Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma.

BACKGROUND: Immune checkpoint inhibitors and targeted therapies have dramatically improved outcomes in patients with advanced melanoma, but approximately half these patients will not have a durable benefit. Phase 1-2 trials of adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) have shown promising responses, but data from phase 3 trials are lacking to determine the role of TILs in treating advanced melanoma. METHODS: In this phase 3, multicenter, open-label trial, we randomly assigned patients with unresectable stage IIIC or IV melanoma in a 1:1 ratio to receive TIL or anti-cytotoxic T-lymphocyte antigen 4 therapy (ipilimumab at 3 mg per kilogram of body weight). Infusion of at least 5×109 TILs was preceded by nonmyeloablative, lymphodepleting chemotherapy (cyclophosphamide plus fludarabine) and followed by high-dose interleukin-2. The primary end point was progression-free survival. RESULTS: A total of 168 patients (86% with disease refractory to anti-programmed death 1 treatment) were assigned to receive TILs (84 patients) or ipilimumab (84 patients). In the intention-to-treat population, median progression-free survival was 7.2 months (95% confidence interval [CI], 4.2 to 13.1) in the TIL group and 3.1 months (95% CI, 3.0 to 4.3) in the ipilimumab group (hazard ratio for progression or death, 0.50; 95% CI, 0.35 to 0.72; P<0.001); 49% (95% CI, 38 to 60) and 21% (95% CI, 13 to 32) of the patients, respectively, had an objective response. Median overall survival was 25.8 months (95% CI, 18.2 to not reached) in the TIL group and 18.9 months (95% CI, 13.8 to 32.6) in the ipilimumab group. Treatment-related adverse events of grade 3 or higher occurred in all patients who received TILs and in 57% of those who received ipilimumab; in the TIL group, these events were mainly chemotherapy-related myelosuppression. CONCLUSIONS: In patients with advanced melanoma, progression-free survival was significantly longer among those who received TIL therapy than among those who received ipilimumab. (Funded by the Dutch Cancer Society and others; ClinicalTrials.gov number, NCT02278887.).

The socioeconomic impact of cancer on patients and their relatives: Organisation of European Cancer Institutes task force consensus recommendations on conceptual framework, taxonomy, and research directions.

Loss of income and out-of-pocket expenditures are important causes of financial hardship in many patients with cancer, even in high-income countries. The far-reaching consequences extend beyond the patients themselves to their relatives, including caregivers and dependents. European research to date has been limited and is hampered by the absence of a coherent theoretical framework and by heterogeneous methods and terminology. To address these shortages, a task force initiated by the Organisation of European Cancer Institutes (OECI) produced 25 recommendations, including a comprehensive definition of socioeconomic impact from the perspective of patients and their relatives, a conceptual framework, and a consistent taxonomy linked to the framework. The OECI task force consensus statement highlights directions for future research with a view towards policy relevance. Beyond descriptive studies into the dimension of the problem, individual severity and predictors of vulnerability should be explored. It is anticipated that the consensus recommendations will facilitate and enhance future research efforts into the socioeconomic impact of cancer and cancer care, providing a crucial reference point for the development and validation of patient-reported outcome instruments aimed at measuring its broader effects.

Differences in time to patient access to innovative cancer medicines in six European countries.

Patients across Europe face inequity regarding access to anticancer medicines. While access is typically evaluated through reimbursement status or sales data, patients can receive first access through early access programs (EAPs) or off-label use. This study aims to assess the time to patient access at the hospital level, considering different indications and countries. (Pre-)registered access to six innovative medicines (Olaparib, Niraparib, Ipilimumab, Osimeritinib, Nivolumab and Ibritunib) was measured using a cross-sectional survey. First patient access to medicines and indications were collected using the hospital databases. Nineteen hospitals from Hungary, Italy, the Netherlands, Belgium, Switzerland and France participated. Analysis showed that some hospitals achieved patient access before national reimbursement, primarily through EAPs. The average time from EMA-approval to patient access for these medicines was 2.1 years (Range: -0.9-7.1 years). Hospitals in Italy and France had faster access compared to Hungary and Belgium. Variation was also found within countries, with specialized hospitals (x̄: -0.9 years; SD: 2.0) more likely to provide patient access prior to national reimbursement than general hospitals (x̄: 0.4 years; SD: 2.9). Contextual differences were observed, with EAPs or off-label use being more prevalent in Switzerland than Hungary. Recent EMA-approved indications and drug combinations reached patients at a later stage. Substantial variation in patient access time was observed between and within countries. Improving pricing and reimbursement timelines, fostering collaboration between national health authorities and market authorization holders, and implementing nationally harmonized, data-generating EAPs can enhance timely and equitable patient access to innovative cancer treatments in Europe.

