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Canada: cancer statistics from IARC GlobalCan (2012)

Population in 2012: 34.7m
People newly diagnosed with cancer (excluding NMSC) / yr: 182,200
Age-standardised rate, incidence per 100,000 people/yr: 295.7
Risk of getting cancer before age 75:29.1%
People dying from cancer /yr: 74,100

Menu: Canadian Cancer Resources Directory

National Organisations: Canada
Cancer Centers
Latest Research Publications from Canada
Alberta / Northwest Territories
British Columbia / Yukon Territory
New Brunswick
Nova Scotia
Prince Edward Islands

National Organisations: Canada (19 links)

Cancer Centers (17 links)

Latest Research Publications from Canada

Miller AB, Wall C, Baines CJ, et al.
Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial.
BMJ. 2014; 348:g366 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: To compare breast cancer incidence and mortality up to 25 years in women aged 40-59 who did or did not undergo mammography screening.
DESIGN: Follow-up of randomised screening trial by centre coordinators, the study's central office, and linkage to cancer registries and vital statistics databases.
SETTING: 15 screening centres in six Canadian provinces,1980-85 (Nova Scotia, Quebec, Ontario, Manitoba, Alberta, and British Columbia).
PARTICIPANTS: 89,835 women, aged 40-59, randomly assigned to mammography (five annual mammography screens) or control (no mammography).
INTERVENTIONS: Women aged 40-49 in the mammography arm and all women aged 50-59 in both arms received annual physical breast examinations. Women aged 40-49 in the control arm received a single examination followed by usual care in the community.
MAIN OUTCOME MEASURE: Deaths from breast cancer.
RESULTS: During the five year screening period, 666 invasive breast cancers were diagnosed in the mammography arm (n=44,925 participants) and 524 in the controls (n=44,910), and of these, 180 women in the mammography arm and 171 women in the control arm died of breast cancer during the 25 year follow-up period. The overall hazard ratio for death from breast cancer diagnosed during the screening period associated with mammography was 1.05 (95% confidence interval 0.85 to 1.30). The findings for women aged 40-49 and 50-59 were almost identical. During the entire study period, 3250 women in the mammography arm and 3133 in the control arm had a diagnosis of breast cancer, and 500 and 505, respectively, died of breast cancer. Thus the cumulative mortality from breast cancer was similar between women in the mammography arm and in the control arm (hazard ratio 0.99, 95% confidence interval 0.88 to 1.12). After 15 years of follow-up a residual excess of 106 cancers was observed in the mammography arm, attributable to over-diagnosis.
CONCLUSION: Annual mammography in women aged 40-59 does not reduce mortality from breast cancer beyond that of physical examination or usual care when adjuvant therapy for breast cancer is freely available. Overall, 22% (106/484) of screen detected invasive breast cancers were over-diagnosed, representing one over-diagnosed breast cancer for every 424 women who received mammography screening in the trial.

Related: Breast Cancer Breast Cancer Screening Cancer Screening and Early Detection
Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario M5T 3M7, Canada.

Metcalfe K, Gershman S, Ghadirian P, et al.
Contralateral mastectomy and survival after breast cancer in carriers of BRCA1 and BRCA2 mutations: retrospective analysis.
BMJ. 2014; 348:g226 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: To compare the survival rates of women with BRCA associated breast cancer who did and did not undergo mastectomy of the contralateral breast.
DESIGN: Retrospective analysis.
SETTING: 12 cancer genetics clinics.
PARTICIPANTS: 390 women with a family history of stage I or II breast cancer who were carriers of BRCA1 and BRCA2 mutations and initially treated with unilateral or bilateral mastectomy. 181 patients had mastectomy of the contralateral breast. Patients were followed for up to 20 years from diagnosis.
MAIN OUTCOME MEASURE: Death from breast cancer.
RESULTS: 79 women died of breast cancer in the follow-up period (18 in the bilateral mastectomy group and 61 in the unilateral mastectomy group). The median follow-up time was 14.3 years (range 0.1-20.0 years). At 20 years the survival rate for women who had mastectomy of the contralateral breast was 88% (95% confidence interval 83% to 93%) and for those who did not was 66% (59% to 73%). In a multivariable analysis, controlling for age at diagnosis, year of diagnosis, treatment, and other prognostic features, contralateral mastectomy was associated with a 48% reduction in death from breast cancer (hazard ratio 0.52, 95% confidence interval 0.29 to 0.93; P=0.03). In a propensity score adjusted analysis of 79 matched pairs, the association was not significant (0.60, 0.34 to 1.06; P=0.08). Based on these results, we predict that of 100 women treated with contralateral mastectomy, 87 will be alive at 20 years compared with 66 of 100 women treated with unilateral mastectomy.
CONCLUSIONS: This study suggests that women who are positive for BRCA mutations and who are treated for stage I or II breast cancer with bilateral mastectomy are less likely to die from breast cancer than women who are treated with unilateral mastectomy. Given the small number of events in this cohort, further research is required to confirm these findings.

Related: Breast Cancer USA
Lawrence S Bloomberg Faculty of Nursing, University of Toronto, Canada.
Research funded by:

Nam RK, Cheung P, Herschorn S, et al.
Incidence of complications other than urinary incontinence or erectile dysfunction after radical prostatectomy or radiotherapy for prostate cancer: a population-based cohort study.
Lancet Oncol. 2014; 15(2):223-31 [PubMed] Related Publications
BACKGROUND: Studies of complications resulting from surgery or radiotherapy for prostate cancer have mainly focused on incontinence and erectile dysfunction. We aimed to assess other important complications associated with these treatments for prostate cancer.
METHODS: We did a population-based retrospective cohort study, in which we used administrative hospital data, physician billing codes, and cancer registry data for men who underwent either surgery or radiotherapy alone for prostate cancer between 2002 and 2009 in Ontario, Canada. We measured the 5-year cumulative incidence of five treatment-related complication endpoints: hospital admissions; urological, rectal, or anal procedures; open surgical procedures; and secondary malignancies.
FINDINGS: In the 32 465 patients included in the study, the 5-year cumulative incidence of admission to hospital for a treatment-related complication was 22·2% (95% CI 21·7-22·7), but was 2·4% (2·2-2·6) for patients whose length of stay was longer than 1 day. The 5-year cumulative incidence of needing a urological procedure was 32·0% (95% CI 31·4-32·5), that of a rectal or anal procedure was 13·7% (13·3-14·1), and that of an open surgical procedure was 0·9% (0·8-1·1). The 5-year cumulative incidence of a second primary malignancy was 3·0% (2·6-3·5). These risks were significantly higher than were those of 32 465 matched controls with no history of prostate cancer. Older age and comorbidity at the time of index treatment were important predictors for a complication in all outcome categories, but the type of treatment received was the strongest predictor for complications. Patients who were given radiotherapy had higher incidence of complications for hospital admissions, rectal or anal procedures, open surgical procedures, and secondary malignancies at 5 years than did those who underwent surgery (adjusted hazard ratios 2·08-10·8, p<0·0001). However, the number of urological procedures was lower in the radiotherapy than in the surgery group (adjusted hazard ratio 0·66, 95% CI 0·63-0·69; p<0·0001) INTERPRETATION: Complications after prostate cancer treatment are frequent and dependent on age, comorbidity, and the type of treatment. Patients and physicians should be aware of these risks when choosing treatment for prostate cancer, and should balance them with the clinical effectiveness of each therapy.
FUNDING: Ajmera Family Chair in Urologic Oncology.

