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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

Canadian Cancer Resources Directory


National Organisations: Canada
Cancer Centers
Latest Research Publications from Canada
Alberta / Northwest Territories
British Columbia / Yukon Territory
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National Organisations: Canada (19 links)


Cancer Centers (17 links)


Latest Research Publications from Canada

Arcand SL, Akbari MR, Mes-Masson AM, et al.
Germline TP53 mutational spectrum in French Canadians with breast cancer.
BMC Med Genet. 2015; 16:24 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Specific germline mutations in the hereditary breast-ovarian cancer susceptibility (HBC/HBOC) genes, BRCA1, BRCA2 and PALB2, have been shown to recur in French Canadians of Quebec, Canada, and this has been attributed to common ancestors. Germline TP53 mutation carriers are known to segregate in Li-Fraumeni syndrome families, which feature young age of onset breast cancer. We have reported rare TP53 mutation carriers in French Canadian HBC families, though none recurred possibly due to the limited number of cancer families investigated. Here we describe TP53 germline mutations found in French Canadian cancer families provided from hereditary cancer clinics; investigate 37 new BRCA1 and BRCA2 mutation-negative HBC/HBOC families for the TP53 mutations; and assess the frequency of TP53 mutations in a 1235 French Canadian breast cancer cases not selected for family history of cancer.
METHODS: TP53 mutation-positive pedigrees from French Canadian cancer families were provided from local hereditary cancer clinics. Bidirectional Sanger sequencing of all protein encoding exons of TP53 was performed using peripheral blood lymphocyte DNA from breast/ovarian cancer probands from 37 HBC/HBOC families of French Canadian descent. Targeted bidirectional Sanger sequencing assay of regions containing the identified TP53 mutations was performed on 1235 French Canadian breast cancer cases not selected for family history cancer.
RESULTS: Five new TP53 mutations were identified in six pedigrees from hereditary cancer clinics. No deleterious mutations were identified in cancer probands from 37 HBC/HBOC families. A targeted mutation screen of the 1235 breast cancer cases identified a c.844C>T [p.Arg282Trp] mutation carrier. This mutation was also found among the six mutation-positive cancer families provided by the local hereditary cancer clinics. The targeted screen also uncovered a new TP53 mutation, c.685T>C [p.Cys229Arg] that was found in two breast cancer cases. All TP53 mutation carriers were among the 656 women with breast cancer diagnosed less than 50 years of age.
CONCLUSIONS: In all six new TP53 mutations were identified in French Canadians, where two each occurred in independently ascertained cases/families. Although all newly identified breast cancer mutation carriers reported a family history of cancer, none were consistent with features of Li-Fraumeni syndrome families.

Xing KH, Kahlon A, Skinnider BF, et al.
Outcomes in splenic marginal zone lymphoma: analysis of 107 patients treated in British Columbia.
Br J Haematol. 2015; 169(4):520-7 [PubMed] Related Publications
Splenic marginal zone lymphoma (SMZL) accounts for less than 2% of all non-Hodgkin lymphomas. We identified 107 cases diagnosed with SMZL between 1985 and 2012 from the British Columbia Cancer Agency Centre for Lymphoid Cancer and Lymphoma Pathology Databases. Patient characteristics were: median age 67 years (range 30-88), male 40%, stage IV 98%, splenomegaly 93%, bone marrow involvement 96%, peripheral blood involvement 87%. As initial treatment, 52 underwent splenectomy (10 with chemotherapy), 38 chemotherapy alone (21 chemoimmunotherapy containing rituximab, 1 rituximab alone), two antivirals for hepatitis C, and 15 were only observed. The 10-year overall survival for first-line splenectomy versus chemotherapy was 61% and 42%, respectively [Hazard Ratio (HR) 0·48, 95% confidence interval (CI) 0·26-0·88, P = 0·017]. The 10-year failure-free survival (FFS) after first-line splenectomy vs chemotherapy was 39% and 14%, respectively (HR 0·48, 95% CI 0·28-0·80, P = 0·004). Among the 38 patients who received first-line chemotherapy, FFS was similar between those receiving rituximab (n = 22) and those who did not (n = 16) (HR 0·64, 95% CI 0·31-1·34, P = 0·238). Fifteen patients transformed to aggressive lymphoma with median time to transformation of 3·5 years (range 6 months to 12 years) and the 10-year transformation rate was 18%. In conclusion, splenectomy remains a reasonable treatment for patients with SMZL.

Catsburg C, Kim RS, Kirsh VA, et al.
Dietary patterns and breast cancer risk: a study in 2 cohorts.
Am J Clin Nutr. 2015; 101(4):817-23 [PubMed] Related Publications
BACKGROUND: Evidence for a role of dietary risk factors in the cause of breast cancer has been inconsistent. The evaluation of overall dietary patterns instead of foods in isolation may better reflect the nature of true dietary exposure in a population.
OBJECTIVE: We used 2 cohort studies to identify and confirm associations between dietary patterns and breast cancer risk.
DESIGN: Dietary patterns were derived by using a principal components factor analysis in 1097 breast cancer cases and an age-stratified subcohort of 3320 women sampled from 39,532 female participants in the Canadian Study of Diet, Lifestyle and Health (CSDLH). We conducted a confirmatory factor analysis in 49,410 subjects in the National Breast Screening Study (NBSS) in whom 3659 cases of incident breast cancer developed. Cox regression models were used to estimate HRs for the association between derived dietary factors and risk of breast cancer in both cohorts.
RESULTS: The following 3 dietary factors were identified from the CSDLH: healthy, ethnic, and meat and potatoes. In the CSDLH, the healthy dietary pattern was associated with reduced risk of breast cancer (HR for high compared with low quintiles: 0.73; 95% CI: 0.58, 0.91; P-trend = 0.001), and the meat and potatoes dietary pattern was associated with increased risk in postmenopausal women only (HR for high compared with low quintiles: 1.26; 95% CI: 0.92, 1.73; P-trend = 0.043). In the NBSS, the association between the meat and potatoes pattern and postmenopausal breast cancer risk was confirmed (HR: 1.31; 95% CI: 0.98, 1.76; P-trend = 0.043), but there was no association between the healthy pattern and risk of breast cancer.
CONCLUSION: Adherence to a plant-based diet that limits red meat intake may be associated with reduced risk of breast cancer, particularly in postmenopausal women.

Mackillop WJ, Kong W, Brundage M, et al.
A comparison of evidence-based estimates and empirical benchmarks of the appropriate rate of use of radiation therapy in ontario.
Int J Radiat Oncol Biol Phys. 2015; 91(5):1099-107 [PubMed] Related Publications
PURPOSE: Estimates of the appropriate rate of use of radiation therapy (RT) are required for planning and monitoring access to RT. Our objective was to compare estimates of the appropriate rate of use of RT derived from mathematical models, with the rate observed in a population of patients with optimal access to RT.
METHODS AND MATERIALS: The rate of use of RT within 1 year of diagnosis (RT1Y) was measured in the 134,541 cases diagnosed in Ontario between November 2009 and October 2011. The lifetime rate of use of RT (RTLIFETIME) was estimated by the multicohort utilization table method. Poisson regression was used to evaluate potential barriers to access to RT and to identify a benchmark subpopulation with unimpeded access to RT. Rates of use of RT were measured in the benchmark subpopulation and compared with published evidence-based estimates of the appropriate rates.
RESULTS: The benchmark rate for RT1Y, observed under conditions of optimal access, was 33.6% (95% confidence interval [CI], 33.0%-34.1%), and the benchmark for RTLIFETIME was 41.5% (95% CI, 41.2%-42.0%). Benchmarks for RTLIFETIME for 4 of 5 selected sites and for all cancers combined were significantly lower than the corresponding evidence-based estimates. Australian and Canadian evidence-based estimates of RTLIFETIME for 5 selected sites differed widely. RTLIFETIME in the overall population of Ontario was just 7.9% short of the benchmark but 20.9% short of the Australian evidence-based estimate of the appropriate rate.
CONCLUSIONS: Evidence-based estimates of the appropriate lifetime rate of use of RT may overestimate the need for RT in Ontario.