Preferences and considerations for interval cytoreductive surgery in advanced ovarian cancer: The patient's perspective.

OBJECTIVE: Treatment of advanced-stage ovarian cancer contains cytoreductive surgery (CRS) and chemotherapy. Achieving successful CRS (≤ 1 cm residual disease) is prognostically important, but may not be feasible peri-operatively while still risking complications. Therefore, patients' treatment expectations are important to discuss. We investigated patient considerations for interval CRS. METHODS: Patients with advanced-stage ovarian cancer planned for interval CRS completed a questionnaire about the impact of chance of successful CRS, survival benefit and becoming care-dependent on decision-making regarding CRS. The questionnaire included a vignette study, in which patients repeatedly chose between two treatment scenarios with varying levels for chance of successful CRS, survival benefit and risk of complications including stoma. Patient preferences were analyzed, including differences between patients aged < 70 and ≥ 70 years. RESULTS: Among 85 included patients, 31 (37%) patients considered interval CRS worthwhile irrespective of survival benefit and 33 (39%) irrespective of chance of successful surgery. However, 34 patients (41%) considered interval CRS only worthwhile if survival benefit was > 12 months, while 41 (49%) thought so if chance of successful surgery was ≥ 25%. Older patients considered these factors more important. Overall, 27% considered becoming permanently dependent of home care unacceptable. In the vignette study (n = 72) risk of complications and stoma were considered less important than chance of successful CRS and survival benefit. CONCLUSION: Survival benefit, chance of successful surgery and becoming care-dependent are important factors in patient's decision for interval CRS, while risk of complications and stoma are less important. Our results are useful in shared decision-making for interval CRS in ovarian cancer.

High-dose chemotherapy for patients with stage III breast cancer with homologous recombination deficiency: a discrete choice experiment among healthcare providers.

BACKGROUND AND PURPOSE: High-dose chemotherapy with autologous stem cell rescue (HDCT) is currently under investigation as a potential therapy for patients with stage III HER2-negative breast cancer with homologous recombination deficiency (HRD). In addition to survival, the impact on short- and long-term side effects might influence the uptake of HDCT by healthcare professionals. As part of the SUBITO trial, we investigated healthcare professionals' treatment (outcome) preferences for patients with HRD stage III HER2-negative breast cancer and established how healthcare professionals make trade-offs between these treatment outcomes. PATIENTS/MATERIAL AND METHODS: We conducted a discrete choice experiment in which healthcare professionals were asked to choose repeatedly between scenarios with two treatment options (HDCT or standard of care (SOC)) that varied in outcome with respect to 10-year overall survival (OS), short-term toxicity, long-term cognitive impairment, and premature menopause. We analysed treatment preferences, relative importance, and trade-offs using a multinomial logistic model. RESULTS AND INTERPRETATION: Thirty-five of the 151 dedicated breast cancer professionals with extensive experience in treating breast cancer patients completed the survey. The 10-year OS and long-term cognitive impairment were the most important attributes. The results indicate a requirement of 10.4% and 25.1% absolute additional improvement in the 10-year survival rate to justify accepting moderate or severe long-term cognitive impairment as a trade-off, respectively. Therefore, we found in our dataset that healthcare professionals expected a large improvement in 10-year OS to accept moderate to severe cognitive impairment. This information calls for further research into chemotherapy-related cognitive impairment, shared decision-making, and treatment preferences for patients with stage III breast cancer.

Organization of head and neck cancer rehabilitation care: a national survey among healthcare professionals in Dutch head and neck cancer centers.

PURPOSE: Head and neck cancer (HNC) treatment often leads to physical and psychosocial impairments. Rehabilitation can overcome these limitations and improve quality of life. The aim of this study is to obtain an overview of rehabilitation care for HNC, and to investigate factors influencing rehabilitation provision, in Dutch HNC centers, and to some extent compare it to other countries. METHODS: An online survey, covering five themes: organizational structure; rehabilitation interventions; financing; barriers and facilitators; satisfaction and future improvements, among HNC healthcare- and financial professionals of Dutch HNC centers. RESULTS: Most centers (86%) applied some type of rehabilitation care, with variations in organizational structure. A speech language therapist, physiotherapist and dietitian were available in all centers, but other rehabilitation healthcare professionals in less than 60%. Facilitators for providing rehabilitation services included availability of a contact person, and positive attitude, motivation, and expertise of healthcare professionals. Barriers were lack of reimbursement, and patient related barriers including comorbidity, travel (time), low health literacy, limited financial capacity, and poor motivation. CONCLUSION: Although all HNC centers included offer rehabilitation services, there is substantial practice variation, both nationally and internationally. Factors influencing rehabilitation are related to the motivation and expertise of the treatment team, but also to reimbursement aspects and patient related factors. More research is needed to investigate the extent to which practice variation impacts individual patient outcomes and how to integrate HNC rehabilitation into routine clinical pathways.

