Gait Speed vs. VES-13: A Pilot Study Comparing Screening Tools to Determine the Need for a Comprehensive Geriatric Assessment in Senior Women with Breast Cancer.

BACKGROUND/OBJECTIVES: Patients aged 70 years and older may be suboptimally treated with cancer therapy because of the lack of clinical trial data in this population. The Comprehensive Geriatric Assessment can be time consuming, and access to geriatricians is limited. This study aims to determine whether gait speed (GS) analysis is equivalent to the widely accepted Vulnerable Elders Survey 13 (VES-13) in identifying vulnerable or frail patients in need of a Comprehensive Geriatric Assessment. METHODS: A pilot prospective cohort study was carried out at a tertiary cancer centre in Toronto, Canada, in a radiation oncology breast follow-up clinic. GS analysis and VES-13 were completed by each patient at the same clinic visit. GS of <1 meter/second (m/s) and VES-13 score ≥3 were considered abnormal. Sensitivity, specificity, positive and negative predictive values, and Kappa characteristic were calculated for GS compared with VES-13. RESULTS AND DISCUSSION: Twenty-nine participants aged 70 years and older with any stage of breast cancer were included. The GS was 67% sensitive and 95% specific for abnormal VES-13 scores. The GS had an 86% positive predictive value and 86% negative predictive value for abnormal scores on VES-13. Overall, the GS showed a substantial strength of agreement with the VES-13 (kappa 0.66, P < .0001). CONCLUSION: The GS analysis compared very well with VES-13 scores, and this may be a reasonable alternative to VES-13 screening. This pilot data warrant further study in a larger group of patients.

Ambulatory Toxicity Management (AToM) in patients receiving adjuvant or neo-adjuvant chemotherapy for early stage breast cancer - a pragmatic cluster randomized trial protocol.

BACKGROUND: Population-based studies suggest that emergency department visits and hospitalizations are common among patients receiving chemotherapy and that rates in routine practice are higher than expected from clinical trials. Chemotherapy-related toxicities are often predictable and, consequently, acute care visits may be preventable with adequate treatment planning and support between visits to the cancer centre. We will evaluate the impact of proactive telephone-based toxicity management on emergency department visits and hospitalizations in women with early stage breast cancer receiving chemotherapy. METHODS: In this pragmatic covariate constraint-based cluster randomized trial, 20 centres in Ontario, Canada are randomly allocated to either proactive telephone toxicity management (intervention) or routine care (control). The primary outcome is the cluster-level mean number of ED + H visits per patient evaluated using Ontario administrative healthcare data. Participants are all patients with early stage (I-III) breast cancer commencing adjuvant or neo-adjuvant chemotherapy at participating institutions during the intervention period. At least 25 patients at each centre participate in a patient reported outcomes sub-study involving the collection of standardized questionnaires to measure: severity of treatment toxicities, self-care, self-efficacy, quality of life, and coordination of care. Patients participating in the patient reported outcomes (PRO) sub-study are asked to provide written consent to link their PRO data to administrative data. Unit costs will be applied to each per person resource utilized, and a total cost per population and patient will be generated. An incremental cost-effectiveness analysis will be undertaken to compare the incremental costs and outcomes between the intervention and control groups from the health system perspective. DISCUSSION: This study evaluates the effectiveness of a proactive toxicity management intervention in a routine care setting. The use of administrative healthcare data to evaluate the primary outcome enables an evaluation in a real world setting and at a much larger scale than previous studies. TRIAL REGISTRATION: Clinicaltrials.gov , NCT02485678. Registered 30 June 2015.

The impact of pricing strategy on the costs of oral anti-cancer drugs.