Hamilton SN, Tyldesley S, Li D, et al.
Second malignancies after adjuvant radiation therapy for early stage breast cancer: is there increased risk with addition of regional radiation to local radiation?
Int J Radiat Oncol Biol Phys. 2015; 91(5):977-85 [PubMed] Related Publications
PURPOSE: This study was undertaken to determine whether there was an increased risk of second malignancies (SM), particularly lung cancer, in early stage breast cancer patients treated with the addition of nodal fields to breast and/or chest wall radiation therapy (RT).
MATERIALS AND METHODS: Subjects were stage I/II female breast cancer patients 20 to 79 years of age, diagnosed between 1989 and 2005 and treated with adjuvant RT at our institution. Patients were included if they survived and did not have SM within 3 years of diagnosis. Standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated to compare SM incidence to cancer incidence in the general sex- and age-matched populations. Secondary malignancy risks in patients treated with local RT (LRT) to the breast/chest wall were compared to those in patients treated with locoregional RT (LRRT) to the breast/chest wall and regional nodes, using multivariate regression analysis (MVA) to account for covariates.
RESULTS: The cohort included 12,836 patients with a median follow-up of 8.4 years. LRRT was used in 18% of patients. The SIR comparing patients treated with LRT to the general population was 1.29 (CI: 1.21-1.38). No statistically significant increased incidence of in-field malignancies (SIR, 1.04; CI: 0.87-1.23) and lung cancers (SIR, 1.06; CI: 0.88-1.26) was detected. The SIR comparing patients treated with LRRT to the general population was 1.39 (CI: 1.17-1.64). No statistically significant increased incidence of in-field malignancies (SIR, 1.26; CI: 0.77-1.94) and lung cancers (SIR, 1.27; CI: 0.76-1.98) was detected. On MVA comparing LRRT to LRT, the adjusted hazard ratio was 1.20 for in-field malignancies (CI: 0.68-2.16) and 1.26 for lung cancer (CI: 0.67-2.36). The excess attributable risk (EAR) to regional RT was 3.1 per 10,000 person years (CI: -8.7 to 9.9).
CONCLUSIONS: No statistically significant increased risk of second malignancy was detected after LRRT relative to that for LRT. The upper limit of the EAR was approximately 1% at 10 years.

Martin LJ, Melnichouk O, Huszti E, et al.
Serum lipids, lipoproteins, and risk of breast cancer: a nested case-control study using multiple time points.
J Natl Cancer Inst. 2015; 107(5) [PubMed] Related Publications
BACKGROUND: There is strong evidence that breast cancer risk is influenced by environmental factors. Blood lipid and lipoprotein levels are also influenced by environmental factors and are associated with some breast cancer risk factors. We examined whether serial measures of serum lipids and lipoproteins were associated with breast cancer risk.
METHODS: We carried out a nested case-control study within a randomized long-term dietary intervention trial with 4690 women with extensive mammographic density followed for an average of 10 years for breast cancer incidence. We measured lipids in an average of 4.2 blood samples for 279 invasive breast cancer case subjects and 558 matched control subjects. We calculated subaverages of lipids for each subject based on menopausal status and use of hormone replacement therapy (HRT) at blood collection and analyzed their association with breast cancer using generalized estimating equations. All statistical tests were two-sided.
RESULTS: High-density lipoprotein-cholesterol (HDL-C) (P = .05) and apoA1 (P = .02) levels were positively associated with breast cancer risk (75(th) vs 25(th) percentile: HDL-C, 23% higher; apoA1, 28% higher) and non-HDL-C (P = .03) and apoB (P = .01) levels were negatively associated (75(th) vs 25(th) percentile: non-HDL-C, 19% lower; apoB, 22% lower). These associations were observed only when lipids were measured when HRT was not used. Total cholesterol and triglyceride levels were not statistically significantly associated with breast cancer risk.
CONCLUSIONS: These results demonstrate that serum lipids are associated with breast cancer risk in women with extensive mammographic density. The possibility that interventions for heart disease prevention, which aim to reduce non-HDL-C or raise HDL-C, may have effects on breast cancer risk merits examination.

Raikhlin A, Curpen B, Warner E, et al.
Breast MRI as an adjunct to mammography for breast cancer screening in high-risk patients: retrospective review.
AJR Am J Roentgenol. 2015; 204(4):889-97 [PubMed] Related Publications
OBJECTIVE: In July 2011, the provincial government of Ontario, Canada, approved funding for the addition of annual breast MRI to mammography screening for all women 30-69 years old considered to be at high risk for breast cancer. The purpose of this study was to evaluate the diagnostic performance of screening breast MRI as compared with mammography in a population-based high-risk screening program.
MATERIALS AND METHODS: A retrospective review identified 650 eligible high-risk women who underwent screening breast MRI and mammography between July 2011 and January 2013 at one institution. Results of 806 screening rounds (comprising both MRI and mammography) were reviewed.
RESULTS: Malignancy was diagnosed in 13 patients (invasive cancer in nine, ductal carcinoma in situ in three [one with microinvasion], and chest wall metastasis in one). Of the 13 cancers, 12 (92.3%) were detected by MRI and four (30.8%) by mammography. In nine of these patients, the cancer was diagnosed by MRI only, resulting in an incremental cancer detection rate of 10 cancers per 1000 women screened. MRI screening had significantly higher sensitivity than mammography (92.3% vs 30.8%) but lower specificity (85.9% vs 96.8%). MRI also resulted in a higher callback rate for a 6-month follow-up study (BI-RADS category 3 assessment) than mammography (119 [14.8%] vs 13 [1.6%]) and more image-guided biopsies than mammography (95 [11.8%] vs 19 [2.4%]).
CONCLUSION: MRI is a useful adjunct to mammography for screening in high-risk women, resulting in a significantly higher rate of cancer detection. However, this was found to be at the cost of more imaging and biopsies for lesions that ultimately proved to be benign.