Surveillance Imaging after Primary Diagnosis of Ductal Carcinoma in Situ.

Background Guidelines recommend annual surveillance imaging after diagnosis of ductal carcinoma in situ (DCIS). Guideline adherence has not been characterized in a contemporary cohort. Purpose To identify uptake and determinants of surveillance imaging in women who underwent treatment for DCIS. Materials and Methods A stratified random sample of women who underwent breast-conserving surgery for primary DCIS between 2008 and 2014 was retrospectively selected from 1330 facilities in the United States. Imaging examinations were recorded from date of diagnosis until first distant recurrence, death, loss to follow-up, or end of study (November 2018). Imaging after treatment was categorized into 10 12-month periods starting 6 months after diagnosis. Primary outcome was per-period receipt of asymptomatic surveillance imaging (mammography, MRI, or US). Secondary outcome was diagnosis of ipsilateral invasive breast cancer. Multivariable logistic regression with repeated measures and generalized estimating equations was used to model receipt of imaging. Rates of diagnosis with ipsilateral invasive breast cancer were compared between women who did and those who did not undergo imaging in the 6-18-month period after diagnosis using inverse probability-weighted Kaplan-Meier estimators. Results A total of 12 559 women (median age, 60 years; IQR, 52-69 years) were evaluated. Uptake of surveillance imaging was 75% in the first period and decreased over time (P < .001). Across the first 5 years after treatment, 52% of women participated in consistent annual surveillance. Surveillance was lower in Black (adjusted odds ratio [OR], 0.80; 95% CI: 0.74, 0.88; P < .001) and Hispanic (OR, 0.82; 95% CI: 0.72, 0.94; P = .004) women than in White women. Women who underwent surveillance in the first period had a higher 6-year rate of diagnosis of invasive cancer (1.6%; 95% CI: 1.3, 1.9) than those who did not (1.1%; 95% CI: 0.7, 1.4; difference: 0.5%; 95% CI: 0.1, 1.0; P = .03). Conclusion Half of women did not consistently adhere to imaging surveillance guidelines across the first 5 years after treatment, with racial disparities in adherence rates. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Rahbar and Dontchos in this issue.

High-dose chemotherapy with stem cell rescue to treat stage III homologous deficient breast cancer: factors influencing clinical implementation.

BACKGROUND: High-dose chemotherapy with autologous stem cell rescue (HDCT) is a promising treatment for patients with stage III, HER2-negative, homologous recombination deficient (HRD) breast cancer. Clinical effectiveness and cost-effectiveness are currently under investigation in an international multicenter randomized controlled trial. To increase the chance of successful introduction of HDCT into daily clinical practice, we aimed to identify relevant factors for smooth implementation using an early comprehensive assessment framework. METHODS: This is a qualitative, multi-stakeholder, exploratory research using semi-structured interviews guided by the Constructive Technology Assessment model, which evaluates the quality of a novel health technology by clinical, economic, patient-related, and organizational factors. Stakeholders were recruited by purposeful stratified sampling and interviewed until sufficient content saturation was reached. Two researchers independently created themes, categories, and subcategories by following inductive coding steps, these were verified by a third researcher. RESULTS: We interviewed 28 stakeholders between June 2019 and April 2021. In total, five overarching themes and seventeen categories were identified. Important findings for optimal implementation included the structural identification and referral of all eligible patients, early integration of supportive care, multidisciplinary collaboration between- and within hospitals, (de)centralization of treatment aspects, the provision of information for patients and healthcare professionals, and compliance to new regulation for the BRCA1-like test. CONCLUSIONS: In anticipation of a positive reimbursement decision, we recommend to take the highlighted implementation factors into consideration. This might expedite and guide high-quality equitable access to HDCT for patients with stage III, HER2-negative, HRD breast cancer in the Netherlands.

Cost-Effectiveness and Budget Impact of Future Developments With Whole-Genome Sequencing for Patients With Lung Cancer.