Related: Prostate Cancer
Division of Urology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada. Electronic address:

Gorey KM, Luginaah IN, Bartfay E, et al.
Better colon cancer care for extremely poor Canadian women compared with American women.
Health Soc Work. 2013; 38(4):240-8 [PubMed] Article available free on PMC after 01/11/2014 Related Publications
Extremely poor Canadian women were recently observed to be largely advantaged on most aspects of breast cancer care as compared with similarly poor, but much less adequately insured, women in the United States. This historical study systematically replicated the protective effects of single- versus multipayer health care by comparing colon cancer care among cohorts of extremely poor women in California and Ontario between 1996 and 2011. The Canadian women were again observed to have been largely advantaged. They were more likely to have received indicated surgery and chemotherapy, and their wait times for care were significantly shorter. Consequently, the Canadian women were much more likely to experience longer survival times. Regression analyses indicated that health insurance nearly completely explained the Canadian advantages. Implications for contemporary and future reforms of U.S. health care are discussed.

Related: USA
School of Social Work, University of Windsor, Ontario, Canada.
Research funded by:

Fitch MI, McAndrew A, Harth T
Measuring trends in performance across time: providing information to cancer patients.
Can Oncol Nurs J. 2013; 23(4):247-61 [PubMed] Related Publications
Providing relevant, up-to-date information is identified as a quality standard of cancer care. Cancer programs need to be able to evaluate whether they are meeting the standard and to monitor their performance on an ongoing basis. Routine collection of clearly defined data, using reliable and valid measures, provides cancer program leaders with dependable information upon which to make decisions and monitor trends in performance over time. This article describes one cancer centre's experience in using standardized data collection regarding provision of patient information. The Cancer Patient Information Importance-Satisfaction Scale has been administered routinely in an outpatient setting over eight years. The profile we create from the data assists us in making informed decisions about patient education initiatives.

Related: Cancer Prevention and Risk Reduction
Odette Cancer Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON M4N 3N5.

DiSilvestro PA, Ali S, Craighead PS, et al.
Phase III randomized trial of weekly cisplatin and irradiation versus cisplatin and tirapazamine and irradiation in stages IB2, IIA, IIB, IIIB, and IVA cervical carcinoma limited to the pelvis: a Gynecologic Oncology Group study.
J Clin Oncol. 2014; 32(5):458-64 [PubMed] Article available free on PMC after 10/02/2015 Related Publications
PURPOSE: This prospective, randomized phase III intergroup trial of the Gynecologic Oncology Group and National Cancer Institute of Canada Clinical Trials Group was designed to test the effectiveness and safety of adding the hypoxic cell sensitizer tirapazamine (TPZ) to standard cisplatin (CIS) chemoradiotherapy in locally advanced cervix cancer.
PATIENTS AND METHODS: Patients with locally advanced cervix cancer were randomly assigned to CIS chemoradiotherapy versus CIS/TPZ chemoradiotherapy. Primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS) and tolerability.
RESULTS: PFS was evaluable in 387 of 402 patients randomly assigned over 36 months, with enrollment ending in September 2009. Because of the lack of TPZ supply, the study did not reach its original target accrual goal. At median follow-up of 28.3 months, PFS and OS were similar in both arms. Three-year PFS for the TPZ/CIS/RT and CIS/RT arms were 63.0% and 64.4%, respectively (log-rank P = .7869). Three-year OS for the TPZ/CIS/RT and CIS/RT arms were 70.5% and 70.6%, respectively (log-rank P = .8333). A scheduled interim safety analysis led to a reduction in the starting dose for the TPZ/CIS arm, with resulting tolerance in both treatment arms.
CONCLUSION: TPZ/CIS chemoradiotherapy was not superior to CIS chemoradiotherapy in either PFS or OS, although definitive commentary was limited by an inadequate number of events (progression or death). TPZ/CIS chemoradiotherapy was tolerable at a modified starting dose.

Related: Cisplatin USA Cervical Cancer
Paul A. DiSilvestro and Margaret M. Steinhoff, Women and Infants Hospital, Providence, RI; Shamshad Ali, Roswell Park Cancer Institute, Buffalo; Yi-Chun Lee, State University of New York Health Science Center, Brooklyn, NY; Peter S. Craighead, Tom Baker Cancer Center, Calgary, Alberta, Canada; Jose...
Research funded by:

Mahmud SM, Kliewer EV, Lambert P, et al.
Effectiveness of the quadrivalent human papillomavirus vaccine against cervical dysplasia in Manitoba, Canada.
J Clin Oncol. 2014; 32(5):438-43 [PubMed] Related Publications
PURPOSE: Effectiveness of the quadrivalent human papillomavirus (QHPV) vaccine against cervical dysplasia has not been estimated using population-based individual level data. We assessed the vaccine effectiveness (VE) of the QHPV vaccine against cervical dysplasia using data collected routinely in Manitoba.
METHODS: Females ≥ 15 years old who received the QHPV vaccine in Manitoba between September 2006 and April 2010 privately (n = 3,541) were matched on age to up to three nonvaccinated females (n = 9,594). We used Cox regression models to estimate the hazard ratios for three outcomes: atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesions (LSILs), and high-grade SILs (HSILs).
RESULTS: Among the 15- to 17-year-olds, the adjusted VE estimates were 35% (95% CI, -19% to 65%), 21% (-10% to 43%), and -1% (-44% to 29%) against the detection of HSILs, LSILs, and ASCUS, respectively. The corresponding estimates were higher (46% [0% to 71%], 35% [10% to 54%], and 23% [-8% to 45%]) among those who had ≥ one Pap smear after enrollment. The QHPV vaccine was associated with 23% (-17% to 48%) reduction in HSIL risk among those ≥ 18 with no history of abnormal cytology, but there was no evidence of protection among those with such a history (-8% [-59% to 27%]).
CONCLUSION: A significant percentage of vaccinated women may not be protected against HSIL and lesser dysplasia especially if they were vaccinated at older age (≥ 18) or had abnormal cytology before vaccination. These findings affirm the importance of vaccination before any significant exposure to HPV occurs and underscore the need for screening programs that cover all sexually active women, even if they were vaccinated.

Related: Cervical Cancer Human Papillomavirus (HPV), Vaccination, and Cervical Cancer
Salaheddin M. Mahmud, Erich V. Kliewer, Songul Bozat-Emre, and Alain A. Demers, University of Manitoba, Winnipeg, Manitoba, Canada; Salaheddin M. Mahmud, Erich V. Kliewer, Pascal Lambert, and Alain A. Demers, Epidemiology and Cancer Registry, CancerCare Manitoba, Winnipeg, Manitoba, Canada; and Eri...

Garland SN, Carlson LE, Stephens AJ, et al.
Mindfulness-based stress reduction compared with cognitive behavioral therapy for the treatment of insomnia comorbid with cancer: a randomized, partially blinded, noninferiority trial.
J Clin Oncol. 2014; 32(5):449-57 [PubMed] Related Publications
PURPOSE: Our study examined whether mindfulness-based stress reduction (MBSR) is noninferior to cognitive behavioral therapy for insomnia (CBT-I) for the treatment of insomnia in patients with cancer.
PATIENTS AND METHODS: This was a randomized, partially blinded, noninferiority trial involving patients with cancer with insomnia recruited from a tertiary cancer center in Calgary, Alberta, Canada, from September 2008 to March 2011. Assessments were conducted at baseline, after the program, and after 3 months of follow-up. The noninferiority margin was 4 points measured by the Insomnia Severity Index. Sleep diaries and actigraphy measured sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), and sleep efficiency. Secondary outcomes included sleep quality, sleep beliefs, mood, and stress.
RESULTS: Of 327 patients screened, 111 were randomly assigned (CBT-I, n = 47; MBSR, n = 64). MBSR was inferior to CBT-I for improving insomnia severity immediately after the program (P = .35), but MBSR demonstrated noninferiority at follow-up (P = .02). Sleep diary-measured SOL was reduced by 22 minutes in the CBT-I group and by 14 minutes in the MBSR group at follow-up. Similar reductions in WASO were observed for both groups. TST increased by 0.60 hours for CBT-I and 0.75 hours for MBSR. CBT-I improved sleep quality (P < .001) and dysfunctional sleep beliefs (P < .001), whereas both groups experienced reduced stress (P < .001) and mood disturbance (P < .001).
CONCLUSION: Although MBSR produced a clinically significant change in sleep and psychological outcomes, CBT-I was associated with rapid and durable improvement and remains the best choice for the nonpharmacologic treatment of insomnia.

