Cost-effectiveness of first-line treatments for patients with KRAS wild-type metastatic colorectal cancer

Background

Combinations of chemotherapy regimens and monoclonal antibodies have been demonstrated to improve clinical outcomes in patients with metastatic colorectal cancer (mcrc). Although these combination treatment strategies are safe and effective in first-line treatment for mcrc, little is known about their economic consequences and resource allocation implications. In the present study, we evaluated the cost-effectiveness of bevacizumab plus folfiri, cetuximab plus folfiri, and panitumumab plus folfiri for patients with KRAS wild-type mcrc.

Methods

A Markov model simulated the lifetime patient outcomes and costs of each first-line treatment strategy and subsequent lines of treatment from the perspective of the health care payer in Ontario. The model was parameterized using data from the Ontario Cancer Registry, Ontario health administrative databases, and published randomized control trials. Patient outcomes were measured in quality-adjusted life years (qalys), and costs were measured in monetary terms. Costs and outcomes were both discounted at 5% and expressed in 2012 Canadian dollars.

Results

For mcrc patients with KRAS wild-type disease, the treatment strategy of bevacizumab plus folfiri was found to dominate the other two first-line treatment strategies. Sensitivity analyses revealed that the incremental cost-effectiveness ratio values were sensitive to the effectiveness of treatment, the costs of bevacizumab and cetuximab, and health utility values.

Conclusions

Evidence from Ontario showed that bevacizumab plus folfiri is the cost-effective first-line treatment strategy for patients with KRAS wild-type mcrc. The panitumumab plus folfiri and cetuximab plus folfiri options were both dominated, but the cetuximab plus folfiri strategy must be further investigated given that, in the sensitivity analyses, the cost-effectiveness of that strategy was found to be superior to that of bevacizumab plus folfiri under certain ranges of parameter values.     

Bevacizumab-based therapy for colorectal cancer: experience from a large Canadian cohort at the Jewish General Hospital between 2004 and 2009

Background

Before its regulatory approval in Canada, bevacizumab to treat patients with colorectal cancer (crc) was accessed through the Bevacizumab Expanded Access Trial and a special-access program at the Jewish General Hospital. We retrospectively evaluated patient outcomes in that large cohort.

Methods

All patients (n = 196) had metastatic crc, were bevacizumab-naïve, and received bevacizumab in combination with chemotherapy at the Jewish General Hospital between 2004 and 2009. We collected patient demographics and clinical characteristics; relevant medical history, disease stage and tumour pathology at diagnosis; type, duration, and line of therapy; grades 3 and 4 adverse events (aes), time to disease progression (ttp), and overall survival (os) from diagnosis.

Results

Median follow-up was 36.0 months. Median ttp was 8.0 months [95% confidence interval (ci): 7.0 to 9.0 months). Median os was 41.0 months (95% ci: 36.0 to 47.0 months). Of the 40 grades 3 and 4 bevacizumab-related aes experienced by 38 patients (19.4%), the most common were thrombocytopenia (n = 17), deep-vein thrombosis (n = 6), pulmonary embolism (n = 4), and hypertension (n = 3).

Conclusions

In an expanded access setting, our data reflect the efficacy and safety of bevacizumab-based therapy in the controlled post-registration clinical trial setting.     

Specialists' perceptions of hereditary colorectal cancer screening in Newfoundland and Labrador

Purpose

Colorectal cancer (crc) screening is particularly valuable in Newfoundland and Labrador (NL), where a substantial proportion of crc cases have a hereditary link. We examined the perceptions of gastroenterologists and general surgeons with respect to screening practices for patients with hereditary crc.

Methods

We surveyed all gastroenterologists and general surgeons in NL to determine demographic and professional practice characteristics and screening knowledge, practices, and attitudes for four groups of patients with hereditary crc.

Results

Of the 43 eligible physicians, 36 (83.7%) responded. Most of the physicians surveyed knew the correct age to start screening, preferred screening by colonoscopy, had a systematic means in their own practice of prioritizing patients for screening, and felt that family doctors or patients (or both) should be responsible for monitoring screening compliance. Most physicians reported that patients with hereditary nonpolyposis crc and familial adenomatous polyposis waited 3 months for screening; patients with a family history of crc or adenomatous polyp waited 6 months or longer. Although respondents agreed on the need for a province-wide crc registry [4.36 on a 5-point Likert scale (1 = strongly disagree; 5 = strongly agree)], they disagreed that wait times were reasonable (2.81) and that other health professionals should perform colonoscopies (2.86). They were equivocal about the need for centralized bookings (3.25) and about whether genetic testing is useful for prioritizing patients (3.25).

