A Pilot Clinical and Technical Validation of an Immersive Virtual Reality Platform for 3D Anatomical Modeling and Contouring in Support of Surgical and Radiation Oncology Treatment Planning.

The aim of this study was to validate a novel medical virtual reality (VR) platform used for medical image segmentation and contouring in radiation oncology and 3D anatomical modeling and simulation for planning medical interventions, including surgery. The first step of the validation was to verify quantitatively and qualitatively that the VR platform can produce substantially equivalent 3D anatomical models, image contours, and measurements to those generated with existing commercial platforms. To achieve this, a total of eight image sets and 18 structures were segmented using both VR and reference commercial platforms. The image sets were chosen to cover a broad range of scanner manufacturers, modalities, and voxel dimensions. The second step consisted of evaluating whether the VR platform could provide efficiency improvements for target delineation in radiation oncology planning. To assess this, the image sets for five pediatric patients with resected standard-risk medulloblastoma were used to contour target volumes in support of treatment planning of craniospinal irradiation, requiring complete inclusion of the entire cerebral-spinal volume. Structures generated in the VR and the commercial platforms were found to have a high degree of similarity, with dice similarity coefficient ranging from 0.963 to 0.985 for high-resolution images and 0.920 to 0.990 for lower resolution images. Volume, cross-sectional area, and length measurements were also found to be in agreement with reference values derived from a commercial system, with length measurements having a maximum difference of 0.22 mm, angle measurements having a maximum difference of 0.04°, and cross-sectional area measurements having a maximum difference of 0.16 mm2. The VR platform was also found to yield significant efficiency improvements, reducing the time required to delineate complex cranial and spinal target volumes by an average of 50% or 29 min.

Immune profiling of dedifferentiated liposarcoma and identification of novel antigens for targeted immunotherapy.

Dedifferentiated liposarcoma (DDLS) is an aggressive, recurring sarcoma with limited treatments. T-cell immunotherapies selectively target malignant cells, holding promise against DDLS. The development of successful immunotherapy for DDLS requires a thorough evaluation of the tumor immune microenvironment and the identification and characterization of targetable immunogenic tumor antigens. To assess the complexity of the human DDLS tumor immune microenvironment and to identify target antigens, we used the nCounter NanoString platform, analyzing gene expression profiles across 29 DDLS and 10 healthy adipose tissue samples. Hierarchical clustering of tumors based on expression of tumor inflammation signature genes revealed two distinct groups, consisting of 15 inflamed tumors and 14 non-inflamed tumors, demonstrating tumor heterogeneity within this sarcoma subtype. Among the identified antigens, PBK and TTK exhibited substantial upregulation in mRNA expression compared to healthy adipose tissue controls, further corroborated by positive protein expression by IHC. This data shows considerable inter-tumoral heterogeneity of inflammation, which should be taken into consideration when designing an immunotherapy for DDLS, and provides a novel targetable antigen in DDLS. The results of this study lay the groundwork for the development of a novel immunotherapy for this highly aggressive sarcoma.

Management of Ipsilateral Fractures After Rotationplasty: A Report of 2 Cases and Review of the Literature.

CASE: Rotationplasty is a surgical procedure used for restoring functionality after skeletal tumor resection. Multiple complications have been described, including the potential occurrence of fractures. Literature on fracture management after rotationplasty is limited. In this article, we present 2 cases of late ipsilateral fractures in rotated limbs successfully treated with intramedullary nailing. CONCLUSION: Effective management of fractures after rotationplasty requires thorough understanding of the rotated limb anatomy and careful planning. The clinical considerations presented in this article aim to provide guidance for surgeons to achieve successful outcomes in the management of fractures after rotationplasty.

Canakinumab in addition to phosphate-binding and phosphaturia-inducing therapy were effective in achieving remission in a child with a large familial calcinotic tumour.

We describe the clinical evolution of a patient with tumoral calcinosis due to a pathogenic variant in the GALNT3 gene presented with a large mass overlying her left hip associated complicated by inflammatory flares. Therapy (sevelamer, acetazolamide, and probenecid) was unsuccessful in preventing tumour surgeries, therefore, interleukin-1ß monoclonal antibody therapy was added; this was successful in the prevention of tumour re-growth. This case highlights the importance of assessing and treating the inflammatory aspect of calcinotic tumour.

LUMiC® endoprosthesis for pelvic reconstruction: A Canadian experience.