OBJECTIVES: This study aimed to investigate the cost-effectiveness, budget impact (BI), and impact of uncertainty of future developments concerning whole-genome sequencing (WGS) as a clinical diagnostic test compared with standard of care (SoC) in patients with locally advanced and metastatic non-small cell lung cancer. METHODS: A total of 3 likely scenarios to take place within 5 years (according to experts) were simulated using a previously developed, peer reviewed, and published decision model. The scenarios concerned "WGS results used for treatment selection" (scenario 1), "WGS-based biomarker for immunotherapy" (scenario 2), and "off-label drug approval for WGS results" (scenario 3). Two diagnostic strategies of the original model, "SoC" and "WGS as a diagnostic test" (base model), were used to compare our scenarios with. Outcomes were reported for the base model, all scenarios separately, combined (combined unweighted), and weighted by likelihood (combined weighted). Cost-effectiveness, BI, and value of information analyses were performed for WGS compared with SoC. RESULTS: Total costs and quality-adjusted life-years for SoC in metastatic non-small cell lung cancer were €149 698 and 1.235. Incremental outcomes of WGS were €1529/0.002(base model), -€222/0.020(scenario 1), -€2576/0.023(scenario 2), €388/0.024(scenario 3), -€5041/0.060(combined unweighted), and -€1715/0.029(combined weighted). The annual BI for adopting WGS for this population in The Netherlands ranged between €682 million (combined unweighted) and €714 million (base model). The consequences of uncertainty amounted to €3.4 million for all scenarios (combined weighted) and to €699 000 for the diagnostic yield of WGS alone (combined weighted). CONCLUSIONS: Our findings suggest that it is likely for WGS to become cost-effective within the near future if it identifies more patients with actionable targets and show the impact of uncertainty regarding its diagnostic yield. Modeling future scenarios can be useful to consider early adoption of WGS while timely anticipating on unforeseen developments before final conclusions are reached.

Image-guided navigation for locally advanced primary and locally recurrent rectal cancer: evaluation of its early cost-effectiveness.

BACKGROUND: A first pilot study showed that an image-guided navigation system could improve resection margin rates in locally advanced (LARC) and locally recurrent rectal cancer (LRRC) patients. Incremental surgical innovation is often implemented without reimbursement consequences, health economic aspects should however also be taken into account. This study evaluates the early cost-effectiveness of navigated surgery compared to standard surgery in LARC and LRRC. METHODS: A Markov decision model was constructed to estimate the expected costs and outcomes for navigated and standard surgery. The input parameters were based on pilot data from a prospective (navigation cohort n = 33) and retrospective (control group n = 142) data. Utility values were measured in a comparable group (n = 63) through the EQ5D-5L. Additionally, sensitivity and value of information analyses were performed. RESULTS: Based on this early evaluation, navigated surgery showed incremental costs of €3141 and €2896 in LARC and LRRC. In LARC, navigated surgery resulted in 2.05 Quality-Adjusted Life Years (QALYs) vs 2.02 QALYs for standard surgery. For LRRC, we found 1.73 vs 1.67 QALYs respectively. This showed an Incremental Cost-Effectiveness Ratio (ICER) of €136.604 for LARC and €52.510 for LRRC per QALY gained. In scenario analyses, optimal utilization rates of the navigation technology lowered the ICER to €61.817 and €21.334 for LARC and LRRC. The ICERs of both indications were most sensitive to uncertainty surrounding the risk of progression in the first year after surgery, the risk of having a positive surgical margin, and the costs of the navigation system. CONCLUSION: Adding navigation system use is expected to be cost-effective in LRRC and has the potential to become cost-effective in LARC. To increase the probability of being cost-effective, it is crucial to optimize efficient use of both the hybrid OR and the navigation system and identify subgroups where navigation is expected to show higher effectiveness.

Developing a dynamic simulation model to support the nationwide implementation of whole genome sequencing in lung cancer.

BACKGROUND: This study shows how dynamic simulation modeling can be applied in the context of the nationwide implementation of Whole Genome Sequencing (WGS) for non-small cell lung cancer (NSCLC) to inform organizational decisions regarding the use of complex and disruptive health technologies and how these decisions affect their potential value. METHODS: Using the case of the nationwide implementation of WGS into clinical practice in lung cancer in the Dutch healthcare system, we developed a simulation model to show that including service delivery features across the diagnostic pathway can provide essential insight into the affordability and accessibility of care at the systems level. The model was implemented as a hybrid Agent-Based Model and Discrete-Event Simulation model in AnyLogic and included 78 hospital agents, 7 molecular tumor board agents, 1 WGS facility agent, and 5313 patient agents each year in simulation time. RESULTS: The model included patient and provider heterogeneity, including referral patterns, capacity constraints, and diagnostic workflows. Patient preference and adoption by healthcare professionals were also modeled. The model was used to analyze a scenario in which only academic hospitals have implemented WGS. To prevent delays in the diagnostic pathway, the capacity to sequence at least 1600 biopsies yearly should be present. There is a two-fold increase in mean diagnostic pathway duration between no patients referred or all patients referred for further diagnostics. CONCLUSIONS: The systems model can complement conventional health economic evaluations to investigate how the organization of the workflow can influence the actual use and impact of WGS. Insufficient capacity to provide WGS and referral patterns can substantially impact the duration of the diagnostic pathway and thus should be considered in the implementation of WGS.

