bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective pooled analysis of six phase III trials investigating duration of adjuvant (adjuv) oxaliplatin-based therapy (3 vs 6 months) for patients (pts) with stage III colon cancer (CC): The IDEA (International Duration Evaluation of Adjuvant chemotherapy) collaboration.
Authors: Shi Qian , Sobrero Alberto F. , Shields Anthony Frank , Yoshino Takayuki , Paul James , Taieb Julien , Sougklakos Ioannis , Kerr Rachel , Labianca Roberto , Meyerhardt Jeffrey A. , Bonnetain Franck , Watanabe Toshiaki , Boukovinas Ioannis , Renfro Lindsay A. , Grothey Axel , Niedzwiecki Donna , Torri Valter , Andre Thierry , Sargent Daniel J. , Iveson Timothy 
Published: June 2017

LBA1 Background: Since 2004, 6 months (m) of oxaliplatin (oxali)-based treatment has been the standard of care as adjuvant therapy for stage III CC. Since oxali is associated with cumulative neurotoxicity, shorter duration of adjuv therapy could spare pts toxicity and lead to substantial saving in health expenditures. Methods: A prospective, pre-planned pooled analysis of 6 concurrently conducted randomized phase III trials (SCOT, TOSCA, Alliance/SWOG 80702, IDEA France (GERCOR/PRODIGE), ACHIEVE, HORG) was performed to evaluate the non-inferiority (NI) of 3m compared with 6m (ref) of adjuv FOLFOX/XELOX. The primary endpoint was disease-free survival (DFS), defined as time from enrolment to relapse, 2nd CRC, and death (all causes). NI was to be declared if the 2-sided 95% confidence interval (CI) for DFS hazard ratio (HR 3m v 6m) estimated by a stratified Cox model was below 1.12. NI was examined within regimen and stage subgroups as pre-planned. Results: The analysis included 12,834 pts from 12 countries, accrued from 6/07 to 12/15. Stage distribution: 13% T1-2, 66% T3, 21% T4; 28% N2; 40% received XELOX. G3+ neurotoxicity was higher in the 6m v 3m arm (16 v 3% FOLFOX, 9 v 3% XELOX, p<0.0001). With a median follow-up of 39 mos, 3263 DFS events were observed. Overall, the 3 year DFS rate was 74.6% (3m) and 75.5% (6m), with estimated DFS HR of 1.07 (95%CI, 1.00-1.15). The 3m v 6m DFS HRs were 1.16 (95%CI, 1.06-1.26) and 0.95 (95% CI, 0.85-1.06) for FOLFOX and XELOX treated pts, respectively. The 3m v 6m DFS HRs were 1.01 (95%CI, 0.90-1.12) in T1-3 N1, and 1.12 (95%CI, 1.03-1.23) for T4 or N2 pts. Conclusions: While NI was not established for the overall cohort, NI of 3m v 6m oxali-based adjuv therapy was supported for XELOX. As each IDEA trial treated varying proportions of pts with XELOX (0 to 75%), the regimen interaction likely produced the differential outcomes observed between individual studies. Certain substages (T1-3 N1) also showed NI for 3m v 6m. These data provide a framework for discussions on risks and benefits of individualized adjuv therapy approaches. Support: U10CA180821, U10CA180882, U10CA180888, U10CA180835, INCA, PHRC2009, EME 09/800/34, HTA 14/140/84, CRUK C1348/A15960, JFMC. Clinical trial information: NCT01150045.
Web-based stress management for newly diagnosed cancer patients (STREAM): A randomized, wait-list controlled intervention study.