Related: Cancer Prevention and Risk Reduction
Sheila N. Garland, Abramson Cancer Center, University of Pennsylvania Health System, and Perelman School of Medicine; Alisa J. Stephens, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA; Sheila N. Garland, Linda E. Carlson, Michael C. Antle, Charles S...

Chow E, van der Linden YM, Roos D, et al.
Single versus multiple fractions of repeat radiation for painful bone metastases: a randomised, controlled, non-inferiority trial.
Lancet Oncol. 2014; 15(2):164-71 [PubMed] Related Publications
BACKGROUND: Although repeat radiation treatment has been shown to palliate pain in patients with bone metastases from multiple primary origin sites, data for the best possible dose fractionation schedules are lacking. We aimed to assess two dose fractionation schedules in patients with painful bone metastases needing repeat radiation therapy.
METHODS: We did a multicentre, non-blinded, randomised, controlled trial in nine countries worldwide. We enrolled patients 18 years or older who had radiologically confirmed, painful (ie, pain measured as ≥2 points using the Brief Pain Inventory) bone metastases, had received previous radiation therapy, and were taking a stable dose and schedule of pain-relieving drugs (if prescribed). Patients were randomly assigned (1:1) to receive either 8 Gy in a single fraction or 20 Gy in multiple fractions by a central computer-generated allocation sequence using dynamic minimisation to conceal assignment, stratified by previous radiation fraction schedule, response to initial radiation, and treatment centre. Patients, caregivers, and investigators were not masked to treatment allocation. The primary endpoint was overall pain response at 2 months, which was defined as the sum of complete and partial pain responses to treatment, assessed using both Brief Pain Inventory scores and changes in analgesic consumption. Analysis was done by intention to treat. This study is registered with, number NCT00080912.
FINDINGS: Between Jan 7, 2004, and May 24, 2012, we randomly assigned 425 patients to each treatment group. 19 (4%) patients in the 8 Gy group and 12 (3%) in the 20 Gy group were found to be ineligible after randomisation, and 140 (33%) and 132 (31%) patients, respectively, were not assessable at 2 months and were counted as missing data in the intention-to-treat analysis. In the intention-to-treat population, 118 (28%) patients allocated to 8 Gy treatment and 135 (32%) allocated to 20 Gy treatment had an overall pain response to treatment (p=0·21; response difference of 4·00% [upper limit of the 95% CI 9·2, less than the prespecified non-inferiority margin of 10%]). In the per-protocol population, 116 (45%) of 258 patients and 134 (51%) of 263 patients, respectively, had an overall pain response to treatment (p=0·17; response difference 6·00% [upper limit of the 95% CI 13·2, greater than the prespecified non-inferiority margin of 10%]). The most frequently reported acute radiation-related toxicities at 14 days were lack of appetite (201 [56%] of 358 assessable patients who received 8 Gy vs 229 [66%] of 349 assessable patients who received 20 Gy; p=0·011) and diarrhoea (81 [23%] of 357 vs 108 [31%] of 349; p=0·018). Pathological fractures occurred in 30 (7%) of 425 patients assigned to 8 Gy and 20 (5%) of 425 assigned to 20 Gy (odds ratio [OR] 1·54, 95% CI 0·85-2·75; p=0·15), and spinal cord or cauda equina compressions were reported in seven (2%) of 425 versus two (<1%) of 425, respectively (OR 3·54, 95% CI 0·73-17·15; p=0·094).
INTERPRETATION: In patients with painful bone metastases requiring repeat radiation therapy, treatment with 8 Gy in a single fraction seems to be non-inferior and less toxic than 20 Gy in multiple fractions; however, as findings were not robust in a per-protocol analysis, trade-offs between efficacy and toxicity might exist.
FUNDING: Canadian Cancer Society Research Institute, US National Cancer Institute, Cancer Council Australia, Royal Adelaide Hospital, Dutch Cancer Society, and Assistance Publique-Hôpitaux de Paris.

Related: Australia
Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada. Electronic address:
Research funded by:

Vlaanderen J, Portengen L, Schüz J, et al.
Effect modification of the association of cumulative exposure and cancer risk by intensity of exposure and time since exposure cessation: a flexible method applied to cigarette smoking and lung cancer in the SYNERGY Study.
Am J Epidemiol. 2014; 179(3):290-8 [PubMed] Article available free on PMC after 01/02/2015 Related Publications
The indiscriminate use of the cumulative exposure metric (the product of intensity and duration of exposure) might bias reported associations between exposure to hazardous agents and cancer risk. To assess the independent effects of duration and intensity of exposure on cancer risk, we explored effect modification of the association of cumulative exposure and cancer risk by intensity of exposure. We applied a flexible excess odds ratio model that is linear in cumulative exposure but potentially nonlinear in intensity of exposure to 15 case-control studies of cigarette smoking and lung cancer (1985-2009). Our model accommodated modification of the excess odds ratio per pack-year of cigarette smoking by time since smoking cessation among former smokers. We observed negative effect modification of the association of pack-years of cigarette smoking and lung cancer by intensity of cigarette smoke for persons who smoked more than 20-30 cigarettes per day. Patterns of effect modification were similar across individual studies and across major lung cancer subtypes. We observed strong negative effect modification by time since smoking cessation. Application of our method in this example of cigarette smoking and lung cancer demonstrated that reducing a complex exposure history to a metric such as cumulative exposure is too restrictive.

Related: Lung Cancer Smoking and Smoking Cessation

Wu RC, Ayhan A, Maeda D, et al.
Frequent somatic mutations of the telomerase reverse transcriptase promoter in ovarian clear cell carcinoma but not in other major types of gynaecological malignancy.
J Pathol. 2014; 232(4):473-81 [PubMed] Article available free on PMC after 01/03/2015 Related Publications
Up-regulated expression of telomerase reverse transcriptase (TERT) and subsequent maintenance of telomere length are essential in tumour development. Recent studies have implicated somatic gain-of-function mutations at the TERT promoter as one of the mechanisms that promote transcriptional activation of TERT; however, it remains unclear whether this genetic abnormality is prevalent in gynaecological neoplasms. We performed mutational analysis in a total of 525 gynaecological cancers, and correlated TERT promoter mutations with clinicopathological features. With the exception of ovarian clear cell carcinomas, in which mutations were found in 37 (15.9%) of 233 cases, the majority of gynaecological malignancies were wild-type. TERT promoter mutation does not appear to be an early event during oncogenesis, as it was not detected in the contiguous endometriosis associated with ovarian clear cell carcinoma. Ovarian clear cell carcinoma cell lines with TERT promoter mutations exhibited higher TERT mRNA expression than those with wild-type sequences (p = 0.0238). TERT promoter mutation tended to be mutually exclusive with loss of ARID1A protein expression (p = 4.4 × 10(-9) ) and PIK3CA mutation (p = 0.0019) in ovarian clear cell carcinomas. No associations with disease-specific survival were observed for ovarian clear cell carcinoma. The above results, in conjunction with our previous report showing longer telomeres in ovarian clear cell carcinomas relative to other types of ovarian cancer, suggests that aberrations in telomere biology may play an important role in the pathogenesis of ovarian clear cell carcinoma.

