Anthony Fields

Survival impact of surgical resection of primary tumor in patients with stage IV colorectal cancer: Results from a large population‐based cohort study

Currently, there is very low‐quality evidence available regarding benefit of surgical resection of the primary tumor (SRPT), in patients with stage IV colorectal cancer (CRC). In the absence of randomization, the reported benefit may reflect selection of younger and healthier patients with good performance status. A large population‐based cohort study was undertaken to determine the survival benefit of SRPT in advanced CRC by eliminating various biases reported in the literature.

Outpatient 5-Fluorouracil, Folinic Acid and Cisplatin in Patients with Advanced Esophageal Carcinoma

In a multicenter phase II study, 30 patients with unresectable, locally advanced or metastatic squamous cell or adenocarcinoma of the esophagus were treated with folinic acid 200 mg/m2/d, 5-FU 300 mg/m2/d, and cisplatin 20 mg/m2/d intravenously for 5 days every 4 weeks. Two of 13 patients with squamous cell carcinoma (SCC) had a complete response (CR), but one died of pneumonia after 9 months while still in CR, and the other still in CR after more than 5 years. Six other patients (3 SCC, 2 of 16 with adenocarcinoma, 1 mixed histology) had a partial response with a median duration of 9 months (range 5 to 57 + months) for an overall response rate of 27%. A further 6 patients (20%) had stable disease. Grade 4 neutropenia occurred in 6 patients (20%), with 5 requiring antibiotics for associated fever. Other grade 4 toxicities were nausea and vomiting (1), anemia (1), and thrombocytopenia (1); there were three early deaths (emphysema, cardiac arrest, pulmonary embolism). This combination appears to be an active, convenient regimen for advanced esophageal cancer, resulting in prolonged remission and survival in some patients.

A retrospective study on the use of post-operative colonoscopy following potentially curative surgery for colorectal cancer in a Canadian province

BackgroundSurveillance colonoscopy is commonly recommended following potentially curative surgery for colorectal cancer. We determined factors associated with patients undergoing a least one colonoscopy within five years of surgery.MethodsIn this historical cohort study, data on 3918 patients age 30 years or older residing in Alberta, Canada, who had undergone a potentially curative surgical resection for local or regional stage colorectal cancer between 1983 and 1995 were obtained from the provincial cancer registry, ministry of health and cancer clinic charts. Kaplan-Meier estimates of the probability of undergoing a post-operative colonoscopy were calculated for patient, tumor and treatment-related variables of interest.ResultsA colonoscopy was performed within five years of surgery in 1979 patients. The probability of undergoing a colonoscopy for those diagnosed in the 1990s was greater than for those diagnosed earlier (0.65 vs 0.55, P < 0.0001). The majority of the difference was seen at one-year following surgery, consistent with changes in surveillance practices. Those most likely to undergo a colonoscopy were those under age 70 (0.74 vs 0.50 for those age 70 – 79, P < 0.0001), who underwent a pre-operative colonoscopy (0.69 vs 0.54, P < 0.0001), and who underwent a resection with reanastomosis (0.62 vs 0.47 for abdominoperineal resection, P < 0.0001) by a surgeon who performs colonoscopies (0.68 vs 0.54, P < 0.0001).ConclusionsThe majority of patients undergo colonoscopy following colorectal cancer surgery. However, there are important variations in surveillance practices across different patient and treatment characteristics.

Does it Matter Whether Canada’s Separate Health Technology Assessment Process for Cancer Drugs has an Economic Rationale?

