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Background: Tamoxifen (TAM) is recommended as the first-line strategy for men with estrogen receptor (ER)-positive early breast cancer who are candidates for adjuvant endocrine therapy in ASCO guideline. Our study aims to analyze the cost-effectiveness of receiving adjuvant endocrine therapy with TAM compared to no TAM, and to assess the cost-effectiveness of using TAM with high adherence over low adherence for ER-positive early male breast cancer in the USA., Methods: Two Markov models comprising three mutually exclusive health states were constructed: (1) the first Markov model compared the cost-effectiveness of adding TAM with not using TAM (TAM versus Not-TAM); (2) the second model compared the cost-effectiveness of receiving TAM with high adherence and low adherence (High-adherence-TAM versus Low-adherence-TAM). The simulation time horizon for both models was the lifetime of patients. The efficacy and safety data of two models were elicited from the real-world studies. Model inputs were derived from the US website and published literature. The main outcomes of two models both included the total cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs)., Results: In the first model, TAM yielded an ICER of $5707.29 per QALY compared to Not-TAM, which was substantially below the WTP threshold of $50,000.00 per QALY in the USA. Probabilistic sensitivity analysis results demonstrated a 100.00% probability of cost-effectiveness for this strategy. In the second model, High-adherence-TAM was dominated absolutely compared to Low-adherence-TAM. The High-adherence-TAM was cost-effective with a 99.70% probability over Low-adherence-TAM when WTP was set as $50,000.00/QALY. All of these parameters within their plausible ranges did not reversely change the results of our models., Conclusions: Our study will offer valuable guidance for physicians or patients when making treatment decisions and provide an effective reference for decision-making to consider the appropriate allocation of funds to this special group., (© 2024. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Objective: Icotinib has been approved for adjuvant treatment of stage II-IIIA non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations in China, yet the long-term costs and outcomes of this strategy are unknown. Thus, we examined the cost effectiveness of adjuvant icotinib, compared with adjuvant chemotherapy, for the treatment of resected stage II-IIIA EGFR-mutated NSCLC., Design: We performed a cost-effectiveness analysis from the perspective of the Chinese healthcare system, comparing 2-year adjuvant icotinib with four cycles of adjuvant chemotherapy. Costs and quality-adjusted life years (QALYs) were estimated using a Markov model. Model inputs were obtained from local data and literature. The influence of model parameters and assumptions was explored in sensitivity analyses. All costs are expressed in 2022 US dollars, and costs and QALYs were discounted at a rate of 5% per year. The willingness-to-pay (WTP) threshold was set at three times the per capita gross domestic product., Setting: The Chinese healthcare system perspective., Participants: A hypothetical Chinese cohort of patients with resected stage II-IIIA EGFR-mutated NSCLC., Interventions: Icotinib versus chemotherapy., Primary Outcome Measure: Costs, QALYs, incremental cost-effectiveness ratio., Results: The incremental cost per QALY gained with the use of 2-year icotinib, from the Chinese healthcare system perspective, was $3440.66 compared with adjuvant chemotherapy. At a WTP threshold of $40 500, adjuvant icotinib was the optimal treatment in over 99% of replications. The interpretation of the results was insensitive to model and input assumptions., Conclusions: Compared with adjuvant chemotherapy, adjuvant icotinib may be a cost-effective treatment for resected stage II-IIIA EGFR-mutated NSCLC as the WTP threshold is set at $40 500 per QALY., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The optimal adjuvant therapy (antiestrogen therapy [ET] + radiation therapy or ET alone, or in some reports radiation therapy alone) in older women with early-stage breast cancer has been highly debated. However, granular details on the role of insurance in the out-of-pocket cost for patients receiving ET with or without radiation therapy are lacking. This project disaggregates out-of-pocket costs by insurance plans to increase treatment cost transparency., Methods and Materials: Several radiation therapy schedules are accepted standards as per the National Comprehensive Cancer Network guidelines. For our financial estimate model, we used the 5-fraction and 15-fraction radiation therapy and ET prescribed over a 5-year duration. The total aggregate out-of-pocket costs were determined from the sum of treatment costs, deductibles, and copays/coinsurance based on Medicaid, Original Medicare, Medigap Plan G, and Medicare Part D Rx plans. The model assumes a Medicare- and/or Medicaid-eligible patient ≥70 years of age with node-negative, early-stage estrogen-receptor-positive breast cancer. Patient out-of-pocket costs were estimated from publicly available insurance data from plan-specific benefit coverage materials using a 5-year time horizon., Results: Original Medicare beneficiaries face a total out-of-pocket treatment charge of $2738.52 for ET alone, $2221.26 for 5-fraction radiation therapy alone, $2573.92 for 15-fraction radiation therapy alone, $3361.26 for combined ET+ 5-fraction radiation therapy, and $3713.92 for combined ET + 15-fraction radiation therapy. Medigap Plan G beneficiaries have an out-of-pocket charge of $1130.00 with radiation therapy alone and face an out-of-pocket of $2270.00 for ET alone and combined ET+ radiation therapy. For Medicaid beneficiaries, all treatments approved by Medicaid are covered without limit, resulting in no out-of-pocket expense for either adjuvant treatment option., Conclusions: This model (based on actual cost estimates per insurance plan rather than claims data), by estimating expenses within Medicare and Medicaid plans, provides a level of transparency to patient cost. With knowledge of the costs borne by patients themselves, treatment decisions informed by patients' individual priorities and preferences may be further enhanced., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Incorporating adjuvant cyclin-dependent kinase (CDK) 4/6 inhibitors abemaciclib and ribociclib along with endocrine therapy has been shown to improve invasive disease-free survival (iDFS) for hormone receptor-positive (HR+) human epidermal receptor 2-negative (HER2-) early breast cancer (EBC). This study assesses the cost-effectiveness of this strategy, along with adjuvant aromatase inhibitors from an Indian perspective., Methods: A Markov chain model evaluated the cost-effectiveness of abemaciclib and ribociclib with letrozole compared with letrozole alone for HR+/HER2- EBC from a payer perspective in India. Key measures included lifetime quality-adjusted life-years (QALY), life-years (LY), and total costs. This study explores two scenarios for effectiveness: a best-case (BC) scenario, where the benefit of CDK4/6 inhibitors in improving iDFS lasts a lifetime, and a worst-case (WC) scenario, where benefits disappear after 5 years. Probabilistic sensitivity analyses (PSA) were used to account for simulation uncertainty., Results: In the BC scenario, abemaciclib added 2.17 QALY and 4.96 LY, incurring ₹2,317,957.7 ($27,756.65 in US dollars [USD]) in additional costs. However, the incremental cost-effectiveness ratio (ICER) for abemaciclib exceeded India's willingness-to-pay threshold in the BC and WC scenarios. In the BC scenario, ribociclib added 0.98 QALY and 2.58 LY with added costs of ₹1,711,504.32 ($20,494.6 USD). The ICER for ribociclib also surpassed India's threshold in both scenarios. PSA showed that neither drug was cost-effective at the current market prices in either BC/WC scenario. The cost of abemaciclib and ribociclib needs to be reduced by at least 78.61% and 87.19%, respectively, to be cost-effective in the BC scenario., Conclusion: The combination of adjuvant abemaciclib or ribociclib with letrozole is not cost-effective for HR+/HER2- EBC in India in either the BC or WC scenario.

This epidemiological model forecasted reductions in recurrences and recurrence treatment cost savings with adjuvant atezolizumab vs best supportive care among Canadians with stage II-IIIA non-small cell lung cancer (NSCLC) at national and provincial levels. The population had resected, programmed cell death 1 ligand 1 (PD-L1)-high (≥50%), EGFR -, ALK -, stage II-IIIA NSCLC eligible for adjuvant treatment. Patients with recurrence or death and the costs of treating recurrences were estimated for those receiving adjuvant atezolizumab or best supportive care each year (2024-2034). Proportions of patients expected to be event free up to 10 years after treatment initiation were extrapolated with parametric survival analyses. In the base case analysis, 240 fewer recurrences were estimated to occur over 10 years (2024-2034) with adjuvant atezolizumab vs best supportive care across Canada, with 136 (57%) and 104 (43%) fewer locoregional and metastatic recurrences, respectively. Projected costs of treated recurrences were CAD 33.2 million less over 10 years with adjuvant atezolizumab at a national level (adjuvant atezolizumab, CAD 135.8 million; best supportive care, CAD 169.0 million). This model predicts a considerable long-term reduction in recurrences and substantial treatment cost savings with adjuvant atezolizumab vs best supportive care for patients with PD-L1-high early-stage NSCLC in Canada.