Conclusions

Gastroenterologists and general surgeons in NL were knowledgeable about screening, but had varying opinions about individual roles in screening, wait times, and the means for prioritizing and providing screening for patients with hereditary crc.     

Generalizability of toxicity data from oncology clinical trials to clinical practice: toxicity of irinotecan-based regimens in patients with metastatic colorectal cancer

Background

The relevance of oncology trial results to clinical practice depends on whether the trial participants are similar to the actual population of patients receiving treatment for the malignancy and whether the patients are treated similarly in both circumstances. Chemotherapy treatments may be more toxic in patients of advanced age and poor performance status—patients typically excluded from clinical trials.

Methods

In a retrospective chart review that included all non-trial patients with metastatic colorectal cancer treated with irinotecan-based chemotherapy from January 2004 to September 2006 at our institution, we quantified and subsequently compared the toxicity rates of the irinotecan regimens in clinical practice with published toxicity rates from corresponding phase iii clinical trials. The primary endpoint was the incidence of grades 3 and 4 diarrhea.

Results

The study included 203 patients, and the irinotecan regimens considered included

• folfiri [irinotecan, leucovorin, 5-fluorouracil (5fu)],
• ifl (bevacizumab, irinotecan, 5fu, leucovorin),
• xeliri (capecitabine, 3-weekly irinotecan), and
• irinotecan monotherapy.

The rates of grades 3 and 4 diarrhea for folfiri, ifl, xeliri, and irinotecan monotherapy in clinical practice were 10%, 15%, 17%, and 21% as compared with 10%, 23%, 20%, and 31% respectively in clinical trials. When only patients meeting trial performance status and age criteria were analyzed, the rates of grades 3 and 4 diarrhea by regimen were 11%, 20%, 19%, and 26% respectively.

Conclusions

Overall, the toxicity rates for folfiri and irinotecan monotherapy in non-trial patients were not statistically different from the rates quoted in published clinical trials.     

Using the Cancer Risk Management Model to evaluate colorectal cancer screening options for Canada

Background

Several screening methods for colorectal cancer (crc) are available, and some have been shown by randomized trials to be effective. In the present study, we used a well-developed population health simulation model to compare the risks and benefits of a variety of screening scenarios. Tests considered were the fecal occult blood test (fobt), the fecal immunochemical test (fit), flexible sigmoidoscopy, and colonoscopy. Outcomes considered included years of life gained, crc cases and deaths prevented, and direct health system costs.

Methods

A natural history model of crc was implemented and calibrated to specified targets within the framework of the Cancer Risk Management Model (crmm) from the Canadian Partnership Against Cancer. The crmm-crc permits users to enter their own parameter values or to use program-specified base values. For each of 23 screening scenarios, we used the crmm-crc to run 10 million replicate simulations.

Results

Using base parameter values and some user-specified values in the crmm-crc, and comparing our screening scenarios with no screening, all screening scenarios were found to reduce the incidence of and mortality from crc. The fobt was the least effective test; it was not associated with lower net cost. Colonoscopy screening was the most effective test; it had net costs comparable to those for several other strategies considered, but required more than 3 times the colonoscopy resources needed by other approaches. After colonoscopy, strategies based on the fit were predicted to be the most effective. In sensitivity analyses performed for the fobt and fit screening strategies, fobt parameter values associated with high-sensitivity formulations were associated with a substantial increase in test effectiveness. The fit was more cost-effective at the 50 ng/mL threshold than at the 100 ng/mL threshold.

Conclusions

The crmm-crc provides a sophisticated and flexible environment in which to evaluate crc control options. All screening scenarios considered in this study effectively reduced crc mortality, although sensitivity analyses demonstrated some uncertainty in the magnitude of the improvements. Where possible, local data should be used to reduce uncertainty in the parameters.     