Abunassar M, Reinders J, Jonker DJ, Asmis T
Review of anal cancer patients at the Ottawa hospital.
Eur J Surg Oncol. 2015; 41(5):653-8 [PubMed] Related Publications
BACKGROUND: Anal cancer is uncommon. We reviewed the treatment and outcomes of anal cancer patients in a population referred to the Ottawa Hospital Cancer Centre (TOHCC) over a 12-year period.
METHODS: A chart review was conducted with patient data collected from hospital records, including: demographic, treatment and outcome information. Outcomes of interest included: overall survival (OS), disease free survival (DFS), and colostomy free survival (CFS).
RESULTS: 180 patients were included in the study population. 72% (n = 130) female and 28% (n = 50) male. 6.7% (n = 12 males) of patients were HIV positive - all were on anti-retroviral therapy. 60% (n = 108) of patients were ever-smokers, mean patient age was 62 [range 35-90] years. The most frequent presenting symptoms were blood per rectum and anal pain. Treatment intent was curative in 87%. Treatment included radiotherapy (94%), brachytherapy (26%), chemotherapy (73%). Among patients treated with curative-intent, 72% had a complete response, 31% had local/regional recurrence, 16% required salvage surgery and 21% had distant recurrence. The colostomy rate was 23%. 5 year overall survival (OS) was not significantly different for patients by HIV status. Survival was superior if MMC-FU was used first vs. CIS-FU; OS HR 0.47 (0.24-0.94), p < 0.033.
CONCLUSIONS: The outcomes of patients in this large retrospective cohort study are similar to the outcomes of patients in highly selective clinical trials. Five year overall survival and colostomy free survival are encouraging. MMC-FU was found to be superior to CIS-FU.

Angarita FA, Chesney T, Elser C, et al.
Treatment patterns of elderly breast cancer patients at two Canadian cancer centres.
Eur J Surg Oncol. 2015; 41(5):625-34 [PubMed] Related Publications
BACKGROUND: Treatment of breast cancer in elderly women is limited by declining functional status and life expectancy. The impact of providing less aggressive treatment remains controversial. This study assessed the treatment patterns of elderly breast cancer patients.
METHODS: Retrospective chart review of women ≥70 y with breast cancer treated between 2004 and 2011 at two large Canadian cancer centres. Tumour and treatment characteristics were collected across three subgroups: 70-74 y (n = 314), 75-79 y (n = 233), and ≥80 y (n = 219). Comparisons were made using Chi-squared test, Fisher-Freeman-Halton exact test, or ANOVA. Disease free (DFS) and overall (OS) survival were estimated by Kaplan-Meier analysis and compared by log-rank test.
RESULTS: Women ≥80 y had larger tumours that were better differentiated, hormone receptor-positive, HER2-negative, and lymph node (LN)-positive relative to younger women (p < 0.05). Women ≥80 y more frequently underwent mastectomy than breast conserving surgery and lacked LN staging (p < 0.05). Chemotherapy was provided in few patients, especially ≥80 y. Radiation therapy was provided less often in women ≥80 y despite indications. Hormone therapy was more frequently provided in women ≥80 y. Women ≥80 y had a significantly lower DFS (17.5 m) relative to women 70-74 y (31 m, p = 0.02) and 75-79 y (35 m, p = 0.006). Women ≥80 y had the lowest median OS (53 m) relative to 70-74 y (79 m, p = 0.001) and 75-79 y (75 m, p = 0.003) women.
CONCLUSIONS: Women ≥80 y received less aggressive treatment than younger women and had less favourable DFS and OS. Until age-specific recommendations are available physicians must use clinical judgement and assess the tumour biology with the patient's comorbidties to make the best choice.

Platt J, Baxter NN, McLaughlin J, Semple JL
Does breast reconstruction after mastectomy for breast cancer affect overall survival? Long-term follow-up of a retrospective population-based cohort.
Plast Reconstr Surg. 2015; 135(3):468e-476e [PubMed] Related Publications
BACKGROUND: This study compared overall and breast cancer-specific survival using long-term follow-up data among women diagnosed with invasive breast cancer undergoing mastectomy or breast reconstruction.
METHODS: Retrospective study using population-based data from Ontario Cancer Registry (1980 to 1990) including women receiving breast reconstruction within 5 years after mastectomy and controls of age- and cancer histology-matched women with mastectomy alone. We compared overall and breast cancer-specific survival using an extended Cox hazards model. Secondary analysis examined conditional survival across early, intermediate, and late follow-up.
RESULTS: Seven hundred fifty-eight matched pairs formed the cohort, with a median follow-up of 23.4 years (interquartile range, 1.1 to 33.0 years). Fewer breast reconstruction patients died overall or from breast cancer compared with controls (overall survival, 44.5 percent versus 56.7 percent, p < 0.0001; breast cancer-specific survival, 31.8 percent versus 42.6 percent, p = 0.0002, respectively). Breast reconstruction was associated with a 17 percent reduced risk of death and a 19 percent reduced risk of breast cancer death, after adjustment (overall survival hazard ratio, 0.83; 95 percent CI, 0.72 to 0.96; breast cancer-specific survival hazard ratio, 0.81; 95 percent CI, 0.68 to 0.99). Among 885 women (58 percent) surviving 20 or more years, there was no difference in risk of death from breast cancer (hazard ratio, 0.59; 95 percent CI, 0.31 to 1.10).
CONCLUSION: In a large cohort with invasive breast cancer followed over 20 years, there is no evidence that breast reconstruction is associated with worse survival outcomes compared with mastectomy alone.
CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Boulanger J, Ducharme A, Dufour A, et al.
Management of the extravasation of anti-neoplastic agents.
Support Care Cancer. 2015; 23(5):1459-71 [PubMed] Related Publications
BACKGROUND: Extravasation is a potentially severe complication that can occur during the administration of chemotherapy. The scarcity of evidence available makes it difficult to develop an optimal management scheme. The purpose of this guideline is to review the relevant scientific literature on the prevention, management, and treatment of extravasation occurring during the administration of chemotherapy to cancer patients.
METHOD: A scientific literature review was conducted using the PubMed search tool. The period covered was from database inception to April 2014, inclusively. Since the literature on extravasation treatment is often empirical, anecdotal, and controversial, the review also identified clinical practice guidelines and expert consensuses published by relevant international organizations and cancer agencies.
RESULTS: Identification of potential risk factors and preventive measures can reduce the risk of extravasation. Recognition and management of symptoms are crucial in patients with this complication. Provision of adequate instruction to personnel responsible for administering chemotherapy and to patients on recognizing symptoms, preventing, and managing extravasation is essential. Extravasation can be treated with dry warm or cold compresses and various antidotes such as dimethyl sulfoxide, dexrazoxane, hyaluronidase, or sodium thiosulfate, depending on the agent that has caused extravasation. Patient monitoring to assess the progression or regression of symptoms and to thus take the appropriate measures is necessary.
CONCLUSION: Several strategies must be established to ensure that extravasation is recognized and properly managed. Given the evidence available at this time, the Comité de l'évolution des pratiques en oncologie (CEPO) has made recommendations for clinical practice in Quebec.

Healey R, Patel JL, de Koning L, Naugler C
Incidence of chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis in Calgary, Alberta, Canada.
Leuk Res. 2015; 39(4):429-34 [PubMed] Related Publications
This study provides an update on the incidence of chronic lymphocytic leukemia (CLL) and monoclonal B-cell lymphocytosis (MBL) in a major Canadian city using the 2008 World Health Organization (WHO) diagnostic criteria. Incidence calculations were performed using data from a centralized flow cytometry laboratory servicing southern Alberta, Canada. The age-standardized incidence of 4.01 cases of CLL per 100,000 person-years is nearly half the rate previously reported in Canada. Compared to previous criteria based on absolute lymphocyte count rather than absolute B-cell count, utilizing the 2008 WHO criteria resulted in a 47.6% decline in CLL incidence (8.42 cases per 100,000 using 1996 criteria). As a consequence, MBL rates are 64% higher. In contrast to 1996 criteria showing a peak CLL incidence between ages 70-74, age-specific incidence rates show a continuous increase with advancing age using the 2008 guidelines. We also report a higher male to female ratio of CLL than previous Canadian reports (1.80:1). CLL incidence in southern Alberta is lower than rates recently reported in the United States using the same criteria. This difference may be due in part to the low median age and the lower proportion of persons of Caucasian European ancestry present in our study population.