PharmacoEconomics DOI 10.1007/s40273-015-0278-7 LETTER TO THE EDITOR Does it Matter Whether Canada’s Separate Health Technology Assessment Process for Cancer Drugs has an Economic Rationale? Jeffrey S. Hoch 1,2,3,4 • Jaclyn Beca 1,2,3 • Mona Sabharwal 5 • Scott W. Livingstone 6 Anthony L. A. Fields 7 The Author(s) 2015. This article is published with open access at Springerlink.com ‘‘What our health-care systems need to do with their limited budgets is maximize value and no dimensions of health … will be a good measure of value because people consider other aspects in their evaluations … We must back out of the dead end that is pursuing overall efficiency’’ [1]. 1 Introduction We are grateful for the opportunity to comment on the results of McDonald et al. [2]. In this note, we summarize their findings, build on their interpretations, and suggest future directions for researchers interested in improving a health technology assessment (HTA) process. 2 Summary of the Findings McDonald et al. searched for reasons why Canada and other countries might separate their cancer drug HTA process. They appraised whether any of the rationales they & Jeffrey S. Hoch jeffrey.hoch@utoronto.ca Pharmacoeconomics Research Unit, Cancer Care Ontario, Toronto, ON, Canada Jaclyn Beca becaj@smh.ca Canadian Centre for Applied Research in Cancer Control (ARCC), Toronto, ON, Canada Mona Sabharwal monas@cadth.ca Institute for Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada Scott W. Livingstone scott.livingstone@saskcancer.ca Pan-Canadian Oncology Drug Review (pCODR), Canadian Agency for Drugs and Technologies in Health (CADTH), Toronto, ON, Canada Saskatchewan Cancer Agency, Saskatoon, SK, Canada University of Alberta, 11560 University Ave NW, Edmonton, AB T6G 1Z2, Canada Anthony L. A. Fields afields@ualberta.ca found were derived from the assumption commonly made by health economists that ‘‘the goal of society or decision makers is to maximize the total aggregate health benefit conferred to a population for a given level of resources’’. They found that this rationale was not used by Canada or any country to support the use of a separate HTA process for cancer drugs. The researchers were also not able to find another country besides Canada that had a separate cancer drug HTA process. These findings may seem surprising: Canada is the only country in the world that has a separate cancer drug HTA process; and McDonald et al. could find no justification based in economic theory for a separate process. To be clear, the authors reported that other countries (e.g. Den- mark, Belgium, the UK) set aside a separate budget for cancer drugs, and the authors found several ‘‘non-eco- nomic’’ rationales for Canada’s separate HTA process. There are two potential interpretations of these search re- sults: (1) the search missed something or (2) there really is no economic rationale in print for a separate cancer drug HTA process. Although their study might not be Centre for Excellence in Economic Analysis Research (CLEAR), Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, ON, Canada

Surgical Resection of Primary Tumor in Asymptomatic or Minimally Symptomatic Patients With Stage IV Colorectal Cancer: A Canadian Province Experience

BACKGROUND Surgical resection of the primary tumor in patients with stage IV colorectal cancer (CRC) remains controversial. Survival benefit reported in the literature has been attributed to the selection of younger and healthier patients with good performance status. We have recently reported that resection of the primary tumor improved survival of patients with stage IV CRC. In this study we examined survival benefit of surgery in patients with asymptomatic or minimally symptomatic primary tumor. PATIENTS AND METHODS A cohort of patients with stage IV CRC and asymptomatic or minimally symptomatic primary tumor, who were diagnosed during the period of 1992 to 2005, in the province of Saskatchewan Canada, was evaluated. The Kaplan-Meier method was used to determine survival. A multivariate Cox proportional hazard regression analysis was performed to determine prognostic importance of resection of primary tumor. A test for interaction was performed for resection of primary tumor and other important clinicopathological variables. RESULTS A total of 834 patients with a median age of 70 years (range, 22-93) and male:female ratio of 58:42 were identified. Among them 521 (63%) patients underwent surgery and 361 (43.3%) received chemotherapy. Patients who underwent surgery and received any chemotherapy had a median overall survival of 19.7 months (95% confidence interval [CI], 16.9-22.6) compared with 8.4 months (95% CI, 6.9-10.0) if they did not have surgery (P < .0001). In multivariate analysis, 5-fluorouracil-based chemotherapy (hazard ratio [HR], 0.43; 95% CI, 0.36-0.53), surgical resection of the primary tumor (HR, 0.47; 95% CI, 0.39-0.57), metastasectomy (HR, 0.48; 95% CI, 0.38-0.62), and second-line chemotherapy (HR, 0.72; 95% CI, 0.58-0.92) were correlated with superior survival. A test for interaction between ≥ 1 metastatic sites and surgery was significant, which suggests a larger benefit of surgery in patients with stage IVA disease. CONCLUSION Results of this large population-based cohort study suggest that resection of the primary tumor in asymptomatic or minimally symptomatic patients with stage IV CRC improved survival independent of other prognostic variables. The benefit was more pronounced in stage IVA disease.

Surgical Management of the Primary Tumor in Stage IV Colorectal Cancer: A Confirmatory Retrospective Cohort Study.

Background: Observational studies have suggested that patients with stage IV colorectal cancer who undergo surgical resection of the primary tumor (SRPT) have better survival. Yet the results are not confirmed in the setting of a randomized controlled trial. Lack of randomization and failure to control prognostic variables such as performance status are major critiques to the findings of the observational studies. We previously have shown that SRPT, independent of chemotherapy and performance status, improves survival of stage IV CRC patients. The current study aims to validate our findings in patients with stage IV CRC who were diagnosed during the period of modern chemotherapy. Methods: A cohort of 569 patients with stage IV CRC diagnosed during 2006-2010 in the province of Saskatchewan was evaluated. Cox regression model was used for the adjustment of prognostic variables. Results: Median age was 69 years (59-95) and M: F was 1.4:1. Fifty-seven percent received chemotherapy, 91.4% received FOLFIRI or FOLFOX & 67% received a biologic agent. Median overall survival (OS) of patients who underwent SRPT and received chemotherapy was 27 months compared with 14 months of the non-resection group (p<0.0001). Median OS of patients who received all active agents and had SRPT was 39 months (95%CI: 25.1-52.9). On multivariate analysis, SRPT, hazard ratio (HR):0.44 (95%CI: 0.35-0.56), use of chemotherapy, HR: 0.33 (95%CI: 0.26-0.43), metastasectomy, HR: 0.43 (95%CI: 0.31-0.58), second line therapy, HR: 0.50 (95%CI: 0.35-0.70), and third line therapy, HR: 0.58 (95%CI: 0.41-0.83) were correlated with superior survival. Conclusions: This study confirms our findings and supports a favorable association between SRPT and survival in patients with stage IV CRC who are treated with modern therapy.

