Risk and predictors of suicide in colorectal cancer patients: a Surveillance, Epidemiology, and End Results analysis.

BACKGROUND: The risk of suicide is higher for patients with colorectal cancer (crc) than for the general population. Given known differences in morbidity and sites of recurrence, we sought to compare the predictors of suicide for patients with colon cancer and with rectal cancer. METHODS: Using the U.S. Surveillance, Epidemiology, and End Results database, adult patients with confirmed adenocarcinoma of the colon or rectum during 1973-2009 were identified. Parametric and nonparametric tests were used to assess selected variables, and Cox proportional hazards regression models were used to determine predictors of suicide. RESULTS: The database identified 187,996 patients with rectal cancer and 443,368 with colon cancer. Compared with the rectal cancer group, the colon cancer group was older (median age: 70 years vs. 67 years; p < 0.001) and included more women (51% vs. 43%, p < 0.001). Suicide rates were similar in the colon and rectal cancer groups [611 (0.14%) vs. 337 (0.18%), p < 0.001]. On univariate analysis, rectal cancer was a predictor of suicide [hazard ratio (hr): 1.26; 95% confidence interval (ci): 1.10 to 1.43]. However, after adjusting for clinical and pathology factors, rectal cancer was not a predictor of suicide (hr: 1.05; 95% ci: 0.83 to 1.33). In the colon cancer cohort, independent predictors of suicide included older age, male sex, white race, and lack of primary resection. The aforementioned predictors, plus metastatic disease, similarly predicted suicide in the rectal cancer cohort. CONCLUSIONS: The suicide risk in crc patients is low (<0.2%), and no difference was found based on location of the primary tumour. Sex, age, race, distant spread of disease, and intact primary tumour were the main predictors of suicide among crc patients. Further studies and interventions are needed to target these high-risk groups.

Significance of baseline and change in quality of life scores in predicting clinical outcomes in an international phase III trial of advanced pancreatic cancer: NCIC CTG PA.3.

BACKGROUND: There is insufficient information regarding the prognostic significance of baseline and change in quality of life (QoL) scores on overall survival (OS) in advanced pancreatic cancer. METHODS: QoL was assessed prospectively using the EORTC QLQ-C30 as part of the PA.3 trial of gemcitabine + erlotinib (G + E) vs. gemcitabine + placebo (G + P). Relevant variables and QoL scores at baseline and change at 8 weeks were analyzed by Cox stepwise regression to determine predictors of OS. RESULTS: 222 of 285 patients (pts) treated with G + E and 220 of 284 pts treated with G + P completed baseline QoL assessments. In a multivariable Cox analysis combining all pts, better QoL physical functioning (PF) score independently predicted longer OS (HR 0.86; CI: 0.80-0.93), as did non-white race (HR 0.64; CI: 0.44-0.95), PS 0-1 (HR 0.65; CI: 0.50-0.85), locally advanced disease (HR 0.55; CI: 0.43-0.71) and G + E (HR 0.78; CI: 0.64-0.96). Improvement in physical function at week 8 also predicted for improved survival (HR 0.89; CI: 0.81-0.97 for 10 point increase in score, p = 0.02). CONCLUSION: In addition to clinical variables, patient reported QoL scores at baseline and change from baseline to week 8 added incremental predictive information regarding survival for advanced pancreatic cancer patients.

Clinical outcomes of elderly patients receiving neoadjuvant chemoradiation for locally advanced rectal cancer.