Palliative chemotherapy for patients 70 years of age and older with metastatic colorectal cancer: a single-centre experience

BackgroundMetastatic colorectal cancer (mcrc) commonly affects elderly people, an understudied subset of patients. We analyzed the survival impact of the first and subsequent lines of chemotherapy in eligible non-trial patients 70 years of age and older with mcrc treated between 2004 and 2012.MethodsThis single-centre retrospective analysis estimated overall survival (os) and progression-free survival (pfs) using the Kaplan–Meier method. Multivariate analysis was used to adjust for age, sex, Eastern Cooperative Oncology Group performance status, score on the Charlson comorbidity index, dependency in activities of daily living, and exposure to 1 or more chemotherapy doublets, capecitabine alone, or best supportive care (bsc).ResultsOf 109 patients identified, 29 elected bsc, and 80 received chemotherapy. In multivariate analysis, age was not associated with os [hazard ratio (hr): 0.99; 95% confidence interval (ci): 0.92 to 1.05], but a performance status of 2 or higher was associated with a decreased likelihood of survival (hr: 3.12; 95% ci: 1.87 to 5.76), and exposure to 1 or more doublets was associated with improved survival (hr: 0.33; 95% ci: 0.17 to 0.66). In univariate analysis, a trend toward improved os was observed for first-line doublet chemotherapy compared with capecitabine (hr: 0.66; 95% ci: 0.41 to 1.07), and pfs was superior (hr: 0.46; 95% ci: 0.26 to 0.84). Compared with exposure to 1 doublet, exposure to the 3 potential cytotoxic chemotherapies was not associated with improved os (hr: 0.77; 95% ci: 0.41 to 1.43). The incidence of neutropenia with first-line folfiri was 40%; the incidences of bevacizumab-related arterial and venous thrombosis were both 8%.ConclusionsExposure to 1 or more doublet chemotherapies for mcrc was associated with better outcomes in non-trial patients 70 years of age and older. Elderly patients treated with palliative chemotherapy and bevacizumab should be monitored carefully for arterial and venous thrombotic events.     

Colorectal cancer screening in Canada: results from the first round of screening for five provincial programs

Background

Early implementation of programmatic colorectal cancer (crc) screening for average-risk individuals 50–74 years of age in Canada has used fecal occult blood tests [fts (guaiac or immunochemical)] and colonoscopy for follow-up of abnormal fts. This paper presents results of an evaluation of this crc screening.

Methods

Five Canadian provincial programs provided aggregated data for individuals with a first-round ft processed between January 1, 2009, and December 31, 2011.

Results

The 104,750 people who successfully completed a first round of screening represented 16.1% of those who had access to the programs between January 1, 2009, and December 31, 2011 (mean age: 61.2 years; men: 61.4 years; women: 61.1 years). Of those participants, 4661 had an abnormal ft (4.4%). Uptake of colonoscopy within 180 days after an abnormal ft was 80.5%, ranging from 67.8% to 89.5% by program. The positive predictive value (ppv) for adenoma was 35.9% for guaiac ft and 50.6% for immunochemical ft. Adenoma and crc detection rates were, respectively, 16.9 and 1.8 per 1000 screened. Of invasive crcs detected, 64.6% were stage i or ii.

Conclusions

Considering the variation in characteristics and stage of implementation of each provincial program, the collaboration of the provinces leading to this report on the early performance of crc screening in Canada is a major milestone. Targets are met or nearly met for significant indicators such as ppv for adenoma and cancer detection rate. Participation is expected to increase as programs are fully implemented in the provinces. Additional effort may be needed to improve timely access to follow-up colonoscopy.     

Prognostic factors associated with the response to sunitinib in patients with metastatic renal cell carcinoma

Objective

We investigated the prognostic clinicopathologic factors associated with overall survival (os) and progression-free survival (pfs) in the once-daily continuous administration of first-line sunitinib in a consecutive cohort of Turkish patients with metastatic renal cell carcinoma (rcc).

Methods

The study enrolled 77 Turkish patients with metastatic rcc who received sunitinib in a continuous once-daily dosing regimen between April 2006 and April 2011. Univariate analyses were performed using the log-rank test.

Results

Median follow-up was 18.5 months. In univariate analyses, poor pfs and os were associated with 4 of the 5 factors in the Memorial Sloan–Kettering Cancer Center (mskcc) score: Eastern Cooperative Oncology Group performance status of 2 or higher, low hemoglobin, high corrected serum calcium, and high lactate dehydrogenase. In addition to those factors, hypoalbuminemia, more than 2 metastatic sites, liver metastasis, non–clear cell histology, and the presence of sarcomatoid features on pathology were also associated with poor pfs; and male sex, hypoalbuminemia, prior radiotherapy, more than 2 metastatic sites, lung metastasis, nuclear grade of 3 or 4 for the primary tumour, and the presence of sarcomatoid features were also associated with poorer os. The application of the mskcc model distinctly separated the pfs and os curves (p < 0.001).