Comparing assessment frameworks for cancer drugs between Canada and Europe: What can we learn from the differences?

The increasing burden of costs associated with novel cancer therapies is becoming untenable. In Europe and Canada, assessment frameworks have been developed to attribute value to novel therapies and ultimately facilitate access to cancer drug funding. A review of the two frameworks has not previously been undertaken. This review provides insight into the relative strengths and benefits of each approach, the various perspectives of value (patient, physician and societal) and how the frameworks relate to their unique context and core principles. Both frameworks assess the clinical benefit of a new cancer therapy. The European framework considers effectiveness, quality of life, and toxicity in its determination of benefit and has the advantage of providing a simple summary score to facilitate priority setting. The Canadian framework considers other elements including cost-effectiveness, patient preferences and adoption feasibility; its deliberative framework precludes a simple summative presentation of value but can address complex and nuanced drug funding considerations with flexibility. Both frameworks have evolved to meet the needs unique to their jurisdictions and offer potentially complementary tools in the assessment of new cancer drugs. Lessons learnt in both systems can be applied to future iterations of the frameworks, which remain works in progress.

Esophageal ulcer in a patient who received bevacizumab

SummaryA 60-year-old woman with metastatic rectal cancer who after surgical resection of the primary and creation of a palliative ileostomy in May 2006, was started on a regimen of bevacizumab, irinotecan, 5-fluouracil and leucovorin. After 3 cycles, she presented with solid food dysphagia. An endoscopy showed a large, deep ulcer in the lower third of the esophagus. We assumed that it was related to bevacizumab treatment. Bevacizumab was stopped and she was started on pantoprazole. Over the ensuing months, the ulcer improved notably. To the best of our knowledge, an esophageal ulcer associated with bevacizumab treatment has not been reported. This is likely the precursor lesion to a gastrointestinal tract perforation.

Predictive Factors of the Use of Systemic Therapy in Stage IV Colorectal Cancer: Who Gets Chemotherapy?

Background: Chemotherapy improves survival in patients with stage IV colorectal cancer (CRC). Although in a clinical trial setting, strict eligibility criteria are used for chemotherapy, little is known about the use of chemotherapy in the general population. The study aims to assess clinicopathological variables that correlate with the use of chemotherapy in patients with stage IV CRC. Methods: A retrospective cohort study involving patients with stage IV CRC, diagnosed between 1992 and 2005, in the province of Saskatchewan was carried out. A logistic regression analysis was performed to assess the correlation of various clinicopathological factors with the use of chemotherapy. Results: A total of 1,237 eligible patients were identified. Their median age was 70 years (range: 22-98) and the male:female ratio was 1.3:1. 23.8% had an ECOG performance status (PS) of ≥2 and 61.8% of the patients had a comorbid illness. 46.8% of the patients received chemotherapy. The multivariate logistic regression analysis revealed that an age of <65 years [odds ratio (OR) 3.82, 95% CI: 2.59-5.63], metastasectomy (OR 3.60, 95% CI: 1.82-7.10), normal albumin (OR 3.26, 95% CI: 2.44-4.36), no comorbid illness (OR 2.87, 95% CI: 1.34-6.16), ECOG PS of <2 (OR 2.72, 95% CI: 1.94-3.82), normal blood urea nitrogen (OR 2.24, 95% CI: 1.40-3.59), palliative radiation (OR 2.03, 95% CI: 1.38-2.99), primary tumor resection (OR 2.00, 95% CI: 1.47-2.73), and the time period (OR 1.85, 95% CI: 1.41-2.42) were significantly correlated with the use of chemotherapy. Conclusions: The use of chemotherapy appears to be increasing in stage IV CRC. Patients treated with curative intention or who underwent primary tumor resection were more likely to receive chemotherapy. Despite a known benefit of chemotherapy in elderly patients, a differential use of chemotherapy was noted in this population.

Engaging specialist oncologists in the assessment of oncology drugs in Canada

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