Wallis CJ, Cheung P, Herschorn S, et al.
Complications following surgery with or without radiotherapy or radiotherapy alone for prostate cancer.
Br J Cancer. 2015; 112(6):977-82 [PubMed] Article available free on PMC after 17/03/2016 Related Publications
BACKGROUND: Men undergoing treatment of clinically localised prostate cancer may experience a number of treatment-related complications, which affect their quality of life.
METHODS: On the basis of population-based retrospective cohort of men undergoing surgery, with or without subsequent radiotherapy, or radiotherapy alone for prostate cancer in Ontario, Canada, we measured the incidence of treatment-related complications using administrative and billing data.
RESULTS: Of 36 984 patients, 15 870 (42.9%) underwent surgery alone, 4519 (12.2%) underwent surgery followed by radiotherapy, and 16 595 (44.9%) underwent radiotherapy alone. For all end points except urologic procedures, the 5-year cumulative incidence rates were lowest in the surgery only group and highest in the radiotherapy only group. Intermediary rates were seen in the surgery followed by radiotherapy group, except for urologic procedures where rates were the highest in this group. Although age and comorbidity were important predictors, radiotherapy as the primary treatment modality was associated with higher rates for all complications (adjusted hazard ratios 1.6-4.7, P=0.002 to <0.0001).
CONCLUSIONS: In patients treated for prostate cancer, radiation after surgery increases the rate of complications compared with surgery alone, though these rates remain lower than patients treated with radiation alone. This information may inform patient and physician decision making in the treatment of prostate cancer.

Bischof DA, Kim Y, Dodson R, et al.
Conditional disease-free survival after surgical resection of gastrointestinal stromal tumors: a multi-institutional analysis of 502 patients.
JAMA Surg. 2015; 150(4):299-306 [PubMed] Related Publications
IMPORTANCE: Gastrointestinal stromal tumors (GISTs) are the most commonly diagnosed mesenchymal tumors of the gastrointestinal tract. The risk of recurrence following surgical resection of GISTs is typically reported from the date of surgery. However, disease-free survival (DFS) over time is dynamic and changes based on disease-free time already accumulated following surgery.
OBJECTIVES: To assess the comparative performance of established GIST recurrence risk prognostic scoring systems and to characterize conditional DFS following surgical resection of GISTs.
DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of 502 patients who underwent surgery for a primary, nonmetastatic GIST between January 1, 1998, and December 31, 2012, at 7 major academic cancer centers in the United States and Canada.
MAIN OUTCOMES AND MEASURES: Disease-free survival of the patients was classified according to 5 prognostic scoring systems, including the National Institutes of Health criteria, modified National Institutes of Health criteria, Memorial Sloan Kettering Cancer Center GIST nomogram, and American Joint Committee on Cancer gastric and nongastric categories. The concordance index (also known as the C statistic or the area under the receiver operating curve) of established GIST recurrence risk prognostic scoring systems. Conditional DFS estimates were calculated.
RESULTS: Overall 1-year, 3-year, and 5-year DFS following resection of GISTs was 95%, 83%, and 74%, respectively. All the prognostic scoring systems had fair prognostic ability. For all tumor sites, the American Joint Committee on Cancer gastric category demonstrated the best discrimination (C = 0.79). Using conditional DFS, the probability of remaining disease free for an additional 3 years given that a patient was disease free at 1 year, 3 years, and 5 years was 82%, 89%, and 92%, respectively. Patients with the highest initial recurrence risk demonstrated the greatest increase in conditional survival as time elapsed.
CONCLUSIONS AND RELEVANCE: Conditional DFS improves over time following resection of GISTs. This is valuable information about long-term prognosis to communicate to patients who are disease free after a period following surgery.

Ball A, Chu P, Ghatage P, et al.
The importance of surgical staging in women with uterine serous carcinoma: experience in a single institution reveals a survival benefit.
J Obstet Gynaecol Can. 2014; 36(12):1085-92 [PubMed] Related Publications
OBJECTIVE: To assess the appropriate extent of surgical staging in women with clinically early stage uterine serous carcinoma (USC).
METHODS: We conducted a single-institution retrospective cohort study of all women with USC between 2007 and 2012. Treatment practices, outcomes, and factors affecting survival were analyzed using univariate and multivariate analysis.
RESULTS: Eighty-four patients were identified, 76 of whom were included in the analysis. Preoperative pathology correctly identified USC in 73.3% of cases. Surgical stage distribution was 44.7% stage I, 7.9% stage II, 31.6% stage III, and 15.8% stage IV. Women thought to have early stage disease preoperatively encompassed 84.2% (64) of the cohort. Fifty-two (81.3%) of these women with clinically early stage disease had complete surgical staging. Thirty-four (53.1%) were determined to have surgical stage I, and the remaining 30 (46.9%) had occult advanced stage disease. Median follow-up was 43.2 months. Univariate analysis found a significant increase in progression-free survival and overall survival for women with clinically early stage disease with positive lymphovascular space invasion (P < 0.001 and P = 0.002, respectively), positive peritoneal cytology (P = 0.022 and P = 0.04, respectively), early stage (P < 0.001 and P = 0.004, respectively), and elevated serum CA125 at diagnosis (P = 0.003 and P = 0.001, respectively). On multivariate analysis, early stage (hazard ratio [HR] 9.87; 95% CI 2.79 to 34.92, P < 0.001) and complete surgical staging (HR 2.96; 95% CI 1.05 to 8.37, P = 0.040) were associated with prolonged progression-free survival, while overall survival was not affected by complete surgical staging (HR 1.92; 95% CI 0.64 to 5.76, P = 0.79).
CONCLUSION: Complete surgical staging prolongs the progression-free survival of women with clinical early-stage uterine serous cancer. Although this does not extend to overall survival, this enables patients to have an improved quality of life with a longer interval without the burden of disease.

