals compared with younger survivors. Survivorship programs need to consider age when counseling on lifestyle behaviors.

BACKGROUND The NCIC CTG LY.12 study showed that gemcitabine, dexamethasone, and cisplatin (GDP) were noninferior to dexamethasone, cytarabine, and cisplatin (DHAP) in patients with relapsed or refractory aggressive histology lymphoma prior to autologous stem cell transplantation. We conducted an economic evaluation from the perspective of the Canadian public healthcare system based on trial data. METHODS The primary outcome was an incremental cost utility analysis comparing costs and benefits associated with GDP vs DHAP. Resource utilization data were collected from 519 Canadian patients in the trial. Costs were presented in 2012 Canadian dollars and disaggregated to highlight the major cost drivers of care. Benefit was measured as quality-adjusted life-years (QALYs) based on utilities translated from prospectively collected quality-of-life data. All statistical tests were two-sided. RESULTS The mean overall costs of treatment per patient in the GDP and DHAP arms were $19 961 (95% confidence interval (CI) = $17 286 to $24 565) and $34 425 (95% CI = $31 901 to $39 520), respectively, with an incremental difference in direct medical costs of $14 464 per patient in favor of GDP (P < .001). The predominant cost driver for both treatment arms was related to hospitalizations. The mean discounted quality-adjusted overall survival with GDP was 0.161 QALYs and 0.152 QALYs for DHAP (difference = 0.01 QALYs, P = .146). In probabilistic sensitivity analysis, GDP was associated with both cost savings and improved quality-adjusted outcomes compared with DHAP in 92.6% of cost-pair simulations. CONCLUSIONS GDP was associated with both lower costs and similar quality-adjusted outcomes compared with DHAP in patients with relapsed or refractory lymphoma. Considering both costs and outcomes, GDP was the dominant therapy.

179 Background: Smoking cessation is becoming an integral part of cancer survivorship. To help improve survivorship education, clinicians need an understanding of patient knowledge of the harms of continued smoking. Methods: Patients with various cancer subtypes were surveyed with respect to self-awareness of the harms of continued smoking on cancer outcomes. Multivariable logistic regression models assessed factors associated with the level of awareness. Results: Among 985 patients, 23% smoked at diagnosis; 34% quit > 1 year prior to diagnosis; 25% had lung, 30% had head and neck cancers; 77% received curative therapy. Many patients reported being unaware that smoking can negatively impact cancer surgery (65%), radiation (74%), chemo outcomes (64%), treatment efficacy (70%), cancer prognosis (54%) and second primary development (52%). Among all patients, those smoking at diagnosis were significantly more likely to be unaware of radiation (aOR = 1.73, 95% CI [1.16-2.57]) and chemo (aOR = 2.10 [1.17-3.79]) toxicities, cancer prognosis (aOR = 1.63 [1.16-2.29]) and second primary risk (aOR = 1.61 [1.14-2.26]). Those with poorer health status were more likely unaware of effects on prognosis (aOR = 1.56 [1.18-2.08]) and second primaries (aOR = 1.54 [1.14-2.08]). Patients with non-tobacco related cancers (non-TRCs) were more likely unaware smoking impacts cancer surgery (aOR = 1.45 [1.04-2.04]) and radiation (aOR = 1.37 [1.01-1.85]). Among smokers at diagnosis, those with non-TRCs (aOR = 4.00 [1.45-11.11]) were more likely unaware smoking can impact chemo outcomes. Awareness was not associated with stage, second-hand smoke exposure, cessation or interest in a smoking cessation program (SCP), but was associated with patients believing that a SCP would be beneficial to their health (aORs = 2.33-4.35, P < 0.03). Among smokers at diagnosis, believing that a SCP is beneficial (51%) was associated with both interest in an in-patient (aOR = 4.65 [2.15-10.03]) and ambulatory (aOR = 4.08 [2.14-7.79]) SCP. Conclusions: Many cancer patients were unaware of the harms of continued smoking; mainly smokers at diagnosis and those with non-TRCs. Patient education should focus on emphasizing awareness, which may help improve patient interest in smoking cessation.