BACKGROUND AND OBJECTIVES: The LUMiC® prosthesis was introduced to reduce the mechanical complications encountered with periacetabular reconstruction after pelvic tumor resection. Few have evaluated the outcomes associated with its use. METHODS: A retrospective study from five Orthopedic Oncology Canadian centers was conducted. All patients with a LUMiC® endoprosthesis were included. Their charts were reviewed for surgical and functional outcomes. RESULTS: A total of 16 patients were followed for 28 months (3-60). A total of 12 patients (75%) had a LUMiC® after a resection of a primary sarcoma. Mean surgical time was 555 min. Four patients (25%) had a two-stages procedure. MSTS score was 60.3 preoperatively and 54.3 postoperatively. Patients got a dual mobility bearing and the silver coated implant was used in 7 patients (43.7%). Five patients (31.3%) underwent capsular reconstruction using a fabric. Silver-coating was not found to reduce infection risk (p = 0.61) and capsuloplasty did not prevent dislocation (p = 0.6). Five patients had peroperative complications (31.3%). Eight patients (50%) had an infection including all four with two-stages surgery. Dislocation occurred in five patients (31.3%) whereas no cases of aseptic loosening were reported. A total of 10 patients (62.5%) needed a reoperation. CONCLUSION: LUMiC® endoprosthesis provides low rates of aseptic loosening on medium-term follow-up. Infection and dislocation are common complications but we were unable to show benefits of capsuloplasty and silver-coated implants.

Enhancing COVID Rehabilitation with Technology (ECORT): protocol for an open-label, single-site randomized controlled trial evaluating the effectiveness of electronic case management for individuals with persistent COVID-19 symptoms.

BACKGROUND: As of May 2022, Ontario has seen more than 1.3 million cases of COVID-19. While the majority of individuals will recover from infection within 4 weeks, a significant subset experience persistent and often debilitating symptoms, known as "post-COVID syndrome" or "Long COVID." Those with Long COVID experience a wide array of symptoms, with variable severity, including fatigue, cognitive impairment, and shortness of breath. Further, the prevalence and duration of Long COVID is not clear, nor is there evidence on the best course of rehabilitation for individuals to return to their desired level of function. Previous work with chronic conditions has suggested that the addition of electronic case management (ECM) may help to improve outcomes. These platforms provide enhanced connection with care providers, detailed symptom tracking and goal setting, and access to relevant resources. In this study, our primary aim is to determine if the addition of ECM with health coaching improves Long COVID outcomes at 3 months compared to health coaching alone. METHODS: The trial is an open-label, single-site, randomized controlled trial of ECM with health coaching (ECM+) compared to health coaching alone (HC). Both groups will continue to receive usual care. Participants will be randomized equally to receive health coaching (± ECM) for a period of 8 weeks and a 12-week follow-up. Our primary outcome is the WHO Disability Assessment Scale (WHODAS), 36-item self-report total score. Participants will also complete measures of cognition, fatigue, breathlessness, and mental health. Participants and care providers will be asked to complete a brief qualitative interview at the end of the study to evaluate acceptability and implementation of the intervention. DISCUSSION: There is currently little evidence about the optimal treatment of Long COVID patients or the use of digital health platforms in this population. The results of this trial could result in rapid, scalable, and personalized care for people with Long COVID which will decrease morbidity after an acute infection. Results from this study will also inform decision making in Long COVID and treatment guidelines at provincial and national levels. TRIAL REGISTRATION: ClinicalTrials.gov NCT05019963. Registered on 25 August 2021.

Mammary-type myofibroblastoma of the thigh mimicking liposarcoma.

Myofibroblastoma is a rare tumor that was originally described in the breast but has since been found in extra-mammary locations, where it been renamed mammary-type myofibroblastoma (MTM). We describe a case of MTM occurring in the anterior compartment of the thigh, which was initially interpreted as a possible a liposarcoma on MRI. Two subsequent biopsy samples and eventual excision revealed the tumor to have the characteristic pathology of MTM. This benign tumor, albeit rare, needs to be considered in the imaging differential diagnosis of fat containing deep soft tissue masses of the extremity.

Immunotherapy for sarcomas: new frontiers and unveiled opportunities.

Sarcomas are a rare malignancy of mesenchymal tissues, comprizing a plethora of unique subtypes, with more than 60 types. The sheer heterogeneity of disease phenotype makes this a particularly difficult cancer to treat. Radiotherapy, chemotherapy and surgery have been employed for over three decades and, although effective in early disease (stages I-II), in later stages, where metastatic tumors are present, these treatments are less effective. Given the spectacular results obtained by cancer immunotherapy in a variety of solid cancers and leukemias, there is now a great interest in appliying this new realm of therapy for sarcomas. The widespread use of immunotherapy for sarcoma relies on immuno-profiling of subtypes, immunomonitoring for prognosis, preclinical studies and insight into the safety profile of these novel therapies. Herein, we discuss preclinical and clinical data highlighting how immunotherapy is being used in soft tissue sarcoma and bone sarcomas.

