Nazik Hammad

Carbohydrate antigen 19-9 is a prognostic and predictive biomarker in patients with advanced pancreatic cancer who receive gemcitabine-containing chemotherapy: a pooled analysis of 6 prospective trials.

Carbohydrate antigen 19‐9 (CA19‐9) is a widely used biomarker in pancreatic cancer. There is no consensus on the interpretation of the change in CA19‐9 serum levels and its role in the clinical management of patients with pancreatic cancer.

Characterization of the association between 8q24 and colon cancer: gene-environment exploration and meta-analysis

BackgroundGenome-wide association studies and subsequent replication studies have shown that single nucleotide polymorphisms (SNPs) in the chromosomal region 8q24 are associated with colorectal cancer susceptibility.MethodsWe examined 11 SNP markers in the 8q24 region between 128.47 and 128.54 Mb, using a total of 1,987 colon cases and 2,339 controls who self-reported as white from two independent, well-characterized study populations. Analysis was performed separately within each study, and combined using random effects meta-analysis. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) and to test for effect modification by known colon cancer risk factors. We also performed a meta-analysis combining our results with previous studies.ResultsWe observed evidence of association for four SNPs in low to high linkage disequilibrium (r2 ranging from 0.18 to 0.93) localized in a 16.2 kb region defined by rs10505477 and rs1056368. The combined results for our two studies of colon cancer showed an OR of 1.10 (95% CI: 1.01-1.20, Ptrend = 0.023), and a meta-analysis of our results with previously reported studies of colon and colorectal cancer strongly support the association for this SNP (combined OR for rs6983267 = 1.21, 95% CI: 1.18-1.24, p = 5.5 × 10-44). We did not observe any notable evidence of effect modification by known colon cancer risk factors, and risk did not differ significantly by tumor site or stage.ConclusionsOur study confirms the association between polymorphisms on chromosome 8q24 and colon cancer risk and suggests that the susceptibility locus in region 8q24 is not strongly modified by various lifestyle, environmental, and demographic risk factors for colon cancer.

Characterization of 9p24 risk locus and colorectal adenoma and cancer: gene-environment interaction and meta-analysis

Background: A potential susceptibility locus for colorectal cancer on chromosome 9p24 (rs719725) was initially identified through a genome-wide association study, though replication attempts have been inconclusive. Methods: We genotyped this locus and explored interactions with known risk factors as potential sources of heterogeneity, which may explain the previously inconsistent replication. We included Caucasians with colorectal adenoma or colorectal cancer and controls from 4 studies (total 3,891 cases, 4,490 controls): the Womens Health Initiative (WHI); the Diet, Activity and Lifestyle Study (DALS); a Minnesota population-based case–control study (MinnCCS); and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). We used logistic regression to evaluate the association and test for gene–environment interactions. Results: SNP rs719725 was statistically significantly associated with risk of colorectal cancer in WHI (OR per A allele 1.19; 95% CI, 1.01–1.40; P trend = 0.04), marginally associated with adenoma risk in PLCO (OR per A allele 1.11; 95% CI, 0.99–1.25; Ptrend = 0.07), and not associated in DALS and MinnCCS. Evaluating for gene–environment interactions yielded no consistent results across the studies. A meta-analysis of 17 studies (including these 4) gave an OR per A allele of 1.07 (95% CI, 1.03–1.12; Ptrend = 0.001). Conclusions: Our results suggest the Aallele for SNP rs719725 at locus 9p24 is positively associated with a small increase in risk for colorectal tumors. Environmental risk factors for colorectal cancer do not appear to explain heterogeneity across studies. Impact: If this finding is supported by further replication and functional studies, it may highlight new pathways underlying colorectal neoplasia. Cancer Epidemiol Biomarkers Prev; 19(12); 3131–9. ©2010 AACR.

A retrospective study on the role of diabetes and metformin in colorectal cancer disease survival.