Objectives: Accurate risk stratification of patients with stage II and III colorectal cancer (CRC) prior to treatment selection enables limited health resources to be efficiently allocated to patients who are likely to benefit from adjuvant chemotherapy. We aimed to investigate the cost-effectiveness of a recently developed deep learning-based prognostic method, Histotyping, from the perspective of the Norwegian healthcare system., Methods: Two partitioned survival models were developed to assess the cost-effectiveness of Histotyping for two treatment cohorts: patients with CRC stage II and III. For each of the two cohorts, Histotyping was used for risk stratification to assign adjuvant chemotherapy and was compared with the standard of care (SOC) (adjuvant chemotherapy to all patients). Health outcomes measured in the model were quality-adjusted life years (QALYs) and life years (LYs) gained. Deterministic and probabilistic sensitivity analyses were performed to determine the impact of uncertainty. Scenario analyses were performed to assess the impact of the parameters with the greatest uncertainty., Results: Risk-stratifying patients with CRC stage II and III using Histotyping was dominant (less costly and more effective) compared to SOC. In patients with CRC stage II, the net monetary benefit of Histotyping was 270,934 Norwegian kroners (NOK) (year of valuation is 2021), and the net health benefit of Histotyping was 0.99. In stage III, the net monetary benefit of Histotyping was 195,419 NOK, and the net health benefit of Histotyping was 0.71., Conclusions:  Risk-stratifying patients with CRC using Histotyping prior to the administration of adjuvant chemotherapy is likely to be a cost-effective strategy in Norway., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: In the absence of evidence on whether neoadjuvant (NAC) or adjuvant chemotherapy (AC) is more beneficial for various tumor treatments, economic evaluation (EE) can assist medical decision making. There is limited evidence on their cost-effectiveness and their prospective evaluation is less likely in the future. Therefore, a systematic review and meta-analysis about EE for NAC versus AC in solid tumor help compare these therapies from various perspectives., Methods: Various databases were searched for studies published from inception to 2021. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines and economic-specific guidelines. The data were pooled using a random effects model when possible., Results: The retrieval identified 15 EE studies of NAC versus AC in 8 types of cancer. NAC is the dominant strategy for pancreatic, head and neck, rectal, prostate cancers and colorectal liver metastases. For ovarian cancer, NAC is cost-effective with a lower cost and higher or similar quality-adjusted life-year. There were no significant differences in cost and outcomes for lung cancer. For stage IV or high-risk patients with ovarian or prostate cancer, NAC was cost-effective but not for patients who were not high risk., Conclusions: The EEs results for NAC versus AC were inconsistent because of their different model structures, assumptions, cost inclusions, and a shortage of studies. There are multiple sources of heterogeneity across EEs evidence synthesis. More high-quality EE studies on NAC versus AC in initial cancer treatment are necessary., Competing Interests: Author Disclosures Author disclosure forms can be accessed in the Supplemental Material section., (Copyright © 2023 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer that can impact patients' employment and workforce participation. This study estimates how the employment effects of TNBC impact government tax revenue and public benefits expenditure in Switzerland, representing the fiscal burden of disease (FBoD), and likely consequences of introducing new treatment options., Methods: A four-state cohort model was used to calculate fiscal effects for two treatments: Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab monotherapy (P + C→P) and neoadjuvant chemotherapy alone (C). Lifetime present values of tax revenue, social benefit payments, and healthcare costs were calculated for the average population and those undergoing treatment to assess the FBoD., Results: An average TNBC patient treated with C and P + C→P is expected to generate CHF128,999 and CHF97,008 less tax than the average population, respectively, and require increased social benefit payments. Compared to C, 75% of the incremental healthcare costs of P + C→P are estimated to be offset through tax revenue gains., Conclusions: This analysis demonstrates that 75% of the additional costs of a new TNBC treatment option can be offset by gains in tax revenue. Fiscal analysis can be a useful tool to complement existing methods for evaluating new treatments.

Aims: Use of gene expression signatures to predict adjuvant chemotherapy benefit in women with early-stage breast cancer is increasing. However, high cost, limited access, and eligibility for these tests results in the adoption of less precise assessment approaches. This study evaluates the cost impact of PreciseDx Breast (PDxBr), an AI-augmented histopathology platform that assesses the 6-year risk of recurrence in early-stage invasive breast cancer patients to help improve informed use of adjuvant chemotherapy., Materials and Methods: A decision-tree Markov model was developed to compare the costs of treatment guided by standard of care (SOC) risk assessment (i.e. clinical diagnostic workup with or without Oncotype DX) versus PDxBr with SOC in a hypothetical cohort of U.S. women with early-stage invasive breast cancer. A commercial payer perspective compares costs of testing, adjuvant therapy, recurrence, adverse events, surveillance, and end-of-life care., Results: PDxBr use in prognostic evaluation resulted in savings of $4 million (M) in year one compared to current SOC in 1 M females members. Over 6-years, savings increased to $12.5 M. The per-treated patient costs in year one amounted to $19.5 thousand (K) for SOC and $16.9K for PDxBr., Limitations: For simplicity, recurrence was not specified. We performed scenario analyses to account for variations in rates for local, regional, and distant recurrence. Second, a recurrent patient incurs the total cost of treated recurrence in the first year and goes back to remission or death. Third, CDK4/6i treatment is only incorporated in the recurrence costs but not in the first line of treatment for early-stage breast cancer due to limited data., Conclusions: Sensitivity analyses demonstrated robust overall savings to changes in all variables in the model. The use of PDxBr to assess breast cancer recurrence risk has the potential to fill gaps in care and reduce costs when gene expression signatures are not available.

Objectives: Adjuvant chemotherapy is not recommended for patients with average-risk stage II (T3N0) colon cancer. Nevertheless, a subgroup of these patients who are CDX2-negative might benefit from adjuvant chemotherapy. We evaluated the cost-effectiveness of testing for the absence of CDX2 expression followed by adjuvant chemotherapy (fluorouracil combined with oxaliplatin [FOLFOX]) for patients with stage II colon cancer., Methods: We developed a decision model to simulate a hypothetical cohort of 65-year-old patients with average-risk stage II colon cancer with 7.2% of these patients being CDX2-negative under 2 different interventions: (1) test for the absence of CDX2 expression followed by adjuvant chemotherapy for CDX2-negative patients and (2) no CDX2 testing and no adjuvant chemotherapy for any patient. We derived disease progression parameters, adjuvant chemotherapy effectiveness and utilities from published analyses, and cancer care costs from the Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Sensitivity analyses were conducted., Results: Testing for CDX2 followed by FOLFOX for CDX2-negative patients had an incremental cost-effectiveness ratio of $5500/quality-adjusted life-years (QALYs) compared with no CDX2 testing and no FOLFOX (6.874 vs 6.838 discounted QALYs and $89 991 vs $89 797 discounted US dollar lifetime costs). In sensitivity analyses, considering a cost-effectiveness threshold of $100 000/QALY, testing for CDX2 followed by FOLFOX on CDX2-negative patients remains cost-effective for hazard ratios of <0.975 of the effectiveness of FOLFOX in CDX2-negative patients in reducing the rate of developing a metastatic recurrence., Conclusions: Testing tumors of patients with stage II colon cancer for CDX2 and administration of adjuvant treatment to the subgroup found CDX2-negative is a cost-effective and high-value management strategy across a broad range of plausible assumptions., (Copyright © 2021 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Introduction: As the availability of new economic evaluations (EE) on adjuvant trastuzumab therapy for early-stage breast cancer (EBC) with HER2-positive since last search and other EEs missed warrant a more extensive review, this study aimed to systematically review EEs of adjuvant trastuzumab compared with chemotherapy alone for HER2-positive EBC., Area Covered: The search was performed in February 2019 using MEDLINE and Scopus. Reviewers independently selected studies based on eligibility criteria, extracted data, assessed quality of reporting, and appraised quality of data sources., Expert Opinion: 22 studies were included which were from high-income (HICs) and upper-middle income countries (UMICs). Incremental cost-effectiveness ratios (ICERs) from HICs were within their cost-effectiveness thresholds and ranged from 6,018 to 78,929 USD per quality-adjusted life year (QALY) gained. ICERs from UMICs mostly exceeded their thresholds ranging from 3,526 to 174,901 USD per QALY gained. Evidence shows cost-effectiveness of trastuzumab for HER2-positive EBC in HICs. There were no methodological variations. The extent and adequacy of reporting were high. The quality of data sources was moderate to high. The quality of future EEs can be improved by enhancing the reporting quality, by using context-based data and real-world efficacy data, which would impact cost-effectiveness.

Background: To explore the potential value of consensus molecular subtypes (CMS) in stage II colon cancer treatment selection, we carried out an early cost-effectiveness assessment of a CMS-based strategy for adjuvant chemotherapy., Methods: We used a Markov cohort model to evaluate three selection strategies: (i) the Dutch guideline strategy (MSS+pT4), (ii) the mutation-based strategy (MSS plus a BRAF and/or KRAS mutation or MSS plus pT4), and (iii) the CMS-based strategy (CMS4 or pT4). Outcomes were number of colon cancer deaths per 1,000 patients, total discounted costs per patient (pp), and quality-adjusted life-years (QALY) pp. The analyses were conducted from a Dutch societal perspective. The robustness of model predictions was assessed in sensitivity analyses. To evaluate the value of future research, we performed a value of information (VOI) analysis., Results: The Dutch guideline strategy resulted in 8.10 QALYs pp and total costs of €23,660 pp. The CMS-based and mutation-based strategies were more effective and more costly, with 8.12 and 8.13 QALYs pp and €24,643 and €24,542 pp, respectively. Assuming a threshold of €50,000/QALY, the mutation-based strategy was considered as the optimal strategy in an incremental analysis. However, the VOI analysis showed substantial decision uncertainty driven by the molecular markers (expected value of partial perfect information: €18M)., Conclusions: On the basis of current evidence, our analyses suggest that the mutation-based selection strategy would be the best use of resources. However, the extensive decision uncertainty for the molecular markers does not allow selection of an optimal strategy at present., Impact: Future research is needed to eliminate decision uncertainty driven by molecular markers., (©2021 American Association for Cancer Research.)

Background: Safety-net hospitals serve a vital role in society by providing care for vulnerable populations. Existing data regarding oncologic outcomes of patients with colon cancer treated at safety-net hospitals are limited and variable. The objective of this study was to delineate disparities in treatment and outcomes for patients with colon cancer treated at safety-net hospitals., Methods: This retrospective cohort study identified 802,304 adult patients with colon adenocarcinoma from the National Cancer Database between 2004-2016. Patients were stratified according to safety-net burden of the treating hospital as previously described. Patient, tumor, facility, and treatment characteristics were compared between groups as were operative and short-term outcomes. Cox proportional hazards regression was utilized to compare overall survival between patients treated at high, medium, and low burden hospitals., Results: Patients treated at safety-net hospitals were demographically distinct and presented with more advanced disease. They were also less likely to receive surgery, adjuvant chemotherapy, negative resection margins, adequate lymphadenectomy, or a minimally invasive operative approach. On multivariate analysis adjusting for patient and tumor characteristics, survival was inferior for patients at safety-net hospitals, even for those with stage 0 (in situ) disease., Conclusion: This analysis revealed inferior survival for patients with colon cancer treated at safety-net hospitals, including those without invasive cancer. These findings suggest that unmeasured population differences may confound analyses and affect survival more than provider or treatment disparities., Competing Interests: Disclosure KAH, CJR, IN, ST, LMS, SK, DSM, AHZ, RSH – none declared. Dr. Zureikat is a member of the Editorial Board of the Journal of Surgical Research; as such, he was excluded from the entire peer-review and editorial process for this manuscript., (Copyright © 2021. Published by Elsevier Inc.)

