Individualized Positron Emission Tomography-Based Isotoxic Accelerated Radiation Therapy Is Cost-Effective Compared With Conventional Radiation Therapy: A Model-Based Evaluation

Purpose: To evaluate long-term health effects, costs, and cost-effectiveness of positron emission tomography (PET)-based isotoxic accelerated radiation therapy treatment (PET-ART) compared with conventional fixed-dose CT-based radiation therapy treatment (CRT) in non-small cell lung cancer (NSCLC). Methods and Materials: Our analysis uses a validated decision-model, based on data of 200 NSCLC patients with inoperable stage I-IIIB. Clinical outcomes, resource use, costs, and utilities were obtained from the Maastro Clinic and the literature. Primary model outcomes were the difference in life-years (LYs), quality-adjusted life-years (QALYs), costs, and the incremental cost-effectiveness and cost/utility ratio (ICER and ICUR) of PET-ART versus CRT. Model outcomes were obtained from averaging the predictions for 50,000 simulated patients. A probabilistic sensitivity analysis and scenario analyses were carried out. Results: The average incremental costs per patient of PET-ART were V569 (95% confidence interval [CI] (sic)-5327-(sic)6936) for 0.42 incremental LYs (95% CI 0.19-0.61) and 0.33 QALYs gained (95% CI 0.13-0.49). The base-case scenario resulted in an ICER of (sic)1360 per LY gained and an ICUR of (sic)1744 per QALY gained. The probabilistic analysis gave a 36% probability that PET-ART improves health outcomes at reduced costs and a 64% probability that PET-ART is more effective at slightly higher costs. Conclusion: On the basis of the available data, individualized PET-ART for NSCLC seems to be cost-effective compared with CRT

Prognostic value of microvessel density in stage II and III colon cancer patients:a retrospective cohort study

Background Microvessel density (MVD), as a derived marker for angiogenesis, has been associated with poor outcome in several types of cancer. This study aimed to evaluate the prognostic value of MVD in stage II and III colon cancer and its relation to tumour-stroma-percentage (TSP) and expression of HIF1A and VEGFA. Methods Formalin-fixed paraffin-embedded (FFPE) colon cancer tissues were collected from 53 stage II and 54 (5-fluorouracil-treated) stage III patients. MVD was scored by digital morphometric analysis of CD31-stained whole tumour sections. TSP was scored using haematoxylin-eosin stained slides. Protein expression of HIF1A and VEGFA was determined by immunohistochemical evaluation of tissue microarrays. Results Median MVD was higher in stage III compared to stage II colon cancers (11.1% versus 5.6% CD31-positive tissue area, p <0.001). High MVD in stage II patients tended to be associated with poor disease free survival (DFS) in univariate analysis (p = 0.056). In contrast, high MVD in 5FU-treated stage III patients was associated with better DFS (p = 0.006). Prognostic value for MVD was observed in multivariate analyses for both cancer stages. Conclusions MVD is an independent prognostic factor associated with poor DFS in stage II colon cancer patients, and with better DFS in stage III colon cancer patients treated with adjuvant chemotherapy

Micro-costing diagnostics in oncology:from single-gene testing to whole- genome sequencing

Purpose: Predictive diagnostics play an increasingly important role in personalized medicine for cancer treatment. Whole-genome sequencing (WGS)-based treatment selection is expected to rapidly increase worldwide. This study aimed to calculate and compare the total cost of currently used diagnostic techniques and of WGS in treatment of non-small cell lung carcinoma (NSCLC), melanoma, colorectal cancer (CRC), and gastrointestinal stromal tumor (GIST) in the Netherlands. Methods: The activity-based costing (ABC) method was conducted to calculate total cost of included diagnostic techniques based on data provided by Dutch pathology laboratories and the Dutch-centralized cancer WGS facility. Costs were allocated to four categories: capital costs, maintenance costs, software costs, and operational costs. Results: The total cost per cancer patient per technique varied from € 58 (Sanger sequencing, three amplicons) to € 2925 (paired tumor-normal WGS). The operational costs accounted for the vast majority (over 90%) of the total per cancer patient technique costs. Conclusion: This study outlined in detail all costing aspects and cost prices of current and new diagnostic modalities used in treatment of NSCLC, melanoma, CRC, and GIST in the Netherlands. Detailed cost differences and value comparisons between these diagnostic techniques enable future economic evaluations to support decision-making