Conclusions

Our study identified prognostic factors for pfs and os with the use sunitinib as first-line metastatic rcc therapy and confirmed that the mskcc model still appears to be valid for predicting survival in metastatic rcc in the era of molecular targeted therapy.     

Role of oxaliplatin combined with 5-fluorouracil and folinic acid in the first- and second-line treatment of advanced colorectal cancer

Question

What is the role of oxaliplatin combined with 5-fluorouracil (5-fu) and folinic acid (fa) in the first- and second-line treatment of advanced (unresectable locally advanced or metastatic) colorectal cancer?

Perspectives

Evidence was selected and reviewed by two members of the Gastrointestinal Cancer Disease Site Group (gi dsg) of Cancer Care Ontario’s Program in Evidence-Based Care (pebc) and by a methodologist. The resulting practice guideline report has been reviewed and approved by the gi dsg, which comprises medical and radiation oncologists, surgeons, a pathologist, and patient representatives.External review by Ontario practitioners was obtained through a mailed survey. Final approval of the original guideline report was obtained from the Practice Guidelines Coordinating Committee.

Outcomes

Outcomes of interest were 1-year survival, response rates, and quality of life.

Methodology

The medline, cancerlit, embase, Guidelines International Network, and Cochrane Library databases were systematically searched for relevant studies. Recommendations were formed based on the evidence reviewed. Through a survey, these recommendations were appraised by Ontario clinicians; the recommendations were then revised by the gi dsg. The systematic review and modified recommendations were approved by a review body within pebc.

Results

The literature review found twenty-one randomized controlled trials and two meta-analyses. Evidence on first-line treatment found infusional 5-fu/fa/oxaliplatin (folfox) to be superior to bolus 5-fu/fa/irinotecan (ifl) for rates of median survival and tumour response, with lower incidences of most adverse effects except peripheral neuropathy. For second-line treatment after fluoropyrimidine monotherapy, folfox is a reasonable alternative for patients with contraindications to second-line irinotecan. After progression on infusional 5-fu/fa/irinotecan (folfiri), folfox is the preferred therapy. Evidence from a single randomized trial suggests that additional benefits can be expected with the addition of bevacizumab to the folfox regimen in second-line treatment.

Practice Guideline

These recommendations apply to adult patients with advanced colorectal cancer who have high performance status (Eastern Cooperative Oncology Group score 0–2).Refer to Appendix A for available treatment options and to Appendix b for recommended dosages and schedules.The folfox regimen is an important component of therapy for advanced colorectal cancer.

First-line Therapy

In one trial, folfox was shown to be superior to ifl. The folfox regimen has superior rates of median survival and tumour response. Compared with ifl, folfox has lower incidences of severe nausea, vomiting, diarrhea, and febrile neutropenia, but a higher incidence of peripheral neuropathy.Short-term infusional 5-fu/fa in combination with either oxaliplatin (folfox) or irinotecan (folfiri) are both acceptable alternatives for fit patients when combination therapy is the preferred treatment. Choice of first-line therapy may rely on patient factors and preferences—for example, less neuropathy with irinotecan versus less alopecia with oxaliplatin.

Second-line Therapy

After progression on first-line anti-thymidylate synthase monotherapy (for example, 5-fu/fa, capecitabine), irinotecan is standard second-line therapy. The folfox regimen is a reasonable alternative for patients with contraindications to the use of second-line irinotecan.After progression on both irinotecan and an anti-thymidylate synthase agent, folfox is the preferred therapy. Recent trials suggest that, as compared with folfox alone, folfox combined with bevacizumab provides additional survival benefits.

Qualifying Statements

The role of radiation therapy, either alone or in combination with chemotherapy, for locally advanced unresectable colorectal cancer is not addressed in this guideline.Use of chronomodulated regimens is a topic that intersects with the use of oxaliplatin/5-fu combinations, particularly chronomodulation of 5-fu in these combinations. Chronomodulation of oxaliplatin has not been extensively studied, and the topic of chronomodulation is beyond the scope of this guideline and is not addressed.Although data exist to support the use of bevacizumab in combination with folfox in second-line treatment, no first-line treatment data are available on which to make a recommendation.     

Cost-effectiveness of zoledronic acid compared with clodronate in multiple myeloma

Background

In the U.K. Medical Research Council Myeloma IX trial (mmix), zoledronic acid 4 mg once every 3–4 weeks, compared with clodronate 1600 mg daily, reduced the incidence of skeletal related events (sres), increased progression-free survival (pfs), and prolonged overall survival (os) in 1970 patients with newly-diagnosed multiple myeloma. The incidence of confirmed osteonecrosis of the jaw was higher with zoledronic acid than with clodronate. The objective of the present study was to evaluate, based on the findings in mmix, the cost-effectiveness of zoledronic acid compared with clodronate in patients with newly-diagnosed multiple myeloma.