Objective: Ado-trastuzumab emtansine (T-DM1) was recently approved for patients with human epidermal growth factor receptor 2 positive (HER2+) early breast cancer (eBC) with residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment. Cost-effectiveness analysis was conducted to compare T-DM1 versus trastuzumab in the United States., Materials and Methods: A Markov cohort-based model tracked clinical and economic outcomes over a lifetime horizon from a US payer perspective. The model included 6 health states: invasive disease-free, nonmetastatic (locoregional) recurrence, remission, first-line and second-line metastatic BC and death. Model state transitions were based on statistical extrapolation of the head-to-head KATHERINE study and published sources. Dosing and treatment duration reflected prescribing information and trials. Costs (2019 US dollars) associated with pharmaceutical treatment (wholesale acquisition costs), health state specific care, adverse events, and end-of-life care were included. Health state utilities were obtained from KATHERINE and published literature., Results: T-DM1 dominated trastuzumab, yielding lower lifetime costs (-$40,271), and higher life-years (2.980) and quality-adjusted life-years (2.336). Results were driven by patients receiving T-DM1 spending less time in more costly downstream health states, as these patients are less likely to experience a recurrence overall, despite having a higher likelihood of metastatic disease (distant recurrence) in the subset of patients who experience recurrence. Probabilistic sensitivity analysis indicated robust results, with 96.7% of 5000 stochastic simulations producing dominance for T-DM1. The most influential variables were related to treatment costs, off treatment utilities, and health state costs. Additional scenario analyses tested a range of model inputs and assumptions, and produced consistent results., Conclusion: Relative to trastuzumab, T-DM1 treatment for patients with HER2+ eBC who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment is likely to reduce the overall financial burden of cancer, while simultaneously improving patient outcomes., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Genomic tests can guide the decision to administer adjuvant chemotherapy in women with hormone receptor (HR)-positive, Human Epidermal growth Factor 2 (HER2)-negative breast cancer (BC) at intermediate risk of recurrence. We assessed the decision-making and economic impact of the Prosigna test in a real-life setting., Methods: Retrospective cohort study of HR + , HER2- BC patients managed from 2016 to 2020, potential candidates for adjuvant chemotherapy, at intermediate risk of recurrence, in whom a Prosigna test was performed according to contemporary guidelines. The additional cost of chemotherapy over one year in terms of direct medical and non-medical costs was estimated in this study to be €9,737 (derived from a previous study, NCT02813317). The cost of the Prosigna test, as defined by the reimbursement system, was €1,849., Results: Among the 809 patients included in this study, 2.3 Prosigna tests had to be performed to avoid adjuvant chemotherapy for one patient. The number of tests that had to be performed to avoid chemotherapy for one patient was higher for patients with grade 3 tumors and pN1mic axillary node involvement and lower for grade 1 tumors or in the absence of axillary node involvement (pN0), but did not vary according to the 10-year overall survival gain predicted by the Predict online test. The cost saving related to withholding of adjuvant chemotherapy for one patient on the basis of the Prosigna test results was €5,485., Conclusion: We present one of the largest cohorts of HR + , HER2- BC patients at intermediate risk of recurrence, in whom a Prosigna test was used to guide the adjuvant therapy decision in a real-life setting, resulting in a 44% decrease in the indication for chemotherapy.

Background: Hepatopancreatobiliary (HPB) and gastric oncologic operations are frequently performed at referral centers. Postoperatively, many patients experience care fragmentation, including readmission to "outside hospitals" (OSH), which is associated with increased mortality. Little is known about patient-level and hospital-level variables associated with this mortality difference., Study Design: Patients undergoing HPB or gastric oncologic surgery were identified from select states within the Healthcare Cost and Utilization Project database (2006-2014). Follow-up was 90 days after discharge. Analyses used Kruskal-Wallis test, Youden index, and multilevel modeling at the hospital level., Results: There were 7,536 patients readmitted within 90 days of HPB or gastric oncologic surgery to 636 hospitals; 28% of readmissions (n = 2,123) were to an OSH, where 90-day readmission mortality was significantly higher: 8.0% vs 5.4% (p < 0.01). Patients readmitted to an OSH lived farther from the index surgical hospital (median 24 miles vs 10 miles; p < 0.01) and were readmitted later (median 25 days after discharge vs 12; p < 0.01). These variables were not associated with readmission mortality. Surgical complications managed at an OSH were associated with greater readmission mortality: 8.4% vs 5.7% (p < 0.01). Hospitals with <100 annual HPB and gastric operations for benign or malignant indications had higher readmission mortality (6.4% vs 4.7%, p = 0.01), although this was not significant after risk-adjustment (p = 0.226)., Conclusions: For readmissions after HPB and gastric oncologic surgery, travel distance and timing are major determinants of care fragmentation. However, these variables are not associated with mortality, nor is annual hospital surgical volume after risk-adjustment. This information could be used to determine safe sites of care for readmissions after HPB and gastric surgery. Further analysis is needed to explore the relationship between complications, the site of care, and readmission mortality., (Copyright © 2021 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Approximately 20% of UK women aged 70+ with early breast cancer receive primary endocrine therapy (PET) instead of surgery. PET reduces surgical morbidity but with some survival decrement. To complement and utilize a treatment dependent prognostic model, we investigated the cost-effectiveness of surgery plus adjuvant therapies versus PET for women with varying health and fitness, identifying subgroups for which each treatment is cost-effective., Methods: Survival outcomes from a statistical model, and published data on recurrence, were combined with data from a large, multicenter, prospective cohort study of over 3400 UK women aged 70+ with early breast cancer and median 52-month follow-up, to populate a probabilistic economic model. This model evaluated the cost-effectiveness of surgery plus adjuvant therapies relative to PET for 24 illustrative subgroups: Age {70, 80, 90} × Nodal status {FALSE (F), TRUE (T)} × Comorbidity score {0, 1, 2, 3+}., Results: For a 70-year-old with no lymph node involvement and no comorbidities (70, F, 0), surgery plus adjuvant therapies was cheaper and more effective than PET. For other subgroups, surgery plus adjuvant therapies was more effective but more expensive. Surgery plus adjuvant therapies was not cost-effective for 4 of the 24 subgroups: (90, F, 2), (90, F, 3), (90, T, 2), (90, T, 3)., Conclusion: From a UK perspective, surgery plus adjuvant therapies is clinically effective and cost-effective for most women aged 70+ with early breast cancer. Cost-effectiveness reduces with age and comorbidities, and for women over 90 with multiple comorbidities, there is little cost benefit and a negative impact on quality of life., (Copyright © 2021 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objective: To assess social and clinical correlates of neoadjuvant chemotherapy (NAC) utilization among Medicare beneficiaries., Materials and Methods: A cohort of SEER-Medicare (2004-2015) patients with muscle-invasive bladder cancer treated by radical cystectomy were stratified into 3-groups: standard of care NAC (cisplatin-based combination), non-standard of care NAC, and upfront cystectomy. Multivariable logistic regression analysis was used to assess social, demographic and clinical correlates of each treatment category. Survival analyses were performed to compare propensity matched treatment groups., Results: In total, 6214 patients were identified with a median follow-up of 21 [IQR 7-54] months. NAC utilization increased from 10.7% to 39.1%, between 2004 and 2015, largely due to increased use of standard of care regimens. The most commonly used nonstandard regimen was gemcitabine/carboplatin (50.2%). Older age, Hispanic and Black race, lower socioeconomic status, and contraindications to cisplatin were associated with increased odds of receiving nonstandard of care NAC compared to standard of care. Standard of care NAC was associated with improved overall survival HR 0.85 (95% CI 0.76, 0.94) and HR 0.75 (95% CI 0.63, 0.89) compared to both upfront cystectomy and nonstandard of care NAC, respectively., Conclusion: NAC utilization has increased to nearly 40%; however, the use of non-standard of care NAC regimen have persisted (~8%). Cisplatin-ineligibility, older age, race/ethnicity, and lower socioeconomic status were correlated with nonstandard of care NAC, which provided no clinical benefit at the risk of potential harm. In accordance with current clinical guidelines, cisplatin-ineligible patients should be considered for timely upfront cystectomy or novel clinical trials., (Published by Elsevier Inc.)

Background: Indiscriminate use of adjuvant therapy in stage IIIA melanoma is controversial. We sought to model the clinical impact and cost of implementing a gene expression profile (GEP) test to guide adjuvant therapy., Study Design: A Markov decision-analysis model was created to represent resected stage IIIA melanoma with 3 treatment options: observation (OBS), adjuvant pembrolizumab for all patients (ALL), and selective adjuvant therapy (SEL). In the SEL option, only high-risk patients based on GEP stratification were treated with pembrolizumab. Cost of adjuvant therapy was normalized to reflect Medicare reimbursement schedules. The primary outcome was cost per mortality avoided at 10 years., Results: Model projections for 10-year overall survival were 68% for OBS, 73% for SEL, and 76% for ALL. The estimated incremental cost-per-mortality-avoided (compared to OBS) was $2.1 million for SEL and $2.4 million for ALL. These translate to costs of $583.0K and $697.1K per life-year for the SEL and ALL strategies, respectively., Conclusions: Routine adjuvant pembrolizumab for stage IIIA melanoma is costly, and risk-stratification by GEP only marginally improves the value of therapy., (Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

The ALLIANCE A041202 trial found that continuously administered ibrutinib in the first-line setting significantly prolonged progression-free survival compared with a fixed-duration treatment of rituximab and bendamustine in older adults with chronic lymphocytic leukemia (CLL). In this study, we created a Markov model to assess the cost-effectiveness of ibrutinib in the first-line setting, compared with a strategy of using ibrutinib in the third-line after failure of time-limited bendamustine and venetoclax-based regimens. We estimated transition probabilities from randomized trials using parametric survival modeling. Lifetime direct health care costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated from a US payer perspective. First-line ibrutinib was associated with an improvement of 0.26 QALYs and 0.40 life-years compared with using ibrutinib in the third-line setting. However, using ibrutinib in the first-line led to significantly higher health care costs (incremental cost of $612 700), resulting in an ICER of $2 350 041 per QALY. The monthly cost of ibrutinib would need to be decreased by 72% for first-line ibrutinib therapy to be cost-effective at a willingness-to-pay threshold of $150 000 per QALY. In a scenario analysis where ibrutinib was used in the second-line in the delayed ibrutinib arm, first-line ibrutinib had an incremental cost of $478 823, an incremental effectiveness of 0.05 QALYs, and an ICER of $9 810 360 per QALY when compared with second-line use. These data suggest that first-line ibrutinib for unselected older adults with CLL is unlikely to be cost-effective under current pricing. Delaying ibrutinib for most patients with CLL until later lines of therapy may be a reasonable strategy to limit health care costs without compromising clinical outcomes., (© 2020 by The American Society of Hematology.)

