Rates of Smoking Cessation at 6 and 12 Months after a Clinical Tobacco Smoking Cessation Intervention in Head and Neck Cancer Patients in Northern Ontario, Canada.

Smoking during cancer treatment is associated with reduced treatment response and cancer recurrence in patients with tobacco-related cancers. The purpose of this study was to examine smoking characteristics in head and neck cancer patients (n = 503) with a history of smoking and examine the impact of an intensive clinical tobacco intervention to patients who were currently smoking. All participants completed an interviewer-administered questionnaire at study enrollment which examined smoking behaviours, motivations to quit, and strategies used to cessate smoking. Follow-up assessments were completed at 6- and 12-months which monitored whether patients had quit smoking, remained cessated, or continued to smoke since study recruitment. For those who were currently smoking (n = 186, 37.0%), an intensive clinical tobacco intervention that utilized the 3A's-Ask, Advise, Arrange-and the Opt-Out approach was offered to assist with smoking cessation at their new patient visit and followed-up weekly during their head and neck radiation therapy for 7 weeks. At 6 months, 23.7% (n = 41) of those who were smoking successfully quit; 51.2% quit 'cold turkey' (defined as using no smoking cessation assistance, aids or pharmacotherapy to quit), while 34.9% used pharmacotherapy (varenicline (Champix)) to quit. On average, it took those who were smoking 1-5 attempts to quit, but once they quit they remained cessated for the duration of the study. Although the head and neck cancer patients in this study reported high levels of nicotine dependence, many were able to successfully cessate.

Impact of comprehensive hospice palliative care on end-of-life care: a propensity-score-matched retrospective observational study.

BACKGROUND: Access to hospice palliative care may improve quality of life, reduce the use of potentially aggressive end-of-life care and allow for death to occur outside of an acute care hospital. The aim of this study was to examine the impact of an ambulatory hospice palliative care program on end-of-life care compared to care received by a matched control group of deceased patients. METHODS: This retrospective study included patients who received hospice palliative care through the Symptom Management Program in Sudbury, Ontario, during 2012-2015. Using linked administrative health records, we defined a propensity-matched control group and derived 4 previously defined variables associated with aggressive end-of-life care (chemotherapy received in the last 2 wk of life, > 1 emergency department visit within 30 d of death, > 1 hospital admission within 30 d of death and at least 1 intensive care unit admission within 30 d of death). We also examined place of death. We measured family/caregiver satisfaction with care 3 months after the patient's death using the FAMCARE questionnaire. RESULTS: Of 914 eligible decedents enrolled in the Symptom Management Program, 754 (82.5%) were matched. Receiving care through the program was protective for most measures of aggressive end-of-life care (absolute risk reduction [ARR] 12.73, 95% confidence interval [CI] 12.65-12.81 for any end-of-life care outcome) and death in an acute care setting (ARR 19.89, 95% CI 19.78-20.00). Of the 450 family caregivers invited to complete the FAMCARE questionnaire, 190 (42.2%) returned completed surveys; following data linkage and matching, 96 (21.3%) were available for analysis. Satisfaction with care received within the program appeared high (mean total score 85.72/100). INTERPRETATION: Provision of hospice palliative care through this ambulatory program was associated with lower use of aggressive end-of-life care and death outside of an acute care hospital. Improving access could be expected to provide positive benefits at the individual and system level.

Cancer incidence and mortality in northeastern Ontario, 1991-1998.

BACKGROUND: This descriptive epidemiology study reports the cancer incidence and mortality experience of Northeastern Ontario residents during the 8-year period from 1991-1998. METHODS: Standardized Incidence Ratios (SIRs), Standardized Mortality Ratios (SMRs) and 95% confidence intervals (CI) were calculated for a number of cancer sites (n = 25 for males, n = 26 for females), using rates determined from the Ontario population as the referent population. RESULTS: During the period 1991-1998, 24,019 cases of primary incident cancers (excluding non-melanotic skin cancer) and 11,677 deaths attributed to cancer occurred in Northeastern Ontario residents. Several cancer sites were significantly elevated in Northeastern Ontario residents. For example, trachea-bronchus-lung cancer incidence and mortality rates were significantly elevated. Rates were over 20% higher than those for the province of Ontario, for both males and females (SIR = 122, 95% CI = 118-127; SIR = 123, 95% CI = 117-129 for males and females, respectively; SMR = 125, 95% CI = 120-130; SMR = 125, 95% CI = 118-132 for males and females, respectively). CONCLUSIONS: For both males and females, the cancer incidence and mortality experience of residents of Northeastern Ontario were significantly higher than would be expected based on Ontario cancer rates, overall, and for a number of individual sites. While this study does not identify causal associations between risk factors and disease, these data should aid in cancer control planning, and generating hypotheses for further study.

