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... Show moreBACKGROUND 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 5x10(9) 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. Show less
Byng, D.; Retel, V.P.; Engelhardt, E.G.; Groothuis-Oudshoorn, C.G.M.; Til, J.A. van; Schmitz, R.S.J.M.; ... ; Grand Challenge Precision Consorti 2021
Simple Summary Preferences for treatment strategies for low-risk ductal carcinoma in situ (DCIS), a potential precursor of invasive breast cancer (IBC) including a new active surveillance strategy,... Show moreSimple Summary Preferences for treatment strategies for low-risk ductal carcinoma in situ (DCIS), a potential precursor of invasive breast cancer (IBC) including a new active surveillance strategy, were elicited with a discrete choice experiment among recently-diagnosed women and oncologists involved in the care of women with DCIS. Patients exhibited strong preferences for active surveillance and seemed prepared to accept much higher levels of 10-year risk of developing ipsilateral invasive breast cancer than oncologists. Both patients and oncologists showed a strong aversion toward more extensive locoregional treatments (i.e., breast conserving surgery followed by radiotherapy, and mastectomy), while both groups demonstrated a strong preference toward shorter follow-up intervals.As ongoing trials study the safety of an active surveillance strategy for low-risk ductal carcinoma in situ (DCIS), there is a need to explain why particular choices regarding treatment strategies are made by eligible women as well as their oncologists, what factors enter the decision process, and how much each factor affects their choice. To measure preferences for treatment and surveillance strategies, women with newly-diagnosed, primary low-risk DCIS enrolled in the Dutch CONTROL DCIS Registration and LORD trial, and oncologists participating in the Dutch Health Professionals Study were invited to complete a discrete choice experiment (DCE). The relative importance of treatment strategy-related attributes (locoregional intervention, 10-year risk of ipsilateral invasive breast cancer (iIBC), and follow-up interval) were discerned using conditional logit models. A total of n = 172 patients and n = 30 oncologists completed the DCE. Patient respondents had very strong preferences for an active surveillance strategy with no surgery, irrespective of the 10-year risk of iIBC. Extensiveness of the locoregional treatment was consistently shown to be an important factor for patients and oncologists in deciding upon treatment strategies. Risk of iIBC was least important to patients and most important to oncologists. There was a stronger inclination toward a twice-yearly follow-up for both groups compared to annual follow-up. Show less
Doorn-Khosrovani, S.B.V. van; Pisters-van Roy, A.; Saase, L. van; Graaff, M. van der; Gijzen, J.; Sleijfer, S.; ... ; Voest, E.E. 2019
BACKGROUND\nReturn-to-work (RTW)-interventions support cancer survivors in resuming work, but come at additional healthcare costs. The objective of this study was to assess the budget impact of a... Show moreBACKGROUND\nReturn-to-work (RTW)-interventions support cancer survivors in resuming work, but come at additional healthcare costs. The objective of this study was to assess the budget impact of a RTW-intervention, consisting of counselling sessions with an occupational physician and an exercise-programme. The secondary objective was to explore how the costs of RTW-interventions and its financial revenues are allocated among the involved stakeholders in several EU-countries.\nMETHODS\nThe budget impact (BI) of a RTW-intervention versus usual care was analysed yearly for 2015-2020 from a Dutch societal- and from the perspective of a large cancer centre. The allocation of the expected costs and financial benefits for each of the stakeholders involved was compared between the Netherlands, Belgium, England, France, Germany, Italy, and Sweden.\nRESULTS\nThe average intervention costs in this case were €1,519/patient. The BI for the Netherlands was €-14.7 m in 2015, rising to €-71.1 m in 2020, thus the intervention is cost-saving as the productivity benefits outweigh the intervention costs. For cancer centres the BI amounts to €293 k in 2015, increasing to €1.1 m in 2020. Across European countries, we observed differences regarding the extent to which stakeholders either invest or receive a share of the benefits from offering a RTW-intervention.\nCONCLUSION\nThe RTW-intervention is cost-saving from a societal perspective. Yet, the total intervention costs are considerable and, in many European countries, mainly covered by care providers that are not sufficiently reimbursed. Show less
Retel, V.P.; Molen, L. van der; Hilgers, F.J.M.; Rasch, C.R.N.; L'Ortye, A.A.A.M.H.J.; Steuten, L.M.G.; Harten, W.H. van 2011
Background: Concomitant chemo-radiotherapy (CCRT) has become an indispensable organ, but not always function preserving treatment modality for advanced head and neck cancer. To prevent/limit the... Show moreBackground: Concomitant chemo-radiotherapy (CCRT) has become an indispensable organ, but not always function preserving treatment modality for advanced head and neck cancer. To prevent/limit the functional side effects of CCRT, special exercise programs are increasingly explored. This study presents cost-effectiveness analyses of a preventive (swallowing) exercise program (PREP) compared to usual care (UC) from a health care perspective.Methods: A Markov decision model of PREP versus UC was developed for CCRT in advanced head and neck cancer. Main outcome variables were tube dependency at one-year and number of post-CCRT hospital admission days. Primary outcome was costs per quality adjusted life years (cost/QALY), with an incremental cost-effectiveness ratio (ICER) as outcome parameter. The Expected Value of Perfect Information (EVPI) was calculated to obtain the value of further research.Results: PREP resulted in less tube dependency (3% and 25%, respectively), and in fewer hospital admission days than UC (3.2 and 4.5 days respectively). Total costs for UC amounted to (sic)41,986 and for PREP to (sic)42,271. Quality adjusted life years for UC amounted to 0.68 and for PREP to 0.77. Based on costs per QALY, PREP has a higher probability of being cost-effective as long as the willingness to pay threshold for 1 additional QALY is at least (sic)3,200/QALY. At the prevailing threshold of (sic)20,000/QALY the probability for PREP being cost-effective compared to UC was 83%. The EVPI demonstrated potential value in undertaking additional research to reduce the existing decision uncertainty.Conclusions: Based on current evidence, PREP for CCRT in advanced head and neck cancer has the higher probability of being cost-effective when compared to UC. Moreover, the majority of sensitivity analyses produced ICERs that are well below the prevailing willingness to pay threshold for an additional QALY (range from dominance till (sic)45,906/QALY). Show less