Methods

An economic model was used to project pfs, os, the incidence of sres and adverse events, and expected lifetime health care costs for patients with newly diagnosed multiple myeloma who are alternatively assumed to receive zoledronic acid or clodronate. The incremental cost-effectiveness ratio (icer) of zoledronic acid compared with clodronate was calculated as the ratio of the difference in cost to the difference in quality-adjusted life years (qalys). Model inputs were based on results of mmix and published sources. Results were generated under different assumptions regarding the beneficial effects of zoledronic acid on os beyond 5 years after treatment initiation.

Results

Assuming lifetime treatment effects of zoledronic acid, treatment with zoledronic acid (compared with clodronate) increased qalys by 0.27 at an additional cost of CA$13,407, yielding an icer of CA$49,829 per qaly gained. If the threshold icer is CA$100,000 per qaly, the estimated probability that zoledronic acid is cost-effective is 80%. Assuming that the benefits of zoledronic acid on pfs and os diminish over 5 years beginning at the end of year 5, the icer is CAN$63,027 per qaly gained. If the benefits of zoledronic acid on pfs and os are assumed to persist for 5 years only, the icer is CAN$76,948 per qaly gained.

Conclusions

Compared with clodronate, zoledronic acid represents a cost-effective treatment alternative in patients with multiple myeloma.     

Relationship between progression-free survival and overall survival in chronic lymphocytic leukemia: a literature-based analysis

Background

The endpoints of progression-free survival (pfs) and time-to-progression (ttp) are frequently used to evaluate the clinical benefit of anticancer drugs. However, the surrogacy of those endpoints for overall survival (os) is not validated in all cancer settings. In the present study, we used a trial-based approach to assess the relationship between median pfs or ttp and median os in chronic lymphocytic leukemia (cll).

Methods

The pico (population, interventions, comparators, outcomes) method was used to conduct a systematic review of the literature. The population consisted of patients with cll; the interventions and comparators were standard therapies for cll; and the outcomes were median pfs, ttp, and os. Two independent reviewers screened titles, abstracts, and full papers for eligibility and then extracted data from selected studies. Correlation coefficients were calculated to assess the relationship between median pfs or ttp and median os. Subgroup correlation analyses were also conducted according to the characteristics of the selected studies (such as line of treatment and type of treatment under investigation).

Results

Of the 1263 potentially relevant articles identified during the literature search, twenty-three were included. On average, median pfs or ttp was 16.0 months (standard deviation: 12.4 months) and median os was 43.5 months (standard deviation: 31.2 months). Results of the correlation analysis indicated that median pfs or ttp is highly correlated with median os (Spearman correlation coefficient: 0.813; p ≤ 0.001). A significant correlation between median pfs or ttp and median os was observed in second- and subsequent-line therapies, but not in the first-line setting.

Conclusions

Our study demonstrates a strong correlation between median pfs or ttp and median os in previously treated cll, which reinforce the hypothesis that pfs and ttp could be adequate surrogate endpoints for os in this cancer setting.     

Making lifestyle changes after colorectal cancer: insights for program development

Background

Healthy lifestyle behaviours may improve outcomes for people with colorectal cancer (crc), but the intention to take action and to change those behaviours may vary with time and resource availability. We aimed to estimate the prevalence of current lifestyle behaviours in people with and without crc in our community, and to identify their desire to change and their resource preferences.

Methods

A mixed-methods survey was completed by people diagnosed with crc who were pre-treatment (n = 54), undergoing treatment (n = 62), or done with treatment for less than 6 months (n = 67) or for more than 6 months (n = 178), and by people without cancer (n = 83).

Results

Current lifestyle behaviours were similar in all groups, with the exception of vigorous physical activity levels, which were significantly lower in the pre-treatment and ongoing treatment respondents than in cancer-free respondents. Significantly more crc respondents than respondents without cancer had made lifestyle changes. Among the crc respondents, dietary change was the change most frequently made (39.3%), and increased physical activity was the change most frequently desired (39.1%). Respondents wanted to use complementary and alternative medicine (cam), reading materials, self-efficacy, and group activities to make future changes.

Conclusions

Resources for lifestyle change should be made available for people diagnosed with crc, and should be tailored to address physical activity, cam, and diet. Lifestyle programs offered throughout the cancer trajectory and beyond treatment completion might be well received by people with crc.     