Related: Ovarian Cancer
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.
Research funded by:

Baker JM, To T, Beyene J, et al.
Influence of length of time to diagnosis and treatment on the survival of children with acute lymphoblastic leukemia: a population-based study.
Leuk Res. 2014; 38(2):204-9 [PubMed] Related Publications
The objectives were to describe times to diagnosis and initiation of treatment in pediatric ALL in Ontario from 1997 to 2007, and to measure their impact on OS and EFS. In 1000 children, the median times to diagnosis and treatment were both 1 day (IQR = 1-2). Those who began treatment >3 days after diagnosis had inferior OS (AHR = 2.49; 95% CI = 1.40-4.43; p = 0.002), and inferior EFS (AHR = 1.73; 95% CI = 1.01-2.96; p = 0.047) compared to those who began treatment ≤ 3 days after diagnosis. There was no statistically significant relationship between time to diagnosis and survival. Longer time to treatment was associated with worse survival in pediatric ALL; reasons for this relationship may be multi-factorial.

Related: Acute Lymphocytic Leukemia (ALL) Childhood Acute lymphoblastic leukaemia (ALL) ALL - Molecular Biology
Department of Pediatrics and Department of Internal Medicine, St. Michael's Hospital, University of Toronto, Toronto, Canada. Electronic address:

Gupta S, Kong W, Booth CM, Mackillop WJ
Impact of concomitant chemotherapy on outcomes of radiation therapy for head-and-neck cancer: a population-based study.
Int J Radiat Oncol Biol Phys. 2014; 88(1):115-21 [PubMed] Related Publications
PURPOSE: Clinical trials have shown that the addition of chemotherapy to radiation therapy (RT) improves survival in advanced head-and-neck cancer. The objective of this study was to describe the effectiveness of concomitant chemoradiation therapy (C-CRT) in routine practice.
METHODS AND MATERIALS: This was a population-based cohort study. Electronic records of treatment from all provincial cancer centers were linked to a population--based cancer registry to describe the adoption of C-CRT for head-and-neck cancer patients in Ontario, Canada. The study population was then divided into pre- and postadoption cohorts, and their outcomes were compared.
RESULTS: Between 1992 and 2008, 18,867 patients had diagnoses of head-and-neck cancer in Ontario, of whom 7866 (41.7%) were treated with primary RT. The proportion of primary RT cases that received C-CRT increased from 2.2% in the preadoption cohort (1992-1998) to 39.3% in the postadoption cohort (2003-2008). Five-year survival among all primary RT cases increased from 43.6% in the preadoption cohort to 51.8% in the postadoption cohort (P<.001). Over the same period, treatment-related hospital admissions increased significantly, but there was no significant increase in treatment-related deaths.
CONCLUSIONS: C-CRT was widely adopted in Ontario after 2003, and its adoption was temporally associated with an improvement in survival.

Related: Head and Neck Cancers Head and Neck Cancers - Molecular Biology
Division of Cancer Care and Epidemiology, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada.
Research funded by:

Villeneuve PJ, Jerrett M, Brenner D, et al.
A case-control study of long-term exposure to ambient volatile organic compounds and lung cancer in Toronto, Ontario, Canada.
Am J Epidemiol. 2014; 179(4):443-51 [PubMed] Related Publications
Few studies have investigated associations between nonoccupational exposure to ambient volatile organic compounds and lung cancer. We conducted a case-control study of 445 incident lung cancers and 948 controls (523 hospital, 425 general population) in Toronto, Ontario, Canada, between 1997 and 2002. Participants provided information on several risk factors, including tobacco use, secondhand exposure to cigarette smoke, obesity, and family history of cancer. Exposure to benzene, hydrocarbons, and nitrogen dioxide was estimated using land-use regression models. Exposures were linked to residential addresses to estimate exposure at the time of interview, 10 years before interview, and across past residences (time-weighted average). Logistic regression was used to estimate adjusted odds ratios. Analyses involving the population-based controls found that an interquartile-range increase in the time-weighted average benzene concentration (0.15 µg/m(3)) across previous residences was associated with lung cancer (odds ratio = 1.84, 95% confidence interval: 1.26, 2.68). Similarly, an interquartile-range increase in the time-weighted average nitrogen dioxide concentration (4.8 ppb) yielded an odds ratio of 1.59 (95% confidence interval: 1.19, 2.12). Our study suggests that long-term exposure to ambient volatile organic compounds and nitrogen dioxide at relatively low concentrations is associated with lung cancer. Further work is needed to evaluate joint relationships between these pollutants, smoking, and lung cancer.

Related: Lung Cancer

McGuire AL, Hopman WM, Petsikas D, Reid K
Outcomes: wedge resection versus lobectomy for non-small cell lung cancer at the Cancer Centre of Southeastern Ontario 1998-2009.
Can J Surg. 2013; 56(6):E165-70 [PubMed] Article available free on PMC after 01/03/2015 Related Publications
BACKGROUND: Sublobar resection for non-small cell lung cancer (NSCLC) remains controversial owing to concern about local recurrence and long-term survival outcomes. We sought to determine the efficacy of wedge resection as an oncological procedure.
METHODS: We analyzed the outcomes of all patients with NSCLC undergoing surgical resection at the Cancer Centre of Southeastern Ontario between 1998 and 2009. The standard of care for patients with adequate cardiopulmonary reserve was lobectomy. Wedge resection was performed for patients with inadequate reserve to tolerate lobectomy. Predictors of recurrence and survival were assessed. Appropriate statistical analyses involved the χ(2) test, an independent samples t test and Kaplan-Meier estimates of survival. Outcomes were stratified for tumour size and American Joint Committee on Cancer seventh edition TNM stage for non-small cell lung cancer.
RESULTS: A total of 423 patients underwent surgical resection during our study period: wedge resection in 71 patients and lobectomy in 352. The mean age of patients was 64 years. Mean follow-up for cancer survivors was 39 months. There was no significant difference between wedge resection and lobectomy for rate of tumour recurrence, mortality or disease-free survival in patients with stage IA tumours less than 2 cm in diameter.
CONCLUSION: Wedge resection with lymph node sampling is an adequate oncological procedure for non-small cell lung cancer in properly selected patients, specifically, those with stage IA tumours less than 2 cm in diameter.

Related: Non-Small Cell Lung Cancer Lung Cancer
From the Division of Thoracic Surgery, the Ottawa Hospital, Ottawa, Ont.

Lam E, Strugnell SS, Bajdik C, et al.
Limited adequacy of thyroid cancer patient follow-up at a Canadian tertiary care centre.
Can J Surg. 2013; 56(6):385-92 [PubMed] Article available free on PMC after 01/03/2015 Related Publications
BACKGROUND: We sought to evaluate the adequacy of follow-up of thyroid cancer patients at a Canadian centre.
METHODS: We mailed a survey to the family physicians of thyroid cancer patients and analyzed the findings relative to follow-up guidelines published by the American Thyroid Association (ATA). Statistical significance between early and late follow-up patterns was analyzed using the χ(2) test.
RESULTS: Our survey response rate was 56.2% (91 of 162). The time from operation ranged from 1.24-7.13 (mean 3.96) years, and 87.9% of patients had undergone a physical exam within the previous year. Only 37.4% and 14% of patients had a serum thyroglobulin measurement within 6 and between 6 and 12 months before the survey, respectively. Thyroid simulating hormone (TSH) levels were measured within the prior 6 months in 67% of patients and between 6 and 12 months in 13.2%. The TSH levels were suppressed (< 0.1 μIU/L) in 24.2% of patients, 0.1-2 μIU/L in 44% and greater than 2 μIU/L in 17.6%. Ultrasonography was the most common imaging test performed.
CONCLUSION: There is significant variation in the follow-up patterns of patients with thyroid cancer, and there is considerable deviation from current ATA guidelines.