The effect of the Dependent Coverage Expansion (DCE) under the Affordable Care Act (ACA) on receipt of colorectal cancer treatment has yet to be determined. We identified newly diagnosed DCE-eligible (aged 19-25 years, n = 1924) and DCE-ineligible (aged 27-34 years, n = 8313) colorectal cancer patients from the National Cancer Database from 2007 to 2013. All statistical tests were two-sided. Post-ACA, there was a statistically significant increase in early-stage diagnosis among DCE-eligible (15 percentage point increase, confidence interval = 9.8, 20.2; P < .001), but not DCE-ineligible (P = .09), patients. DCE-eligible patients resected for IIB-IIIC colorectal cancer were more likely to receive timely adjuvant chemotherapy (hazard ratio = 1.34, 95% confidence interval = 1.05 to 1.71; 7.0 days' decrease in restricted mean time from surgery to chemotherapy, P = .01), with no differences in DCE-ineligible patients (hazard ratio = 1.10, 95% confidence interval = 0.98 to 1.24; 2.1 days' decrease, P = .41) post-ACA. Our findings highlight the role of the ACA in improving access to potentially lifesaving cancer care, including a shift to early-stage diagnosis and more timely receipt of adjuvant chemotherapy., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aim: To develop a decision model for the population-level evaluation of strategies to improve the selection of stage II colon cancer (CC) patients who benefit from adjuvant chemotherapy., Methods: A Markov cohort model with a one-month cycle length and a lifelong time horizon was developed. Five health states were included; diagnosis, 90-day mortality, death other causes, recurrence and CC death. Data from the Netherlands Cancer Registry were used to parameterize the model. Transition probabilities were estimated using parametric survival models including relevant clinical and pathological covariates. Subsequently, biomarker status was implemented using external data. Treatment effect was incorporated using pooled trial data. Model development, data sources used, parameter estimation, and internal and external validation are described in detail. To illustrate the use of the model, three example strategies were evaluated in which allocation of treatment was based on (A) 100% adherence to the Dutch guidelines, (B) observed adherence to guideline recommendations and (C) a biomarker-driven strategy., Results: Overall, the model showed good internal and external validity. Age, tumor growth, tumor sidedness, evaluated lymph nodes, and biomarker status were included as covariates. For the example strategies, the model predicted 83, 87 and 77 CC deaths after 5 years in a cohort of 1000 patients for strategies A, B and C, respectively., Conclusion: This model can be used to evaluate strategies for the allocation of adjuvant chemotherapy in stage II CC patients. In future studies, the model will be used to estimate population-level long-term health gain and cost-effectiveness of biomarker-based selection strategies.

Background: Accurate detection of patients with minimal residual disease (MRD) after surgery for stage II colon cancer (CC) remains an urgent unmet clinical need to improve selection of patients who might benefit form adjuvant chemotherapy (ACT). Presence of circulating tumor DNA (ctDNA) is indicative for MRD and has high predictive value for recurrent disease. The MEDOCC-CrEATE trial investigates how many stage II CC patients with detectable ctDNA after surgery will accept ACT and whether ACT reduces the risk of recurrence in these patients., Methods/design: MEDOCC-CrEATE follows the 'trial within cohorts' (TwiCs) design. Patients with colorectal cancer (CRC) are included in the Prospective Dutch ColoRectal Cancer cohort (PLCRC) and give informed consent for collection of clinical data, tissue and blood samples, and consent for future randomization. MEDOCC-CrEATE is a subcohort within PLCRC consisting of 1320 stage II CC patients without indication for ACT according to current guidelines, who are randomized 1:1 into an experimental and a control arm. In the experimental arm, post-surgery blood samples and tissue are analyzed for tissue-informed detection of plasma ctDNA, using the PGDx elio™ platform. Patients with detectable ctDNA will be offered ACT consisting of 8 cycles of capecitabine plus oxaliplatin while patients without detectable ctDNA and patients in the control group will standard follow-up according to guideline. The primary endpoint is the proportion of patients receiving ACT when ctDNA is detectable after resection. The main secondary outcome is 2-year recurrence rate (RR), but also includes 5-year RR, disease free survival, overall survival, time to recurrence, quality of life and cost-effectiveness. Data will be analyzed by intention to treat., Discussion: The MEDOCC-CrEATE trial will provide insight into the willingness of stage II CC patients to be treated with ACT guided by ctDNA biomarker testing and whether ACT will prevent recurrences in a high-risk population. Use of the TwiCs design provides the opportunity to randomize patients before ctDNA measurement, avoiding ethical dilemmas of ctDNA status disclosure in the control group., Trial Registration: Netherlands Trial Register: NL6281/NTR6455 . Registered 18 May 2017, https://www.trialregister.nl/trial/6281.

Introduction: Breast cancer is the most prevalent cancer among women in Egypt. Trastuzumab is administered with chemotherapy for patients with HER2-positive advanced breast cancer (HER2 + ve ABC) in the metastatic and adjuvant settings resulting in improved treatment outcomes, and long-term follow-up. Some studies have evaluated whether equivalent outcomes can be achieved with reduced treatment duration. This study evaluates the cost-effectiveness of 6-month versus 1-year trastuzumab treatments from payer perspective over a 10 year time horizon. Methods: A half-cycle corrected Markov model was developed with five mutually exclusive health states; patient with HER2 +ve ABC, disease-free survival (DFS), local or regional relapse, metastatic relapse, and death. A cycle length of 6 months was applied, direct medical costs including cost of treatments, day-care, surgery, health states and follow-up visits were collected, and indirect costs such as lost productivity were not estimated. The transition probabilities and utilities were extracted from published literature, and deterministic sensitivity analyses were conducted. Results: Among the HER2 +ve ABC patient population in Egypt, the total QALYs of the 6-month trastuzumab were estimated to be 2.99 compared with 2.93 for the 1-year trastuzumab which resulted in a difference of 0.06 QALYs. The total costs were EGP 271,647 ($106,947) and EGP 381,248 ($150,097), respectively. These costs yielded an ICER of -109,600 EGP/QALY (-43,149 $/QALY) for the 6-month trastuzumab. The 6-month trastuzumab is a dominant strategy when compared to 1-year trastuzumab, resulting in improved effectiveness at a reduced cost. All analyses results confirmed the dominance of 6-month trastuzumab and our model robustness. Conclusions: This study concluded that 6-month trastuzumab is a cost-effective option when compared to 1-year trastuzumab in patients with HER2 +ve ABC in Egypt. Our findings provide health care decision makers with additional insights to best allocate available resources concurrently with the improvement of the Egyptian patient's outcomes.

Purpose: Achieving a pathologic complete response (pCR) with neoadjuvant therapy for HER2-positive breast cancer is associated with less recurrence and improved clinical outcomes compared to having residual cancer at surgery. However, recent data have demonstrated favorable outcomes for patients with residual HER2-positive cancer who received adjuvant trastuzumab emtansine (TDM-1). Therefore, we sought to determine the optimal chemotherapy/anti-HER2 treatment strategy., Methods: We created a decision-analytic model for patients with stage II-III HER2-positive cancer that incorporated utilities based on toxicity and recurrence. We separately modeled hormone receptor-negative (HR-) and positive (HR+) disease and calculated quality-adjusted life years (QALYs) and costs through 5 years. Simulated patients received one of the following neoadjuvant treatments: three 'intensive' regimens (TCHP: docetaxel, carboplatin, trastuzumab, pertuzumab; THP + AC: taxol, trastuzumab, pertuzumab then doxorubicin and cyclophosphamide; THP: taxol, trastuzumab, pertuzumab) and two 'de-escalated' regimens (TH: taxol, trastuzumab; TDM-1) followed by adjuvant treatment based on pathologic response., Results: Among 'intensive' neoadjuvant strategies, treatment with THP was more effective and less costly than TCHP or THP + AC. When 'de-escalated' strategies were included, TH became the most cost-effective. For HR-negative cancer, TH had 0.003 fewer quality-adjusted life years (QALYs) than THP but was less costly by $55,831, resulting in an incremental cost-effectiveness ratio of over $18M/QALY for THP, well above any threshold. For HR-positive cancer, neoadjuvant TH dominated the THP strategy., Conclusion: An adaptive-treatment strategy beginning with neoadjuvant THP or TH followed by tailoring post-operative therapy reduces treatment costs, and spares toxicity compared to more intensive chemotherapy regimens for women with HER2-positive breast cancer.