Leveridge MJ, Siemens DR, Mackillop WJ, et al.
Radical cystectomy and adjuvant chemotherapy for bladder cancer in the elderly: a population-based study.
Urology. 2015; 85(4):791-8 [PubMed] Related Publications
OBJECTIVE: To assess radical cystectomy (RC) outcomes and adjuvant chemotherapy (ACT) use in the elderly in routine practice. Bladder cancer occurs most commonly in the elderly. RC, standard treatment for muscle-invasive bladder cancer, presents challenges in older patients. Suboptimal evidence guides ACT use.
METHODS: All patients undergoing RC for urothelial cancer in Ontario from 1994 to 2008 were identified using the Ontario Cancer Registry. Pathology reports and treatment records were linked to the database. Patients were age stratified as <70, 70-74, 75-79 and ≥80 years. Logistic regression and Cox proportional hazards identified associations with and effectiveness of ACT use.
RESULTS: We identified 3320 patients: 1362 (41%) aged <70 years; 674 (20%) aged 70-74 years; 674 (19%) aged 75-79 years, and 657 (20%) aged ≥80 years. Thirty-day (1%, 2%, 2%, 6%; P <.0001) and 90-day (5%, 8%, 9%, 15%; P <.0001) mortality increased with age. Age-stratified 5-year cancer-specific survival was 42%, 37%, 34%, and 32%, respectively (P <.001); 5-year overall survival was 40%, 34%, 28%, and 23%, respectively (P <.001). ACT decreased with age (27%, 16%, 12%, 5%; P <.0001). Among ACT patients, 87% aged <70 years received cisplatin vs 73% aged ≥70 years (P = .003). ACT was associated with improved cancer-specific survival (hazard ratio [HR] = 0.73 and 95% confidence interval [CI] = 0.59-0.89 for age <70 years and HR = 0.73 [95% CI = 0.59-0.89] for ≥70 years) and overall survival (HR = 0.70 [95% CI = 0.58-0.85] for age <70 years and HR = 0.70 [95% CI = 0.59-0.84] for ≥70 years) across all age groups.
CONCLUSION: Cystectomy carries a higher risk of postoperative mortality in elderly patients in routine clinical practice. ACT is used infrequently in older patients despite a substantial survival benefit observed across all age groups.

Vujovic O, Yu E, Cherian A, et al.
Time interval from breast-conserving surgery to breast irradiation in early stage node-negative breast cancer: 17-year follow-up results and patterns of recurrence.
Int J Radiat Oncol Biol Phys. 2015; 91(2):319-24 [PubMed] Related Publications
PURPOSE: A retrospective chart review was conducted to determine whether the time interval from breast-conserving surgery to breast irradiation (surgery-radiation therapy interval) in early stage node-negative breast cancer had any detrimental effects on recurrence rates.
METHODS AND MATERIALS: There were 566 patients with T1 to T3, N0 breast cancer treated with breast-conserving surgery and breast irradiation and without adjuvant systemic treatment between 1985 and 1992. The surgery-to-radiation therapy intervals used for analysis were 0 to 8 weeks (201 patients), >8 to 12 weeks (233 patients), >12 to 16 weeks (91 patients), and >16 weeks (41 patients). Kaplan-Meier estimates of time to local recurrence, disease-free survival, distant disease-free survival, cause-specific survival, and overall survival rates were calculated.
RESULTS: Median follow-up was 17.4 years. Patients in all 4 time intervals were similar in terms of characteristics and pathologic features. There were no statistically significant differences among the 4 time groups in local recurrence (P=.67) or disease-free survival (P=.82). The local recurrence rates at 5, 10, and 15 years were 4.9%, 11.5%, and 15.0%, respectively. The distant disease relapse rates at 5, 10, and 15 years were 10.6%, 15.4%, and 18.5%, respectively. The disease-free failure rates at 5, 10, and 15 years were 20%, 32.3%, and 39.8%, respectively. Cause-specific survival rates at 5, 10, and 15 years were 92%, 84.6%, and 79.8%, respectively. The overall survival rates at 5, 10, and 15 years were 89.3%, 79.2%, and 66.9%, respectively.
CONCLUSIONS: Surgery-radiation therapy intervals up to 16 weeks from breast-conserving surgery are not associated with any increased risk of recurrence in early stage node-negative breast cancer. There is a steady local recurrence rate of 1% per year with adjuvant radiation alone.

Jang RW, Krzyzanowska MK, Zimmermann C, et al.
Palliative care and the aggressiveness of end-of-life care in patients with advanced pancreatic cancer.
J Natl Cancer Inst. 2015; 107(3) [PubMed] Related Publications
BACKGROUND: We examined the impact of palliative care (PC) on aggressiveness of end-of-life care for patients with advanced pancreatic cancer. Measures of aggressive care included chemotherapy within 14 days of death; and at least one intensive care unit (ICU) admission, more than one emergency department (ED) visit, and more than one hospitalization, all within 30 days of death.
METHODS: A retrospective population-based cohort study using administrative data was conducted in patients with advanced pancreatic cancer from 2005 to 2010 in Ontario, Canada. Multivariable logistic regression was performed with the above measures of aggressive care as the outcomes of interest and PC as the main exposure, adjusting for covariables. Secondary analyses examined intensity of PC as the main exposure defined in two ways: 1) absolute number of PC visits before the outcome of interest (0, 1, 2, 3+ visits) and 2) monthly rate of PC visits.
RESULTS: The cohort included 5381 patients (median survival 75 days); 2816 (52.3%) had received a PC consultation. PC consultation was associated with decreased use of chemotherapy near death (odds ratio [OR] = 0.34, 95% confidence interval [CI] = 0.25 to 0.46); lower risk of ICU admission: OR = 0.12, 95% CI = 0.08 to 0.18; multiple ED visits: OR = 0.19, 95% CI = 0.16 to 0.23; multiple hospitalizations near death: OR = 0.24, 95% CI = 0.19 to 0.31). A per-unit increase in the monthly rate of PC visits was associated with lower odds of aggressive care for all four outcomes.
CONCLUSION: PC consultation and a higher intensity of PC were associated with less aggressive care near death in patients with advanced pancreatic cancer.

McCormick B, Winter K, Hudis C, et al.
RTOG 9804: a prospective randomized trial for good-risk ductal carcinoma in situ comparing radiotherapy with observation.
J Clin Oncol. 2015; 33(7):709-15 [PubMed] Article available free on PMC after 01/03/2016 Related Publications
PURPOSE: The Radiation Therapy Oncology Group 9804 study identified good-risk patients with ductal carcinoma in situ (DCIS), a breast cancer diagnosis found frequently in mammographically detected cancers, to test the benefit of radiotherapy (RT) after breast-conserving surgery compared with observation.
PATIENTS AND METHODS: This prospective randomized trial (1998 to 2006) in women with mammographically detected low- or intermediate-grade DCIS, measuring less than 2.5 cm with margins ≥ 3 mm, compared RT with observation after surgery. The study was designed for 1,790 patients but was closed early because of lower than projected accrual. Six hundred thirty-six patients from the United States and Canada were entered; tamoxifen use (62%) was optional. Ipsilateral local failure (LF) was the primary end point; LF and contralateral failure were estimated using cumulative incidence, and overall and disease-free survival were estimated using the Kaplan-Meier method.
RESULTS: Median follow-up time was 7.17 years (range, 0.01 to 11.33 years). Two LFs occurred in the RT arm, and 19 occurred in the observation arm. At 7 years, the LF rate was 0.9% (95% CI, 0.0% to 2.2%) in the RT arm versus 6.7% (95% CI, 3.2% to 9.6%) in the observation arm (hazard ratio, 0.11; 95% CI, 0.03 to 0.47; P < .001). Grade 1 to 2 acute toxicities occurred in 30% and 76% of patients in the observation and RT arms, respectively; grade 3 or 4 toxicities occurred in 4.0% and 4.2% of patients, respectively. Late RT toxicity was grade 1 in 30%, grade 2 in 4.6%, and grade 3 in 0.7% of patients.
CONCLUSION: In this good-risk subset of patients with DCIS, with a median follow-up of 7 years, the LF rate was low with observation but was decreased significantly with the addition of RT. Longer follow-up is planned because the timeline for LF in this setting seems protracted.