Related: Thyroid Cancer
The Department of Surgery, St. Paul's Hospital & University of British Columbia, Vancouver, BC.

Elit LM, O'Leary EM, Pond GR, Seow HY
Impact of wait times on survival for women with uterine cancer.
J Clin Oncol. 2014; 32(1):27-33 [PubMed] Related Publications
PURPOSE: To determine whether wait time from histologic diagnosis of uterine cancer to time of definitive surgery by hysterectomy had an impact on all-cause survival.
PATIENTS AND METHODS: Women in Ontario with a confirmed histopathologic diagnosis of uterine cancer between April 1, 2000, and March 31, 2009, followed by surgery were identified in the Ontario Cancer Registry. Survival was calculated by using the Kaplan-Meier method. Factors were evaluated for their prognostic effect on survival by using Cox proportional hazards regression. Wait time was evaluated in a multivariable model after adjusting for other significant factors.
RESULTS: The final study population included 9,417 women; 51.9% had surgery by a gynecologist, and 69.9% had endometrioid adenocarcinoma. Five-year survival for women with wait times of 0.1 to 2, 2.1 to 6, 6.1 to 12, or more than 12 weeks was 71.1%, 81.8%, 79.5%, and 71.9%, respectively. Wait times of ≤ 2 weeks were adversely prognostic for survival after adjusting for other significant factors in the multivariable model, and patients with wait times of more than 12 weeks had worse survival than those who had wait times between 2.1 and 12.0 weeks.
CONCLUSION: To the best of our knowledge, this is the first report in a large population-based cohort demonstrating that longer wait times from diagnosis of uterine cancer to definitive surgery have a negative impact on overall survival.
All authors: Escarpment Cancer Research Institute, McMaster University, Hamilton, ON, Canada.

Akbari MR, Lepage P, Rosen B, et al.
PPM1D mutations in circulating white blood cells and the risk for ovarian cancer.
J Natl Cancer Inst. 2014; 106(1):djt323 [PubMed] Related Publications
We compared the frequency of PPM1D mutation in the white blood cells from 1295 ovarian cancer case patients and 834 control subjects. We found a truncating mutation in 20 case patients vs 1 control subject (odds ratio [OR] = 13.07; 95% confidence interval [CI] = 1.75 to 97.55; P < .001). The 12-year mortality of the PPM1D-positive case patients was higher than that of the PPM1D-negative case patients (hazard ratio = 2.02; 95% CI = 1.21 to 3.39; P = .007). Three of the 20 PPM1D carrier case patients had a past history of breast cancer compared with 29 of 1129 noncarriers (OR = 6.69; 95% CI = 1.86 to 24.11; P = .007). The lifetime risks for breast or ovarian cancer among female first-degree relatives of PPM1D mutation carriers were not increased compared with that of case patients without mutations. These observations suggest PPM1D mutations in the mosaic state predispose women to breast and ovarian cancer in the absence of a family history of cancer.

Related: Breast Cancer Ovarian Cancer
Affiliations of authors: Womens College Research Institute, Womens College Hospital (MRA, SAN), Dalla Lana School of Public Health (MRA, JM, SAN), Samuel Lunenfeld Research Institute (JM), University of Toronto, Toronto, Canada; Genome Quebec Innovation Centre, McGill University, Montreal, Canada (...

Sin DD, Tammemagi CM, Lam S, et al.
Pro-surfactant protein B as a biomarker for lung cancer prediction.
J Clin Oncol. 2013; 31(36):4536-43 [PubMed] Article available free on PMC after 20/12/2014 Related Publications
PURPOSE: Preliminary studies have identified pro-surfactant protein B (pro-SFTPB) to be a promising blood biomarker for non-small-cell lung cancer. We conducted a study to determine the independent predictive potential of pro-SFTPB in identifying individuals who are subsequently diagnosed with lung cancer.
PATIENTS AND METHODS: Pro-SFTPB levels were measured in 2,485 individuals, who enrolled onto the Pan-Canadian Early Detection of Lung Cancer Study by using plasma sample collected at the baseline visit. Multivariable logistic regression models were used to evaluate the predictive ability of pro-SFTPB in addition to known lung cancer risk factors. Calibration and discrimination were evaluated, the latter by an area under the receiver operating characteristic curve (AUC). External validation was performed with samples collected in the Carotene and Retinol Efficacy Trial (CARET) participants using a case-control study design.
RESULTS: Adjusted for age, sex, body mass index, personal history of cancer, family history of lung cancer, forced expiratory volume in one second percent predicted, average number of cigarettes smoked per day, and smoking duration, pro-SFTPB (log transformed) had an odds ratio of 2.220 (95% CI, 1.727 to 2.853; P < .001). The AUCs of the full model with and without pro-SFTPB were 0.741 (95% CI, 0.696 to 0.783) and 0.669 (95% CI, 0.620 to 0.717; difference in AUC P < .001). In the CARET Study, the use of pro-SFPTB yielded an AUC of 0.683 (95% CI, 0.604 to 0.761).
CONCLUSION: Pro-SFTPB in plasma is an independent predictor of lung cancer and may be a valuable addition to existing lung cancer risk prediction models.

Related: Non-Small Cell Lung Cancer Cancer Screening and Early Detection Lung Cancer
Don D. Sin, Stephen Lam, and Anthony Tam, University of British Columbia; Don D. Sin and Anthony Tam, Institute of Heart and Lung Health, James Hogg Research Center, St. Paul's Hospital; Stephen Lam and Xiaobo Duan, British Columbia Cancer Agency, Vancouver, British Columbia; C. Martin Tammemagi, B...
Research funded by:

Chaturvedi AK, Anderson WF, Lortet-Tieulent J, et al.
Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers.
J Clin Oncol. 2013; 31(36):4550-9 [PubMed] Article available free on PMC after 20/12/2014 Related Publications
PURPOSE: Human papillomavirus (HPV) has been identified as the cause of the increasing oropharyngeal cancer (OPC) incidence in some countries. To investigate whether this represents a global phenomenon, we evaluated incidence trends for OPCs and oral cavity cancers (OCCs) in 23 countries across four continents.
METHODS: We used data from the Cancer Incidence in Five Continents database Volumes VI to IX (years 1983 to 2002). Using age-period-cohort modeling, incidence trends for OPCs were compared with those of OCCs and lung cancers to delineate the potential role of HPV vis-à-vis smoking on incidence trends. Analyses were country specific and sex specific.
RESULTS: OPC incidence significantly increased during 1983 to 2002 predominantly in economically developed countries. Among men, OPC incidence significantly increased in the United States, Australia, Canada, Japan, and Slovakia, despite nonsignificant or significantly decreasing incidence of OCCs. In contrast, among women, in all countries with increasing OPC incidence (Denmark, Estonia, France, the Netherlands, Poland, Slovakia, Switzerland, and United Kingdom), there was a concomitant increase in incidence of OCCs. Although increasing OPC incidence among men was accompanied by decreasing lung cancer incidence, increasing incidence among women was generally accompanied by increasing lung cancer incidence. The magnitude of increase in OPC incidence among men was significantly higher at younger ages (< 60 years) than older ages in the United States, Australia, Canada, Slovakia, Denmark, and United Kingdom.
CONCLUSION: OPC incidence significantly increased during 1983 to 2002 predominantly in developed countries and at younger ages. These results underscore a potential role for HPV infection on increasing OPC incidence, particularly among men.