Authors: Hess Viviane , Grossert Astrid , Alder Judith , Scherer Sandra , Handschin Barbara , Borislavova Borislava , Degen Sven , Faessler Alexandra , Hartung Jennifer , Schibli Sarah , Werndli Celine , Gaab Jens , Berger Thomas , Zumbrunn Thomas , Urech Corinne 
Published: June 2017

LBA10002 Background: Being diagnosed with cancer causes major distress, yet the majority of newly diagnosed cancer patients (pts) lack psychological support. Internet interventions overcome many barriers for seeking support. We assess efficacy and feasibility of a web-based minimal-contact stress management intervention (STREAM) for newly diagnosed cancer pts. Methods: In a prospective, wait-list controlled trial, newly diagnosed cancer pts were randomized within 12 weeks of starting anti-cancer treatment to an immediate or delayed (control group) 8-week, web-based intervention. The intervention consisted of 8 modules with weekly written feedback by a psychologist (“minimal-contact”) based on well-established stress management manuals. The aim of this study was to evaluate efficacy in terms of improvement in QoL (FACIT-F), decrease in distress (DT), anxiety/depression (HADS), as compared to pts in the wait-list group. 120 pts were needed to show (80% power, 2-sided α of 0.05) a clinically meaningful difference of ≥ 9 in FACT score after the immediate intervention (week 8 = T2). Results: 225 pts applied online. 128 pts were randomized. Median age was 52 (22-77)y. 108 (84%) were female. The majority of pts were treated in the curative setting (117pts; 91%), with chemotherapy (74 pts; 58%), for breast cancer (91pts; 71%). Self-reported distress at baseline ( = stratification factor) was above 4 on a 10-point scale (DT) with 96 pts (75%). At T2, QoL (FACIT-F) was sign. increased (p = 0.044; ANCOVA adjusted for baseline-distress) and distress sign. lowered (p = 0.032) in the intervention group as compared to the wait-list control. Median score (lower/upper quartile) for FACIT-F at baseline/T2 was 101.0(80.8/120)/119.0(98.0/132) and 108.3(87.8/124.0) /109.5(97.2/121.0); of DT at baseline/T2 was 6(5/8)/4(3/6) and 6(5/8)/6(4/7) for the intervention and control group, respectively. Decrease in HADS was not sign. different between the groups (p = 0.273). Conclusions: With STREAM, we open the field of minimal-contact online interventions to newly diagnosed cancer pts and show that an 8-week web-based stress management program is feasible and effective in improving QoL and distress. Clinical trial information: NCT02289014.
Adverse health outcomes in relationship to hypogonadism (HG) after platinum-based chemotherapy: A multicenter study of North American testicular cancer survivors (TCS).
Authors: Abu Zaid Mohammad Issam , Menendez Alvaro G. , El Charif Omar , Fung Chunkit , Monahan Patrick O. , Feldman Darren R. , Hamilton Robert James , Vaughn David J. , Beard Clair , Cook Ryan , Althouse Sandra K. , Sesso Howard D. , Ardeshirrouhanifard Shirin , Dinh Paul C , Einhorn Lawrence , Fosså Sophie , Travis Lois B. ,   For the Platinum Study Group
Published: June 2017

LBA10012 Background: HG affects a substantial percentage of TCS and can contribute to significant morbidity, but few studies have examined the relationship between HG and adverse health outcomes (AHO), taking into account genetic variation. Methods: Eligible TCS were < 55 y at diagnosis and treated with only first line chemotherapy after 1990. TCS underwent physical exams and genotyping, and completed questionnaires regarding 16 AHO and health behaviors. HG was defined as serum testosterone ≤ 3.0 ng/mL or the use of testosterone replacement therapy. Results: We evaluated 491 TCS. Median age at evaluation was 38 y (range 19-68). 38.5% had HG. Two SNPs in the sex-hormone-binding globulin ( SHBG) locus previously implicated in increased HG risk in the general population (Ohlsson et al, PLOS Genetics 2011) displayed effect sizes consistent with prior reports (rs6258, OR = 1.3; rs12150660, OR = 0.79), but were not statistically significant. However, TCS with ≥ 2 risk alleles for the two SNPs in the SHBG locus vs no risk alleles had 2-fold increased risk for HG (OR = 2.2, P = .12). Multivariate analysis identified risk factors for HG including: age (OR = 1.4 per 10 year increase, P = .007), and BMI ≥ 25 kg/m2 (OR = 2.2, P = .003). Vigorous-intensity physical activity appeared protective (OR = 0.6, P = .06). Type of chemotherapy regimen and socioeconomic factors did not correlate with HG. Only 35% of TCS with HG vs 49% of those without HG reported none or 1 AHO ( P = .003). TCS with HG were more likely to take medications for dyslipidemia (20% vs 6%, P < .001), hypertension (19% vs 11%, P = .01), erectile dysfunction (ED) (20% vs 12%, P = .02), diabetes (6% vs 3%, P = .07), or anxiety/depression (15% vs 10%, P = 0.06) compared to TCS with normal levels, and also to have peripheral neuropathy (PN) (31% vs 23%, P = .04). HG status did not correlate with oto- or renal toxicity. Conclusions: Over a third of TCS have HG at a relatively young age. HG was associated with increased cardiovascular disease risk factors, ED, and PN. SHBG polymorphisms appear important in TCS, but our study was underpowered to confirm an association. Providers should screen TCS for HG and treat those who are symptomatic.