BACKGROUND: Studies of clinical outcomes of elderly patients treated with neoadjuvant chemoradiation (nCRT) for locally advanced rectal cancer (LARC) are limited. Our aim was to assess the impact of age on clinical outcomes in a large multi-institutional database. PATIENTS AND METHODS: Data for patients diagnosed with LARC who received nCRT and curative-intent surgery between 2005 and 2012 were collected from five major Canadian cancer centers. Age was analyzed as a continuous and dichotomous variable (< 70 versus ≥ 70 years) and correlated with disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS). Cox regression models were used to adjust for important prognostic factors. RESULTS: Of 1172 patients included, 295 (25%) were ≥ 70 years, and they were less likely to receive adjuvant chemotherapy (ACT; 60% versus 79%, P < 0.0001), oxaliplatin-based ACT (12% versus 31%, P < 0.0001), less likely to complete nCT (76% versus 86%, P < 0.001), and more likely to be anemic at initiation of nCRT (42% versus 30%, P = 0.0004). In multivariate analyses, age ≥ 70 years was associated with similar DFS [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.68-1.26, P = 0.63], similar CSS (HR 0.81, 95% CI 0.46-1.41, P = 0.45), and similar OS (HR 1.28, 95% CI 0.88-1.86, P = 0.20), compared with the younger age group. As a continuous variable, increasing age was not predictive of DFS (HR 1.00, 95% CI 0.99-1.02, P = 0.49) or CSS (HR 1.002, 95% CI 0.98-1.02, P = 0.88); however, it correlated with an inferior OS (HR 1.02, 95% CI 1.00-1.03, P = 0.04). CONCLUSIONS: Elderly patients (≥ 70 years) who receive nCRT followed by surgery appear to have similar outcomes compared with younger patients. Decisions regarding eligibility for nCRT and surgery should not be based on age alone.

One compared with two cycles of mitomycin C in chemoradiotherapy for anal cancer: analysis of outcomes and toxicity.

BACKGROUND: Concurrent chemoradiation with fluorouracil (5fu) and mitomycin C (mmc) is standard treatment for anal canal carcinoma (acc). The current protocol in Alberta is administration of 5fu and mmc during weeks 1 and 5 of radiation. However, administration of the second bolus of mmc has been based largely on centre preference. Given limited published data on outcomes with different mmc regimens, our objective was to compare the efficacy and toxicity of 1 compared with 2 cycles of mmc in acc treatment. METHODS: Our retrospective study evaluated 169 acc patients treated with radical chemoradiotherapy between 2000 and 2010 at two tertiary cancer centres. All patients were treated with 2 cycles of 5fu and with 1 cycle (mmc1) or 2 cycles (mmc2) of mmc. Acute toxicities, disease-free (dfs) and overall survival (os) were analyzed. RESULTS: Baseline demographics, performance status, and stage were similar in the groups of patients who received mmc1 (52%) and mmc2 (48%). Before treatment, median hematologic parameters were comparable, except for white blood cell count, which was higher in the mmc2 group, but within normal range. The 5-year os and dfs were similar (75.1% and 54.2% for mmc1 vs. 70.7% and 44.2% for mmc2, p = 0.98 and p = 0.63 respectively). On multivariate analysis, mmc2 was the factor most strongly associated with specific acute toxicities: grade 3+ leukopenia (hazard ratio: 4.82; p < 0.01), grade 3+ skin toxicity (hazard ratio: 4.76; p < 0.001), and hospitalizations secondary to febrile neutropenia (hazard ratio: 9.91; p = 0.001). CONCLUSIONS: In definitive chemoradiotherapy for acc, 1 cycle of mmc appears to offer outcomes similar to those achieved with 2 cycles, with significantly less acute toxicity.

Association of hypomagnesemia with inferior survival in a phase III, randomized study of cetuximab plus best supportive care versus best supportive care alone: NCIC CTG/AGITG CO.17.