We assessed the usefulness of ChemoCalc, a software package for calculating drug costs, in helping patients understand these costs. We randomly assigned, in a 1 : 1 ratio, 20 women who had undergone surgery for early breast cancer to a group that discussed adjuvant treatment with their physicians using the ChemoCalc software (ChemoCalc group) or a group that discussed adjuvant treatment without ChemoCalc (Usual Explanation group). The participants completed a five-grade evaluation questionnaire after these discussions. The primary endpoint was the intergroup comparison of the questionnaire scores regarding participants' understanding of their treatment-associated drug costs. Median age was not significantly different between the ChemoCalc group and Usual Explanation group (57 vs. 50, respectively; p=0.27). Patients in the ChemoCalc group had a significantly higher perceived level of understanding of the drug cost than those in the Usual Explanation group (5 [4-5] vs. 2.5 [1-5], respectively; p=0.002). Scores related to the patients' perception that understanding drug costs is an important part of breast cancer treatment were also higher in the ChemoCalc group than the Usual Explanation group (5 [2-5] vs. 3 [1-5], respectively; p=0.049). ChemoCalc was found to be useful for understanding drug costs., Competing Interests: No potential conflict of interest relevant to this article was reported.

Background: There has been no comprehensive study determining the financial burden of breast cancer in the South African (SA) public sector., Objectives: To develop a method to determine the cost of breast cancer treatment with chemotherapy per episode of care and to quantify the associated costs relating to chemotherapy at Groote Schuur Hospital (GSH), a government hospital in SA. These costs included costs associated with the management of adverse events arising from chemotherapy., Methods: Retrospective patient-level data were collected for 200 patients from electronic databases and patient folders between 2013 and 2015. Direct medical costs were determined from the health funder's perspective. The information collected was categorised into the following cost components: chemotherapy medicines, support medicines, administration of chemotherapy, laboratory tests, radiology scans and imaging, doctor consultations and adverse events. Time-and-motion studies were conducted on a set of new patients and the data obtained were used for the study sample of 200 patients. All the above costs were used to determine the cost of chemotherapy per episode of care. The episode of care was defined as the care provided from 2 months prior to the date of commencing chemotherapy (pre-chemotherapy phase), during chemotherapy (treatment phase) and until 6 months after the date when the last cycle of chemotherapy was administered (follow-up phase)., Results: A method was developed to determine the episode-of-care costs for breast cancer at GSH. The total direct medical cost for treatment of breast cancer at GSH for 200 patients was ZAR3 154 877, and the average episode-of-care cost per patient was ZAR15 774. The average cost of management of adverse events arising from the various treatment modalities was ZAR13 133 per patient. It was found that the cost of treating a patient with adverse events was 1.8 times higher than the cost of treating a patient without adverse events. Of the patients, 86.5% managed to complete their prescribed chemotherapy treatment cycles, and the average cost of treatment of these patients was 1.3 times more than the average cost for patients who could not complete their treatment, based on the number of treatment cycles received., Conclusion: A comprehensive method to determine the costs associated with breast cancer management per episode of care was developed, and costs were quantified at GSH according to the treatment protocol used at the hospital.

Gene expression profiling (GEP) testing using 12-gene recurrence score (RS) assay (EndoPredict®), 58-gene RS assay (Prosigna®), and 21-gene RS assay (Oncotype DX®) is available to aid in chemotherapy decision-making when traditional clinicopathological predictors are insufficient to accurately determine recurrence risk in women with axillary lymph node-negative, hormone receptor-positive, and human epidermal growth factor-receptor 2-negative early-stage breast cancer. We examined the cost-effectiveness of incorporating these assays into standard practice. A decision model was built to project lifetime clinical and economic consequences of different adjuvant treatment-guiding strategies. The model was parameterized using follow-up data from a secondary analysis of the Anastrozole or Tamoxifen Alone or Combined randomized trial, cost data (2017 Canadian dollars) from the London Regional Cancer Program (Canada) and secondary Canadian sources. The 12-gene, 58-gene, and 21-gene RS assays were associated with cost-effectiveness ratios of $36,274, $48,525, and $74,911/quality-adjusted life year (QALY) gained and resulted in total gains of 379, 284.3, and 189.5 QALYs/year and total budgets of $12.9, $14.2, and $16.6 million/year, respectively. The total expected-value of perfect information about GEP assays' utility was $10.4 million/year. GEP testing using any of these assays is likely clinically and economically attractive. The 12-gene and 58-gene RS assays may improve the cost-effectiveness of GEP testing and offer higher value for money, although prospective evidence is still needed. Comparative field evaluations of GEP assays in real-world practice are associated with a large societal benefit and warranted to determine the optimal and most cost-effective assay for routine use.

Background: Evidence-based timeliness benchmarks have been established to assess quality of breast cancer care, as delays in treatment are associated with poor clinical outcomes. However, few studies have evaluated how current breast cancer care meets these benchmarks and what factors may delay the timely initiation of treatment., Patients and Methods: Demographic and disease characteristics of 377 newly diagnosed patients with breast cancer who initiated treatment at Tufts Medical Center (2009-2015) were extracted from electronic medical records. Time from diagnosis to initial surgery and time from diagnosis to initiation of hormone therapy were estimated with Kaplan-Meier curves. Multivariable regression analysis was used to identify factors associated with treatment delays. Thematic analysis was performed to categorize reasons for delay., Results: Of 319 patients who had surgery recommended as the first treatment, 248 (78%) met the 45-day benchmark (median, 28 days; 25th-75th %, 19-43). After adjusting for potential confounders, multivariable regression analysis revealed that negative hormone receptor status (odds ratio, 3.48; 95% confidence interval, 1.44-8.43) and mastectomy (odds ratio, 4.07; 95% confidence interval, 2.10-8.06) were significantly associated with delays in surgery. Delays were mostly owing to clinical complexity or logistical/financial reasons. Of 241 patients eligible for hormone therapy initiation, 232 (96%) met the 1-year benchmark (median, 147 days; 25th-75th %, 79-217)., Conclusion: Most patients met timeliness guidelines for surgery and initiation of hormone therapy, although risk factors for delay were identified. Knowledge of reasons for breast cancer treatment delay, including clinical complexity and logistical/financial issues, may allow targeting interventions for patients at greatest risk of care delays., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Population-based survival and costs of pancreas adenocarcinoma patients receiving adjuvant chemoradiation and chemotherapy following pancreaticoduodenectomy are poorly understood., Methods: This retrospective cohort study used linked administrative and pathological datasets to identify all patients diagnosed with pancreas adenocarcinoma and undergoing pancreaticoduodenectomy in Ontario between April 2004 and March 2014, who received postoperative chemoradiation or chemotherapy. Stage and margin status were defined by using pathology reports. Kaplan-Meier and Cox proportional hazards regression survival analyses were used to determine associations between adjuvant treatment approach and survival, while stratifying by margin status. Median overall health system costs were calculated at 1 and 3 years for chemoradiation and chemotherapy, and differences were tested using the Kruskal-Wallis test., Results: Among 709 patients undergoing pancreaticoduodenectomy for pancreas cancer during the study period, the median survival was 21 months. Median survival was 19 months for chemoradiation and 22 months for chemotherapy. Patients receiving chemoradiation were more likely to have positive margins: 47.7% compared with 19.2% in chemotherapy. After stratifying by margin status and controlling for confounders, adjusted hazard ratio of death were not statistically different between chemotherapy and chemoradiation [margin positive, hazard ratio (HR) = 0.99, 95% confidence interval (CI) = 0.88-1.27; margin negative, HR 0.95, 95% CI 0.91-1.18]. Overall 1-year health system costs were significantly higher for chemoradiation (USD $70,047) than chemotherapy (USD $54,005) (p ≤ 0.001)., Conclusions: Chemotherapy and chemoradiation yielded similar survival, but chemoradiation resulted in higher costs. To create more sustainable healthcare systems, both the efficacy and costs of therapies should be considered.

Background: Breast cancer is the leading malignancy among Filipino women, with about 23.50% of cases characterized by human epidermal growth factor receptor-2 (HER2) overexpression. Trastuzumab, in addition to standard chemotherapy, is currently recommended as primary treatment for HER2-positive early-stage breast cancer (EBC) in the adjuvant settings, and has been listed in the Philippine National Formulary (PNF) since 2008, but with no current evidence yet on its value for money, to date. Hence, despite several policy enablers, its accessibility remains to be limited in the Philippines. We performed an economic evaluation to assess the cost-effectiveness and budget impact of adjuvant trastuzumab therapy for HER2-positive EBC in the Philippines, using healthcare system and societal perspectives, in aid of guiding coverage decisions., Methods: A Markov model-based cost-utility and budget impact analyses were conducted to estimate the total costs incurred and outcomes gained in using 1 year of adjuvant trastuzumab added to standard chemotherapy versus standard chemotherapy alone, over a lifetime horizon. We discounted both costs and outcomes at 3.5% per annum. Parameters were estimated using country survival data, systematic review and meta-analysis of the relative treatment effect, local and international cost data, and published utility data. Univariate and probabilistic sensitivity analyses were used to account for parameter uncertainty., Results: Trastuzumab therapy was dominated with an incremental cost-effectiveness ratio (ICER) at PHP 453,505 per QALY gained from a healthcare system perspective or PHP 458,686 per QALY gained from a societal perspective, with 10% cost-effectiveness probability at the country cost-effectiveness threshold of PHP 120,000 per QALY gained. National implementation will cost an additional amount of PHP 13,909 million in year one alone, plus about PHP 2000 to 3000 million annually for the succeeding fiscal years., Conclusion: At its current cost, 1 year of adjuvant trastuzumab therapy compared to standard chemotherapy alone for HER2-positive EBC does not represent value for money in the Philippines. Its current cost will have to significantly lower down by one-half to achieve cost-effectiveness.