Treating (low-risk) DCIS patients: What can we learn from real-world cancer registry evidence?

PURPOSE: Results from active surveillance trials for ductal carcinoma in situ (DCIS) will not be available for > 10 years. A model based on real-world data (RWD) can demonstrate the comparative impact of non-intervention for women with low-risk features. METHODS: Multi-state models were developed using Surveillance, Epidemiology, and End Results Program (SEER) data for three treatment strategies (no local treatment, breast conserving surgery [BCS], BCS + radiotherapy [RT]), and for women with DCIS low-risk features. Eligible cases included women aged ≥ 40 years, diagnosed with primary DCIS between 1992 and 2016. Five mutually exclusive health states were modelled: DCIS, ipsilateral invasive breast cancer (iIBC) ≤ 5 years and > 5 years post-DCIS diagnosis, contralateral IBC, death preceded by and death not preceded by IBC. Propensity score-weighted Cox models assessed effects of treatment, age, diagnosis year, grade, ER status, and race. RESULTS: Data on n = 85,982 women were used. Increased risk of iIBC ≤ 5 years post-DCIS was demonstrated for ages 40-49 (Hazard ratio (HR) 1.86, 95% Confidence Interval (CI) 1.34-2.57 compared to age 50-69), grade 3 lesions (HR 1.42, 95%CI 1.05-1.91) compared to grade 2, lesion size ≥ 2 cm (HR 1.66, 95%CI 1.23-2.25), and Black race (HR 2.52, 95%CI 1.83-3.48 compared to White). According to the multi-state model, propensity score-matched women with low-risk features who had not died or experienced any subsequent breast event by 10 years, had a predicted probability of iIBC as first event of 3.02% for no local treatment, 1.66% for BCS, and 0.42% for BCS+RT. CONCLUSION: RWD from the SEER registry showed that women with primary DCIS and low-risk features demonstrate minimal differences by treatment strategy in experiencing subsequent breast events. There may be opportunity to de-escalate treatment for certain women with low-risk features: Hispanic and non-Hispanic white women aged 50-69 at diagnosis, with ER+, grade 1 + 2, < 2 cm DCIS lesions.

Whole genome sequencing in oncology: using scenario drafting to explore future developments.

BACKGROUND: In oncology, Whole Genome Sequencing (WGS) is not yet widely implemented due to uncertainties such as the required infrastructure and expertise, costs and reimbursements, and unknown pan-cancer clinical utility. Therefore, this study aimed to investigate possible future developments facilitating or impeding the use of WGS as a molecular diagnostic in oncology through scenario drafting. METHODS: A four-step process was adopted for scenario drafting. First, the literature was searched for barriers and facilitators related to the implementation of WGS. Second, they were prioritized by international experts, and third, combined into coherent scenarios. Fourth, the scenarios were implemented in an online survey and their likelihood of taking place within 5 years was elicited from another group of experts. Based on the minimum, maximum, and most likely (mode) parameters, individual Program Evaluation and Review Technique (PERT) probability density functions were determined. Subsequently, individual opinions were aggregated by performing unweighted linear pooling, from which summary statistics were extracted and reported. RESULTS: Sixty-two unique barriers and facilitators were extracted from 70 articles. Price, clinical utility, and turnaround time of WGS were ranked as the most important aspects. Nine scenarios were developed and scored on likelihood by 18 experts. The scenario about introducing WGS as a clinical diagnostic with a lower price, shorter turnaround time, and improved degree of actionability, scored the highest likelihood (median: 68.3%). Scenarios with low likelihoods and strong consensus were about better treatment responses to more actionable targets (26.1%), and the effect of centralizing WGS (24.1%). CONCLUSIONS: Based on current expert opinions, the implementation of WGS as a clinical diagnostic in oncology is heavily dependent on the price, clinical utility (both in terms of identifying actionable targets as in adding sufficient value in subsequent treatment), and turnaround time. These aspects and the optimal way of service provision are the main drivers for the implementation of WGS and should be focused on in further research. More knowledge regarding these factors is needed to inform strategic decision making regarding the implementation of WGS, which warrants support from all relevant stakeholders.