BACKGROUND: The soaring costs of anti-cancer drugs pose a threat to the sustainability of cancer care. The pricing strategy chosen by manufacturers can impact the costs of oral anti-cancer drugs during dose modifications, but this issue remains under-recognized in the literature. In general, with the flat pricing strategy, there is a single fixed price for each tablet regardless of dosage strength, whereas with linear pricing, the price of each tablet increases with its dose. We hypothesize that flat pricing will have increased drug costs compared to linear pricing during dose reductions since the cost remains fixed despite decreased dose requirements. This practice may have significant financial implications considering the high costs, extensive utilization, and frequent occurence of dose reductions with anti-cancer drugs.  METHODS: Oral anti-cancer drugs reviewed by the pan-Canadian Oncology Drug Review program between 2011 and 2018 were identified. The cost per mg and cost per 28-day cycle were calculated for dose levels -2 to +2. The percent change in cost per mg and cost per cycle during dose modifications from the standard dose were calculated. We conducted Mann-Whitney U and Fisher-exact tests to compare the association between drug costs during dose reductions and pricing strategy. RESULTS: In this study, 30 oral anti-cancer drugs for use in 41 indications were analyzed; 44% of drugs used linear pricing and 56% used flat pricing. Dose reductions increased the mean cost per mg for drugs with linear pricing by 14.7% (range: 0%-50%) at dose level -1 and 17.2% (range: 0%-50%) at dose level -2 and flat pricing by 60.8% (range: 19%-100%) at dose level -1 and 99.1% (range: 0%-300%) at dose level -2. The cost per mg was significantly increased in drugs using flat pricing compared to linear pricing when dose reduction to either level -1 (P = 0.010) or level -2 (P = 0.006) occurred. The mean cost per cycle was decreased for drugs using linear pricing by 20.9% (range: -40% to 0%) at dose level -1 and 48.7% (range: -60% to -25%) at dose level -2 and flat pricing by 0.8% (range -6% to 0%) at dose level -1 and 11.0% (range: -50% to 100%) at dose level -2. The cost per cycle was significantly decreased in drugs with linear pricing compared to flat pricing when the standard dose is reduced to either dose level -1 (P = 0.005) or dose level -2 (P = 0.026). CONCLUSIONS: Overall, flat pricing had significantly greater costs compared to linear pricing during dose reductions of anti-cancer drugs. While there is a general expectation that the cost of drugs should decrease with dose reduction, drugs with flat pricing were generally found to have increased cost per mg and no change in the cost per cycle. The resultant increased spending on drug acquisition (despite purchasing lower doses) lead to financial wastage, which has significant implications on cost-effectiveness considerations and budgets. Future economic evaluations should take into consideration the hidden costs associated with dose reductions of flat priced drugs.

The impact of cancer drug wastage on economic evaluations.

BACKGROUND: The objective of this study was to determine the impact of modeling cancer drug wastage in economic evaluations because wastage can result from single-dose vials on account of body surface area- or weight-based dosing. METHODS: Intravenous chemotherapy drugs were identified from the pan-Canadian Oncology Drug Review (pCODR) program as of January 2015. Economic evaluations performed by drug manufacturers and pCODR were reviewed. Cost-effectiveness analyses and budget impact analyses were conducted for no-wastage and maximum-wastage scenarios (ie, the entire unused portion of the vial was discarded at each infusion). Sensitivity analyses were performed for a range of body surface areas and weights. RESULTS: Twelve drugs used for 17 indications were analyzed. Wastage was reported (ie, assumptions were explicit) in 71% of the models and was incorporated into 53% by manufacturers; this resulted in a mean incremental cost-effectiveness ratio increase of 6.1% (range, 1.3%-14.6%). pCODR reported and incorporated wastage for 59% of the models, and this resulted in a mean incremental cost-effectiveness ratio increase of 15.0% (range, 2.6%-48.2%). In the maximum-wastage scenario, there was a mean increase in the incremental cost-effectiveness ratio of 24.0% (range, 0.0%-97.2%), a mean increase in the 3-year total incremental budget costs of 26.0% (range, 0.0%-83.1%), and an increase in the 3-year total incremental drug budget cost of approximately CaD $102 million nationally. Changing the mean body surface area or body weight caused 45% of the drugs to have a change in the vial size and/or quantity, and this resulted in increased drug costs. CONCLUSIONS: Cancer drug wastage can increase drug costs but is not uniformly modeled in economic evaluations. Cancer 2017;123:3583-90. © 2017 American Cancer Society.

Quantitative ultrasound assessment of breast tumor response to chemotherapy using a multi-parameter approach.