Neumann K, Mahmud SM, McKay A, et al.
Is obesity associated with advanced stage or grade of colon cancer?
Can J Surg. 2015; 58(2):140-2 [PubMed] Article available free on PMC after 01/03/2016 Related Publications
Population-based studies from Europe have suggested that obesity is associated with more advanced stage colorectal cancer on presentation. Obesity is an even more prevalent issue in North America, but comparable data on associations with cancer are lacking. We reviewed the cases of 672 patients with colon cancer diagnosed between 2004 and 2008 in the province of Manitoba who underwent surgical resection at a Winnipeg Regional Health Authority–affiliated hospital. We tested if obesity was associated with more advanced cancer stage or grade. On multivariate analysis, after adjusting for age, sex,tumour location and socioeconomic status, we were unable to show any significant associations between body mass index of 30 or more and advanced stage or grade cancer on presentation. The reasons for the lack of association are likely multifactorial, including the pathophysiology of the disease and process factors, such as screening habits and colonoscopic diagnostic success rates in obese patients.

Smith GD, Pickles T, Crook J, et al.
Brachytherapy improves biochemical failure-free survival in low- and intermediate-risk prostate cancer compared with conventionally fractionated external beam radiation therapy: a propensity score matched analysis.
Int J Radiat Oncol Biol Phys. 2015; 91(3):505-16 [PubMed] Related Publications
PURPOSE: To compare, in a retrospective study, biochemical failure-free survival (bFFS) and overall survival (OS) in low-risk and intermediate-risk prostate cancer patients who received brachytherapy (BT) (either low-dose-rate brachytherapy [LDR-BT] or high-dose-rate brachytherapy with external beam radiation therapy [HDR-BT+EBRT]) versus external beam radiation therapy (EBRT) alone.
METHODS AND MATERIALS: Patient data were obtained from the ProCaRS database, which contains 7974 prostate cancer patients treated with primary radiation therapy at four Canadian cancer institutions from 1994 to 2010. Propensity score matching was used to obtain the following 3 matched cohorts with balanced baseline prognostic factors: (1) low-risk LDR-BT versus EBRT; (2) intermediate-risk LDR-BT versus EBRT; and (3) intermediate-risk HDR-BT+EBRT versus EBRT. Kaplan-Meier survival analysis was performed to compare differences in bFFS (primary endpoint) and OS in the 3 matched groups.
RESULTS: Propensity score matching created acceptable balance in the baseline prognostic factors in all matches. Final matches included 2 1:1 matches in the intermediate-risk cohorts, LDR-BT versus EBRT (total n=254) and HDR-BT+EBRT versus EBRT (total n=388), and one 4:1 match in the low-risk cohort (LDR-BT:EBRT, total n=400). Median follow-up ranged from 2.7 to 7.3 years for the 3 matched cohorts. Kaplan-Meier survival analysis showed that all BT treatment options were associated with statistically significant improvements in bFFS when compared with EBRT in all cohorts (intermediate-risk EBRT vs LDR-BT hazard ratio [HR] 4.58, P=.001; intermediate-risk EBRT vs HDR-BT+EBRT HR 2.08, P=.007; low-risk EBRT vs LDR-BT HR 2.90, P=.004). No significant difference in OS was found in all comparisons (intermediate-risk EBRT vs LDR-BT HR 1.27, P=.687; intermediate-risk EBRT vs HDR-BT+EBRT HR 1.55, P=.470; low-risk LDR-BT vs EBRT HR 1.41, P=.500).
CONCLUSIONS: Propensity score matched analysis showed that BT options led to statistically significant improvements in bFFS in low- and intermediate-risk prostate cancer patient populations.

Chetty R, Hafezi-Bakhtiari S, Serra S, et al.
Traditional serrated adenomas (TSAs) admixed with other serrated (so-called precursor) polyps and conventional adenomas: a frequent occurrence.
J Clin Pathol. 2015; 68(4):270-3 [PubMed] Related Publications
BACKGROUND: Traditional serrated adenoma (TSA) is a very characteristic type of serrated polyp that has a predilection for the left colon. Recent molecular advances have shown two molecular phenotypes of TSA: one associated with BRAF mutations and the other with KRAS mutations. The former is associated with hyperplastic polyps (HPs) and sessile serrated adenomas (SSAs), while the latter is associated with more conventional adenomatous dysplasia.
AIMS: The association of TSAs with so-called precursor lesions (HPs and SSAs) is not well recognised and the purpose of this study was to explore the coexistent presence of HPs, SSAs and adenomatous polyps within a large cohort of TSAs.
METHODS: In total 149 TSAs were examined for the presence of HP, SSA and adenomatous polyps.
RESULTS: Seen in 83 men and 65 women ranging in age from 32 to 89 years and 127 were left sided with 22 in the right colon. Seventy-eight of the 149 TSAs showed evidence of another polyp (52.34%): 32 were low-grade tubular/tubulovillous adenomas (TAs/TVAs; 41%), 28 were HPs (36%) and 18 were SSAs (23%). Eleven of the 22 right-sided TSAs were associated with a precursor lesion (1 HP and 7 SSA). In addition, five TSAs showed more than one polyp type: TSA with TA/TVA and HP (3); TSA with TA/TVA and SSA (2). The TAs/TVAs were adjacent to the TSA but occurred as a separate discrete polyp, while HPs and SSAs were intermingled with the TSA and present at the base and surface of the lesion.
CONCLUSIONS: More than 50% of TSAs are associated with a precursor lesion or adjacent TA/TVA. Their recognition is important as this may have surveillance and management ramifications.

Schneider C, Ramaswamy V, Kulkarni AV, et al.
Clinical implications of medulloblastoma subgroups: incidence of CSF diversion surgery.
J Neurosurg Pediatr. 2015; 15(3):236-42 [PubMed] Related Publications
OBJECT: While medulloblastoma was initially thought to comprise a single homogeneous entity, it is now accepted that it in fact comprises 4 discrete subgroups, each with its own distinct demographics, clinical presentation, transcriptomics, genetics, and outcome. Hydrocephalus is a common complication of medulloblastoma and not infrequently requires CSF diversion. The authors report the incidence of CSF diversion surgery in each of the subgroups of medulloblastoma (Wnt, Shh, Group 3, and Group 4).
METHODS: The medical and imaging records for patients who underwent surgery for medulloblastoma at The Hospital for Sick Children were retrospectively reviewed. The primary outcome was the requirement for CSF diversion surgery either before or within 60 days of tumor resection. The modified Canadian Preoperative Prediction Rule for Hydrocephalus (mCPPRH) was compared among subgroups.
RESULTS: Of 143 medulloblastoma patients, treated from 1991 to 2013, sufficient data were available for 130 patients (15 with Wnt, 30 with Shh, 30 with Group 3, and 55 with Group 4 medulloblastomas). Of these, 28 patients (22%) ultimately underwent CSF diversion surgery: 0% with Wnt, 29% with Shh, 29% with Group 3, and 43% with Group 4 tumors. Patients in the Wnt subgroup had a lower incidence of CSF diversion than all other patients combined (p = 0.04). Wnt patients had a lower mCPPRH score (lower risk of CSF diversion, p = 0.045), were older, had smaller ventricles at diagnosis, and had no leptomeningeal metastases.
CONCLUSIONS: The overall rate of CSF diversion surgery for Shh, Group 3, and Group 4 medulloblastomas is around 30%, but no patients in the present series with a Wnt medulloblastoma required shunting. The low incidence of hydrocephalus in patients with Wnt medulloblastoma likely reflects both host factors (age) and disease factors (lack of metastases). The absence of hydrocephalus in patients with Wnt medulloblastomas likely contributes to their excellent rate of survival and may also contribute to a higher quality of life than for patients in other subgroups.