251 Background: With improvements in cancer therapies, palliative patients with cancer now enjoy improved and sometimes prolonged survival. Continued smoking after a cancer diagnosis negatively impacts treatment response/toxicities, survival and quality of life and is influenced by SHS exposure. Little is known about the perceptions of palliative patients with cancer in comparison to patients who are considered potentially curative, on smoking after a cancer diagnosis and of SHS exposure. We assessed such potential differences in perception. Methods: Patients with cancer across all sites were surveyed with respect to their smoking habits and perceptions on how smoking and SHS influences cancer-related QofL, fatigue and overall survival (OS). Review of patient charts confirmed which patients were considered palliative versus potentially curative. Multivariable logistic regression models assessed for associations between treatment intent and patient perceptions, adjusted for significant co-variables. Results: Among 985 patients with cancer, 22% were considered palliative; 23% of surveyed patients smoked at diagnosis; 10% continued smoking at follow-up. Most patients perceived that continued smoking and SHS exposure negatively impacted QofL (continued smoking: 83%, SHS: 82%), fatigue (83%, 79%) and OS (86%, 81%). Palliative patients were more likely to believe that SHS worsened their cancer-related fatigue (adjusted odds ratio (aOR) = 1.65, 95% CI [1.05-2.56], P = 0.03) and worsened OS (unadjusted OR = 1.92, [1.12-3.33], P= 0.02; aOR = 1.56 [0.98-2.50], P = 0.06). Yet palliative/non-palliative status was not found to be associated with perceived benefits of smoking cessation on QofL, fatigue, or OS (P > 0.10, all comparisons). Conclusions: When compared with non-palliative patients, palliative patients with cancer perceived a greater negative impact of SHS on fatigue and survival, but had similar views of continued smoking after a cancer diagnosis. We are encouraged that palliative status did not lead to patients having diluted perceptions on the negative impact of smoking on cancer outcomes. Health care providers should continue to focus on the positive impacts of smoking cessation and SHS in this setting.

10086Background: Smoking cessation is becoming an integral part of cancer survivorship. To help improve survivorship education, clinicians need an understanding of patient knowledge of the harms of...

10090Background: Smoking cessation is becoming an integral part of cancer survivorship care. We assessed cancer patients’ interest and preferences in the design of a SCP. Methods: Cancer patients f...

6019Background: Lymph node ratio (LNR, number of positive lymph nodes/total number of excised lymph nodes) has been shown to be associated with outcomes in multiple malignancies. In this study, the impact of LNR on distant metastasis (DM) and overall survival (OS) in oral cavity squamous cell carcinoma (OSCC) was investigated. Methods: Retrospective review of pN0-2 OSCC patients (pts) treated between 1994-2012 with curative surgery with neck dissection (ND) +/- postoperative radiotherapy (PORT) with or without concurrent chemotherapy (CCT). LNR was subjected to multivariable analysis (MVA) of DM and OS, adjusted for pT3-4, extracapsular extension (ECE), high grade (G3), lymphovascular invasion (LVI), perineural invasion (PNI), and tumor subsite. Results: Overall 914 pts were identified; median age: 61 yr (18-92); median follow-up: 51 months (1–189); pT3-4: 283 (31%); pN-classification: N0: 482 (53%), N1: 128 (14%), N2a: 6 (0.5%); N2b: 225 (24.5%); N2c: 73 (8%); median number of dissected nodes: 36 (6-125)...

183 Background: Exposure to SHS after a cancer diagnosis is associated with continued smoking in lung and HN cancer patients (PMID: 24419133, 23765604). However, smoking is a social activity. We evaluated whether elimination of SHS exposure around and after a diagnosis of lung or HN cancer is associated with smoking cessation in the cancer patient. Methods: Lung and HN cancer patients from Princess Margaret Cancer Centre (2006-12) completed questionnaires at diagnosis and follow-up (median 2 years apart) that assessed smoking history and SHS exposures (cohort study). Multivariate logistic regression analysis evaluated the association of elimination of SHS exposure after a diagnosis of cancer with subsequent smoking cessation, adjusted for significant covariates. A cross-sectional study (2014-15) of 183 lung and HN smoking patients assessed consistency in associations and interest in SHS cessation programs. Results: For the cohort study, 261/731 lung and 145/450 HN cancer patients smoked at diagnosis; subsequent quit rates were 69% and 50% respectively. 91% of lung and 94% of HN cancer patients were exposed to SHS at diagnosis while only 40% (lung) and 62% (HN) were exposed at follow-up. Elimination of SHS exposure was associated with smoking cessation in lung (aOR = 4.76, 95% CI [2.56-9.09], P< 0.001), HN (aOR = 5.00 [1.61-14.29], P< 0.001), and combined cancers (aOR = 5.00 [3.03-8.33], P< 0.001). The cross-sectional study has similar cessation and SHS exposure rates and a similar association for elimination of SHS with smoking cessation (aOR = 3.42 [1.16-10.10], P= 0.03). However when asked directly, only 26% of patients quit smoking with another individual and 13% of patients exposed to SHS had at least 1 interested party in joining a SHS cessation program. Conclusions: Elimination of SHS exposure around patients is significantly associated with smoking cessation in lung and HN cancer patients, but few patients quit smoking together with others around them, despite the ‘teachable moment’ with a cancer diagnosis. Clinicians should encourage patients and their household/friends to quit smoking together to improve cessation rates in cancer patients and those around them.

9591 Background: Some cancer survivorship programs incorporate components of healthy lifestyle behavior modification. We evaluated the role that various clinical variables and smoking habits play i...

9556 Background: Exposure to second-hand smoke (SHS) after a cancer diagnosis is associated with continued smoking in lung and head and neck (HN) cancer patients (PMID: 24419133, 23765604). We eval...