Oncolytic Rhabdovirus Vaccine Boosts Chimeric Anti-DEC205 Priming for Effective Cancer Immunotherapy.

Prime-boost vaccination employing heterologous viral vectors encoding an antigen is an effective strategy to maximize the antigen-specific immune response. Replication-deficient adenovirus serotype 5 (Ad5) is currently being evaluated clinically in North America as a prime in conjunction with oncolytic rhabdovirus Maraba virus (MG1) as a boost. The use of an oncolytic rhabdovirus encoding a tumor antigen elicits a robust anti-cancer immune response and extends survival in murine models of cancer. Given the prevalence of pre-existing immunity to Ad5 globally, we explored the potential use of DEC205-targeted antibodies as an alternative agent to prime antigen-specific responses ahead of boosting with an oncolytic rhabdovirus expressing the same antigen. We found that a prime-boost vaccination strategy, consisting of an anti-DEC205 antibody fused to the model antigen ovalbumin (OVA) as a prime and oncolytic rhabdovirus-OVA as a boost, led to the formation of a robust antigen-specific immune response and improved survival in a B16-OVA tumor model. Overall, our study shows that anti-DEC205 antibodies fused to cancer antigens are effective to prime oncolytic rhabdovirus-boosted cancer antigen responses and may provide an alternative for patients with pre-existing immunity to Ad5 in humans.

Guidance for management of cancer surgery during the COVID-19 pandemic.

Summary: During the coronavirus disease 2019 (COVID-19) pandemic, delaying lifesaving cancer surgeries must be done with extreme caution and thoughtfulness. Modelling indicates that delays in high-risk cancer surgeries beyond 6 weeks could affect long-term outcomes for thousands of Canadians. Consequently, it is possible that postponing cancer surgery without consideration of its implications could cost more lives than can be saved by diverting all surgical resources to COVID-19. This article provides general guidance on supporting curative surgical treatment where appropriate and with available resources.

An evidence-based guideline on the application of molecular testing in the diagnosis, prediction of prognosis, and selection of therapy in non-GIST soft tissue sarcomas.

AIMS: To make recommendations on the indications for molecular testing regarding the diagnosis, prediction of prognosis, and treatment selection in adult patients with s oft tissue sarcomas (STS) excluding gastrointestinal stromal tumour. MATERIALS AND METHODS: This guideline was developed by the Cancer Care Ontario's Program in Evidence-Based Care (PEBC) and the Sarcoma Disease Site Group (DSG). The medline, embase, and Cochrane Library databases, main guideline websites, abstracts of relevant annual meetings, and PROSPERO databases were searched (January 2005 to October 2016). Internal and external reviews were conducted, with final approval by the PEBC and the Sarcoma DSG. RESULTS: Based on the available evidence, we made three S trong Recommendations, 14 Recommendations, 9 Qualified Statements, and seven No Recommendations. The three Strong Recommendations include: i) MDM2 amplification by fluorescence in situ hybridization (FISH) is recommended as a sensitive and specific test to differentiate patients with atypical lipomatous tumour/well-differentiated liposarcoma, or dedifferentiated liposarcoma from lipoma or other STS in the differential diagnosis; ii) SS18 (SYT) break-apart by FISH or SS18-SSX (SYT-SSX) fusion by reverse transcription-polymerase chain reaction is recommended as a sensitive and specific test to differentiate patients with synovial sarcoma from other sarcomas; iii) CTNNB1 S45F mutation by polymerase chain reaction is recommended as a prognostic factor for poor recurrence-free survival in patients with desmoid tumours. CONCLUSION: This guideline may serve as a framework for the thoughtful implementation of molecular studies at cancer centres and other jurisdictions. Some of the recommendations may need to be updated when new evidence appears in the future.

Extended intralesional curettage preferred over resection-arthrodesis for giant cell tumour of the distal radius.

