Thirty-six patients with advanced colorectal cancer whose disease progressed during treatment with 5-fluorouracil (5-FU) chemotherapy were treated with methyl-CCNU and methotrexate. Five patients (14%) achieved a partial response (PR), three (8%) showed disease regression less than that required for a PR, and three (8%) showed evidence of stable disease. Twenty-five patients (69%) progressed on treatment. Tumor regression was seen only in patients with good performance status (ECOG 0.1). The median survival time of patients achieving a PR was 31 weeks. Those patients with stable disease or disease regression less than a PR had median survival times of 49 and 32 weeks, respectively. The comparable figure for those patients with disease progression was 17 weeks. Myelosuppression, principally in the form of leukopenia and thrombocytopenia, was common. Nausea and vomiting were universal with methyl-CCNU, and mucositis and diarrhea occurred commonly due to methotrexate. These results demonstrate the limited activity of chemotherapy in refractory colorectal cancer. They also reaffirm that poor pretreatment performance status should exclude patients from futile attempts at palliative therapy or phase II clinical trials, as these patients derive little or no benefit from them.
The National Lung Screening Trial (NLST) is a randomized multicenter study comparing low-dose helical computed tomography (CT) with chest radiography in the screening of older current and former heavy smokers for early detection of lung cancer, which is the leading cause of cancer-related death in the United States. Five-year survival rates approach 70% with surgical resection of stage IA disease; however, more than 75% of individuals have incurable locally advanced or metastatic disease, the latter having a 5-year survival of less than 5%. It is plausible that treatment should be more effective and the likelihood of death decreased if asymptomatic lung cancer is detected through screening early enough in its preclinical phase. For these reasons, there is intense interest and intuitive appeal in lung cancer screening with low-dose CT. The use of survival as the determinant of screening effectiveness is, however, confounded by the well-described biases of lead time, length, and overdiagnosis. Despite previous attempts, no test has been shown to reduce lung cancer mortality, an endpoint that circumvents screening biases and provides a definitive measure of benefit when assessed in a randomized controlled trial that enables comparison of mortality rates between screened individuals and a control group that does not undergo the screening intervention of interest. The NLST is such a trial. The rationale for and design of the NLST are presented.
IntroductionLung cancer risk prediction models have the potential to make programs more affordable; however, the economic evidence is limited.MethodsParticipants in the National Lung Cancer Screening Trial (NLST) were retrospectively identified with the risk prediction tool developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. The high-risk subgroup was assessed for lung cancer incidence and demographic characteristics compared with those in the low-risk subgroup and the Pan-Canadian Early Detection of Lung Cancer Study (PanCan), which is an observational study that was high-risk–selected in Canada. A comparison of high-risk screening versus standard care was made with a decision-analytic model using data from the NLST with Canadian cost data from screening and treatment in the PanCan study. Probabilistic and deterministic sensitivity analyses were undertaken to assess uncertainty and identify drivers of program efficiency.ResultsUse of the risk prediction tool developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial with a threshold set at 2% over 6 years would have reduced the number of individuals who needed to be screened in the NLST by 81%. High-risk screening participants in the NLST had more adverse demographic characteristics than their counterparts in the PanCan study. High-risk screening would cost $20,724 (in 2015 Canadian dollars) per quality-adjusted life-year gained and would be considered cost-effective at a willingness-to-pay threshold of $100,000 in Canadian dollars per quality-adjusted life-year gained with a probability of 0.62. Cost-effectiveness was driven primarily by non–lung cancer outcomes. Higher noncurative drug costs or current costs for immunotherapy and targeted therapies in the United States would render lung cancer screening a cost-saving intervention.ConclusionsNon–lung cancer outcomes drive screening efficiency in diverse, tobacco-exposed populations. Use of risk selection can reduce the budget impact, and screening may even offer cost savings if noncurative treatment costs continue to rise.
The case of acute lymphoblastic leukemia developing shortly after the diagnosis and treatment of a mediastinal germ cell tumor, is reported. The close temporal relationship of these two rare diseases and the presence of a population of mononuclear cells with features of lymphoblasts in the resected germ cell tumor, suggest that the leukemic process originated from the mediastinal tumor.
e17531 Background: Cancer Care Ontario (CCO) is the provincial agency mandated to improve the quality of cancer care in Ontario. CCO has driven quality improvement (QI) on a programmatic basis but in 2008, introduced Disease Pathway Management (DPM) as an additional QI approach. The lung cancer (LC DPM) began in 2009 as a two-year, phased initiative. Methods: The LC DPM team, consisting of clinicians, patients and system stakeholders, was organized into five groups and focused on aspects of the patient journey from diagnosis to end-of-life care, guided by draft pathway maps of the ideal state. 17 improvement concepts were identified of which 8 were selected for detailed development at a provincial consensus conference and validated as LC DPM’s Priorities for Action. 14 regional road shows presented region-specific performance and quality data to practitioners involved in LC patient care to promote ideas for improvement. Funding was provided to support both provincial and regional initiatives that addressed identified gaps. Results: Key outputs of the LC DPM initiative were: establishment of lung diagnostic assessment programs in 14 regions; completion of diagnostic and treatment pathways for NSCLC and SCLC which were grounded in evidence; 10 improvement projects on various stages of the cancer continuum; and 6 one-year Dyspnea Management Pilot Projects. For the dyspnea projects, each funded centre used different approaches and evaluated impacts on patient symptom burden, measured by Edmonton Symptom Assessment System (ESAS), patient satisfaction and quality of life. The learnings from each project have been summarized and will be shared with all regional cancer programs to facilitate knowledge transfer. Tools to support the patient experience include a LC Patient Pathway Map (PPM) and a document, Understanding Lung Cancer. The physician and patient pathways and related materials are available on CCO's website at https://www.cancercare.on.ca Conclusions: LC DPM has proven an effective strategy to accomplish system changes across a large geography that impact the quality of LC care, processes and patient experience. Indicator development and performance management will be used to sustain the gains achieved.
The Breast Cancer Prevention Trial (BCPT-P-1) demonstrated that tamoxifen could reduce the risk of invasive breast cancer in high-risk women by 49%, but that it could also increase the risk of endometrial cancer, vascular events and cataracts. This paper provides an estimate of the net health impacts of tamoxifen administration on high-risk Canadian women with no prior history of breast cancer. The results of the BCPT-P-1 were incorporated into the breast cancer and other modules of Statistics Canada's microsimulation POpulation HEalth Model (POHEM). While the main intervention scenario conformed as closely as possible to the eligibility criteria for tamoxifen in the BCPT-P-1 protocol, 3 additional scenarios were simulated. Predicted absolute risks of breast cancer at 5 years of 1.66%, 3.32% and 4.15% were calculated for women 35 to 70 years of age. When the BCPT-P-1 results were incorporated into the simulation model, the analysis suggests no increase in life expectancy in this risk group. Tamoxifen appeared to be beneficial for women with a 5-year predicted risk of 3.32% or greater. The results of these simulations are particularly sensitive to the reduction in mortality observed in the BCPT-P-1, as well as being sensitive to other characteristics of the simulation model. Overall, the analysis raises questions about the use of tamoxifen in otherwise healthy women at high risk of breast cancer.