Selecting Image-Guided Surgical Technologies in Oncology: A Surgeon's Perspective.

BACKGROUND: To improve surgical performance, image-guided (IG) technologies are increasingly introduced. Yet, it is unknown which oncological procedures yield most value from these technologies. This study aimed to select the most promising IG technology per oncologic indication. METHODS: An Analytic Hierarchical Process was used to evaluate three IG technologies: navigation, optical imaging, and augmented reality, in five oncologic indications compared with usual care. Sixteen decision criteria were selected. The relative importance of the criteria and the expected performance of the technologies were evaluated among surgeons. The combination of these scores gives the expected value per technology. RESULTS: On criteria level, sparing critical tissue (9%-18%) and reducing the risk of local recurrence (11%-27%) were most important. Navigation was preferred in three indications-removal of lymph nodes (42%), liver (47%), and rectal tumors (33%). In removing rectal tumors, optical imaging was equally preferred (34%). In removing breast and tongue tumors, no technology was clearly preferred. CONCLUSIONS: In selecting IG technologies, especially optical and navigation technologies are expected to add value in addition to usual care. Further development of those technologies for the preferred indications seems valuable. Multi-attribute analysis showed to be useful in prioritization of conducting clinical studies and steer research and development initiatives.

Supporting participation in paid work of cancer survivors and their partners in the Netherlands: protocol of the SusTained Employability in cancer Patients and their partnerS (STEPS) multi-centre randomized controlled trial and cohort study.

BACKGROUND: Many cancer survivors experience physical and/or psychosocial problems affecting return to work (RTW) and work retention. Current interventions on RTW lack evidence regarding effectiveness, while interventions for work retention are missing. Partners of cancer survivors may also experience work- and health-related outcomes; yet, these consequences are not well understood. Here, the protocol of the STEPS study is described. The study aims are to: 1) evaluate the (cost-)effectiveness of a rehabilitation program for RTW and work retention in cancer survivors, and 2) assess health- and work-related outcomes among cancer survivors' partners. METHODS: In a multicentre Randomized Controlled Trial (RCT), 236 working-age cancer survivors with an employment contract will be randomly allocated to a usual care group or an intervention group receiving a multidisciplinary rehabilitation program, combining occupational therapy facilitating work retention (e.g., energy management and self-efficacy training) and reintegration consultation addressing work-related issues (e.g., RTW planning and discussing workplace or task modifications with the supervisor). Alongside the RCT, a prospective cohort study will be conducted among cancer survivors' partners (n = 267). Participants in the RCT and cohort study will be asked to complete questionnaires at baseline, and after six and 12 months, assessing work- and health-related outcomes. Generalized estimating equations will be used to assess intervention's effectiveness, compared to usual care, regarding primary (i.e., working hours per week) and secondary outcomes. Also economic and process evaluations will be performed. For the cohort study, logistic or linear regression modelling will be applied assessing work- and health-related outcomes (primary outcome: working hours) of cancer survivors' partners, and what factors predict these outcomes. RESULTS: The study is planned to start in September 2021; results are expected in 2023. CONCLUSION: Compared to usual care, the STEPS intervention is hypothesized to be (cost-)effective and the intervention could be a valuable addition to standard care helping cancer survivors to sustain employment. Further, it is expected that living with a cancer survivor has a substantial impact on work and health of partners, while specific groups of partners that are at particular risk for this impact are likely to be identified. TRIAL REGISTRATION: Dutch Trial Register ( NTR;NL9094 ; 15-12-2020).

Evaluating different adoption scenarios for TIL-therapy and the influence on its (early) cost-effectiveness.