BACKGROUND: Cetuximab-induced hypomagnesemia has been associated with improved clinical outcomes in advanced colorectal cancer (CRC). We explored this relationship from a randomized clinical trial of cetuximab plus best supportive care (BSC) versus BSC alone in patients with pretreated advanced CRC. PATIENTS AND METHODS: Day 28 hypomagnesemia grade (0 versus ≥1) and percent reduction (<20% versus ≥20%) of Mg from baseline was correlated with outcome. RESULTS: The median percentage Mg reduction at day 28 was 10% (-42.4% to 63.0%) for cetuximab (N = 260) versus 0% (-21.1% to 25%) for BSC (N = 251) [P < 0.0001]. Grade ≥1 hypomagnesemia and ≥20% reduction from baseline at day 28 were associated with worse overall survival (OS) [hazard ratio, HR 1.61 (95% CI 1.12-2.33), P = 0.01 and 2.08 (95% CI 1.32-3.29), P = 0.002, respectively] in multivariate analysis including grade of rash (0-1 versus 2+). Dyspnea (grade ≥3) was more common in patients with ≥20% versus < 20% Mg reduction (68% versus 45%; P = 0.02) and grade 3/4 anorexia were higher in patients with grade ≥1 hypomagnesemia (81% versus 63%; P = 0.02). CONCLUSIONS: In contrast to prior reports, cetuximab-induced hypomagnesemia was associated with poor OS, even after adjustment for grade of rash.

Report from the 13th annual Western canadian gastrointestinal cancer consensus conference; calgary, alberta; september 8-10, 2011.

The 13th annual Western Canadian Gastrointestinal Cancer Consensus Conference was held in Calgary, Alberta, September 8-10, 2011. Health care professionals involved in the care of patients with gastrointestinal cancers participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management neuroendocrine tumours and locally advanced pancreatic cancer.

Epidermal growth factor receptor inhibitor-induced hypomagnesemia: a survey of practice patterns among Canadian gastrointestinal medical oncologists.

Background: The optimal management of hypomagnesemia (hMg) induced by epidermal growth factor receptor inhibitors (egfris) for advanced colorectal cancer is unclear. We surveyed gastrointestinal medical oncologists in Canada to determine practice patterns for the management of egfri-induced hMg. Methods: Based on distribution lists from the Eastern Canadian Colorectal Cancer Consensus Conference and the Western Canadian Gastrointestinal Cancer Consensus Conference, medical oncologists were invited to participate in an online questionnaire between November 2013 and February 2014. Results: From the 104 eligible physicians, 40 responses were obtained (38.5%). Panitumumab was more commonly prescribed than cetuximab by 70% of respondents, with 25% prescribing cetuximab and panitumumab equally. Most respondents obtain a serum magnesium level before initiating a patient on an egfri (92.5%) and before every treatment (90%). Most use a reactive strategy for magnesium supplementation (90%) and, when using supplementation, favour intravenous (iv) alone (40%) or iv and oral (45%) dosing. Magnesium sulfate was used for iv replacement, and the most common oral strategies were magnesium oxide (36.4%) and magnesium rougier (18.2%). Under the reactive strategy, intervention occurred at hMg grade 1 (70.3%) or grade 2 (27%). Of the survey respondents, 45% felt that 1-5 of their patients have ever developed symptoms attributable to hMg, and 35% have had to interrupt egfri therapy because of this toxicity, most commonly at grade 3 (30%) or grade 4 (45%) hMg. The most important question about egfri-induced hMg was its relevance to clinical outcomes (45%) and its symptoms (37.5%). Conclusions: In Canada, various strategies are used in the management of egfri-induced hMg, including prophylactic and reactive approaches that incorporate iv, oral, or a combination of iv and oral supplementation. Clinicians are concerned about the effect of hMg on clinical outcomes and about the symptoms that patients experience as a result of this toxicity.

Continuity clinics in oncology training programs in Canada.