BACKGROUND Recent studies have suggested an effect of metformin on mortality for patients with both diabetes and colorectal cancer (crc). However, the literature is contradictory, with both positive and negative effects being identified. We set out to determine the effect of metformin with respect to prognosis in crc patients. METHODS After a retrospective chart review of crc patients treated at the Cancer Centre of Southeastern Ontario, Kaplan-Meier analyses and Cox proportional hazards regression models were used to compare overall survival (os) in patients with and without diabetes. RESULTS We identified 1304 crc patients treated at the centre. No significant differences between the diabetic and nondiabetic groups were observed with respect to tumour pathology, extent of metastatic disease, time or toxicity of chemotherapy, and the os rate (1-year os: 85.6% vs. 86.4%, p = 0.695; 2-year os: 73.6% vs. 77.0%, p = 0.265). In subgroup analysis, diabetic patients taking metformin survived significantly longer than their counterparts taking other diabetes treatments (os for the metformin group: 91% at 1 year; 80.5% at 2 years; os for the group taking other treatments, including diet control: 80.6% at 1 year, 67.4% at 2 years). Multivariate analysis suggests that patients with diabetes taking treatments other than metformin experience worse survival (p = 0.025). CONCLUSIONS Our results suggest that crc patients with diabetes, excluding those taking metformin, might have a worse crc prognosis. Taking metformin appears to have a positive association with prognosis. The protective nature of metformin needs further evaluation in prospective analyses.

Delivery of Global Cancer Care: An International Study of Medical Oncology Workload

Background To our knowledge, there is no literature that has described medical oncology (MO) workload in the global context. Here, we report results of an international study of global MO workload. Methods An online survey was distributed through a snowball method via national oncology societies to chemotherapy-prescribing physicians in 65 countries. Countries were classified into low- or low-middle–income countries (LMICs), upper-middle–income countries (UMICs), and high-income countries (HICs) on the basis of World Bank criteria. Workload was measured as the annual number of new consultations provided to patients with cancer per oncologist. Results A total of 1,115 physicians completed the survey: 13% (147 of 1,115) from LMICs, 17% (186 of 1,115) from UMICs, and 70% (782 of 1,115) from HICs. Eighty percent (897 of 1,115) of respondents were medical oncologists, 10% (109 of 1,115) were clinical oncologists, and 10% (109 of 1,115) were other. The median number of annual consults per oncologist was 175 (interquartile range, 75 to 275); 13% (140 of 1,103) saw ≥ 500 new patients in a year. Annual case volume in LMICs (median consults, 425; 40% of respondents seeing > 500 consults) was substantially higher than in UMICs (median consults, 175; 14% > 500) and HICs (median consults, 175; 7% > 500; P < .001). Among LMICs, UMICs, and HICs, median working days per week were 6, 5, and 5, respectively (P < .001). The highest annual case volumes per oncologist were in Pakistan (median consults, 950; 73% > 500 consults), India (median consults, 475; 43% > 500), and Turkey (median consults, 475; 27% > 500). Conclusion There is substantial global variation in medical oncology case volumes and clinical workload; this is most striking among LMICs, where huge deficits exist. Additional work is needed, particularly detailed country-level mapping, to quantify activity-based global MO practice and workload to inform training needs and the design of new pathways and models of care.

Medical oncology workload in Canada: infrastructure, supports, and delivery of clinical care

Background In 2000, a Canadian task force recommended that medical oncologists (mos) meet a target of 160-175 new patient consultations per year. Here, we report the Canadian results of a global survey of mo workload compared with mo workload in other high-income countries (hics). Methods Using a snowball method, an online survey was distributed by national oncology societies to chemotherapy-prescribing physicians in 22 hics (World Bank criteria). The survey was distributed within Canada to all members of the Canadian Association of Medical Oncologists. Workload was measured as the annual number of new cancer patient consults per oncologist. Results The survey was completed by 782 oncologists from hics, including 58 from Canada. Median annual consults per mo were 175 in Canada compared with 125 in other hics. The proportions of mos having 100 or fewer consults or more than 300 consults per year were 3% (2/58) and 5% (3/58) in Canada compared with 31% (222/724) and 16% (116/724) in other hics (p < 0.001 and p = 0.023 respectively). The median number of patients seen in a full-day clinic was 15 in Canada and 25 in other hics (p = 0.220). Canadian mos reported spending a median of 55 minutes per new consultation; new consultations of 35 minutes were reported in other hics (p < 0.001). Median hours worked per week was 55 in Canada and 45 in other hics (p = 0.200). Conclusions Although the median annual clinical volume for Canadian mos aligns with recommended targets, half the respondents exceeded that level of activity. Health policymakers and educators have to consider mo workforce supply and alternative models of care in preparation for the anticipated surge in cancer incidence in the coming decade.

Thrombocytosis as a predictor of poor prognosis in colorectal cancer patients.

