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Objective: We aimed to perform an early cost-effectiveness analysis of using a whole-genome sequencing-based tumor mutation burden (WGS-TMB), instead of programmed death-ligand 1 (PD-L1), for immunotherapy treatment selection in patients with non-squamous advanced/metastatic non-small cell lung cancer ineligible for targeted therapy, from a Dutch healthcare perspective. Methods: A decision-model simulating individual patients with metastatic non-small cell lung cancer was used to evaluate diagnostic strategies to select first-line immunotherapy only or the immunotherapy plus chemotherapy combination. Treatment was selected using PD-L1 [A, current practice], WGS-TMB [B], and both PD-L1 and WGS-TMB [C]. Strategies D, E, and F take into account a patient's disease burden, in addition to PD-L1, WGS-TMB, and both PD-L1 and WGS-TMB, respectively. Disease burden was defined as a fast-growing tumor, a high number of metastases, and/or weight loss. A threshold of 10 mutations per mega-base was used to classify patients into TMB-high and TMB-low groups. Outcomes were discounted quality-adjusted life-years (QALYs) and healthcare costs measured from the start of first-line treatment to death. Healthcare costs includes drug acquisition, follow-up costs, and molecular diagnostic tests (i.e., standard diagnostic techniques and/or WGS for strategies involving TMB). Results were reported using the net monetary benefit at a willingness-to-pay threshold of €80,000/QALY. Additional scenario and threshold analyses were performed. Results: Strategy B had the lowest QALYs (1.84) and lowest healthcare costs (€120,800). The highest QALYs and healthcare costs were 2.00 and €140,400 in strategy F. In the base-case analysis, strategy A was cost effective with the highest net monetary benefit (€27,300), followed by strategy B (€26,700). Strategy B was cost effective when the cost of WGS testing was decreased by at least 24% or when immunotherapy results in an additional 0.5 year of life gained or more for TMB high compared with TMB low. Strategies C and F, which combined TMB and PD-L1 had the highest net monetary benefit (≥ €76,900) when the cost of WGS testing, immunotherapy, and chemotherapy acquisition were simultaneously reduced by at least 47%, 39%, and 43%, respectively. Furthermore, strategy C resulted in the highest net monetary benefit (≥ €39,900) in a scenario where patients with both PD-L1 low and TMB low were treated with chemotherapy instead of immunotherapy plus chemotherapy. Conclusions: The use of WGS-TMB is not cost effective compared to PD-L1 for immunotherapy treatment selection in non-squamous metastatic non-small cell lung cancer in the Netherlands. WGS-TMB could become cost effective provided there is a reduction in the cost of WGS testing or there is an increase in the predictive value of WGS-TMB for immunotherapy effectiveness. Alternatively, a combination strategy of PD-L1 testing with WGS-TMB would be cost effective if used to support the choice to withhold immunotherapy in patients with a low expected benefit of immunotherapy. [ABSTRACT FROM AUTHOR]

Evidence on the cost-effectiveness of eHealth in palliative care is scarce. Oncokompas, a fully automated behavioral intervention technology, aims to support self-management in cancer patients. This study aimed to assess the cost-utility of the eHealth application Oncokompas among incurably ill cancer patients, compared to care as usual. In this randomized controlled trial, patients were randomized into the intervention group (access to Oncokompas) or the waiting-list control group (access after three months). Healthcare costs, productivity losses, and health status were measured at baseline and three months. Intervention costs were also taken into account. Non-parametric bootstrapping with 5000 replications was used to obtain 95% confidence intervals around the incremental costs and quality-adjusted life years (QALYs). A probabilistic approach was used because of the skewness of cost data. Altogether, 138 patients completed the baseline questionnaire and were randomly assigned to the intervention group (69) or the control group (69). In the base case analysis, mean total costs and mean total effects were non-significantly lower in the intervention group (−€806 and −0.01 QALYs). The probability that the intervention was more effective and less costly was 4%, whereas the probability of being less effective and less costly was 74%. Among patients with incurable cancer, Oncokompas does not impact incremental costs and seems slightly less effective in terms of QALYs, compared to care as usual. Future research on the costs of eHealth in palliative cancer care is warranted to assess the generalizability of the findings of this study. [ABSTRACT FROM AUTHOR]