Abstract PRACTICABLE SENSITIVITY ANALYSIS OF BAYESIAN BELIEF NETWORKS

By subjecting a Bayesian belief network to a sensitivity analysis with respect to its conditional probabilities, the reliability of its output can be evaluated. Unfortunately, straightforward sensitivity analysis of a belief network is highly time-consuming, as a result of the usually large number of probabilities to be investigated. In this paper, we show that the graphical independence structure of a Bayesian belief network induces various properties that allow for reducing the computational burden of a sensitivity analysis. We show that several analyses can be identi ed as being uninformative because the conditional probabilities under study cannot a ect the network&apos;s output. In addition, we show that the analyses that are informative comply with simple mathematical functions. By exploiting these properties, the practicability of sensitivity analysis of Bayesian belief networks is enhanced considerably. AMS classi cation: 60K10, 62A15, 62N05, 68Q25

A Review on Cost-Effectiveness and Cost-Utility of Psychosocial Care in Cancer Patients

Several psychosocial care interventions have been found effective in improving psychosocial outcomes in cancer patients. At present, there is increasingly being asked for information on the value for money of this type of intervention. This review therefore evaluates current evidence from studies investigating cost-effectiveness or cost-utility of psychosocial care in cancer patients. A systematic search was conducted in PubMed and Web of Science yielding 539 unique records, of which 11 studies were included in the study. Studies were mainly performed in breast cancer populations or mixed cancer populations. Studied interventions included collaborative care (four studies), group interventions (four studies), individual psychological support (two studies), and individual psycho-education (one study). Seven studies assessed the cost-utility of psychosocial care (based on quality-adjusted-life-years) while three studies investigated its cost-effectiveness (based on profile of mood states [mood], Revised Impact of Events Scale [distress], 12-Item Health Survey [mental health], or Fear of Progression Questionnaire [fear of cancer progression]). One study did both. Costs included were intervention costs (three studies), intervention and direct medical costs (five studies), or intervention, direct medical, and direct nonmedical costs (three studies). In general, results indicated that psychosocial care is likely to be cost-effective at different, potentially acceptable, willingness-to-pay thresholds. Further research should be performed to provide more clear information as to which psychosocial care interventions are most cost-effective and for whom. In addition, more research should be performed encompassing potential important cost drivers from a societal perspective, such as productivity losses or informal care costs, in the analyses

Molecular stool testing as an alternative for surveillance colonoscopy:a cross-sectional cohort study

Background: As in many other European countries, a nationwide screening program for colorectal cancer (CRC) has recently been introduced in the Netherlands. As a side effect, such a screening program will inherently yield an increase in the demand for surveillance after removal of polyps/adenomas or CRC. Although these patients are at increased risk of metachronous colorectal neoplasia, solid evidence on CRC-related mortality reduction as a result of colonoscopy-based surveillance programs is lacking. Furthermore, colonoscopy-based surveillance leads to high patient burden, high logistic demands and high costs. Therefore, new surveillance strategies are needed. The aim of the present study, named Molecular stool testing for Colorectal CAncer Surveillance (MOCCAS), is to determine the performance characteristics of two established non-invasive tests, i.e., the multitarget stool DNA test Cologuard (R) and the faecal immunochemical test (FIT) in the detection of CRC and advanced adenomas as an alternative for colonoscopy surveillance. Methods: In this observational cross-sectional cohort study, subjects aged 50 to 75 years will be approached to collect (whole-) stool samples for molecular testing and a FIT prior to their scheduled surveillance colonoscopy. The results of the tests will allow calculation of test sensitivities and specificities in the context of surveillance. This will provide the required input for the Dutch ASCCA model (Adenoma and Serrated pathway to Colorectal CAncer) to simulate surveillance strategies differing in frequency and duration. The model will allow predictions of lifetime health effects and costs. Multiple centres in the Netherlands will participate in the study that aims to include 4,000 individuals. Discussion: The outcome of this study will inform on the (cost-) effectiveness of stool based molecular testing as an alternative for colonoscopy in the rapidly expanding surveillance populatio