Panitumumab monotherapy compared with cetuximab and irinotecan combination therapy in patients with previously treated KRAS wild-type metastatic colorectal cancer

Background

The survival benefit for single-agent anti–epidermal growth factor receptor (egfr) therapy compared with combination therapy with irinotecan in KRAS wildtype (wt) metastatic colorectal cancer (mcrc) patients in the third-line treatment setting is not known. The objective of the present study was to describe the characteristics of, and to compare survival outcomes in, two cohorts of patients treated with either singleagent panitumumab or combination therapy with cetuximab and irinotecan.

Methods

The study enrolled patients with KRAS wt mcrc previously treated with both irinotecan and oxaliplatin who had received either panitumumab or combination cetuximab–irinotecan before April 1, 2011, at the BC Cancer Agency (bcca). Patients were excluded if they had received anti-egfr agents in earlier lines of therapy. Data were prospectively collected, except for performance status (ps), which was determined by chart review. Information about systemic therapy was extracted from the bcca Pharmacy Database.

Results

Of 178 eligible patients, 141 received panitumumab, and 37 received cetuximab–irinotecan. Compared with patients treated with cetuximab–irinotecan, panitumumab-treated patients were significantly older and more likely to have an Eastern Cooperative Oncology Group (ecog) ps of 2 or 3 (27.7% vs. 2.7%, p = 0.001). Other baseline prognostic variables and prior and subsequent therapies were similar. Median overall survival was 7.7 months for the panitumumab group and 8.3 months for the cetuximab–irinotecan group. Multivariate analysis demonstrated that survival outcomes were similar regardless of the therapy selected (hazard ratio: 1.28; p = 0.34). An ecog ps of 2 or 3 compared with 0 or 1 was the only significant prognostic factor in this treatment setting (hazard ratio: 3.37; p < 0.01).

Conclusions

Single-agent panitumumab and cetuximab–irinotecan are both reasonable third-line treatment options, with similar outcomes, for patients with chemoresistant mcrc.     

Surgical process improvement tools: defining quality gaps and priority areas in gastrointestinal cancer surgery

Background

Surgery is a cornerstone of cancer treatment, but significant differences in the quality of surgery have been reported. Surgical process improvement tools (spits) modify the processes of care as a means to quality improvement (qi). We were interested in developing spits in the area of gastrointestinal (gi) cancer surgery. We report the recommendations of an expert panel held to define quality gaps and establish priority areas that would benefit from spits.

Methods

The present study used the knowledge-to-action cycle was as a framework. Canadian experts in qi and in gi cancer surgery were assembled in a nominal group workshop. Participants evaluated the merits of spits, described gaps in current knowledge, and identified and ranked processes of care that would benefit from qi. A qualitative analysis of the workshop deliberations using modified grounded theory methods identified major themes.

Results

The expert panel consisted of 22 participants. Experts confirmed that spits were an important strategy for qi. The top-rated spits included clinical pathways, electronic information technology, and patient safety tools. The preferred settings for use of spits included preoperative and intraoperative settings and multidisciplinary contexts. Outcomes of interest were cancer-related outcomes, process, and the technical quality of surgery measures.

Conclusions

Surgical process improvement tools were confirmed as an important strategy. Expert panel recommendations will be used to guide future research efforts for spits in gi cancer surgery.     

Pan-Canadian initiatives in colorectal cancer screening: adopting knowledge translation tools to accelerate uptake and impact

Background

Despite the positive conclusions of several randomized controlled trials and the publication of national recommendations on colorectal cancer (crc) screening, uptake remained low. The inauguration of the National Colorectal Cancer Screening Network in 2007, the same year that the first screening program was announced in Canada, provided an opportunity for integrated knowledge translation to accelerate the processes of program implementation and screening uptake.

Aim

Two primary aims were identified. The first focused on means to monitor the effects of various implementation plans in delivering high-quality population-based crc screening. The second focused on identifying and addressing knowledge gaps that may impair screening participation.

Method

The methods used are described in the context of the knowledge-to-action cycle and demonstrate that the initiative itself dictates the point in the cycle at which to start.

Results

The identified need to monitor various implementation plans resulted in the shared development of a quality determinants document. All programs committed to designing data collection so that core components could be measured and compared; 6 operating programs have conducted the first data collection, which will allow for monitoring and for new knowledge creation as the process develops further. The knowledge gap identification project started with new knowledge creation, which identified a higher-than-expected willingness of Canadians to discuss crc screening with physicians, but a low level of understanding of screening as a wellness-related behaviour. Knowledge translation interventions have been developed with the stakeholders to address those gaps, and ongoing surveys to be carried out later in 2011 will help to gauge progress in the understanding and acceptance of crc screening by the population.