In December 2017, ESMO Open-Cancer Horizons convened a round-table discussion on the background and latest data regarding cyclin-dependent kinase (CDK)4/6 inhibitors with endocrine therapy (ET) in the treatment of endocrine-sensitive breast cancer (BC). A review on this discussion was published in summer 2018 (https://esmoopen.bmj.com/content/3/5/e000368).Endocrine-sensitive BC with non-visceral disease and limited spread of the metastases.Endocrine-sensitive BC with non-life-threatening visceral involvement. Several open questions were identified, which led to a second ESMO Open discussion on CDK4/6 inhibitors, taking place in December 2018 and covered in this article. The panel discussed two important clinical scenarios and the pro and cons of a treatment approach with CDK4/6 inhibitors for each scenario:Endocrine-sensitive BC with non-visceral disease and limited spread of the metastases.Endocrine-sensitive BC with non-life-threatening visceral involvement. Regarding scenario 1, the panel agreed that CDK4/6 inhibitors should be recommended in first-line therapy for most patients if cost and practicality allow. However, the use of single-agent ET with an aromatase inhibitor in the first-line treatment of these patients is still a possibility for a small group of patients with very limited disease, such as one or two bone lesions or limited lymph node involvement. Regarding scenario 2, chemotherapy is the first approach for patients with endocrine-sensitive metastatic BC with life-threatening visceral involvement because of the need for a faster response. The therapeutic approaches for patients with non-life-threatening visceral involvement are still under debate. Nevertheless, CDK4/6 inhibitors are currently the treatment of choice for most patients with a close follow-up of tumour response. A treatment algorithm has been suggested at the round table., Competing Interests: Competing interests: MP: honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo and Merck Sharp & Dome. JG: research support from Eisai, Genomic Health, Novartis, Pfizer and Roche; travel grants from Eisai, Genomic Health, Novartis, Pfizer and Roche; honoraria for advisory boards and speaker fees from Daiichi, Eisai, Genomic Health, Ipsen, Macrogenics, MSD, Novartis, Onxeo, Pfizer and Roche. GJ: grants, personal fees and non-financial support from Novartis and Roche; personal fees and non-financial support from Pfizer, Lilly, Amgen, BMS, Astra-Zeneca; personal fees from Celgene, Puma Technology, Daiichi Sankyo and Abbvie. AA: advisory boards, travel grants, speaker fees: Novartis, Roche, Lilly, Amgen, Eisai, BMS, MSD, LeoPharma, Genomic Health and Ipsen. CS: honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Novartis, Gerson Lehrman Group, Astra-Zeneca, Lilly, Roche, Amgen, Pfitzer, Merck KGaA, and Tesaro. CCZ: honoraria from Roche, Novartis, BMS, MSD, Imugene, Ariad, Pfizer, Merrimack, Merck KGaA, Fibrogen, AstraZeneca, Tesaro, Gilead, Servier and Shire., (© Author (s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Background: Before the approval of dabrafenib and trametinib in combination, there were no approved therapies in the adjuvant setting that target the RAS/RAF/MEK/ERK pathway., Objective: To evaluate the budget impact of dabrafenib and trametinib in combination for adjuvant treatment of patients with BRAF V600 mutation-positive resected Stage IIIA, IIIB, or IIIC melanoma from a U.S. commercial payer perspective using data from the COMBI-AD trial, as well as other sources., Methods: The budget impact of dabrafenib and trametinib in combination for patients with BRAF V600E/K mutation-positive, resected Stage IIIA, IIIB, or IIIC melanoma was evaluated from the perspective of a hypothetical population of 1 million members with demographic characteristics consistent with those of a commercially insured U.S. insurance plan (i.e., adults aged less than 65 years) using an economic model developed in Microsoft Excel. The model compared melanoma-related health care costs over a 3-year projection period under 2 scenarios: (1) a reference scenario in which dabrafenib and trametinib are assumed to be unavailable for adjuvant therapy and (2) a new scenario in which the combination is assumed to be available. Treatments potentially displaced by dabrafenib and trametinib were assumed to include observation, high-dose interferon alpha-2b, ipilimumab, and nivolumab. Costs considered in the model include those of adjuvant therapies and treatment of locoregional and distant recurrences. The numbers of patients eligible for treatment with dabrafenib and trametinib were based on data from cancer registries, published sources, and assumptions. Treatment mixes under the reference and new scenarios were based on market research data, clinical expert opinion, and assumptions. Probabilities of recurrence and death were based on data from the COMBI-AD trial and an indirect treatment comparison. Medication costs were based on wholesale acquisition cost prices. Costs of distant recurrence were from a health insurance claims study., Results: In a hypothetical population of 1 million commercially insured members, 48 patients were estimated to become eligible for treatment with dabrafenib and trametinib in combination over the 3-year projection period; in the new scenario, 10 patients were projected to receive such treatment. Cumulative costs of melanoma-related care were estimated to be $6.3 million in the reference scenario and $6.9 million in the new scenario. The budget impact of dabrafenib and trametinib in combination was an increase of $549 thousand overall and 1.5 cents per member per month., Conclusions: For a hypothetical U.S. commercial health plan of 1 million members, the budget impact of dabrafenib and trametinib in combination as adjuvant treatment for melanoma is likely to be relatively modest and within the range of published estimates for oncology therapies. These results may assist payers in making coverage decisions regarding the use of adjuvant dabrafenib and trametinib in melanoma., Disclosures: Funding for this research was provided to Policy Analysis Inc. (PAI) by Novartis Pharmaceuticals. Stellato, Moynahan, and Delea are employed by PAI. Ndife, Koruth, Mishra, and Gunda are employed by Novartis. Ghate was employed by Novartis at the time of this study and is shareholder in Novartis, Provectus Biopharmaceuticals, and Mannkind Corporation. Gerbasi was employed by PAI at the time of this study and is currently an employee, and stockholder, of Sage Therapeutics. Delea reports grant funding from Merck and research funding from Amgen, Novartis, Sanofi, Seattle Genetics, Takeda, Jazz, EMD Serono, and 21st Century Oncology, unrelated to this work.

Background: Communicating healthcare costs to patients is an important component of delivering high-quality value-based care, yet cost data are lacking. This is especially relevant for ovarian cancer, where no clinical consensus on optimal first-line treatment exists., Objective: The objective of this study was to generate cost estimates of different primary management strategies in ovarian cancer., Study Design: All women who underwent treatment for ovarian cancer from 2006-2015 were identified from the MarketScan database (n=12,761) in this observational cohort study. Total and out-of-pocket costs were calculated with the use of all claims within 8 months from initial treatment and normalized to 2017 US dollars. The generalized linear model method was used to assess cost by strategy., Results: Among patients who underwent neoadjuvant chemotherapy and those who underwent primary debulking, mean adjusted total costs were $113,660 and $107,153 (P<.001) and mean out-of-pocket costs were $2519 and $2977 (P<.001), respectively. Total costs for patients who had intravenous standard, intravenous dose-dense, and intraperitoneal/intravenous chemotherapy were $105,047, $115,099, and $121,761 (P<.001); and out-of-pocket costs were $2838, $3405, and $2888 (P<.001), respectively. Total costs for regimens that included bevacizumab were higher than those without it ($171,468 vs $104,482; P<.001); out-of-pocket costs were $3127 vs $2898 (P<.001). Among patients who did not receive bevacizumab, 25% paid ≥$3875, and 10% paid ≥$6265. For patients who received bevacizumab, 25% paid ≥$4480, and 10% paid ≥$6635. Among patients enrolled in high-deductible health plans, median out-of-pocket costs were $4196, with 25% paying ≥$6680 and 10% paying ≥$9751., Conclusion: Costs vary across different treatment strategies, and patients bear a significant out-of-pocket burden, especially those enrolled in high-deductible health plans., (Copyright © 2019. Published by Elsevier Inc.)

Objectives: The objective of this study was to evaluate the cost-effectiveness of abatacept, tocilizumab, and tumor necrosis factor (TNF) inhibitors as compared with rituximab in Finnish rheumatoid arthritis patients, who have previously been treated with TNF inhibitors., Methods: A patient-level simulation model was developed to predict costs and outcomes associated with four biological drugs (abatacept, tocilizumab, rituximab and TNF inhibitors) in the treatment of rheumatoid arthritis. Following lack of efficacy or adverse events, the patients were switched to another biological drug until all four options were exhausted. After that, the patients were assumed to receive a 6th line treatment until death. The patients' baseline characteristics and regression models used in the simulation were based on observational data from the National Register for Biological Treatments in Finland. Direct costs comprised drug costs, administration costs, costs of switching, and outpatient and inpatient care, while indirect costs included disability pension and sick leaves due to rheumatoid arthritis. Several subgroup and deterministic sensitivity analyses were conducted., Results: Drug costs were the lowest for rituximab, but when administration costs and costs of switching were included, drug costs were the lowest for TNF inhibitors. Abatacept was associated with the highest drug costs, whereas rituximab was associated with the highest healthcare costs. In total, TNF inhibitors had the lowest direct costs, while rituximab had the highest direct costs. The amount of quality-adjusted life years (QALY) gained ranged from 9.405 for rituximab to 9.661 for TNF inhibitors. TNF inhibitors, abatacept, and tocilizumab were dominant in comparison to RTX., Conclusions: TNF inhibitors, abatacept, and tocilizumab had lower costs and higher QALYs than rituximab, and therefore, they were dominant in comparison to rituximab. As TNF inhibitors had the lowest costs and highest QALYs, they were the most cost-effective treatment option., Competing Interests: HR has received a fee for speaking from Pfizer. KT has received fees for consultancy from Novartis and Pfizer. KP has received fees for speaking and consultancy from Pfizer, MSD, Abbvie, BMS, Roche, Lilly, Novartis, Sandoz, and Sanofi. DN has received fees for consultancy from AbbVie, BMS, Lilly, MSD, Novartis, Pfizer, Roche, and UCB. SH works at ESiOR Oy, which carries out studies, consultancy, education, reporting and health economic evaluations for several pharmaceutical (including companies producing biologic RA drugs), food industry, diagnostics and device companies, hospitals, and academic institutions. ESiOR Oy did not play any role in study design, data collection and analysis, decision to publish and did not provide any financial support to work or author. All other authors have declared no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: At present, palliative systemic chemotherapy is the standard treatment in the Netherlands for gastric cancer patients with peritoneal dissemination. In contrast to lymphatic and haematogenous dissemination, peritoneal dissemination may be regarded as locoregional spread of disease. Administering cytotoxic drugs directly into the peritoneal cavity has an advantage over systemic chemotherapy since high concentrations can be delivered directly into the peritoneal cavity with limited systemic toxicity. The combination of a radical gastrectomy with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results in patients with gastric cancer in Asia. However, the results obtained in Asian patients cannot be extrapolated to Western patients. The aim of this study is to compare the overall survival between patients with gastric cancer with limited peritoneal dissemination and/or tumour positive peritoneal cytology treated with palliative systemic chemotherapy, and those treated with gastrectomy, CRS and HIPEC after neoadjuvant systemic chemotherapy., Methods: In this multicentre randomised controlled two-armed phase III trial, 106 patients will be randomised (1:1) between palliative systemic chemotherapy only (standard treatment) and gastrectomy, CRS and HIPEC (experimental treatment) after 3-4 cycles of systemic chemotherapy.Patients with gastric cancer are eligible for inclusion if (1) the primary cT3-cT4 gastric tumour including regional lymph nodes is considered to be resectable, (2) limited peritoneal dissemination (Peritoneal Cancer Index < 7) and/or tumour positive peritoneal cytology are confirmed by laparoscopy or laparotomy, and (3) systemic chemotherapy was given (prior to inclusion) without disease progression., Discussion: The PERISCOPE II study will determine whether gastric cancer patients with limited peritoneal dissemination and/or tumour positive peritoneal cytology treated with systemic chemotherapy, gastrectomy, CRS and HIPEC have a survival benefit over patients treated with palliative systemic chemotherapy only., Trial Registration: clinicaltrials.gov NCT03348150 ; registration date November 2017; first enrolment November 2017; expected end date December 2022; trial status: Ongoing.