Nucleotide excision repair polymorphisms and survival outcome for patients with metastatic breast cancer.

PURPOSE: Inter-individual variations in treatment efficacy may be influenced by polymorphisms in DNA repair genes. We investigated the association of 3 functional polymorphisms in the nucleotide excision repair (NER) pathway with survival outcome of 95 patients with metastatic breast cancer (MBC) treated with DNA-damaging chemotherapy. METHODS: ERCC1 8092 C/A, ERCC2 Asp312Asn and ERCC2 Lys751Gln were determined using Taqman-based genotyping assays. Genotype associations with breast cancer-specific survival (BCSS) and progression-free survival (PFS) were evaluated using Kaplan-Meier estimates and hazard ratios calculated using Cox regression analysis. Tests for trend were conducted by calculating P-values for the HR coefficient in proportional hazards regression models. RESULTS: ERCC2 Lys751Gln was significantly associated with BCSS (median: 24.8 months for AA/AC combined and 14.2 months for CC, HR: 1.9 (95% CI 1.06-3.26)). Median BCSS decreased with increasing number of designated adverse genotypes for the 3 polymorphisms (P (trend) = 0.003). Risk estimates for PFS were nonsignificantly elevated and were significantly elevated for BCSS for patients with 2 (HR = 2.21, 95% CI: 1.04-4.72) or 3 (HR = 6.67, 95% CI: 2.19-20.29) adverse genotypes. In treatment subgroup analysis, risk estimates for BCSS were significantly elevated for patients with 3 adverse genotypes treated with cyclophosphamide, mitoxantrone and vinblastine (HR: 11.9, 95% CI 1.77-79.51) and P (trend) = 0.02 for increasing number of adverse genotypes. Risk of progression was significantly increased for patients with 1 adverse genotype treated with cyclophosphamide, mitoxantrone and carboplatin (HR: 3.5, 95% CI 1.19-10.6) and P (trend) = 0.02 for increasing number of adverse genotypes. CONCLUSION: Polymorphisms in NER pathway may impact survival outcome for patients with MBC following treatment with DNA-damaging chemotherapy. These results provide support for a polygenic pathway approach for assessing the prognostic and predictive potential of polymorphisms in treatment outcome.

Smoking (active and passive), N-acetyltransferase 2, and risk of breast cancer.

BACKGROUND: The relationship between smoking and breast cancer remains controversial. The study aim was to assess the relationship of passive and active smoking to breast cancer risk by N-acetyltransferase 2 (NAT2) phenotype, using a comprehensive assessment of both passive and active smoking. METHODS: We undertook a population-based case-control study in Northeastern Ontario, Canada of 347 women diagnosed (2002-2004) with breast cancer and 775 population-based controls. The mailed study package included a questionnaire requesting information about established breast cancer risk factors, passive and active smoking, and a buccal swab for genetic analyses. RESULTS: Among never-active smokers, a long duration of passive smoking was associated with an increased risk of breast cancer (odds ratio (OR) 1.86 (95% confidence interval (95% CI) 1.01-3.44) (test for trend (p=0.07)); that risk was more elevated for NAT2 slow acetylators (OR 2.76, 95% CI 1.16-6.59) (and highest in extremely slow acetylators), but not elevated for NAT2 fast acetylators (OR 1.17, 95% CI 0.42-3.23). Among active smokers more than 20 pack-years of smoking was associated with an OR of 1.34 (95% CI 0.92-1.96); more elevated among NAT2 fast acetylators OR 1.93 (95% CI 1.01-3.69) but not elevated among NAT2 slow acetylators. Women who were NAT2 fast acetylators in the highest quartile for duration of active smoking had an OR of 2.74 (95% CI 1.42-5.27), with a significant test of trend (p=0.005). CONCLUSIONS: These findings suggest that passive and active smoking may be related to breast cancer, and the effect may be differentially modified by NAT2 phenotype. Further research into the genetic modification of a breast cancer-smoking relationship may help to reconcile earlier discrepant findings.