Related: Australia Lung Cancer Oral Cancer Oropharyngeal Cancer USA
Anil K. Chaturvedi, William F. Anderson, and Philip S. Rosenberg, National Cancer Institute, Rockville, MD; Maura L. Gillison, The Ohio State University, Columbus, OH; Joannie Lortet-Tieulent, Jacques Ferlay, Silvia Franceschi, and Freddie Bray, International Agency for Research on Cancer; and Mari...

Zablotska LB, Lane RS, Thompson PA
A reanalysis of cancer mortality in Canadian nuclear workers (1956-1994) based on revised exposure and cohort data.
Br J Cancer. 2014; 110(1):214-23 [PubMed] Article available free on PMC after 20/12/2014 Related Publications
BACKGROUND: A 15-country study of nuclear workers reported significantly increased radiation-related risks of all cancers excluding leukaemia, with Canadian data a major factor behind the pooled results. We analysed mortality (1956-1994) in the updated Canadian cohort and provided revised risk estimates.
METHODS: Employment records were searched to verify and revise exposure data and to restore missing socioeconomic status. Excess relative risks per sievert (ERR/Sv) of recorded radiation dose and 95% confidence intervals (CIs) were estimated using Poisson regression.
RESULTS: A significant heterogeneity of the dose-response for solid cancer was identified (P=0.02), with 3088 early (1956-1964) Atomic Energy of Canada Limited (AECL) workers having a significant increase (ERR/Sv=7.87, 95% CI: 1.88, 19.5), and no evidence of radiation risk for 42,228 workers employed by three nuclear power plant companies and post-1964 AECL (ERR/Sv=-1.20, 95% CI: <-1.47, 2.39). Radiation risks of leukaemia were negative in early AECL workers and non-significantly increased in other workers. In analyses with separate terms for tritium and gamma doses, there was no evidence of increased risk from tritium exposure. All workers had mortality lower than the general population.
CONCLUSION: Significantly increased risks for early AECL workers are most likely due to incomplete transfer of AECL dose records to the National Dose Registry. Analyses of the remainder of the Canadian nuclear workers (93.2%) provided no evidence of increased risk, but the risk estimate was compatible with estimates that form the basis of radiation protection standards. Study findings suggest that the revised Canadian cohort, with the exclusion of early AECL workers, would likely have an important effect on the 15-country pooled risk estimate of radiation-related risks of all cancer excluding leukaemia by substantially reducing the size of the point estimate and its significance.
Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco, CA 94118, USA.
Research funded by:

Kim ES, Neubauer M, Cohn A, et al.
Docetaxel or pemetrexed with or without cetuximab in recurrent or progressive non-small-cell lung cancer after platinum-based therapy: a phase 3, open-label, randomised trial.
Lancet Oncol. 2013; 14(13):1326-36 [PubMed] Related Publications
BACKGROUND: Available preclinical and phase 2 clinical data suggest that the addition of cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor (EGFR), to chemotherapy might improve outcome in patients with advanced non-small-cell lung cancer (NSCLC). We aimed to assess whether the addition of cetuximab to chemotherapy improved progression-free survival in patients with recurrent or progressive NSCLC after platinum-based therapy.
METHODS: In this unmasked, open-label randomised phase 3 trial we enrolled patients with metastatic, unresectable, or locally advanced NSCLC from 121 sites in Canada and the USA. Eligible patients were those aged 18 years or older who had experienced progressive disease during or after one previous platinum-based regimen. Initially, patients were randomly assigned to receive either pemetrexed (500 mg/m(2)) or docetaxel (75 mg/m(2)) and then randomly assigned within each group to receive their chemotherapy with or without cetuximab (400 mg/m(2) at first dose and 250 mg/m(2) weekly thereafter) until disease progression or unacceptable toxicity. However, after a change in the standard of care, investigators chose whether to treat with pemetrexed or docetaxel on a patient-by-patient basis. The primary analysis was changed to compare progression-free survival with cetuximab plus pemetrexed versus pemetrexed, on an intention-to-treat basis. This study is registered with, number NCT00095199.
FINDINGS: Between Jan 10, 2005, and Feb 10, 2010, we enrolled 939 patients; data for one patient was accidentally discarded. Of the remaining 938 patients, 605 received pemetrexed (301 patients with cetuximab and 304 alone) and 333 received docetaxel (167 in combination with cetuximab and 166 alone). Median progression-free survival with cetuximab plus pemetrexed was 2·9 months (95% CI 2·7-3·2) versus 2·8 months (2·5-3·3) with pemetrexed (HR 1·03, 95% CI 0·87-1·21; p=0·76). The most common grade 3-4 adverse events with cetuximab plus pemetrexed were fatigue (33 [11%] of 292 patients), acneiform rash (31 [11%]), dyspnoea (29 [10%]), and decreased neutrophil count (28 [10%]), and with pemetrexed alone were dyspnoea (35 [12%] of 289 patients), decreased neutrophil count (26 [9%]), and fatigue (23 [8%]). A significantly higher proportion of patients in the cetuximab plus pemetrexed group (119 [41%] of 292 patients) experienced at least one serious adverse event than those patients in the pemetrexed group (85 [29%] of 289 patients; p=0·0054). Nine (3%) of 292 treated patients in the cetuximab and pemetrexed group died of adverse events compared with five (2%) of 289 treated patients in the pemetrexed alone group.
INTERPRETATION: The use of cetuximab is not recommended in combination with chemotherapy in patients previously treated with platinum-based therapy.
FUNDING: Eli Lilly and Company and ImClone Systems LLC, a wholly owned subsidiary of Eli Lilly and Company.

Related: Non-Small Cell Lung Cancer Lung Cancer USA Pemetrexed Docetaxel Cetuximab (Erbitux)
Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, USA. Electronic address:

Meyerhardt JA, Mangu PB, Flynn PJ, et al.
Follow-up care, surveillance protocol, and secondary prevention measures for survivors of colorectal cancer: American Society of Clinical Oncology clinical practice guideline endorsement.
J Clin Oncol. 2013; 31(35):4465-70 [PubMed] Related Publications
PURPOSE: The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing recent clinical practice guidelines that have been developed by other professional organizations.
METHODS: The Cancer Care Ontario (CCO) Guideline on Follow-up Care, Surveillance Protocol, and Secondary Prevention Measures for Survivors of Colorectal Cancer was reviewed by ASCO for methodologic rigor and considered for endorsement.
RESULTS: The ASCO Panel concurred with the CCO recommendations and recommended endorsement, with the addition of several qualifying statements.
CONCLUSION: Surveillance should be guided by presumed risk of recurrence and functional status of the patient (important within the first 2 to 4 years). Medical history, physical examination, and carcinoembryonic antigen testing should be performed every 3 to 6 months for 5 years. Patients at higher risk of recurrence should be considered for testing in the more frequent end of the range. A computed tomography scan (abdominal and chest) is recommended annually for 3 years, in most cases. Positron emission tomography scans should not be used for surveillance outside of a clinical trial. A surveillance colonoscopy should be performed 1 year after the initial surgery and then every 5 years, dictated by the findings of the previous one. If a colonoscopy was not preformed before diagnosis, it should be done after completion of adjuvant therapy (before 1 year). Secondary prevention (maintaining a healthy body weight and active lifestyle) is recommended. If a patient is not a candidate for surgery or systemic therapy because of severe comorbid conditions, surveillance tests should not be performed. A treatment plan from the specialist should have clear directions on appropriate follow-up by a nonspecialist.

Related: Colorectal (Bowel) Cancer USA
Jeffrey A. Meyerhardt and Deborah H. Schrag, Dana-Farber Cancer Institute, Boston, MA; Pamela B. Mangu, American Society of Clinical Oncology; Kim Ryan, Fight Colorectal Cancer, Alexandria, VA; Patrick J. Flynn, Minnesota Oncology, Minneapolis; Charles L. Loprinzi, Mayo Clinic, Rochester, MN; Laris...

