Innovative targeted therapies are being developed rapidly, with new trials providing evidence almost continuously. Even though the European Medicines Agency (EMA) makes efforts to expedite their review and approval, individual countries have longer approval processes. Early Access Program (EAP) permits patients who have exhausted all treatment options to obtain innovative treatment.

Supplementary Figures 1-11 from A Combined Preclinical Therapy of Cannabinoids and Temozolomide against Glioma

Background For women with lymph node (LN)-positive, estrogen receptor-positive, and HER2 (human epidermal growth factor receptor 2)-negative breast cancer (BCA), current guidelines recommend treatment with both hormonal therapy and chemotherapy. The 21-gene Recurrence Score (RS) assay might be helpful in selecting patients with BCA who can be spared chemotherapy when they have 1-3 positive LNS and a lower risk of recurrence. In the present study, we performed a cost-utility analysis comparing use of the 21-gene RS assay with current practice from the perspective of a Canadian health care payer. Methods A Markov model was developed to determine costs and quality-adjusted life-years (QALYS) over a patient's lifetime. Patient outcomes in both study groups were examined based on published clinical trials. Costs were derived primarily from published Canadian sources. Costs and outcomes were discounted at 1.5% annually, and costs are reported in 2016 Canadian dollars. A probabilistic analysis was used, and the model parameters were varied in a sensitivity analysis. Results The results indicate that use of the 21-gene RS assay was less costly ($432 less) and more effective (0.22 QALYS) than current practice. The probabilistic analysis revealed that 70% of the 10,000 simulated incremental cost-effectiveness ratios were in the southeast quadrant. The results were sensitive to the probability of a low RS and to the probability of receiving chemotherapy in the low-risk RS category and in current practice. Conclusions Use of the 21-gene RS assay could be a cost-effective strategy for Ontario patients with estrogen receptor-positive, HER2-negative early BCA and 1-3 positive LNS.

BACKGROUND The 21-gene Recurrence Score (RS) assay is only reimbursed in Ontario for node-negative and micrometastatic node-positive (N+) early-stage breast cancer (EBC). We carried out a prospective study to evaluate the impact of the assay on treatment decisions for women with N+ EBC. SUBJECTS, MATERIALS, AND METHODS Women with estrogen receptor-positive, human epidermal growth receptor 2-negative EBC and one to three positive axillary lymph nodes, who were candidates for adjuvant chemotherapy in addition to hormonal treatment, but in whom the benefit of chemotherapy was uncertain, were eligible. The primary objective was to characterize how the results of the RS assay affected physicians' recommendations for adjuvant chemotherapy. Secondary objectives were to characterize changes in the physicians' and patients' level of confidence in treatment recommendations, to determine whether the results of the RS assay affected patients' treatment preferences, and to determine the final treatment administered. RESULTS Seventy-two patients were recruited; the mean age was 61. RS was <18 in 55%, between 18 and 30 in 36%, and ≥31 in 9% of patients. Treatment recommendations changed in 36% of all evaluable patients. The most significant change was in the group with a low RS. Physicians' and patients' confidence in treatment recommendations increased in 49% and 54% of cases, respectively. Upfront chemotherapy was recommended to 79% of patients before the assay; 42% ultimately received chemotherapy. CONCLUSION The RS assay resulted in a substantial decrease in the number of patients who received chemotherapy and in an increase in physicians' and patients' confidence in the adjuvant treatment recommendations. IMPLICATIONS FOR PRACTICE This is the first decision impact study to include exclusively women with ER-positive, HER2-negative, early-stage breast cancer with 1-3 positive lymph nodes, a population typically treated with adjuvant chemotherapy. This study provides evidence that, in these patients, the Oncotype Dx Recurrence Score assay influences systemic treatment decisions. Most of the changes in treatment recommendation resulted in withdrawal of chemotherapy or change in recommendation from a chemotherapy regimen with anthracyclines to a taxane-only regimen. If prospective studies confirm that these decisions result in good outcomes, a reduction in the use of chemotherapy might result in pharmacoeconomic savings.

Background: Routine collection of health state utilities in the clinical setting may produce data more representative of the real-world population for use in cost-utility models and guide decision making. We are currently carrying out a cross-sectional study to assess the feasibility of routine administration of EQ-5D to breast cancer patients in a multidisciplinary oncology clinic, in an academic cancer centre in Ontario, Canada. Methods: English literate women undergoing treatment or on follow-up for their breast cancer (stage I to IV), are being recruited during their scheduled visit to the cancer centre, preferably after completing the implemented routine symptom screening using the Edmonton Symptom Assessment System (ESAS). Consenting patients complete EQ-5D-5L in tablets, followed by a socio-demographic questionnaire and feedback questions pertaining to study conduct. Answers are stored in a research database and linked to diagnostic and treatment data. Feasibility will be assessed primarily by the proportion of patients who fully complete EQ-5D and by their willingness to complete the instrument at each clinic visit. Results: To date, 474 women were approached; 262 (55%) were eligible and consented to participate (target enrolment: 341). Median age of participants was 56 years (range:28-90); 24% had metastatic disease. All participants were English literate, but 59% were born outside Canada and speak primarily other languages at home. Ninety-eight percent of recruited patients completed EQ-5D, compared with 84% who completed ESAS on the same day (63% completed ESAS voluntarily prior to enrolment; 21% agreed on completing ESAS for study purposes only). Median time for EQ-5D completion was 84 seconds. Most patients (82%) had no problems using the tablet. Willingness to continue to complete EQ-5D at each clinic visit was not affected by disease status (stage I to III versus stage IV) and 74% would "definitely"/"very likely" continue to answer EQ-5D regularly at each clinic visit. Conclusions: These preliminary results indicate that routine collection of EQ-5D in clinical practice might be feasible, although the completion rate might be overestimated by the cross-sectional design of the study. Legal entity responsible for the study: Sofia Torres Funding: None Disclosure: All authors have declared no conflicts of interest.