Conclusions

A national network that engaged all programs, policymakers, experts, and lay representatives successfully used knowledge translation principles to enhance the trajectory of crc screening in Canada.     

Fertility risk discussions in young patients diagnosed with colorectal cancer

Purpose

In 2006, the American Society of Clinical Oncology established guidelines on fertility preservation in cancer patients, but recent data suggest that the guidelines are not widely followed. To identify the frequency of fertility discussions and the characteristics that influence the rate of discussion, we performed a retrospective chart review for patients less than 40 years of age with newly diagnosed colorectal cancer (crc).

Methods

Charts of patients aged 18–40 years with newly diagnosed crc presenting to the Juravinski Cancer Centre from 2000 to 2009 were reviewed for documentation of discussions regarding fertility risks with treatment and reproductive options available. The influences of sex, age, year of diagnosis, stage of cancer, and type of treatment on the frequency of discussions were explored.

Results

The review located 59 patients (mean age: 35 years) who met the criteria for inclusion. A fertility discussion was documented in 20 of those patients [33.9%; 95% confidence interval (ci): 22.1% to 47.4%]. In the multivariate analysis, the odds of fertility being addressed was higher for patients receiving radiation [odds ratio (or): 9.31; 95% ci: 2.49 to 34.77, p < 0.001) and lower by age (or: 0.86; 95% ci: 0.74 to 0.99; p = 0.040). Of patients less than 35 years of age undergoing radiation treatment, 85% had a documented fertility discussion. We observed no significant difference in the frequency of discussions after 2006, when the American Society of Clinical Oncology guidelines were published (31.4% for 2000–2006 vs. 37.5% for 2007–2009, p = 0.63).

Conclusions

Discussions about fertility risks associated with crc treatment occur infrequently among young adults with newly diagnosed crc. However, discussions occur more frequently in younger patients and in those undergoing radiation. Further investigations assessing barriers and physician attitudes to fertility risk discussion and reproductive options are planned.     

Treatment outcomes for male breast cancer: a single-centre retrospective case–control study

Background

Male breast cancer (bc) is a rare disease, and the availability of information on treatment outcomes is limited compared with that for female bc. The objective of the present study was to compare disease-free (dfs) and overall survival (os) for men compared with women having early-stage bc.

Methods

This retrospective case–control study compared men and women treated for stage 0–iiib bc at a single institution between 1981 and 2009. Matching was based on age at diagnosis, year of diagnosis, and stage. Treatment, recurrence, and survival data were collected. Kaplan–Meier analysis was used to calculate os and dfs.

Results

For the 144 eligible patients (72 men, 72 women), median age at diagnosis was 66.5 years. Treatments included mastectomy (72 men, 38 women), radiation (29 men, 44 women), chemotherapy (23 men, 20 women), and endocrine therapy (57 men, 57 women). Mean dfs was 127 months for women compared with 93 months for men (p = 0.62). Mean os was 117 months for women compared with 124 months for men (p = 0.35). In multivariate analysis, the only parameter that affected both dfs and os was stage at diagnosis.

Conclusions

This case–control study is one of the largest to report treatment outcomes in early-stage male bc patients treated in a non-trial setting. Male patients received systemic therapy that was comparable to that received by their female counterparts, and they had similar os and dfs. These results add to current evidence from population studies that male sex is not a poor prognostic factor in early-stage breast cancer.     

Impact of granulocyte colony–stimulating factors in metastatic colorectal cancer patients

Background

Delays in chemotherapy because of neutropenia may be associated with poorer outcomes. The purpose of the present study was to examine the effect that granulocyte colony–stimulating factors (g-csfs) have on survival.

Methods

We conducted a chart review of all outpatients diagnosed with metastatic colorectal cancer and treated with folfiri chemotherapy (irinotecan, 5-fluorouracil, leucovorin) with or without bevacizumab at Mount Sinai Hospital between 2007 and 2012. Multivariable Cox proportional hazards models were used to compare survival in neutropenic patients treated with g-csf, in neutropenic patients not so treated, and in patients without neutropenia.