PURPOSE: This study demonstrated the ability of quantitative ultrasound (QUS) parameters in providing an early prediction of tumor response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer (LABC). METHODS: Using a 6-MHz array transducer, ultrasound radiofrequency (RF) data were collected from 58 LABC patients prior to NAC treatment and at weeks 1, 4, and 8 of their treatment, and prior to surgery. QUS parameters including midband fit (MBF), spectral slope (SS), spectral intercept (SI), spacing among scatterers (SAS), attenuation coefficient estimate (ACE), average scatterer diameter (ASD), and average acoustic concentration (AAC) were determined from the tumor region of interest. Ultrasound data were compared with the ultimate clinical and pathological response of the patient's tumor to treatment and patient recurrence-free survival. RESULTS: Multi-parameter discriminant analysis using the κ-nearest-neighbor classifier demonstrated that the best response classification could be achieved using the combination of MBF, SS, and SAS, with an accuracy of 60 ± 10% at week 1, 77 ± 8% at week 4 and 75 ± 6% at week 8. Furthermore, when the QUS measurements at each time (week) were combined with pre-treatment (week 0) QUS values, the classification accuracies improved (70 ± 9% at week 1, 80 ± 5% at week 4, and 81 ± 6% at week 8). Finally, the multi-parameter QUS model demonstrated a significant difference in survival rates of responding and non-responding patients at weeks 1 and 4 (p=0.035, and 0.027, respectively). CONCLUSION: This study demonstrated for the first time, using new parameters tested on relatively large patient cohort and leave-one-out classifier evaluation, that a hybrid QUS biomarker including MBF, SS, and SAS could, with relatively high sensitivity and specificity, detect the response of LABC tumors to NAC as early as after 4 weeks of therapy. The findings of this study also suggested that incorporating pre-treatment QUS parameters of a tumor improved the classification results. This work demonstrated the potential of QUS and machine learning methods for the early assessment of breast tumor response to NAC and providing personalized medicine with regards to the treatment planning of refractory patients.

Associations among socioeconomic status, patterns of care and outcomes in breast cancer patients in a universal health care system: Ontario's experience.

BACKGROUND: The Canadian health care system provides equitable access to equivalent standards of care. The authors investigated to determine whether patients with breast cancer who had different socioeconomic status (SES) received different care and had different overall survival (OS) in Ontario, Canada. METHODS: Women who were diagnosed with breast cancer between 2004 and 2009 were identified from the Ontario Cancer Registry and linked to provincial databases to ascertain patient demographics, screening, diagnosis, treatment patterns, and survival. SES was defined as neighborhood income by postal code and was divided into income quintiles (Q1-Q5; with Q5 the highest SES quintile). Univariable and multivariable analyses were used to examine the associations between: 1) SES and mammogram screening and breast cancer treatments, and 2) SES and OS. RESULTS: In total, 34,776 patients with breast cancer who had information on disease stage available at diagnosis were identified. Seventy-six percent of women were aged >50 years. Patients with higher SES were more likely to be diagnosed at an earlier stage (Q5 [44.3%] vs Q1 [37.7%]; odds ratio [OR], 1.31; 95% confidence interval [CI], 1.23-1.41; P < .0001) and also were more likely to receive adjuvant chemotherapy (Q5 vs Q1: OR, 1.18; 95% CI, 1.10-1.26; P < .0001) and radiotherapy (Q5 vs Q1: OR, 1.24; 95% CI, 1.15-1.33; P < .0001). The 5-year OS rates for Q1 through Q5 were 80%, 81%, 82.2%, 83.9%, and 85.7%, respectively (P < .0001). After adjusting for patient demographics, cancer stage at diagnosis, adjuvant chemotherapy, trastuzumab, radiotherapy and surgery types, higher SES remained associated with better OS (P = .0017). CONCLUSIONS: In a universal health care system, higher SES is associated with greater screening and treatments and with better OS after adjusting for screening, cancer stage at diagnosis, and treatments.

Cost-effectiveness of prophylactic granulocyte colony-stimulating factor for febrile neutropenia in breast cancer patients receiving FEC-D.