BACKGROUND: Treatment with tumor-Infiltrating Lymphocytes (TIL) is an innovative therapy for advanced melanoma with promising clinical phase I/II study results and likely beneficial cost-effectiveness. As a randomized controlled trial on the effectiveness of TIL therapy in advanced melanoma compared to ipilimumab is still ongoing, adoption of TIL therapy by the field is confronted with uncertainty. To deal with this, scenario drafting can be used to identify potential barriers and enables the subsequent anticipation on these barriers. This study aims to inform adoption decisions of TIL by evaluating various scenarios and evaluate their effect on the cost-effectiveness. METHODS: First, 14 adoption scenarios for TIL-therapy were drafted using a Delphi approach with a group of involved experts. Second, the likelihood of the scenarios taking place within 5 years was surveyed among international experts using a web-based questionnaire. Third, based on the questionnaire results and recent literature, scenarios were labeled as being either "likely" or "-unlikely". Finally, the cost-effectiveness of TIL treatment involving the "likely" scored scenarios was calculated. RESULTS: Twenty-nine experts from 12 countries completed the questionnaire. The scenarios showed an average likelihood ranging from 29 to 58%, indicating that future developments of TIL-therapy were surrounded with quite some uncertainty. Eight of the 14 scenarios were labeled as "likely". The net monetary benefit per patient is presented as a measure of cost-effectiveness, where a positive value means that a scenario is cost-effective. For six of these scenarios the cost-effectiveness was calculated: "Commercialization of TIL production" (the price was assumed to be 3 times the manufacturing costs in the academic setting) (-€51,550), "Pharmaceutical companies lowering the prices of ipilimumab" (€11,420), "Using TIL-therapy combined with ipilimumab" (-€10,840), "Automatic TIL production" (€22,670), "TIL more effective" (€23,270), "Less Interleukin-2" (€20,370). CONCLUSIONS: Incorporating possible future developments, TIL-therapy was calculated to be cost-effective compared to ipilimumab in the majority of "likely" scenarios. These scenarios could function as facilitators for adoption. Contrary, TIL therapy was expected to not be cost-effective when sold at commercial prices, or when combined with ipilimumab. These scenarios should be considered in the adoption decision as these may act as crucial barriers.

Design of the PROstate cancer follow-up care in Secondary and Primary hEalth Care study (PROSPEC): a randomized controlled trial to evaluate the effectiveness of primary care-based follow-up of localized prostate cancer survivors.

BACKGROUND: In its 2006 report, From cancer patient to cancer survivor: lost in transition, the U.S. Institute of Medicine raised the need for a more coordinated and comprehensive care model for cancer survivors. Given the ever increasing number of cancer survivors, in general, and prostate cancer survivors, in particular, there is a need for a more sustainable model of follow-up care. Currently, patients who have completed primary treatment for localized prostate cancer are often included in a specialist-based follow-up care program. General practitioners already play a key role in providing continuous and comprehensive health care. Studies in breast and colorectal cancer suggest that general practitioners could also consider to provide survivorship care in prostate cancer. However, empirical data are needed to determine whether follow-up care of localized prostate cancer survivors by the general practitioner is a feasible alternative. METHODS: This multicenter, randomized, non-inferiority study will compare specialist-based (usual care) versus general practitioner-based (intervention) follow-up care of prostate cancer survivors who have completed primary treatment (prostatectomy or radiotherapy) for localized prostate cancer. Patients are being recruited from hospitals in the Netherlands, and randomly (1:1) allocated to specialist-based (N = 195) or general practitioner-based (N = 195) follow-up care. This trial will evaluate the effectiveness of primary care-based follow-up, in comparison to usual care, in terms of adherence to the prostate cancer surveillance guideline for the timing and frequency of prostate-specific antigen assessments, the time from a biochemical recurrence to retreatment decision-making, the management of treatment-related side effects, health-related quality of life, prostate cancer-related anxiety, continuity of care, and cost-effectiveness. The outcome measures will be assessed at randomization (≤6 months after treatment), and 12, 18, and 24 months after treatment. DISCUSSION: This multicenter, prospective, randomized study will provide empirical evidence regarding the (cost-) effectiveness of specialist-based follow-up care compared to general practitioner-based follow-up care for localized prostate cancer survivors. TRIAL REGISTRATION: Netherlands Trial Registry, Trial NL7068 (NTR7266). Prospectively registered on 11 June 2018.

Cost-utility, cost-effectiveness, and budget impact of Internet-based cognitive behavioral therapy for breast cancer survivors with treatment-induced menopausal symptoms.

PURPOSE: Internet-based cognitive behavioral therapy (iCBT), with and without therapist support, is effective in reducing treatment-induced menopausal symptoms and perceived impact of hot flushes and night sweats (HF/NS) in breast cancer survivors. The aim of the current study was to evaluate the cost-utility, cost-effectiveness, and budget impact of both iCBT formats compared to a waiting list control group from the Dutch healthcare perspective. METHODS: A Markov model was constructed with a 5-year time horizon. Costs and health outcomes were measured alongside a randomized controlled clinical trial and included quality-adjusted life years (QALYs), overall levels of menopausal symptoms, and perceived impact of HF/NS. Uncertainty was examined using probabilistic and deterministic sensitivity analyses, together with a scenario analysis incorporating a different perspective. RESULTS: iCBT was slightly more expensive than the waiting list control, but also more effective, resulting in incremental cost-utility ratios of €23,331/QALY and €11,277/QALY for the guided and self-managed formats, respectively. A significant reduction in overall levels of menopausal symptoms or perceived impact of HF/NS resulted in incremental costs between €1460 and €1525 for the guided and €500-€753 for the self-managed format. The estimated annual budget impact for the Netherlands was €192,990 for the guided and €74,592 for the self-managed format. CONCLUSION: Based on the current trial data, the results indicate that both guided and self-managed iCBT are cost-effective with a willingness-to-pay threshold of well below €30,000/QALY. Additionally, self-managed iCBT is the most cost-effective strategy and has a lower impact on healthcare budgets.