BACKGROUND: Distal radius giant cell tumour (GCT) is known to be associated with distinct management difficulties, including high rates of local recurrence and lung metastases compared to other anatomic locations. Multiple treatment options exist, each with different outcomes and complications. QUESTIONS/PURPOSES: To compare oncological and functional outcomes and complications following treatment of patients with distal radius GCT by extended intralesional curettage (EIC) or resection-arthrodesis. METHODS: Patients operated on for distal radius GCT were identified from prospectively collected databases at four Canadian musculoskeletal oncology specialty centres. There were 57 patients with a mean age of 35.4 years (range 17-57). Thirteen tumours were Campanacci grade 2, and 40 were Grade 3 (4 unknown). Twenty patients presented with an associated pathologic fracture. There were 34 patients treated by EIC and 23 by en bloc resection and wrist arthrodesis. All resections were performed for grade 3 tumours. The mean follow-up was 86 months (range 1-280). RESULTS: There were a total of 11 (19%) local recurrences: 10 of 34 (29%) in the EIC group compared to only 1 of 23 (4%) in the resection-arthrodesis group (p = 0.028). For the 10 patients with local recurrence following initial treatment by EIC, 7 underwent repeat EIC, while 3 required resection-arthrodesis. The one local recurrence following initial resection was managed with repeat resection-arthrodesis. Six of the 11 local recurrences followed treatment of Campanacci grade 3 tumours, while 4 were in grade 2 lesions and in one case of recurrence the grade was unknown. There were no post-operative complications after EIC, whereas 7 patients (30%) had post-operative complications following resection-arthrodesis including 4 infections, one malunion, one non-union and one fracture (p = 0.001). The mean post-operative Musculoskeletal Tumor Society score was 33.5 in the curettage group compared to 27 in the resection group (p = 0.001). The mean Toronto Extremity Salvage Score was 98.3% following curettage compared to 91.5% after resection (p = 0.006). No patients experienced lung metastasis or death. CONCLUSIONS: EIC is an effective alternative to wide resection-arthrodesis following treatment of distal radius GCT, with the advantage of preserving the distal radius and wrist joint function, but with a higher risk of local recurrence. Most local recurrences following initial treatment by EIC could be managed with iterative curettage and joint preservation. Wide excision and arthrodesis were associated with a significantly lower risk of tumour recurrence but was technically challenging and associated with more frequent post-operative complications. EIC was associated with better functional scores. Resection should be reserved for the most severe grade 3 tumours and recurrent and complex cases not amenable to treatment with EIC and joint salvage. LEVEL OF EVIDENCE: III, retrospective comparative trial.

Local Tumor Recurrence and Escape from Suppression of Bone Resorption With Denosumab Treatment in Two Adolescents With Giant Cell Tumors of Bone.

Giant cell tumors of bone (GCTB) may be difficult to resect because of size or location. We describe two adolescents who were treated with denosumab and followed for tumoral and biochemical responses. Denosumab was effective in achieving sufficient regression to allow surgical resection and in preserving peritumor cortical bone. Reactivation of bone resorption markers was noted while the patients were receiving monthly denosumab. One patient suffered a local tumor recurrence. Denosumab was safe in enabling surgical resection of GCTB. However, the effect was transient, with an escape of resorption markers and tumor recurrence. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

A technique for approximating transition rates from published survival analyses.

BACKGROUND: Quality-adjusted-life-years (QALYs) are used to concurrently quantify morbidity and mortality within a single parameter. For this reason, QALYs can facilitate the discussion of risks and benefits during patient counseling regarding treatment options. QALYs are often calculated using partitioned-survival modelling. Alternatively, QALYs can be calculated using more flexible and informative state-transition models populated with transition rates estimated using multistate modelling (MSM) techniques. Unfortunately the latter approach is considered not possible when only progression-free survival (PFS) and overall survival (OS) analyses are reported. METHODS: We have developed a method that can be used to estimate approximate transition rates from published PFS and OS analyses (we will refer to transition rates estimated using full multistate methods as true transition rates). RESULTS: The approximation method is more accurate for estimating the transition rates out of health than the transition rate out of illness. The method tends to under-estimate true transition rates as censoring increases. CONCLUSIONS: In this article we present the basis for and use of the transition rate approximation method. We then apply the method to a case study and evaluate the method in a simulation study.

The Pediatric Toronto Extremity Salvage Score (pTESS): Validation of a Self-reported Functional Outcomes Tool for Children with Extremity Tumors.