Klotz L, Vesprini D, Sethukavalan P, et al.
Long-term follow-up of a large active surveillance cohort of patients with prostate cancer.
J Clin Oncol. 2015; 33(3):272-7 [PubMed] Related Publications
PURPOSE: Active surveillance is increasingly accepted as a treatment option for favorable-risk prostate cancer. Long-term follow-up has been lacking. In this study, we report the long-term outcome of a large active surveillance protocol in men with favorable-risk prostate cancer.
PATIENTS AND METHODS: In a prospective single-arm cohort study carried out at a single academic health sciences center, 993 men with favorable- or intermediate-risk prostate cancer were managed with an initial expectant approach. Intervention was offered for a prostate-specific antigen (PSA) doubling time of less than 3 years, Gleason score progression, or unequivocal clinical progression. Main outcome measures were overall and disease-specific survival, rate of treatment, and PSA failure rate in the treated patients.
RESULTS: Among the 819 survivors, the median follow-up time from the first biopsy is 6.4 years (range, 0.2 to 19.8 years). One hundred forty-nine (15%) of 993 patients died, and 844 patients are alive (censored rate, 85.0%). There were 15 deaths (1.5%) from prostate cancer. The 10- and 15-year actuarial cause-specific survival rates were 98.1% and 94.3%, respectively. An additional 13 patients (1.3%) developed metastatic disease and are alive with confirmed metastases (n = 9) or have died of other causes (n = 4). At 5, 10, and 15 years, 75.7%, 63.5%, and 55.0% of patients remained untreated and on surveillance. The cumulative hazard ratio for nonprostate-to-prostate cancer mortality was 9.2:1.
CONCLUSION: Active surveillance for favorable-risk prostate cancer is feasible and seems safe in the 15-year time frame. In our cohort, 2.8% of patients have developed metastatic disease, and 1.5% have died of prostate cancer. This mortality rate is consistent with expected mortality in favorable-risk patients managed with initial definitive intervention.

Kramer JL
Medical marijuana for cancer.
CA Cancer J Clin. 2015; 65(2):109-22 [PubMed] Related Publications
Answer questions and earn CME/CNE Marijuana has been used for centuries, and interest in its medicinal properties has been increasing in recent years. Investigations into these medicinal properties has led to the development of cannabinoid pharmaceuticals such as dronabinol, nabilone, and nabiximols. Dronabinol is best studied in the treatment of nausea secondary to cancer chemotherapy and anorexia associated with weight loss in patients with acquired immune deficiency syndrome, and is approved by the US Food and Drug Administration for those indications. Nabilone has been best studied for the treatment of nausea secondary to cancer chemotherapy. There are also limited studies of these drugs for other conditions. Nabiximols is only available in the United States through clinical trials, but is used in Canada and the United Kingdom for the treatment of spasticity secondary to multiple sclerosis and pain. Studies of marijuana have concentrated on nausea, appetite, and pain. This article will review the literature regarding the medical use of marijuana and these cannabinoid pharmaceuticals (with emphasis on indications relevant to oncology), as well as available information regarding adverse effects of marijuana use.

Sternberg CN, Skoneczna I, Kerst JM, et al.
Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial.
Lancet Oncol. 2015; 16(1):76-86 [PubMed] Related Publications
BACKGROUND: Patients with muscle-invasive urothelial carcinoma of the bladder have poor survival after cystectomy. The EORTC 30994 trial aimed to compare immediate versus deferred cisplatin-based combination chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder.
METHODS: This intergroup, open-label, randomised, phase 3 trial recruited patients from hospitals across Europe and Canada. Eligible patients had histologically proven urothelial carcinoma of the bladder, pT3-pT4 disease or node positive (pN1-3) M0 disease after radical cystectomy and bilateral lymphadenectomy, with no evidence of any microscopic residual disease. Within 90 days of cystectomy, patients were centrally randomly assigned (1:1) by minimisation to either immediate adjuvant chemotherapy (four cycles of gemcitabine plus cisplatin, high-dose methotrexate, vinblastine, doxorubicin, and cisplatin [high-dose MVAC], or MVAC) or six cycles of deferred chemotherapy at relapse, with stratification for institution, pT category, and lymph node status according to the number of nodes dissected. Neither patients nor investigators were masked. Overall survival was the primary endpoint; all analyses were by intention to treat. The trial was closed after recruitment of 284 of the planned 660 patients. This trial is registered with ClinicalTrials.gov, number NCT00028756.
FINDINGS: From April 29, 2002, to Aug 14, 2008, 284 patients were randomly assigned (141 to immediate treatment and 143 to deferred treatment), and followed up until the data cutoff of Aug 21, 2013. After a median follow-up of 7.0 years (IQR 5.2-8.7), 66 (47%) of 141 patients in the immediate treatment group had died compared with 82 (57%) of 143 in the deferred treatment group. No significant improvement in overall survival was noted with immediate treatment when compared with deferred treatment (adjusted HR 0.78, 95% CI 0.56-1.08; p=0.13). Immediate treatment significantly prolonged progression-free survival compared with deferred treatment (HR 0.54, 95% CI 0.4-0.73, p<0.0001), with 5-year progression-free survival of 47.6% (95% CI 38.8-55.9) in the immediate treatment group and 31.8% (24.2-39.6) in the deferred treatment group. Grade 3-4 myelosuppression was reported in 33 (26%) of 128 patients who received treatment in the immediate chemotherapy group versus 24 (35%) of 68 patients who received treatment in the deferred chemotherapy group, neutropenia occurred in 49 (38%) versus 36 (53%) patients, respectively, and thrombocytopenia in 36 (28%) versus 26 (38%). Two patients died due to toxicity, one in each group.
INTERPRETATION: Our data did not show a significant improvement in overall survival with immediate versus deferred chemotherapy after radical cystectomy and bilateral lymphadenectomy for patients with muscle-invasive urothelial carcinoma. However, the trial is limited in power, and it is possible that some subgroups of patients might still benefit from immediate chemotherapy. An updated individual patient data meta-analysis and biomarker research are needed to further elucidate the potential for survival benefit in subgroups of patients.
FUNDING: Lilly, Canadian Cancer Society Research.