Lee L, Saleem A, Landry T, et al.
Cost effectiveness of mesh prophylaxis to prevent parastomal hernia in patients undergoing permanent colostomy for rectal cancer.
J Am Coll Surg. 2014; 218(1):82-91 [PubMed] Related Publications
BACKGROUND: Parastomal hernia (PSH) is common after stoma formation. Studies have reported that mesh prophylaxis reduces PSH, but there are no cost-effectiveness data. Our objective was to determine the cost effectiveness of mesh prophylaxis vs no prophylaxis to prevent PSH in patients undergoing abdominoperineal resection with permanent colostomy for rectal cancer.
STUDY DESIGN: Using a cohort Markov model, we modeled the costs and effectiveness of mesh prophylaxis vs no prophylaxis at the index operation in a cohort of 60-year-old patients undergoing abdominoperineal resection for rectal cancer during a time horizon of 5 years. Costs were expressed in 2012 Canadian dollars (CAD$) and effectiveness in quality-adjusted life years. Deterministic and probabilistic sensitivity analyses were performed.
RESULTS: In patients with stage I to III rectal cancer, prophylactic mesh was dominant (less costly and more effective) compared with no mesh. In patients with stage IV disease, mesh prophylaxis was associated with higher cost (CAD$495 more) and minimally increased effectiveness (0.05 additional quality-adjusted life years), resulting in an incremental cost-effectiveness ratio of CAD$10,818 per quality-adjusted life year. On sensitivity analyses, the decision was sensitive to the probability of mesh infection and the cost of the mesh, and method of diagnosing PSH.
CONCLUSIONS: In patients undergoing abdominoperineal resection with permanent colostomy for rectal cancer, mesh prophylaxis might be the less costly and more effective strategy compared with no mesh to prevent PSH in patients with stage I to III disease, and might be cost effective in patients with stage IV disease.
Steinberg-Bernstein Centre for Minimally-Invasive Surgery and Innovation, McGill University Health Centre, Montreal, Quebec, Canada; Department of Surgery, McGill University Health Centre, Montreal, Quebec, Canada.

Drolet M, Laprise JF, Boily MC, et al.
Potential cost-effectiveness of the nonavalent human papillomavirus (HPV) vaccine.
Int J Cancer. 2014; 134(9):2264-8 [PubMed] Related Publications
Randomized clinical trials are currently examining the efficacy of a nonavalent human papillomavirus (HPV) vaccine, including HPV-types 6/11/16/18/31/33/45/52/58. Evidence on the cost-effectiveness of the nonavalent is required for timely policy-decisions. We compared the potential cost-effectiveness of the nonavalent and quadrivalent HPV vaccines. We used a multi-type individual-based transmission-dynamic model of HPV infection and diseases, 70-year time-horizon, 3% discount rate and healthcare payer perspective. We calibrated the model to Canadian sexual behavior and epidemiologic data, and estimated Quality-Adjusted Life-Years (QALYs) lost and costs ($CAN 2010) from the literature. Under base-case assumptions (vaccinating 10-year-old girls, 80% coverage, 95$/dose, vaccine-type efficacy = 95%, cross-protection for the quadrivalent vaccine, duration of vaccine-type protection (cross-protection) = 20 (10) years), using the quadrivalent and nonavalent vaccines is estimated to cost $15,528 [12,056; 19,140] and $12,203 [9,331; 17,292] per QALY-gained, respectively. At equal price, the nonavalent vaccine is more cost-effective than the quadrivalent vaccine, even when assuming both shorter duration of protection (nonavalent = 20 years vs. quadrivalent = lifelong) and lower vaccine-type efficacy (nonavalent = 85% vs. quadrivalent = 95%). However, the additional cost per dose of the nonavalent vaccine should not exceed $11 to remain more cost-effective than the quadrivalent vaccine, and $24 to represent a cost-effective alternative to the quadrivalent vaccine (using a $40,000/QALY-gained threshold). The nonavalent vaccine can be a cost-effective alternative to the quadrivalent vaccine, even in scenarios where nonavalent vaccine efficacy is 85%. However, because most cervical cancers are caused by HPV-16/18, it is unlikely that the nonavalent would be used if its efficacy against these types is lower than current HPV vaccines.

Related: Cervical Cancer Human Papillomavirus (HPV), Vaccination, and Cervical Cancer
Centre de recherche du CHU de Québec, Axe Santé des populations et pratiques optimales en santé, Québec, Canada, G1S 4L8; Département de médecine sociale et préventive, Université Laval, Québec, Canada, G1V 0A6.

Chen J, Moir D
A look at the grouping effect on population-level risk assessment of radon-induced lung cancer.
Glob J Health Sci. 2013; 5(6):1-11 [PubMed] Related Publications
On the basis of considerable knowledge gained by studying health effects in uranium and other underground miners who worked in radon-rich environments, radon exposure has been identified as a cause of lung cancer. Recent pooled analyses of residential studies have shown that radon poses a similar risk of causing lung cancer in the general public when exposure occurs at generally lower levels found in homes. With the increasing accessibility of statistical data via the internet, people are performing their own analyses and asking why, in some cases, the lung cancer occurrence at the community level does not correlate to the radon levels. This study uses statistical data available to the general public from official websites and performs simple analyses. The results clearly show the difficulty in linking observed lung cancer incidence rates at the provincial/territorial level, with possible cause, such as smoking or radon exposure. Even the effect of smoking, a well-documented cause of lung cancer, can be overlooked or misinterpreted if the data being investigated is too general (i.e., summary data at population level) or is influenced by other factors. These difficulties with simple comparisons are one of the main reasons that epidemiological studies of lung cancer incidence and radon exposure requires the use of cohorts or case controls at the individual level as opposed to the more easily performed ecological studies at the population level.

Related: Lung Cancer
Radiation Protection Bureau, Health Canada.

Hystad P, Carpiano RM, Demers PA, et al.
Neighbourhood socioeconomic status and individual lung cancer risk: evaluating long-term exposure measures and mediating mechanisms.
Soc Sci Med. 2013; 97:95-103 [PubMed] Related Publications
Neighbourhood socioeconomic status (SES) has been associated with numerous chronic diseases, yet little information exists on its association with lung cancer incidence. This outcome presents two key empirical challenges: a long latency period that requires study participants' residential histories and long-term neighbourhood characteristics; and adequate data on many risk factors to test hypothesized mediating pathways between neighbourhood SES and lung cancer incidence. Analysing data on urban participants of a large Canadian population-based lung cancer case-control study, we investigate three issues pertaining to these challenges. First, we examine whether there is an association between long-term neighbourhood SES, derived from 20 years of residential histories and five national censuses, and lung cancer incidence. Second, we determine how this long-term neighbourhood SES association changes when using neighbourhood SES measures based on different latency periods or at time of study entry. Third, we estimate the extent to which long-term neighbourhood SES is mediated by a range of individual-level smoking behaviours, other health behaviours, and environmental and occupational exposures. Results of hierarchical logistic regression models indicate significantly higher odds of lung cancer cases residing in the most compared to the least deprived quintile of the long-term neighbourhood SES index (OR: 1.46; 95% CI: 1.13-1.89) after adjustment for individual SES. This association remained significant (OR: 1.38; 1.01-1.88) after adjusting for smoking behaviour and other known and suspected lung cancer risk factors. Important differences were observed between long-term and study entry neighbourhood SES measures, with the latter attenuating effect estimates by over 50 percent. Smoking behaviour was the strongest partial mediating pathway of the long-term neighbourhood SES effect. This research is the first to examine the effects of long-term neighbourhood SES on lung cancer risk and more research is needed to further identify specific, modifiable pathways by which neighbourhood context may influence lung cancer risk.