Temporal trends in chronic disease among survivors of childhood cancer diagnosed across three decades: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Gibson Todd M. , Mostoufi-Moab Sogol , Stratton Kayla , Barnea Dana , Chow Eric Jessen , Donaldson Sarah S. , Howell Rebecca M. , Hudson Melissa M. , Leisenring Wendy M. , Mahajan Anita , Nathan Paul C. , Ness Kirsten K. , Sklar Charles A. , Tonorezos Emily S. , Weldon Christopher Bertero , Wells Elizabeth M. , Yasui Yutaka , Armstrong Gregory T. , Robison Leslie L. , Oeffinger Kevin C. 
Published: June 2017

LBA10500 Background: Modifications in childhood cancer treatments in recent decades have contributed to reductions in late mortality among 5-year survivors. We used the recently expanded CCSS cohort to investigate whether these changes have also reduced the incidence of chronic disease. Methods: We evaluated the incidence of severe, disabling/life-threatening, or fatal chronic health conditions (Common Terminology Criteria for Adverse Events, CTCAE grades 3-5) among 5-year survivors diagnosed prior to age 21 years from 1970 through 1999. We calculated the 15-year cumulative incidence of chronic health conditions by decade of cancer diagnosis and compared risk across decades using Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results: Among 23,601 survivors, median age 28 years (range 5-63), 21 years from diagnosis (5-43), the 15-year cumulative incidence of grade 3-5 conditions decreased from 12.7% in survivors diagnosed in the 1970s to 10.1% and 8.8% in those diagnosed in the 1980s and 1990s (per 10 years, HR 0.84 [95% CI = 0.80-0.89]). The association with diagnosis decade was attenuated (HR 0.92 [0.85-1.00]) when detailed treatment data were included in the model, indicating that treatment reductions mediated risk. Adjusted for sex and attained age, significant reduction in risk over time was found among survivors of Wilms tumor (HR 0.57 [0.46-0.70]), Hodgkin lymphoma (HR 0.75 [0.65-0.85]), astrocytoma (HR 0.77 [0.64-0.92]), non-Hodgkin lymphoma (HR 0.79 [0.63-0.99]), and acute lymphoblastic leukemia (HR 0.86 [0.76-0.98]). Decreases were largely driven by a reduced incidence of endocrine conditions (1970s: 4.0% v. 1990s:1.6%; HR 0.66 [0.59-0.73]) and subsequent malignant neoplasms (1970s: 2.4% v. 1990s: 1.6%; HR 0.85 [0.76-0.96]). Significant reductions were also found for gastrointestinal (HR 0.80 [0.66-0.97]) and neurological conditions (HR 0.77 [0.65-0.91]), but not cardiac or pulmonary conditions. Conclusions: Changes in childhood cancer treatment protocols have not only extended lifespan for many survivors, but have also reduced the incidence of serious chronic morbidity in this population.
LATITUDE: A phase III, double-blind, randomized trial of androgen deprivation therapy with abiraterone acetate plus prednisone or placebos in newly diagnosed high-risk metastatic hormone-naive prostate cancer.