Background: Definitive surgery with total mesorectal excision is the mainstay of treatment for locally advanced rectal cancer. Multimodality therapy improves long-term survival. Current standards advise neoadjuvant chemoradiation followed by radical surgery and adjuvant chemotherapy. Nationally, compliance with adjuvant chemotherapy is only 32%. New research evaluates the effectiveness of total neoadjuvant therapy: complete chemotherapy and chemoradiation before surgery., Objective: The aim of this study is to determine the favored treatment for locally advanced rectal cancer by comparing the cost-effectiveness of total neoadjuvant therapy and the current standard of care., Design: Decision analytical modeling using long-term costs and 5-year disease-free survival was performed to determine the cost-effectiveness after total neoadjuvant therapy and the current standard of care. Sensitivity analysis was used to investigate the effect of uncertainty in model parameters., Settings: Centers for Medicare & Medicaid Services billing data perspective was adopted and outcomes modeled according to local and national databases and literature consensus., Patients: Adult patients with stage II or III rectal cancer were selected., Main Outcome Measures: Cost-effectiveness in disease-free life-years, incremental cost-effectiveness ratio, and net monetary benefit were determined over a 5-year posttreatment period. The favored strategy was determined based on cost-effectiveness and sensitivity analyses., Results: Cost-effectiveness for total neoadjuvant therapy was 40,708 $/life-year, and, for conventional therapy, cost-effectiveness was 44,248 $/life-year. Sensitivity analysis showed that, for an estimated total neoadjuvant therapy completion rate of 90%, total neoadjuvant therapy would remain the dominant strategy for any adjuvant chemotherapy completion rate of less than 93%., Limitations: The samples used to calculate completion rates are small, and survival probabilities are based on existing literature, local database values, and consensus estimates. The model encompasses a 5-year time period from diagnosis., Conclusions: Cost-effectiveness analysis shows that a strategy of total neoadjuvant therapy followed by radical surgery is favored over the current standard of care for locally advanced rectal cancer. Sensitivity analysis shows that a low rate of adjuvant chemotherapy administration plays a key role in decreasing the cost-effectiveness of the current standard of care. See Video Abstract at http://links.lww.com/DCR/A942.

Biologics have dramatically changed breast cancer treatment, and trastuzumab has been an essential treatment drug for HER2-positive breast cancer. The introduction of trastuzumab biosimilar offers the potential to deliver long-term cost savings plus efficiencies for healthcare systems in Japan. The goal of biosimilar development is to demonstrate comparability to the original biologic with a different development concept from that of the original biologic. Hence, a better understanding of the biosimilar itself is urgently needed for appropriate adoption and the integration of trastuzumab biosimilars into oncology clinical practice by all stakeholders. This article focuses on the current situation of biosimilars and future perspectives in Japan by using the trastuzumab biosimilar as an example.

Objective: The APHINITY trial assessed the effectiveness and the safety of adding pertuzumab to trastuzumab and chemotherapy (THP) compared to trastuzumab and chemotherapy (TH) in the adjuvant management of human epidermal growth factor 2-positive (HER2+) breast cancer. We performed a study to project the potential cost-effectiveness of THP vs. TH., Study Design: Trial-based cost-utility modeling analysis., Methods: We performed an economic evaluation from a payer perspective using a Markov model with six health states: invasive disease-free survival, non-metastatic recurrence, remission, first-line metastatic, subsequent line metastatic, and death. We parameterized the model using data from both arms in APHINITY extrapolated to a patient's lifetime horizon. Estimates of health state utilities were based on EQ-5D trial data and the literature, and costs were estimated from government sources and the published literature. The primary outcomes of the model were life-years (LYs), quality-adjusted LYs (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Uncertainty was addressed via univariate and probabilistic sensitivity analyses., Results: For the intention-to-treat population, the model projected improved outcomes (by 0.50 LYs and 0.45 QALYs) and increased costs (by $74 420) for ICERs of $147 774/LY gained and $167 185/QALY gained for PHT vs. HT patients. In the node-positive patient population, the model projected improved outcomes (by 0.86 LYs and 0.76 QALYs) and increased costs (by $66 647) for ICERs of $77 684/LY gained and $87 929/QALY gained. For the hormone-receptor-negative patient population, the model projected health gains, increased costs, and ICERs of $147 022/LY gained and $166 518/QALY gained. The results were sensitive to changes in the model time horizon., Conclusion: The addition of pertuzumab to the available regimens for HER2+ early breast cancer is likely to be cost-effective for patients in the U.S. at high risk of recurrence., (Copyright © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: This study examined whether associations between 21-gene recurrence score (RS) genomic testing and lower costs among patients with early-stage, estrogen receptor-positive breast cancer are observable in real-world data from the Medicare population., Methods: A retrospective cohort study was conducted using SEER-Medicare data for a nationally representative sample of Medicare beneficiaries diagnosed from 2005 through 2011. The main outcomes were associations between RS testing and overall and chemotherapy-specific costs. The primary analysis was restricted to patients aged 66 to 75 years., Results: The primary analysis comprised 30,058 patients. Mean costs 1 year after diagnosis were $35,940 [SD, $28,894] overall, $51,127 [33,386] for clinically high-risk disease, $33,225 [$27,711] for intermediate-risk disease, and $26,695 [$19,532] for low-risk disease. Chemotherapy-specific costs followed similar trends. In multivariable analyses, RS testing was associated with significantly lower costs among high-risk patients in terms of both relative costs (cost ratio, 0.88; 99% CI, 0.82-0.94) and absolute costs ($6,606; 99% CI, $39,223-$9,290). Higher costs among low-risk and intermediate-risk patients were mainly caused by higher noncancer costs. In sensitivity analyses that included all patients aged ≥66 years (N=64,996), associations between RS testing and costs among high-risk patients were similar but less pronounced because of lower overall use of chemotherapy., Conclusions: RS testing was associated with lower overall and chemotherapy-related costs in patients with high-risk disease, consistent with lower chemotherapy use among these patients. Higher overall costs for patients with intermediate-risk and low-risk disease were driven largely by non-treatment-related costs.

The number of breast cancer (BC) cases is growing worldwide, being most frequently diagnosed in the early-setting. Mammaprint™ is a 70-gene-expression signature, originally designed for selecting early BC patients with low risk of developing metastasis, so that they could be spared adjuvant chemotherapy. Its use as a prognostic biomarker has been extensively validated, both retrospectively and prospectively. However, its value as a predictive tool and as a clinically useful tool remains controversial. This review will describe how the test works, its application in the clinic and its limitations. Cost-effectiveness studies will be summarized. Finally, we will provide a perspective on the use of Mammaprint in the near future, as a valuable tool for personalizing the treatment of early BC patients.

Background: Literature suggests that Oncotype DX (ODX) is cost-effective. These studies, however, tend to ignore clinical characteristics and have not incorporated population-based data regarding the distribution of ODX results across different clinical risk groups. Accordingly, this study assessed the cost-effectiveness of ODX across strata of clinical risk groups using population-based ODX data. Methods: We created state-transition models to calculate costs and quality-adjusted life years (QALYs) gained over the lifetime for women with estrogen receptor (ER)-positive, HER2-negative, lymph node-negative breast cancer from a US payer perspective. Using the Connecticut Tumor Registry, we classified the 2,245 patients diagnosed in 2011 through 2013 into 3 clinical risk groups according to the PREDICT model, a risk calculator developed by the National Health Service in the United Kingdom. Within each risk group, we then determined the recurrence score (RS) distributions (<18, 18-30, and ≥31). Other input parameters were derived from the literature. Uncertainty was assessed using deterministic and probabilistic sensitivity analyses. Results: Approximately 82.5%, 11.9%, and 5.6% of our sample were in the PREDICT low-, intermediate-, and high-risk groups, respectively. When combining these 3 groups, ODX had an incremental cost-effectiveness ratio (ICER) of $62,200 per QALY for patients aged 60 years. The ICERs, however, differed across clinical risk groups, ranging from $124,600 per QALY in the low-risk group, to $28,700 per QALY in the intermediate-risk group, to $15,700 per QALY in the high-risk group. Results were sensitive to patient age: the ICER for patients aged 45 to 75 years ranged from $77,100 to $344,600 per QALY in the PREDICT low-risk group, and was lower than $100,000 per QALY in the intermediate- and high-risk groups. Conclusions: ODX is not cost-effective for women with clinical low-risk breast cancer, which constitutes most patients with ER-positive disease., (Copyright © 2019 by the National Comprehensive Cancer Network.)