Related: Lung Cancer
School of Population and Public Health, University of British Columbia, 2206 East Mall, Vancouver, BC, Canada V6T 1Z3. Electronic address:
Research funded by:

Courneya KS, McKenzie DC, Mackey JR, et al.
Effects of exercise dose and type during breast cancer chemotherapy: multicenter randomized trial.
J Natl Cancer Inst. 2013; 105(23):1821-32 [PubMed] Related Publications
BACKGROUND: Exercise improves physical functioning and symptom management during breast cancer chemotherapy, but the effects of different doses and types of exercise are unknown.
METHODS: A multicenter trial in Canada randomized 301 breast cancer patients to thrice-weekly supervised exercise during chemotherapy consisting of either a standard dose of 25 to 30 minutes of aerobic exercise (STAN; n = 96), a higher dose of 50 to 60 minutes of aerobic exercise (HIGH; n = 101), or a combined dose of 50 to 60 minutes of aerobic and resistance exercise (COMB; n = 104). The primary endpoint was physical functioning assessed by the Medical Outcomes Survey-Short Form (SF)-36. Secondary endpoints were other physical functioning scales, symptoms, fitness, and chemotherapy completion. All statistical tests were linear mixed model analyses, and the P values were two-sided.
RESULTS: Follow-up assessment of patient-reported outcomes was 99.0%. Adjusted linear mixed-model analyses showed that neither HIGH (+0.8; 95% confidence interval [CI] = -0.8 to 2.4; P = .30) nor COMB (+0.5; 95% CI = -1.1 to 2.1; P = .52] were superior to STAN for the primary outcome. In secondary analyses not adjusted for multiple comparisons, HIGH was superior to STAN for the SF-36 physical component summary (P = .04), SF-36 bodily pain (P = .02), and endocrine symptoms (P = .02). COMB was superior to STAN for endocrine symptoms (P = .009) and superior to STAN (P < .001) and HIGH (P < .001) for muscular strength. HIGH was superior to COMB for the SF-36 bodily pain (P = .04) and aerobic fitness (P = .03). No differences emerged for body composition or chemotherapy completion.
CONCLUSIONS: A higher volume of aerobic or combined exercise is achievable and safe during breast cancer chemotherapy and may manage declines in physical functioning and worsening symptoms better than standard volumes.

Related: Breast Cancer
Affiliations of authors: Faculty of Physical Education and Recreation (KSC, DC, CCF, LT), Department of Oncology (JRM), School of Public Health (YY), University of Alberta, Edmonton, Canada; School of Kinesiology (DCM, DJ, LBD), Department of Oncology (KG), University of British Columbia, Vancouver...

Alnaami IM, Al-Nuaimi SK, Senthilselvan A, et al.
Effectiveness of adjuvant temozolomide treatment in patients with glioblastoma.
Neurosciences (Riyadh). 2013; 18(4):349-55 [PubMed] Related Publications
OBJECTIVE: To examine whether adjuvant temozolomide treatment improved glioblastoma patients` survival in a large Canadian cohort.
METHODS: We retrospectively studied 364 glioblastoma patients who received different modalities of treatment in 2 Canadian tertiary care centers in Edmonton and Halifax, Canada, between January 2000 and December 2006. The primary outcome was survival following the treatment protocol.
RESULTS: The following variables were associated with an increased risk of death: The hazard risk (HR) of on-gross total resection was 0.50 (95% confidence interval [CI]: 0.39-0.64). The HR for the surgery-only group was 5.2 (95% CI: 3.85-7.06). The standard treatment group (surgery, radiation therapy [RT], and temozolomide) had an HR of 0.52 (95% CI: 0.37-0.74). The HR for patients who presented with seizure or whose presentation included seizures was 0.88 (95% CI: 0.55-0.89). Patient entry into trials had an HR of 0.74 (95% CI: 0.57-0.96). Finally, the HR for age was 1.02 (95% CI: 1.01-1.03) for every extra year.
CONCLUSION: Concomitant temozolomide with RT and surgery was associated with longer survival compared with RT with surgery alone. We also found that younger age, surgical resection, seizure presence, and entry into trials are important prognostic factors for longer survival.

Related: Dacarbazine Temozolomide
Division of Neurosurgery, Department of Surgery, College of Medicine, King Khalid University, PO Box 641, Abha, Kingdom of Saudi Arabia. Tel. +966 541499966. Fax. +966 (17) 2412807. E-mail:

Ramaswamy V, Remke M, Bouffet E, et al.
Recurrence patterns across medulloblastoma subgroups: an integrated clinical and molecular analysis.
Lancet Oncol. 2013; 14(12):1200-7 [PubMed] Article available free on PMC after 01/11/2014 Related Publications
BACKGROUND: Recurrent medulloblastoma is a therapeutic challenge because it is almost always fatal. Studies have confirmed that medulloblastoma consists of at least four distinct subgroups. We sought to delineate subgroup-specific differences in medulloblastoma recurrence patterns.
METHODS: We retrospectively identified a discovery cohort of all recurrent medulloblastomas at the Hospital for Sick Children (Toronto, ON, Canada) from 1994 to 2012 (cohort 1), and established molecular subgroups using a nanoString-based assay on formalin-fixed paraffin-embedded tissues or frozen tissue. The anatomical site of recurrence (local tumour bed or leptomeningeal metastasis), time to recurrence, and survival after recurrence were assessed in a subgroup-specific manner. Two independent, non-overlapping cohorts (cohort 2: samples from patients with recurrent medulloblastomas from 13 centres worldwide, obtained between 1991 and 2012; cohort 3: samples from patients with recurrent medulloblastoma obtained at the NN Burdenko Neurosurgical Institute [Moscow, Russia] between 1994 and 2011) were analysed to confirm and validate observations. When possible, molecular subgrouping was done on tissue obtained from both the initial surgery and at recurrence.
RESULTS: Cohort 1 consisted of 30 patients with recurrent medulloblastomas; nine with local recurrences, and 21 with metastatic recurrences. Cohort 2 consisted of 77 patients and cohort 3 of 96 patients with recurrent medulloblastoma. Subgroup affiliation remained stable at recurrence in all 34 cases with available matched primary and recurrent pairs (five pairs from cohort 1 and 29 pairs from cohort 2 [15 SHH, five group 3, 14 group 4]). This finding was validated in 17 pairs from cohort 3. When analysed in a subgroup-specific manner, local recurrences in cohort 1 were more frequent in SHH tumours (eight of nine [89%]) and metastatic recurrences were more common in group 3 and group 4 tumours (17 of 20 [85%] with one WNT, p=0·0014, local vs metastatic recurrence, SHH vs group 3 vs group 4). The subgroup-specific location of recurrence was confirmed in cohort 2 (p=0·0013 for local vs metastatic recurrence, SHH vs group 3 vs group 4,), and cohort 3 (p<0·0001). Treatment with craniospinal irradiation at diagnosis was not significantly associated with the anatomical pattern of recurrence. Survival after recurrence was significantly longer in patients with group 4 tumours in cohort 1 (p=0·013) than with other subgroups, which was confirmed in cohort 2 (p=0·0075), but not cohort 3 (p=0·70).
INTERPRETATION: Medulloblastoma does not change subgroup at the time of recurrence, reinforcing the stability of the four main medulloblastoma subgroups. Significant differences in the location and timing of recurrence across medulloblastoma subgroups have potential treatment ramifications. Specifically, intensified local (posterior fossa) therapy should be tested in the initial treatment of patients with SHH tumours. Refinement of therapy for patients with group 3 or group 4 tumours should focus on metastases.

Related: USA
Division of Neurosurgery, Hospital for Sick Children, Toronto, ON, Canada; Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Research funded by:

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