Liede A, Bach BA, Stryker S, et al.
Regional variation and challenges in estimating the incidence of giant cell tumor of bone.
J Bone Joint Surg Am. 2014; 96(23):1999-2007 [PubMed] Related Publications
BACKGROUND: Estimating the incidence of giant cell tumor of bone is challenging because few population-based cancer registries record benign bone tumors. We compared two approaches, the indirect (relative index) estimation approach used in The Burden of Musculoskeletal Diseases in the United States (BMUS) and a direct incidence rate approach (from registries that record giant cell tumor), to estimate giant cell tumor incidence in France, Germany, Italy, Spain, the U.K., Sweden, Australia, Canada, Japan, and the U.S.
METHODS: Giant cell tumor of bone incidence was calculated with use of the BMUS relative index of giant cell tumor to osteosarcoma in three scenarios (low, base case, and high) from case series. We compared the BMUS approach with the latest data from tumor registries in Australia (1972 to 1996), Japan (2006 to 2008), and Sweden (1993 to 2011) that record giant cell tumors. United Nations population estimates were used to project results to 2013.
RESULTS: The low scenario in the BMUS approach reflects data from Unni and Inwards; the incidence of giant cell tumor of bone is 0.34 relative to osteosarcoma. As the incidence of osteosarcoma is 31.4% of the total incidence of bone and joint cancers, the incidence of giant cell tumor is 0.11 times that of all bone and joint cancers. The base scenario reflects the series by Mirra et al., with a giant cell tumor incidence of 0.47 relative to osteosarcoma (0.15 to all bone and joint cancers). The high scenario reflects the series by Ward, with an incidence of 0.84 relative to osteosarcoma (0.26 to all bone and joint cancers). Differences among the three series reflect referral to a national center of excellence compared with referral to a local oncology practice. Registry data indicated a giant cell tumor incidence rate per million per year of 1.33 in Australia, 1.03 in Japan, and 1.11 in Sweden in 2013. The estimated incidence rate per million in the ten countries in 2013 ranged from 1.03 (Japan) to 1.17 (Canada) with use of the registry-based approach and from 0.73 (Japan) for the low scenario) to 2.20 (Germany) for the base case with use of the BMUS approach.
CONCLUSIONS: Giant cell tumor of bone affects approximately one person per million per year in the ten countries studied. Estimates derived with use of age-specific incidences from tumor registries were typically within the range of the low and base case BMUS scenarios. We recommend the registry-derived method for estimating the incidence of giant cell tumor.

Siemens DR, Mackillop WJ, Peng Y, et al.
Processes of care and the impact of surgical volumes on cancer-specific survival: a population-based study in bladder cancer.
Urology. 2014; 84(5):1049-57 [PubMed] Related Publications
OBJECTIVE: To describe the relationships between procedure volume and late survival after cystectomy for muscle-invasive bladder cancer (MIBC) and explore variables explaining any effect.
MATERIALS AND METHODS: Electronic records of treatment and surgical pathology reports were linked to a population-based registry to identify patients who underwent cystectomy during 1994-2008 in Ontario, Canada. Explanatory variables included adjuvant chemotherapy, lymph node dissection (LND), and margin status. A Cox proportional hazards regression model was used to explore associations between volume and cancer-specific survival (CSS) as well as overall survival.
RESULTS: The cohort included 2802 MIBC patients treated with cystectomy. High-volume hospitals were more likely to have used adjuvant chemotherapy (25% vs 18%; P <.001), more likely to have performed an LND (83% vs 53%; P <.001), and associated with a lower 90-day mortality (6% vs 10%; P = .032). Low-volume hospitals had a lower 5-year CSS rate of 32% (28%-36%) compared with those of high-volume centers at 38% (33%-42%). Individual surgeon volume was similarly associated with both early- and long-term outcomes. In multivariate analysis, both surgeon and hospital volumes were associated with CSS and overall survival. The surgeon volume effect on long-term outcomes was modestly modified by indicators of the quality of the LND, with little effect of the other explanatory variables.
CONCLUSION: Higher provider volume is associated with higher CSS in patients with MIBC in the general population. The volume effect was modestly mediated by the quality of LND.

Huynh-Le MP, Zhang Z, Tran PT, et al.
Low interrater reliability in grading of rectal bleeding using National Cancer Institute Common Toxicity Criteria and Radiation Therapy Oncology Group Toxicity scales: a survey of radiation oncologists.
Int J Radiat Oncol Biol Phys. 2014; 90(5):1076-82 [PubMed] Article available free on PMC after 01/12/2015 Related Publications
PURPOSE: To measure concordance among genitourinary radiation oncologists in using the National Cancer Institute Common Toxicity Criteria (NCI CTC) and Radiation Therapy Oncology Group (RTOG) grading scales to grade rectal bleeding.
METHODS AND MATERIALS: From June 2013 to January 2014, a Web-based survey was sent to 250 American and Canadian academic radiation oncologists who treat prostate cancer. Participants were provided 4 case vignettes in which patients received radiation therapy and developed rectal bleeding and were asked for management plans and to rate the bleeding according to NCI CTC v.4 and RTOG late toxicity grading (scales provided). In 2 cases, participants were also asked whether they would send the patient for colonoscopy. A multilevel, random intercept modeling approach was used to assess sources of variation (case, respondent) in toxicity grading to calculate the intraclass correlation coefficient (ICC). Agreement on a dichotomous grading scale (low grades 1-2 vs high grades 3-4) was also assessed, using the κ statistic for multiple respondents.
RESULTS: Seventy-two radiation oncologists (28%) completed the survey. Forty-seven (65%) reported having either written or been principal investigator on a study using these scales. Agreement between respondents was moderate (ICC 0.52, 95% confidence interval [CI] 0.47-0.58) when using NCI CTC and fair using the RTOG scale (ICC 0.28, 95% CI 0.20-0.40). Respondents who chose an invasive management were more likely to select a higher toxicity grade (P<.0001). Using the dichotomous scale, we observed moderate agreement (κ = 0.42, 95% CI 0.40-0.44) with the NCI CTC scale, but only slight agreement with the RTOG scale (κ = 0.19, 95% CI 0.17-0.21).
CONCLUSION: Low interrater reliability was observed among radiation oncologists grading rectal bleeding using 2 common scales. Clearer definitions of late rectal bleeding toxicity should be constructed to reduce this variability and avoid ambiguity in both reporting and interpretation.

Gerrie AS, Huang SJ, Bruyere H, et al.
Population-based characterization of the genetic landscape of chronic lymphocytic leukemia patients referred for cytogenetic testing in British Columbia, Canada: the role of provincial laboratory standardization.
Cancer Genet. 2014 Jul-Aug; 207(7-8):316-25 [PubMed] Related Publications
Detection of recurrent chromosome abnormalities by fluorescence in situ hybridization (FISH) is an essential component of care in chronic lymphocytic leukemia (CLL) patients. In the province of British Columbia (BC), Canada, population 4.6 million, CLL patients receive uniform evaluation and therapy with FISH testing performed in three jurisdictions. The aims of this study were to (i) validate CLL-FISH testing among the BC cytogenetic laboratories to ensure standardization of results and (ii) characterize population-level CLL-FISH abnormalities by pooling provincial data. From 2004 to 2011, 585 consecutive patients underwent pretreatment CLL-FISH testing at laboratory A (50.1%), laboratory B (32.3%), or laboratory C (17.6%). For validation purposes, 26 CLL-FISH abnormalities were tested by each laboratory's protocol, with 91% result concordance. Discordant results involved percent abnormalities at or near cutoff values; therefore, a 10% universal cutoff was established when pooling results. Applying the universal cutoff to the provincial cohort, CLL-FISH abnormalities were detected in 74.9%: 54.9% 13q-, 18.8% +12, 8.5% 11q-, and 7.7% 17p-. In this large population-based cohort of patients referred for CLL-FISH testing, frequencies of abnormalities detected by FISH analysis were highly consistent with those reported in single-institution and clinical trial populations. Provinces or districts that work together to care for CLL patients can effectively pool data with appropriate laboratory validation to ensure standardization of results.

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