The prognosis of patients with early stage breast cancer has greatly improved in the past three decades. Following the first adjuvant endocrine therapy and chemotherapy trials, continuous improvements of clinical outcomes have been achieved through intense therapeutic escalation, albeit with increased health-care costs and treatment-related toxicities. In contrast to the advances achieved in surgery or radiotherapy, the identification of the patient subgroups that will derive clinical benefit from therapeutic escalation has proved to be a daunting process hindered by a lack of collaboration between scientific groups and by the pace of drug development. In the past few decades, initiatives towards de-escalation of systemic adjuvant treatment have achieved success. Herein, we summarize attempts to escalate and de-escalate adjuvant systemic treatment for patients with breast cancer and argue that new, creative trial designs focused on patients' actual needs rather than on maximizing drug market size are needed. Ultimately, the adoption of effective treatments that do not needlessly expose patients and health-care systems to harm demands extensive international collaboration between academic groups, governments, and pharmaceutical companies.

Aim: Oral uracil-tegafur/leucovorin (UFT/LV) and intravenous 5-fluorouracil (FU)/LV are common adjuvant therapies for Stages II and III colorectal cancer. This study aims to determine the most cost-effective treatment alternative between UFT/LV and 5-FU/LV in Stages II and III colorectal cancer from Taiwan's National Health Insurance perspective., Patients & Methods: The costs were referenced directly from the National Health Insurance reimbursement price. Chemotherapy regimen considered for the cost analysis calculation was adapted from NSABP-C-06 study, and, a time saving calculation was also included. In addition, we compare the treatment outcome., Result: A total cost saving of US$3620.80-$3709.16 per patient per treatment was achieved with the UFT/LV treatment. UFT/LV provides the comparable outcome to 5-FU/LV., Conclusion: UFT/LV was the more cost-effective treatment as adjuvant chemotherapy.

Background: Timely detection and treatment of breast cancer is important in optimizing survival and minimizing recurrence. Given disparities in breast cancer outcomes based on socioeconomic status, we examined time to diagnosis and treatment in a safety-net hospital. Methods : We conducted a retrospective review of all patients with breast cancer diagnosed between July 1, 2010, and June 30, 2012 (N=120). We limited our analytic sample to patients with nonrecurrent, primary stage 0-III breast cancer (N=105) and determined intervals from presentation to diagnosis, diagnosis to first treatment, last surgery to chemotherapy initiation, and last surgery to start of radiation therapy (RT). Using logistic regression, we calculated unadjusted odds of receiving timely treatment (< median time) versus more delayed treatment (≥ median time) as a function of age, language, ethnicity, insurance, Charlson comorbidity index, disease stage, method of first presentation (screening mammography vs care provider), symptoms at presentation, and type of surgical treatment. Results: Patients aged 55 to 64 years accounted for most of the sample (n=37; 35.2%). Median time from presentation to diagnosis (23 days), time from diagnosis to first treatment, and time from surgery to chemotherapy initiation fell within intervals published in the literature; median time from last surgery to start of RT was greater than recommended intervals. Factors significantly associated with longer intervals than median time included stage, method of presentation, language, surgical treatment, insurance, and ethnicity. Conclusions: Patients in this safety-net setting experienced acceptable diagnosis and treatment intervals, except for time to RT. Focused interventions that help care providers access imaging quickly for their symptomatic patients could improve time to diagnosis. Concentrating additional efforts on non-English-speaking, Hispanic patients and those who need to receive RT could improve time to treatment., (Copyright © 2018 by the National Comprehensive Cancer Network.)

Background: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) have directed the care of patients with cancer for >20 years. Payers are implementing guideline-based pathway programs that restrict reimbursement for non-guideline-based care to control costs, yet evidence regarding impact of guidelines on outcomes, including mortality, Medicare costs, and healthcare utilization, is limited. Patients and Methods: This analysis evaluated concordance of first treatment with NCCN Guidelines for women with de novo stage IV metastatic breast cancer (MBC) included within the SEER-Medicare linked database and diagnosed between 2007 and 2013. Cox proportional hazards models were used to evaluate the association between mortality and guideline concordance. Linear mixed-effects and generalized linear models were used to evaluate total cost to Medicare and rates of healthcare utilization by concordance status. Results : We found that 19% of patients (188/988) with de novo MBC received nonconcordant treatment. Patients receiving nonconcordant treatment were more likely to be younger and have hormone receptor-negative and HER2-positive MBC. The most common category of nonconcordant treatment was use of adjuvant regimens in the metastatic setting (40%). Adjusted mortality risk was similar for patients receiving concordant and nonconcordant treatments (hazard ratio [HR], 0.85; 95% confidence limit [CL], 0.69, 1.05). When considering category of nonconcordance, patients receiving adjuvant regimens in the metastatic setting had a decreased risk of mortality (HR, 0.60; 95% CL, 0.43, 0.84). Nonconcordant treatments were associated with $1,867 higher average Medicare costs per month compared with concordant treatments (95% CL, $918, $2,817). Single-agent HER2-targeted therapy was the highest costing category of nonconcordance at $3,008 (95% CL, $1,014, $5,001). Healthcare utilization rates were similar for patients receiving concordant and nonconcordant treatments. Conclusions : Despite a lack of survival benefit, concordant care was associated with lower costs, suggesting potential benefit to increasing standardization of care. These findings may influence policy decisions regarding implementation of pathway programs as health systems transition to value-based models., (Copyright © 2018 by the National Comprehensive Cancer Network.)

Breast cancer (BC) screening has been developed to detect earlier stage tumors associated with better prognosis. The aim of study was to evaluate the impact of BC screening on therapeutic management of patients with first operable BC, and on costs, patients' needs, and working life. OPTISOINS01 was a multicenter, prospective observational study which aimed to identify the main care pathway of early BC. Among patients aged from 50 to 74 years-old, 2 groups were defined: the "Clinical signs" group and the "Screening" group (national organized screening and individual screening). We compared between these 2 groups: locoregional and systemic treatments, direct medical and non-medical costs from a National Health Insurance perspective, patients' needs assessed by the validated SCNS-BR8 "breast cancer" module of the SCNS-SF34 supportive care needs survey and the duration of sick leave. The "Clinical signs" group included 89 patients, while the"Screening" group included 290 patients. More axillary lymph node dissections and radical breast surgery were performed in the "Clinical signs". The rate of adjuvant chemotherapy was dramatically higher in the "Clinical signs" group. The median direct medical costs of the "Screening" group were €11,860 (€3,643-€41,030) per year and per patient, much lower than in the "Clinical signs" group (€14,940; €5,317-€41,070). Finally, needs specifically assessed by the SCNS-BR8 questionnaire were significantly higher for the postoperative and post-adjuvant periods in the "Clinical signs" group. This study highlighted the benefit of BC screening in terms of reduced therapies and positive impact on work and social life., Competing Interests: SB is currently affiliated with CEMKA-EVAL. However, during the period of study, SB was affiliated with Institut Curie-Department of Health Economics. There are no patents or products to declare. This does not alter our adherence to PLOS ONE's data sharing policy.

Background: The purpose of this study was to present our evaluation of the cost-effectiveness of salvage therapies for patients with recurrent head and neck cancer., Methods: A Markov model was developed with 5 salvage treatment strategies: (1) platinum-based chemotherapy alone; (2) chemotherapy plus cetuximab; (3) stereotactic body radiotherapy (SBRT) alone; (4) SBRT plus cetuximab; and (5) intensity-modulated radiotherapy (IMRT) plus chemotherapy. Clinical parameters were obtained from comprehensive literature review and 2016 Medicare reimbursement. Strategies were compared using the incremental cost-effectiveness ratio (ICER), with effectiveness in quality-adjusted life years (QALYs), and evaluated with a willingness-to-pay (WTP) threshold of $100 000 per QALY gained., Results: In the base case analysis, no treatment strategy was cost-effective at a WTP threshold. The most cost-effective therapy was SBRT alone with $150 866 per QALY gained. If median survival of SBRT alone was ≥11 months, SBRT was considered to be cost-effective., Conclusion: None of the treatment strategies were cost-effective. However, SBRT-based reirradiation has potential to be cost-effective., (© 2018 Wiley Periodicals, Inc.)

Objectives: Neoadjuvant chemotherapy (NACT) versus primary debulking surgery (PDS) for advanced epithelial ovarian cancer (AEOC) remains controversial in the United States. Generalizability of existing trial results has been criticized because of less aggressive debulking procedures than commonly used in the United States. As a result, economic evaluations using input data from these trials may not accurately reflect costs and outcomes associated with more aggressive primary surgery. Using data from an ongoing trial performing aggressive debulking, we investigated the cost-effectiveness and cost-utility of NACT versus PDS for AEOC., Methods: A decision tree model was constructed to estimate differences in short-term outcomes and costs for a hypothetical cohort of 15,000 AEOC patients (US annual incidence of AEOC) treated with NACT versus PDS over a 1-year time horizon from a Medicare payer perspective. Outcomes included costs per cancer-related death averted, life-years and quality-adjusted life-years (QALYs) gained. Base-case probabilities, costs, and utilities were based on the Surgical Complications Related to Primary or Interval Debulking in Ovarian Neoplasms trial. Base-case analyses assumed equivalent survival; threshold analysis estimated the maximum survival difference that would result in NACT being cost-effective at $50,000/QALY and $100,000/QALY willingness-to-pay thresholds. Probabilistic sensitivity analysis was used to characterize model uncertainty., Results: Compared with PDS, NACT was associated with $142 million in cost savings, 1098 fewer cancer-related deaths, and 1355 life-years and 1715 QALYs gained, making it the dominant treatment strategy for all outcomes. In sensitivity analysis, NACT remained dominant in 99.3% of simulations. Neoadjuvant chemotherapy remained cost-effective at $50,000/QALY and $100,000/QALY willingness-to-pay thresholds if survival differences were less than 2.7 and 1.4 months, respectively., Conclusions: In the short term, NACT is cost-saving with improved outcomes. However, if PDS provides a longer-term survival advantage, it may be cost-effective. Research is needed on the role of patient preferences in tradeoffs between survival and quality of life.