5-fluorouracil, epirubicin, cyclophosphamide â†’ docetaxel (FEC-D) has been associated with higher-than-expected rates of febrile neutropenia (FN) that meet the current guideline threshold of 20 % for primary prophylaxis (PP) with granulocyte colony-stimulating factor (G-CSF). We examined the cost-effectiveness of FEC-D with varying strategies of G-CSF prophylaxis from the perspective of the public payer in Ontario, Canada. A state-transition model was developed to compare three strategies: FEC-D with secondary prophylaxis (SP) only, PP starting with the first cycle of D, and PP starting with the first cycle of FEC. Analysis was conducted for a hypothetical cohort of 50-year-old early-stage breast cancer patients undergoing adjuvant chemotherapy, at a 10-year horizon. Results were expressed in quality-adjusted life-years (QALYs) and 2013 Canadian dollars. Costs and benefits were discounted at 5 %. Event rates, costs, and utilities were derived from the literature. One-way and probabilistic sensitivity analyses were conducted. Using filgrastim, the incremental cost-effectiveness ratios (ICERs) for starting PP with the first cycle of D and starting PP with the first cycle of FEC, compared to using SP only, were $57,886/QALY and $116,186/QALY, respectively. With pegfilgrastim, the ICERs for the same strategies were $90,735/QALY and $149,483/QALY. Compared to using filgrastim SP only, starting PP with D had a 24 % chance of being cost-effective at a willingness-to-pay (WTP) threshold of $50,000/QALY, and a 99 % chance at a WTP threshold of $100,000/QALY. Results were sensitive to FN-related parameters, such as the risk of FN per cycle with D and the associated mortality, but were robust to uncertainty in parameters related to breast cancer, such as the utilities and hazard of relapse. FEC-D with PP starting with the first cycle of D is most likely to be cost-effective, especially with increased risk of FN and mortality from FN.

End-of-life home care utilization and costs in patients with advanced colorectal cancer.

OBJECTIVE: To determine overall utilization and costs associated with home care services in Ontario, Canada by linking a home care database to a stage IV colorectal cancer cohort. METHODS: The names of patients with stage IV colorectal cancer at time of diagnosis (diagnosed from 2005 through 2009) were extracted from the Ontario Cancer Registry. The study cohort comprised those who died before the end of the study. The terminal phase of care was the period of time between diagnosis and death, with a maximum value of 180 days (6 months). Patients were linked to home care services datasets. The type, frequency, and cost of home care services were determined. Regression analysis was used to examine factors associated with utilization and cost. RESULTS: In all, 3,613 stage IV colorectal cancer patients (median age, 71 years) were diagnosed and died during the study's time horizon. During the terminal phase, 79.3% received at least 1 home care visit, and 58.0% had at least 1 palliative visit. Terminal metastatic colorectal cancer patients received an average of 8 home care visits at Canadian $800 within a 30-day time horizon. Home care costs were highest in the month before death. Male sex, a history of moderate or high utilization of health care services, and hospitalization were associated with lower home care costs. LIMITATIONS: Administrative data do not reveal the purpose, efficiency, effectiveness/sufficiency, quality, or appropriateness of home care. CONCLUSION: Patients with advanced colorectal cancer who were approaching death required a moderate level of home care support, resulting in costs of about $5,000 over the 6-month time horizon. FUNDING: This study was conducted with the support of the Ontario Institute for Cancer Research and Cancer Care Ontario through funding provided by the government of Ontario. Data were provided by Cancer Care Ontario and the Institute for Clinical Evaluative Sciences. The ICES also provided funding for the study from an annual grant by the Ontario Ministry of Health and Long-term Care.

Health Canada/BIOTECanada Summit on regulatory and clinical topics related to subsequent entry biologics (biosimilars), Ottawa, Canada, 14 May 2012.

In May 2012, Health Canada and other participants held a National Summit on Subsequent Entry Biologics (SEBs). Health Canada released a guidance document in March 2010 describing policy positions and data requirements for approval of SEBs. While Health Canada and health agencies in other regulatory jurisdictions are aligned on many scientific principles related to biosimilar drugs, Health Canada's specific requirements may not be widely understood by many Canadian stakeholders. The Summit provided an opportunity for education and dialog among physicians who prescribe biologics, provincial payers, and industry on the following topics: preclinical and clinical comparability studies; manufacturing and other product differences; extrapolation of indications; substitution and interchangeability of SEBs with reference biologic drugs in clinical practice; payers' current perspective; pharmacovigilance and naming. It is anticipated that the consensus reached at this meeting will further educate Canadian healthcare professionals, provincial payers, and insurers about the appropriate use of SEBs, and may be of general interest to others internationally.