Results

The review identified 93 patients, 31 of whom did not experience a neutropenic event. Of the 62 who experienced neutropenia, 18 were managed with g-csf support, and 44, with reductions or delays in dose. Compared with patients experiencing a neutropenic episode not treated with g-csf, those treated with g-csf experienced a nonsignificant increase in time to event [progression or death: hazard ratio (hr): 1.37; 95% confidence limits (cl): 0.72, 2.61], but compared with patients not having a neutropenic episode, the same patients experienced a significant increase in time to event (hr: 2.07; 95% cl: 1.03, 4.15).

Conclusions

In patients who experienced neutropenia, g-csf did not have a statistically significant impact on survival. Time to event was prolonged in g-csf–treated patients compared with patients who did not experience neutropenia.     

After radiotherapy,do bone metastases from gastrointestinal cancers show response rates similar to those of bone metastases from other primary cancers?

Purpose

Reports investigating whether the response rates to palliative radiation therapy (rt) for painful bone metastases from gastrointestinal (gi) cancers are similar to rates for bone metastases from other primary cancer sites have been limited. The present study evaluated response rates for symptomatic bone metastases from gi cancers after palliative outpatient rt in the Rapid Response Radiotherapy Program (rrrp).

Patients and Methods

We identified 69 patients with bone metastases from gi primaries who received palliative rt in the rrrp clinic during 1999–2006. We extracted records for 31 of these patients during 1999–2003 from an rrrp database that used the Edmonton Symptom Assessment Scale (esas). Record for the remaining 38 patients during 2003–2006 were extracted from an rrrp database that used the Brief Pain Inventory (bpi). Eligibility criteria for encryption in the two rrrp databases and for collection of patient demographic information (age, sex, primary cancer site, and Karnofsky performance status) were identical.Response rates for this cohort of metastatic gi patients were then compared to rates for 479 patients receiving palliative rt for bone metastases from other primary cancer sites. Pain scores from the esas and bpi and data on analgesic consumption were collected at baseline and by telephone follow-up at 4, 8, and 12 weeks after rt for all patients. Complete (cr), partial (pr), and overall (cr+pr) responses were evaluated according to International Consensus Endpoints.

Results

Assessment of the 69 patients with metastatic gi cancers revealed cr, pr, and cr+pr rates of 18%, 42%, and 61% at 4 weeks; 22%, 35%, and 57% at 8 weeks; and 50%, 21%, and 71% at 12 weeks for evaluable patients. The 479 evaluable patients with metastatic cancer from other primary cancer sites had cr, pr, and cr+pr rates of 25%, 27%, and 51% at 4 weeks; 26%, 22%, and 48% at 8 weeks; and 22%, 29%, and 51% at 12 weeks. No statistically significant differences were observed in rt response rates for bone metastases from gi cancers than from other primary cancer sites.

Conclusions

After palliative rt, bone metastases from gi cancers demonstrate response rates that are similar to rates for metastases from other primary cancer sites. Patients with symptomatic bone metastases from gi malignancies should be referred for palliative rt as readily as patients with osseous metastases from other primary cancer sites.     

Cost-effectiveness of pazopanib in advanced soft-tissue sarcoma in Canada

Background

In the phase iii palette trial of pazopanib compared with placebo in patients with advanced or metastatic soft-tissue sarcoma (sts) who had received prior chemotherapy, pazopanib treatment was associated with improved progression-free survival (pfs). We used an economic model and data from palette and other sources to evaluate the cost-effectiveness of pazopanib in patients with advanced sts who had already received chemotherapy.

Methods

We developed a multistate model to estimate expected pfs, overall survival (os), lifetime sts treatment costs, and quality-adjusted life-years (qalys) for patients receiving pazopanib or placebo as second-line therapy for advanced sts. Cost-effectiveness was calculated alternatively from the health care system and societal perspectives for the province of Quebec. Estimated pfs, os, incidence of adverse events, and utilities values for pazopanib and placebo were derived from the palette trial. Costs were obtained from published sources.

Results

Compared with placebo, pazopanib is estimated to increase qalys by 0.128. The incremental cost of pazopanib compared with placebo is CA$20,840 from the health care system perspective and CA$15,821 from the societal perspective. The cost per qaly gained with pazopanib in that comparison is CA$163,336 from the health care system perspective and CA$124,001 from the societal perspective.

Conclusions

Compared with placebo, pazopanib might be cost-effective from the Canadian health care system and societal perspectives depending on the threshold value used by reimbursement authorities to assess novel cancer therapies. Given the unmet need for effective treatments for advanced sts, pazopanib might nevertheless be an appropriate alternative to currently used treatments.