PURPOSE: Continuity clinics (ccs) give trainees an opportunity for longitudinal follow-up of a patient cohort. Trainees can function in a semi-autonomous manner and prepare for independent practice. Data about such clinics in Canada are limited. Our objective was to assess the utility of ccs in Canadian oncology training programs. METHODS: Surveys were developed by the authors for medical and radiation oncology program directors (pds) and trainees, to assess the utility of ccs in Canadian oncology training programs.oncology patients, to assess their attitudes toward ccs. The pds were contacted by e-mail, using the Web site of the Canadian Resident Matching Service; the trainees were contacted by e-mail through the pds and their administrative assistants. Surveys were distributed electronically using SurveyMonkey. Patients were approached by staff oncologists during follow-up visits at The Ottawa Hospital Cancer Centre. RESULTS: Completed surveys were received from 33% of trainees and 63% of pds contacted; patient surveys were completed by 95 patients. Participation in a cc was reported by 47% of responding pds and 37% of responding trainees. Among respondents, 80% rated the ccs as "important" or "very important" to training. The biggest challenge identified by trainees and pds was lack of clinic space. Most pds (57%) and trainees (59%) felt that the staff oncologist should review the patient only if the trainee has concerns, but only 37% of patients shared that view (p = 0.0002). However, many patients expressed the desire to participate in trainee education. CONCLUSIONS: Continuity clinics are considered beneficial by pds and trainees. Patients desire more trainee supervision than the trainees themselves and the pds do, a factor that should be considered when implementing a cc.

Comorbidity, age and overall survival in patients with advanced pancreatic cancer - results from NCIC CTG PA.3: a phase III trial of gemcitabine plus erlotinib or placebo.

BACKGROUND: The effect of comorbidity, age and performance status (PS) on treatment of advanced pancreatic cancer is poorly understood. We examined these factors as predictors of outcome in advanced pancreatic cancer patients treated with gemcitabine +/- erlotinib. PATIENTS AND METHODS: Comorbidity was evaluated by two physicians using the Charlson Comorbidity Index (CCI) and correlated with clinical outcome data from the NCIC Clinical Trials Group (NCIC CTG) PA.3 clinical trial. RESULTS: Five hundred and sixty-nine patients were included; 47% were aged ≥ 65 years old, 36% had comorbidity (CCI>0). In multivariate analysis, neither age (p=0.22) nor comorbidity (p=0.21) was associated with overall survival. The baseline presence of better PS and lower pain intensity scores was associated with better overall survival (p < 0.0001 and p=0.01, respectively). An improvement in survival with the addition of erlotinib therapy was seen in patients age < 65 (adjusted hazard ratio (HR) 0.73, p=0.01) or in the presence of comorbidity (adjusted HR 0.72, p=0.03). However, neither age nor CCI score was predictive of erlotinib benefit after test for interaction. Patients treated with gemcitabine plus erlotinib who were ≥ 65 years of age or those with comorbidity had a higher rate of infections ≥ grade 3. CONCLUSION: Low baseline pain intensity and better PS were associated with improved overall survival, while age and comorbidity were not independent prognostic factors for patients treated with gemcitabine-based therapy.

Characterization of published errors in high-impact oncology journals.

PURPOSE: To assess the frequency and propagation rate of published errors in the oncology literature and to determine possible contributing factors. METHODS: We reviewed 10 major oncology journals to determine variability in the online presentation of errata. Canadian oncologists were surveyed regarding characteristics that may influence error propagation. Errors published during 2004-2007 in the Journal of Clinical Oncology (jco) and the Journal of the National Cancer Institute (jnci) were classified as trivial or serious (that is, whether change in outcome was involved). The frequency of citation and error propagation was determined for serious errors. RESULTS: Of the 10 journals reviewed, 9 present links from the original article to the erratum; in 4 of those 9 journals, at least 1 link was missing. Survey results indicate that 33% of oncologists do not read errata, and 45% have read only the abstract when referencing an article. Although 59% of oncologists have noticed errors in cancer publications, only 13% reported the error. Together, jco and jnci published 190 errata, for an error rate of 4% ± 1% (standard deviation) annually; 26 of 190 errors were serious (14%). The median time from publication of the article to the corresponding erratum was 3.5 months for trivial errors as compared with 8.3 months for serious errors (p = 0.03). Error propagation in citations before and after publication of the erratum was 15% and 2% respectively (p < 0.01). CONCLUSIONS: Error rates in high-impact oncology journals average 4%, which is likely an underestimate, because errors noticed by readers are not consistently reported. Propagation of serious errors decreases, but still continues, after publication of errata.