540 Background: Thrombocytosis has been identified as a prognostic factor in many cancer types including ovarian, breast, and lung cancers. In colorectal cancer (CRC), the literature is divided. Several smaller case studies suggest a negative prognosis in CRC patients with pre-operative thrombocytosis, a larger population study contradicts this. Methods: We performed a retrospective chart review of CRC patients treated at the Cancer Center of Southeastern Ontario diagnosed from January 2005 to December 2011. 1304 confirmed CRC patient charts were identified and patient, tumor, blood work and treatment variables were extracted. Results: 1,096 patients had platelet count available at the time of oncology consult. 222 (20.3%) were characterized as having thrombocytosis (>400x109/L). No difference was identified between those with normal and with thrombocytosis with regards to age, sex, comorbidities, and BMI. However, a statistically significant difference was identified when looking at several pathological ...

A retrospective analysis of the role of proton pump inhibitors in colorectal cancer disease survival

BACKGROUND Proton pump inhibitors (ppis) are a commonly used medication. A limited number of studies have identified a weak-to-moderate association between ppi use and colorectal cancer (crc) risk, but none to date have identified an effect of ppi use on crc survival. We therefore postulated that an association between ppi use and crc survival might potentially exist. METHODS We performed a retrospective chart review of 1304 crc patients diagnosed from January 2005 to December 2011 and treated at the Cancer Centre of Southeastern Ontario. Kaplan-Meier analysis and Cox proportional hazards regression models were used to evaluate overall survival (os). RESULTS We identified 117 patients (9.0%) who were taking ppis at the time of oncology consult. Those taking a ppi were also more often taking asa or statins (or both) and had a statistically significantly increased rate of cardiac disease. No identifiable difference in tumour characteristics was evident in the two groups, including tumour location, differentiation, lymph node status, and stage. Univariate analysis identified a statistically nonsignificant difference in survival, with those taking a ppi experiencing lesser 1-year (82.1% vs. 86.7%, p = 0.161), 2-year (70.1% vs. 76.8%, p = 0.111), and 5-year os (55.2% vs. 62.9%, p = 0.165). When controlling for patient demographics and tumour characteristics, multivariate Cox regression analysis identified a statistically significant effect of ppi in our patient population (hazard ratio: 1.343; 95% confidence interval: 1.011 to 1.785; p = 0.042). CONCLUSIONS Our results suggest a potential adverse effect of ppi use on os in crc patients. These results need further evaluation in prospective analyses.

CA19-9 for the prediction of efficacy of chemotherapy in patients with advanced pancreas cancer: A pooled analysis of six prospective trials.

4071 Background: Carbohydrate antigen 19-9 (CA19-9) is a widely-used serum tumor marker in pancreas cancer. Multiple studies suggest a role for CA19-9 in predicting outcome. A decline of at least 25% from baseline while on treatment is predictive of improved survival. METHODS Individual patient data from six prospective trials evaluating gemcitabine-containing regimens from two institutions were pooled. The primary goal of this study was to correlate outcomes with decline in CA19-9 while on treatment. RESULTS A total of 213 patients with locally advanced (n=51) or metastatic (n=162) adenocarcinoma of the pancreas were included. Median age was 59 years (range: 28 - 90). Ninety-two percent of subjects had performance status of 0 or 1. Median baseline CA19-9 level was 1,113 ng/mL (range: 2 - 492,241). In a first analysis, groups were divided into those levels below (Low) or above (High) the median. Median overall survival (mOS) was 8.7 vs. 5.6 months (p=0.0056) and median time to progression (TTP) was 6.2 vs. 3.7 months (p=0.0043) in the low vs. high groups, respectively. We then confirmed that a decline on treatment of greater than or equal to 25% vs. less than 25% from baseline demonstrated a significant impact on outcome (mOS 10.2 vs. 5.2 months, p<0.0001; TTP 7.3 vs. 3.2 months, p<0.001). Interestingly we showed that any decline vs. no decline in CA19-9 levels conferred a similar likelihood of improved mOS (9.2 vs. 5.1 months, p=0.001) and TTP (7.2 vs. 2.8 months, p=0.0001) respectively. Finally, we showed that any decline vs. no decline of CA19-9 after only the first cycle of chemotherapy did not significantly affect outcome (mOS 9.2 vs. 6.6 months, P=0.3; TTP 6.7 vs. 4 months, p=0.2), whereas a persistent decline after the second cycle of therapy was predictive of improved outcome (mOS 10.3 vs. 5.2 months, p=0.0036; TTP 7.6 vs. 3.9 months, p=0.0091). CONCLUSIONS In this study we demonstrated that any decline in CA19-9 levels during therapy is predictive of improved outcome. We also showed that decline of CA19-9 levels after 2 consecutive cycles of therapy resulted in improved outcome.