Aims: To conduct a cost-utility analysis comparing stereotactic body radiotherapy (SBRT) with low dose rate brachytherapy (LDR-BT) for localised prostate cancer (PCa). Materials and methods: A decision-analytic Markov model was developed from the healthcare payer perspective to simulate the history of a 66-year-old man with low-risk PCa. The model followed patients yearly over their remaining lifetimes. Health states included 'recurrence-free', 'biochemical recurrence' (BR), 'metastatic' and 'death'. Transition probabilities were based on a retrospective cohort analysis undertaken at our institution. Utilities were derived from the literature. Costs were assigned in 2015 Canadian dollars ($) and reflected Ontario's health system and departmental costs. Outcomes included quality-adjusted life years (QALYs), costs and incremental cost-effectiveness ratios. A willingness-to-pay threshold of $ 50 000/QALY was used. Results: SBRT was the dominant strategy with 0.008LYs and 0.029QALYs gained and a reduction in cost of $ 2615. Under base case conditions, our results were sensitive to the BR probability associated with both strategies. LDR-BT becomes the preferred strategy if the BR with SBRT is 1.3*[baseline BR_SBRT] or if the BR with LDR-BT is 0.76*[baseline BR_LDR-BT]. When assuming the same BR for both strategies, LDR-BT becomes marginally more effective with 0.009QALYs gained at a cost of $ 272 848/QALY. Conclusions: SBRT represents an economically attractive radiation strategy. Further research should be carried out to provide longer-term follow-up and high-quality evidence. (C) 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Radiation is a standard treatment option in the management of prostate cancer (PCa). Multiple options are available with similar reported outcomes, yet substantially different costs. Based on a review of the current published literature, low-dose-rate brachytherapy (LDR-BT) is found to be cost-effective when compared to other options, however it remains invasive and offered at selected centres. Fractionated external beam radiotherapy (EBRT) is a commonly used non-invasive treatment for patients with localized PCa however it requires 8 weeks of treatment. Stereotactic body radiotherapy (SBRT) holds the promise of non-invasiveness and convenience but has never been compared to LDR-BT. Herein we conduct a cost-utility analysis comparing LDR-BT to standard fractionated EBRT and SBRT. A decision-analytic Markov model was developed from the Ontario healthcare payer perspective to simulate the history of a 66-year-old man with low-risk PCa. The model followed patients yearly over their remaining lifetimes. Three radiation options were considered for our model: LDR-BT (I-125, minimal peripheral dose=145Gy), EBRT (76 Gy/38 fractions) and SBRT (35Gy/5, weekly fractions). Health states included 'Recurrence-free', 'biochemical recurrence', 'metastatic' and 'death'. Transition probabilities were based on a retrospective cohort analysis undertaken at our institution. Utilities were derived from the literature. Costs were assigned in 2015 Canadian dollars ($) and reflected Ontario's health system and departmental costs. Outcomes included life-years (LYs), Quality adjusted life-years (QALYs), costs and incremental cost-effectiveness ratios (ICER). All outcomes were discounted at 5%. A willingness-to-pay threshold of 50,000$/QALY was used. Deterministic sensitivity analyses were performed to evaluate the degree of uncertainty in the results. Compared to EBRT, both LDR-BT and SBRT were less expensive and more effective (Table 1). These findings were robust to changes in input variables. SBRT was the dominant strategy with 0.008LYs and 0.029QALYs gained and a reduction in cost of $2,615 when compared to LDR-BT. However, these results were sensitive to the biochemical recurrence (BR) probability associated with both strategies. LDR-BT becomes the preferred strategy if the BR with SBRT is 1.3*[baseline BR_SBRT] or if the BR with LDR-BT is 0.76*[baseline BR_LDR-BT]. When assuming the same BR for both strategies, LDR-BT becomes more effective with 0.009QALYs gained at a cost of 272,848$/QALY. In Ontario and comparable jurisdictions, LDR-BT and SBRT are cost-effective when compared to standard fractionated EBRT. SBRT might represent an economically attractive radiation strategy; however longer-term follow-up and higher quality evidence are needed.Table 1Base-Case Analysis Results (discounted at 5%).StrategyEffectivenessCostNMBIncrementalLife-Years GainedQALYs GainedSCADSCADLife-YearsQALYsCostsNMBSBRT11.1749.926$72,378$423,9290.008 [2.9 days]0.029 [10.6 QALD]$2:615$4;074DominantLDR- BT11.1669.897$74,993$419,8550.23 [83.9 days]0.493 [179.9 QALD]$2:651$21211Weakly DominatedDominatedEBRT10.9369.404$77,644$392,578*NMB=Net Monetary Benefit assuming a willingness-to-pay(WTP) threshold of S50,000 then converting health benefits into the CADS Open table in a new tab