Patient's quality of life should be included in clinical decision making regarding the administration of adjuvant chemotherapy (ACT) in stage II/III colon cancer. Therefore, quality of life, summarized as health utility (HU), was evaluated for patients treated with and without ACT. Furthermore, the role of chemotherapy–induced peripheral neuropathy (CIPN) on HU was evaluated. Patients diagnosed with stage II/III colon cancer between 2011 and 2019 and participating in the Prospective Dutch ColoRectal Cancer cohort were included (n = 914). HU scores were assessed with the EQ‐5D‐5L at baseline, 3, 6, 12, 18, and 24 months. Patients treated with ACT received mainly capecitabine and oxaliplatin (57%) or capecitabine monotherapy (40%) (average duration: 3.5 months). HU 3 to 18 months after diagnosis (potential ACT period + 12 months follow‐up) was compared between patients treated with and without ACT using a mixed model adjusted for age, sex and education level. Subsequently, the CIPN sensory, motor and autonomy scales, measured using the EORTC QLQ‐CIPN20, were independently included in the model to evaluate the impact of neuropathy. Using a mixed model, a significant difference of −0.039 (95% confidence interval: −0.062; −0.015) in HU was found between patients treated with and without ACT. Including the CIPN sensory, motor and autonomy scales decreased the difference with 0.019, 0.015 and 0.02, respectively. HU 3 to 18 months after diagnosis is significantly lower in patients treated with ACT vs without ACT. This difference is on the boundary of clinical relevance and appears to be partly related to the sensory and motor neuropathy‐related side effects of ACT. What's new? Given its potentially serious side effects, patient quality of life should be included in clinical decision‐making regarding the administration of adjuvant chemotherapy in stage II/III colon cancer. Using a mixed model which was corrected for relevant covariates, here the authors found a statistically‐significant but small decrease in HU of −0.039 during chemotherapy and the following 12 months for patients treated with adjuvant chemotherapy compared to patients without adjuvant chemotherapy. The decrease in HU, which is on the boundary of clinical relevance, appears to be partly related to sensory and motor neuropathy side effects of adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate the cost-effectiveness of risk-based strategies to improve the selection of surgically treated stage II colon cancer (CC) patients for adjuvant chemotherapy. Methods: Using the 'Personalized Adjuvant TreaTment in EaRly stage coloN cancer' (PATTERN) model, we evaluated five selection strategies: (1) no chemotherapy, (2) Dutch guideline recommendations assuming observed adherence, (3) Dutch guideline recommendations assuming perfect adherence, (4) biomarker mutation OR pT4 stage strategy in which patients with MSS status combined with a pT4 stage or a mutation in BRAF and/or KRAS receive chemotherapy assuming perfect adherence and (5) biomarker mutation AND pT4 stage strategy in which patients with MSS status combined with a pT4 stage tumor and a BRAF and/or KRAS mutation receive chemotherapy assuming perfect adherence. Outcomes were number of CC deaths per 1000 patients and total discounted costs and quality-adjusted life-years (QALYs) per patient (pp). Analyses were conducted from a societal perspective. The robustness of model predictions was assessed in sensitivity analyses. Results: The reference strategy, that is, no adjuvant chemotherapy, resulted in 139 CC deaths in a cohort of 1000 patients, 8.077 QALYs pp and total costs of €22,032 pp. Strategies 2–5 were more effective (range 8.094–8.217 QALYs pp and range 118–136 CC deaths per 1000 patients) and more costly (range €22,404–€25,102 pp). Given a threshold of €50,000/QALY, the optimal use of resources would be to treat patients with either the full adherence strategy and biomarker mutation OR pT4 stage strategy. Conclusion: Selection of stage II CC patients for chemotherapy can be improved by either including biomarker status in the selection strategy or by improving adherence to the Dutch guideline recommendations. [ABSTRACT FROM AUTHOR]