MODEL-BASED COST-EFFECTIVENESS OF CONVENTIONAL AND INNOVATIVE CHEMO-RADIATION IN LUNG CANCER

Introduction: Optimizing radiotherapy with or without chemotherapy through advanced imaging and accelerated radiation schemes shows promising results in locally advanced non–small-cell lung cancer (NSCLC). This study compared the cost-effectiveness of positron emission tomography-computed tomography based isotoxic accelerated sequential chemo-radiation (SRT2) and concurrent chemo-radiation with daily low-dose cisplatin (CRT2) with standard sequential (SRT1) and concurrent chemo-radiation (CRT1). Methods: We used an externally validated mathematical model to simulate the four treatment strategies. The model was built using data from 200 NSCLC patients treated with curative sequential chemo-radiation. For concurrent strategies, data from a meta-analysis and a single study were included in the model. Costs, utilities, and resource use estimates were obtained from literature. Primary outcomes were the incremental cost-effectiveness and cost-utility ratio (ICUR) of each strategy. Scenario analyses were carried out to investigate the impact of uncertainty. Results: Total undiscounted costs and quality-adjusted life-years (QALYs) for SRT1, CRT1, SRT2, and CRT2 were EUR 17,288, EUR 18,756, EUR 19,072, EUR 17,360 and QALYs 1.10, 1.15, 1.40, and 1.40, respectively. Compared with SRT1, the ICURs were EUR 38,024/QALY for CRT1, EUR 6,249/QALY for SRT2, and EUR 346/QALY for CRT2. CRT2 was highly cost-effective compared with SRT1. Moreover, CRT2 was more effective and less costly than CRT1 and SRT2. Therefore, these strategies were dominated by CRT2. Conclusion: Optimized sequential and concurrent chemo-radiation strategies are more effective and cost-effective than the current conventional sequential and concurrent strategies. Concurrent chemo-radiation with a daily low dose cisplatin regimen is the most cost-effective treatment option for locally advanced inoperable NSCLC patients

Lumican and Versican Are Associated with Good Outcome in Stage II and III Colon Cancer

Background. Tumor stroma plays an important role in the progression and metastasis of colon cancer. The glycoproteins versican and lumican are overexpressed in colon carcinomas and are associated with the formation of tumor stroma. The aim of the present study was to investigate the potential prognostic value of versican and lumican expression in the epithelial and stromal compartment of Union for International Cancer Control (UICC) stage II and III colon cancer. Methods. Clinicopathological data and tissue samples were collected from stage II (n = 226) and stage III (n = 160) colon cancer patients. Tissue microarrays were constructed with cores taken from both the center and the periphery of the tumor. These were immunohistochemically stained for lumican and versican. Expression levels were scored on digitized slides. Statistical evaluation was performed. Results. Versican expression by epithelial cells in the periphery of the tumor, i.e., near the invasive front, was correlated to a longer disease-free survival for the whole cohort (P = 0.01), stage III patients only (P = 0.01), stage III patients with microsatellite-instable tumors (P = 0.04), and stage III patients with microsatellite-stable tumors who did not receive adjuvant chemotherapy (P = 0.006). Lumican expression in epithelial cells overall in the tumor was correlated to a longer disea Conclusions. Protein expression of versican and lumican predicted good clinical outcome for stage III and II colon cancer patients, respectively

Can a biomarker triage test reduce colonoscopy burden in fecal immunochemical test screening?

Aim: To assess the potential of biomarker triage testing (BM-TT) in the Dutch colorectal cancer (CRC) screening program. Materials & methods: Using the Adenoma and Serrated pathway to Colorectal CAncer model, we simulated fecal immunochemical test (FIT)47-screening and various FIT plus BM-TT screening scenarios in which only individuals with both a positive FIT and BM-TT are referred to colonoscopy. Results: Adding a low polyp sensitivity BM-TT to FIT-screening reduced colonoscopy burden (89-100%) while increasing CRC mortality (27-41%) compared with FIT47-screening only. The FIT plus high polyp sensitivity BM-TT scenarios also decreased colonoscopy burden (71-89%) while hardly affecting CRC mortality (FIT47 0-4% increase, FIT15 2-7% decrease). Conclusion: Adding a BM-TT to FIT-screening considerably reduces colonoscopy burden, but could also decrease screening effectiveness. Combining FIT15 with a high polyp sensitivity BM-TT seems most promising