Authors: Fizazi Karim , Tran Namphuong , Fein Luis Enrique , Matsubara Nobuaki , Rodríguez Antolín Alfredo , Alekseev Boris Y. , Ozguroglu Mustafa , Ye Dingwei , Feyerabend Susan , Protheroe Andrew , De Porre Peter , Kheoh Thian , Park Youn C. , Todd Mary Beth , Chi Kim N. ,   On Behalf of the LATITUDE Investigators
Published: June 2017

LBA3 Background: Pts with newly diagnosed mHNPC, particularly with high-risk characteristics, have a poor prognosis. ADT+docetaxel showed improved outcomes in mHNPC, but many pts are not candidates for docetaxel and may benefit from alternative therapy. AA+P is indicated for metastatic castration-resistant prostate cancer pts. LATITUDE evaluates clinical benefit of early intervention with AA+P added to ADT in newly diagnosed, high-risk mHNPC pts. Methods: 1199 pts with newly diagnosed (≤ 3 mos prior to randomization) mHNPC (ECOG PS 0-2) with ≥ 2 of 3 risk factors (Gleason ≥ 8, ≥ 3 bone lesions, measurable visceral metastases) were randomized 1:1 to ADT+AA (1 g QD) + P (5 mg QD) or ADT+PBOs of AA and P. Co-primary end points were overall survival (OS) and radiographic progression-free survival (rPFS). One rPFS (~565 events), 2 interim, and 1 final OS analyses (~426, ~554, and ~852 events) were planned. Results: At this first interim analysis (median follow-up of 30.4 mos; 406 deaths [48%]; 593 rPFS events), OS, rPFS, and all secondary end points significantly favored ADT+AA+P (Table). The IDMC unanimously recommended unblinding the study and crossing pts to ADT+AA+P. Grade 3/4 adverse events (ADT+AA+P vs ADT+PBOs) (%): hypertension (20.3 vs 10.0); hypokalemia (10.4 vs 1.3); increased ALT (5.5 vs 1.3) or AST (4.4 vs 1.5). Conclusions: Early use of AA+P added to ADT in pts with high-risk mHNPC yielded significantly improved OS, rPFS, and all secondary end points vs ADT+PBOs alone. ADT+AA+P had a favorable risk/benefit ratio and supports early intervention with AA+P in newly diagnosed, high-risk mHNPC. Clinical trial information: NCT01715285. [Table: see text]
Durable remissions with BCMA-specific chimeric antigen receptor (CAR)-modified T cells in patients with refractory/relapsed multiple myeloma.
Authors: Fan Frank (Xiaohu) , Zhao Wanhong , Liu Jie , He Aili , Chen Yinxia , Cao Xingmei , Yang Nan , Wang Baiyan , Zhang Pengyu , Zhang Yilin , Wang Fangxia , Lei Bo , Gu Liufang , Wang Xugeng , Zhuang Qiuchuan , Zhang Wanggang 
Published: June 2017

LBA3001 Background: Chimeric antigen receptor engineered T cell (CAR-T) is a novel immunotherapeutic approach for cancer treatment and has been clinically validated in the treatment of acute lymphoblastic leukemia (ALL). Here we report an encouraging breakthrough of treating multiple myeloma (MM) using a CAR-T designated LCAR-B38M CAR-T, which targets principally BCMA. Methods: A single arm clinical trial was conducted to assess safety and efficacy of this approach. A total of 19 patients with refractory/relapsed multiple myeloma were included in the trial. The median number of infused cells was 4.7 (0.6 ~ 7.0) × 10e6/ kg. The median follow-up times was 208 (62 ~ 321) days. Results: Among the 19 patients who completed the infusion, 7 patients were monitored for a period of more than 6 months. Six out of the 7 achieved complete remission (CR) and minimal residual disease (MRD)-negative status. The 12 patients who were followed up for less than 6 months met near CR criteria of modified EBMT criteria for various degrees of positive immunofixation. All these effects were observed with a progressive decrease of M-protein and thus expected to eventually meet CR criteria. In the most recent follow-up examination, all 18 survived patients were determined to be free of myeloma-related biochemical and hematologic abnormalities. One of the most common adverse event of CAR-T therapy is acute cytokine release syndrome (CRS). This was observed in 14 (74%) patients who received treatment. Among these 14 patients there were 9 cases of grade 1, 2 cases of grade 2, 1 case of grade 3, and 1 case of grade 4 patient who recovered after treatments. Conclusions: A 100% objective response rate (ORR) to LCAR-B38M CAR-T cells was observed in refractory/relapsed myeloma patients. 18 out of 19 (95%) patients reached CR or near CR status without a single event of relapse in a median follow-up of 6 months. The majority (14) of the patients experienced mild or manageable CRS, and the rest (5) were even free of diagnosable CRS. Based on the encouraging safety and efficacy outcomes, we believe that our LCAR-B38M CAR-T cell therapy is an innovative and highly effective treatment for multiple myeloma.