Polymorphisms in manganese superoxide dismutase, myeloperoxidase and glutathione-S-transferase and survival after treatment for metastatic breast cancer.

Treatments for metastatic breast cancer (MBC) are primarily palliative with variable efficacy and outcomes may be influenced by individual differences in drug metabolism. In this study, we examined the association of single nucleotide polymorphisms (SNPs) in genes involved in drug metabolism with progression free survival (PFS) and breast cancer specific survival (BCSS) in 95 patients with MBC that received high dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT). SNPs in the SOD2 (SOD2-01, Val16Ala), MPO (MPO-02, -463 promoter variant) and GSTP1 [GSTP1-01 (Ile105Val), GSTP1-02 (Ala114Val)] genes were examined in DNA isolated from cryopreserved blood products using genotyping assays. Survival was analysed using Cox proportional hazard models and Kaplan-Meier estimates. Patients with the SOD2-01 (TT) genotype had increased risk of disease progression [hazard ratio (HR): 2.52; 95% confidence interval (CI), 1.31-4.85] and breast cancer specific death (HR: 1.92; 95% CI: 1.03-3.57). Risks were increased for patients with both SOD2-01 (TT) and GSTP1-01 (GG or AG) genotypes (HR for disease progression: 2.57, 95% CI: 1.32-5.00 and HR for breast cancer specific death: 2.27; 95% CI: 1.18-4.34). In multivariable analysis, the combined genotype group of SOD2-01 and GSTP1-01 was an independent predictor of PFS and BCSS. HRs progressively increased with increasing number of genotypes associated with worse survival, with p(trend) of 0.005 and 0.006 for PFS and BCSS, respectively. These results suggest that SNPs in genes involved in drug metabolism may influence survival outcome for patients with MBC receiving HDC and ASCT.

Polymorphisms in XRCC1, XRCC3, and CCND1 and survival after treatment for metastatic breast cancer.

PURPOSE: Single nucleotide polymorphisms (SNPs) in DNA repair and cell cycle control genes may alter protein function and therefore the efficacy of DNA damaging chemotherapy. We retrospectively evaluated the association of SNPs in DNA repair genes, XRCC1-01 (Arg399Gln) and XRCC3-01 (Thr241Met), and a cell cycle control gene, CCND1-02 (A870G), with progression-free survival (PFS) and breast cancer specific survival (BCSS) in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: SNPs in 95 patients with MBC enrolled onto one of five prospective clinical trials of high-dose chemotherapy and autologous stem-cell transplantation were evaluated using genotyping assays. RESULTS: For XRCC1-01, the hazard ratio (HR) for BCSS was 2.8 (95% CI, 1.60 to 5.00) and the HR for PFS was 2.0 (95%CI, 1.12 to 3.43). For XRCC3-01, the HR for BCSS was 2.0 (95%CI, 1.12 to 3.70) and the HR for PFS was 2.0 (95%CI, 1.09 to 3.59). For CCND1-02, the HR for BCSS was 1.8 (95%CI, 1.12 to 2.78) and the HR for PFS was 1.8 (95%CI, 1.15 to 2.85). Patients carrying one variant genotype (HR, 1.7; 95%CI, 1.07 to 2.82) or combinations of any two variant genotypes (HR, 4.7; 95% CI, 2.41 to 8.94) had significantly poorer BCSS compared with patients carrying zero variants. In multivariable analysis, XRCC1-01, presence of liver metastases, and bone metastases independently predicted BCSS. Combinations of any two variant genotypes were stronger independent predictors of BCSS and PFS than the presence of liver or bone metastases. CONCLUSION: XRCC1-01, XRCC3-01, and CCND1-01 may be predictive of survival outcome in patients with MBC treated with DNA damaging chemotherapy.