Background: Our aim was to evaluate the cost effectiveness of 3 months' adjuvant chemotherapy versus 6 months in high-risk (T4 stage + microsatellite stable) stage II colon cancer (CC) patients. Methods: Using the validated PATTERN Markov cohort model, which simulates the disease progression of stage II CC patients from diagnosis to death, we first evaluated a reference strategy in which high-risk patients were treated with chemotherapy for 6 months. In the second strategy, treatment duration was shortened to 3 months. Both strategies were evaluated for CAPOX (capecitabine plus oxaliplatin) and FOLFOX (fluorouracil, leucovorin and oxaliplatin). Based on trial data, we assumed that shortened treatment duration compared with a 6-month regimen was equally effective for CAPOX and less effective for FOLFOX. Adverse events were highest in the 6-month strategy. Analyses were conducted from a societal perspective using a lifelong time horizon. Outcomes were number of CC deaths per 1000 patients and total discounted costs and quality-adjusted life-years (QALYs) per patient (pp). Incremental net monetary benefit (iNMB) was calculated using a willingness-to-pay value of €50,000/QALY. Results: For CAPOX, the 6-month strategy resulted in 316 CC deaths per 1000 patients, 6.71 QALYs pp and total costs of €41,257 pp. The 3-month strategy resulted in an equal number of CC deaths, but higher QALYs (6.80 pp) and lower costs (€37,645 pp), leading to a iNMB of €8454 per person for 3 months versus 6 months. For FOLFOX, the 6-month strategy resulted in 316 CC deaths per 1000 patients, 6.71 QALYs pp and total costs of €47,135 pp. The 3-month strategy resulted in more CC deaths (393), lower QALYs (6.19 pp) and lower costs (€44,389 pp). An iNMB of −€23,189 was found for 3 months versus 6 months. Conclusion: Our findings indicate that 3 months' adjuvant chemotherapy should be considered as standard of care in high-risk stage II CC patients for CAPOX, but not for FOLFOX. [ABSTRACT FROM AUTHOR]

Background: Incurable cancer does not only affect patients, it also affects the lives of their partners. Many partners take on caregiving responsibilities. The burden of these caregiving tasks are often associated with physical, psychological, and social difficulties and many partners have unmet supportive care needs. Oncokompas is an eHealth self-management application to support partners in finding and obtaining optimal supportive care, tailored to their quality of life and personal preferences. A randomized controlled trial will be carried out to determine the efficacy and cost-utility of Oncokompas.Methods: A total of 136 adult partners of patients with incurable cancer will be included. Partners will be randomly assigned to the intervention group, which directly gets access to Oncokompas, or the waiting-list control group, which gets access to Oncokompas after three months. The primary outcome measure is caregiver burden. Secondary outcome measures comprise self-efficacy, health-related quality of life, and costs. Measures will be assessed at baseline, two weeks after randomization, and three months after the baseline measurement.Discussion: This study will result in evidence on the efficacy and cost-utility of Oncokompas among partners of patients with incurable cancer, which might lead to implementation of Oncokompas as a health service for partners of patients with incurable cancer.Trial Registration: Netherlands Trial Register, NTR 7636. Registered on 23 November 2018. [ABSTRACT FROM AUTHOR]

Background: Patients with incurable cancer have to deal with a wide range of symptoms due to their disease and treatment, influencing their quality of life. Nowadays, patients are expected to adopt an active role in managing their own health and healthcare. Oncokompas is an eHealth self-management application developed to support patients in finding optimal palliative care, tailored to their quality of life and personal preferences. A randomized controlled trial will be carried out to determine the efficacy and cost-utility of Oncokompas compared to care as usual. Methods: 136 adult patients with incurable lung, breast, colorectal and head and neck cancer, lymphoma and glioma, will be included. Eligible patients have no curative treatment options and a prognosis of at least three months. Patients will be randomly assigned to the intervention group or the control group. The intervention group directly has access to Oncokompas alongside care as usual, while the waiting list control group receives care as usual and will have access to Oncokompas after three months. The primary outcome measure is patient activation, which can be described as a patient's knowledge, skills and confidence to manage his or her own health and healthcare. Secondary outcome measures comprise self-efficacy, health-related quality of life, and costs. Measures will be assessed at baseline, two weeks after randomization, and three months after the baseline measurement. Discussion: This study will result in knowledge on the efficacy and cost-utility of Oncokompas among patients with incurable cancer. Also, more knowledge will be generated into the need for and costs of palliative care from a societal and healthcare perspective. Trial registration: Netherlands Trial Register identifier: NTR 7494. Registered on 24 September 2018. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]