OlympiAD: Phase III trial of olaparib monotherapy versus chemotherapy for patients (pts) with HER2-negative metastatic breast cancer (mBC) and a germline BRCA mutation (gBRCAm).
Authors: Robson Mark E. , Im Seock-Ah , Senkus Elżbieta , Xu Binghe , Domchek Susan M. , Masuda Norikazu , Delaloge Suzette , Li Wei , Tung Nadine M. , Armstrong Anne , Wu Wenting , Goessl Carsten Dietrich , Runswick Sarah , Conte Pier Franco 
Published: June 2017

LBA4 Background: Olaparib is an oral PARP inhibitor with anti-tumor activity in HER2-negative mBC with a g BRCAm (NCT00494234). OlympiAD (NCT02000622) was a randomized, open-label, phase III study that assessed efficacy and safety of olaparib vs standard single agent chemotherapy treatment of physician’s choice (TPC) in pts with HER2-negative mBC and a g BRCAm. Methods: Pts aged ≥18 y with HER2-negative mBC (hormone receptor positive or triple negative [TN]) and a g BRCAm, who had received ≤2 chemotherapy lines for mBC, were randomized (2:1) to olaparib tablets (300 mg po bid) or TPC (21-day cycles of either capecitabine [2500 mg/m2 po days 1–14], vinorelbine [30 mg/m2 IV days 1 and 8] or eribulin [1.4 mg/m2IV days 1 and 8]). Treatment was continued until objective disease progression (RECIST v1.1) or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review (BICR). Results: 302 pts were randomized (median age 44 y; 50% TN; 71% prior chemotherapy for mBC; 28% prior platinum) of whom 205 received olaparib and 91 received TPC (6 TPC pts were not treated). At 77% data maturity, PFS by BICR was significantly longer in pts treated with olaparib vs TPC (HR 0.58; 95% CI 0.43, 0.80; P=0.0009; 7.0 vs 4.2 months, respectively). Time to second progression (investigator-assessed) was also longer in the olaparib arm (HR 0.57; 95% CI 0.40, 0.83). Objective response rate was 59.9 and 28.8% in olaparib and TPC arms, respectively. Grade ≥3 adverse events (AE) occurred in 36.6 and 50.5% of olaparib and TPC pts, with AEs leading to discontinuation in 4.9 and 7.7% of pts, respectively. Mean change from baseline in global health-related quality of life (HRQoL, EORTC-QLQ-C30) across all timepoints favored olaparib (difference vs TPC 7.5; 95% CI 2.48, 12.44; P=0.0035). Conclusions: Olaparib tablet monotherapy provided a statistically significant and clinically meaningful PFS benefit to HER2-negative mBC pts with a g BRCAm, compared to standard TPC. The safety profile of olaparib was consistent with prior studies. The efficacy benefit was seen beyond the first progression and HRQoL also improved. Clinical trial information: NCT02000622.
Alectinib versus crizotinib in treatment-naive advanced ALK-positive non-small cell lung cancer (NSCLC): Primary results of the global phase III ALEX study.
Authors: Shaw Alice Tsang , Peters Solange , Mok Tony , Gadgeel Shirish M. , Ahn Jin Seok , Ou Sai-Hong Ignatius , Perol Maurice , Dziadziuszko Rafal , Kim Dong-Wan , Rosell Rafael , Zeaiter Ali Hassan , Liu Ting , Golding Sophie , Balas Bogdana , Noé Johannes , Morcos Peter N. , Camidge D. Ross 
Published: June 2017

LBA9008 Background: Alectinib, a TKI targeting ALK, has shown robust efficacy in crizotinib-naïve/resistant ALK+ NSCLC. J-ALEX showed superiority of alectinib 300mg BID vs crizotinib in Japanese pts with crizotinib-naïve ALK+ NSCLC (progression-free survival [PFS] HR 0.34, p<0.0001). We report primary results from the ALEX study of first-line alectinib 600mg BID vs crizotinib in advanced ALK+ NSCLC (NCT02075840). Methods: This open-label randomized multicenter phase III study enrolled pts with stage IIIB/IV ALK+ NSCLC, determined by central IHC testing. Eligible pts had ECOG PS 0–2 and no prior systemic therapy for advanced NSCLC. Pts with asymptomatic CNS metastases were allowed. Pts (n=303) were randomized 1:1 to receive alectinib 600mg or crizotinib 250mg BID. Primary endpoint: Investigator (Inv)-assessed PFS (RECIST v1.1), with systematic CNS imaging in all pts. Secondary endpoints included independent review committee (IRC)-assessed PFS, IRC-assessed time to CNS progression (TTP), objective response rate (ORR), overall survival (OS) and safety. Results: At the primary data cut-off (9 Feb 2017), alectinib demonstrated statistically significant superiority vs crizotinib, reducing risk of progression/death by 53% (HR 0.47, 95% CI 0.34–0.65, p<0.0001); alectinib median PFS was not reached (95% CI 17.7–NE) vs crizotinib 11.1 months (95% CI 9.1–13.1). Key secondary endpoints showed superiority for alectinib vs crizotinib, respectively: IRC PFS, HR 0.50 (95% CI 0.36–0.70; p<0.0001); median PFS 25.7 months (95% CI 19.9–NE) vs 10.4 months (95% CI 7.7–14.6); CNS TTP, cause-specific HR of CNS progression 0.16 (95% CI 0.10–0.28; p<0.0001); ORR (Inv) 83% (95% CI 76–89) vs 76% (95% CI 68–82), p=0.09; OS, based on 25% events, HR 0.76 (95% CI 0.48–1.20; p=0.24). Grade 3/4 AEs were less frequent with alectinib, 41%, vs 50% with crizotinib; fatal AEs occurred in 3% vs 5%, respectively. Rates of AEs leading to discontinuation, dose reduction and interruption were lower with alectinib. Conclusions: Alectinib showed superior efficacy and favorable tolerability compared with crizotinib. ALEX results support alectinib as a new standard of care for treatment-naïve ALK+ NSCLC. Funding: F. Hoffmann-La Roche Clinical trial information: NCT02075840.
Notch2 and Notch3 suppress the proliferation and mediate invasion of trophoblast cell lines
Authors: Zhao Wei-Xiu , Wu Zhen-Ming , Liu Wei , Lin Jian-Hua 
Published: June 2017

ABSTRACT
Notch signaling pathways play important roles in cell fate and many diseases, including preeclampsia, the dysregulation of which may be the main cause of maternal mortality. This study aimed to investigate the roles of Notch2 and Notch3 in proliferation and invasion in trophoblast cell lines (BeWo and JAR). Small hairpin RNAs targeting Notch2/Notch3 and Notch2/Notch3-overexpression vectors were designed, constructed and transfected into BeWo and JAR cells. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were then used to detect Notch2 and Notch3 mRNA and protein levels, and confirm the efficiency of silence and overexpression. Flow cytometry assays were conducted to evaluate the cell cycle of the two cell lines, and transwell assays were used to detect migration and invasion. Western blot analysis was also performed to show the alteration of the cell lines' physiological activities at protein level.
When Notch2 was downregulated in BeWo cells, proliferation was dramatically promoted, while migration and invasion were significantly inhibited. When Notch2 was upregulated in JAR cells, proliferation was inhibited, but migration and invasion were promoted. After overexpression of Notch3 in BeWo cells, proliferation was downregulated, but migration and invasion were both upregulated. By contrast, the silencing of Notch3 expression in JAR cells significantly enhanced proliferation, but suppressed migration and invasion. These data indicated that Notch2 and Notch3 mediate the invasion and migration of BeWo and JAR cells, and may play a potential role in early onset severe preeclampsia.
Game—The BedGame—A Classroom Game Based on Real Healthcare Challenges
Authors: Vliegen I. M. H. , Zonderland M. E. 
Published: June 2017

The BedGame is a classroom game to introduce Operations Management (OM) in healthcare, more specifically to introduce the effects of centralized versus decentralized planning, and the concepts of variability and queueing theory. In the BedGame, players assign medical and surgical specialties to nursing wards to obtain a balanced bed distribution, while fulfilling as many of the specialty-specific requirements as possible. The game was first designed to support decision making in a hospital in The Netherlands, and afterwards converted to a classroom game. The game has been successfully used in several courses at the University of Twente including “Operations Management in Health Care” (undergraduate), “Quantitative Methods for Operations Management in Health Care” (graduate), and a course on patient logistics for healthcare professionals. The online appendices are available at https://doi.org/10.1287/ited.2016.0172 .