Study protocol of a prospective multicenter study comparing (cost-)effectiveness of a tailored interdisciplinary head and neck rehabilitation program to usual supportive care for patients treated with concomitant chemo- or bioradiotherapy.

BACKGROUND: Since 2011, a tailored, interdisciplinary head and neck rehabilitation (IHNR) program, covered by the basic healthcare insurance, is offered to advanced head and neck cancer (HNC) patients in the Netherlands Cancer Institute (NKI). This program is developed to preserve or restore patients' functioning, and to optimize health-related quality of life (HRQoL). It applies an integrated approach to define patients' individual goals and provide rehabilitation care throughout the cancer care continuum. The aim of the current study is to assess the (cost-) effectiveness of the IHNR approach compared to usual supportive care (USC) consisting of monodisciplinary and multidisciplinary care in advanced HNC patients. METHODS: This multicenter prospective observational study is designed to compare (cost-)effectiveness of the IHNR to USC for advanced HNC patients treated with chemoradiotherapy (CRT) or bioradiotherapy (BRT). The primary outcome is HRQoL represented in the EORTC QLQ-C30 summary score. Functional HRQoL, societal participation, utility values, return to work (RTW), unmet needs (UN), patient satisfaction and clinical outcomes are secondary outcomes, assessed using the EORTC QLQ-H&N35, USER-P, EQ-5D-5 L, and study-specific questionnaires, respectively. Both patient groups (required sample size: 64 per arm) are requested to complete the questionnaires at: diagnosis (baseline; T0), 3 months (T1), 6 months (T2), 9 months (T3) and 12 months (T4) after start of medical treatment. Differences in outcomes between the intervention and control group will be analyzed using mixed effects models, Chi-square test and descriptive statistics. In addition, a cost-effectiveness analysis (CEA) will be performed by means of a Markov decision model. The CEA will be performed using a societal perspective of the Netherlands. DISCUSSION: This prospective multicenter study will provide evidence on the effectiveness and cost-effectiveness of IHNR compared to USC. RTW and societal participation, included as secondary outcomes, have not been studied sufficiently yet in cancer rehabilitation. Interdisciplinary rehabilitation has not yet been implemented as usual care in all centers, which offers the opportunity to perform a controlled clinical study. If demonstrated to be (cost-)effective, national provision of the program can probably be advised. TRIAL REGISTRATION: The study has been retrospectively registered in the Netherlands Trial Registry on April 24th 2018 ( NTR7140 ).

The impact of an online patient decision aid for women with breast cancer considering immediate breast reconstruction: study protocol of a multicenter randomized controlled trial.

BACKGROUND: Most breast cancer patients undergoing mastectomy are candidates for breast reconstruction. Deciding about breast reconstruction is complex and the preference-sensitive nature of this decision requires an approach of shared decision making between patient and doctor. Women considering breast reconstruction have expressed a need for decision support. We developed an online patient decision aid (pDA) to support decision making in women considering immediate breast reconstruction. The primary aim of this study is to assess the impact of the pDA in reducing decisional conflict, and more generally, on the decision-making process and the decision quality. Additionally, we will investigate the pDA's impact on health outcomes, explore predictors, and assess its cost-effectiveness. METHODS: A multicenter, two-armed randomized controlled trial (1:1) will be conducted. Women with breast cancer or ductal carcinoma in situ who will undergo a mastectomy and are eligible for immediate breast reconstruction will be invited to participate. The intervention group will receive access to the online pDA, whereas the control group will receive a widely available free information leaflet on breast reconstruction. Participants will complete online questionnaires at: baseline (T0), 1 week after consultation with a plastic surgeon (T1), and 3 (T2) and 12 months (T3) after surgery. The primary outcome is decisional conflict. Secondary outcomes include other measures reflecting the decision-making process and decision quality (e.g., decision regret), patient-reported health outcomes (e.g., satisfaction with the breasts) and costs. DISCUSSION: This study will provide evidence about the impact of an online pDA for women who will undergo mastectomy and are deciding about breast reconstruction. It will contribute to the knowledge on how to optimally support women in making this difficult decision. TRIAL REGISTRATION: This study is retrospectively registered at ClinicalTrials.gov ( NCT03791138 ).