BACKGROUND: The physical function of children with sarcoma after surgery has not been studied explicitly. This paucity of research is partly because of the lack of a sufficiently sensitive pediatric functional measure. The goal of this study was to establish and validate a standardized measure of physical function in pediatric patients with extremity tumors. QUESTIONS/PURPOSES: (1) What is the best format and content for new upper- and lower-extremity measures of physical function in the pediatric population? (2) Do the new measures exhibit floor and/or ceiling effects, internal consistency, and test-retest reliability? (3) Are the new measures valid? METHODS: In Phase 1, interviews with 17 consecutive children and adolescents with bone tumors were conducted to modify the format and content of draft versions of the pediatric Toronto Extremity Salvage Score (pTESS). In Phase 2, the pTESS was formally translated into French. In Phase 3, 122 participants between 7 and 17.9 years old with malignant or benign-aggressive bone tumors completed the limb-specific measure on two occasions. Older adolescents also completed the adult TESS. Floor and ceiling effects, internal consistency, test-retest reliability, and validity were evaluated. RESULTS: Feedback from interviews resulted in the removal, addition, and modification of draft items, and the pTESS-Leg and pTESS-Arm questionnaires were finalized. Both versions exhibited no floor or ceiling effects and high internal consistency (α > 0.92). The test-retest reliability was excellent for the pTESS-Leg (intraclass correlation coefficient [ICC] = 0.94; 95% CI, 0.90-0.97) and good for the pTESS-Arm (ICC = 0.86; 95% CI, 0.61-0.96). Known-group validity (ability to discriminate between groups) was demonstrated by lower mean pTESS-Leg scores for participants using gait aids or braces (mean = 68; SD = 21) than for those who did not (mean = 87; SD = 11; p < 0.001). There was no significant difference between pTESS arm scores among respondents using a brace (n = 5; mean = 73; SD = 11) and those without (n = 22; mean = 83; SD = 19; p = 0.13). To evaluate construct validity, we tested a priori hypotheses. The duration since chemotherapy correlated moderately with higher pTESS-Leg scores (r = 0.4; p < 0.001) but not with pTESS-Arm scores (r = 0.1; p = 0.80), and the duration since tumor resection correlated moderately with higher pTESS-Leg scores (r = 0.4; p < 0.001) but not pTESS-Arm scores (r = 0.2; p = 0.4). Higher VAS scores (that is, it was harder to do things) antecorrelated with both pTESS versions (pTESS-Leg: r = -0.7; p < 0.001; pTESS-Arm: r = -0.8; p < 0.001). To assess criterion validity, we compared the pTESS with the current "gold standard" (adult TESS). Among adolescents, strong correlations were observed between the TESS and pTESS-Leg (r = 0.97, p < 0.001) and pTESS-Arm (r = 0.9, p = 0.007). CONCLUSIONS: Both pTESS versions exhibited no floor or ceiling effects and had high internal consistency. The pTESS-Leg demonstrated excellent reliability and validity, and the pTESS-Arm demonstrated good reliability and reasonable validity. The pTESS is recommended for cross-sectional evaluation of self-reported physical function in pediatric patients with bone tumors. LEVEL OF EVIDENCE: Level II, outcome measurement development.

A General Population Utility Valuation Study for Metastatic Epidural Spinal Cord Compression Health States.

STUDY DESIGN: General population utility valuation study. OBJECTIVE: This study obtained utility valuations from a Canadian general population perspective for 31 unique metastatic epidural spinal cord compression (MESCC) health states and determined the relative importance of MESCC-related consequences on quality-of-life. SUMMARY OF BACKGROUND DATA: Few prospective studies on the treatment of MESCC have collected quality-adjusted-life-year weights (termed "utilities"). Utilities are an important summative measure which distills health outcomes to a single number that can assist healthcare providers, patients, and policy makers in decision making. METHODS: We recruited a sample of 1138 adult Canadians using a market research company. Quota sampling was used to ensure that the participants were representative of the Canadian population in terms of age, sex, and province of residence. Using the validated MESCC module for the "Self-administered Online Assessment of Preferences" (SOAP) tool, participants were asked to rate six of the 31 MESCC health states, each of which presented varying severities of five MESCC-related dysfunctions (dependent; non-ambulatory; incontinent; pain; other symptoms). RESULTS: Participants equally valued all MESCC-related dysfunctions which followed a pattern of diminishing marginal disutility (each additional consequence resulted in a smaller incremental decrease in utility than the previous). These results demonstrate that the general population values physical function equal to other facets of quality-of-life. CONCLUSION: We provide a comprehensive set of ex ante utility estimates for MESCC health states that can be used to help inform decision making. This is the first study reporting direct utility valuation for a spinal disorder. Our methodology offers a feasible solution for obtaining quality-of-life data without collecting generic health status questionnaire responses from patients. LEVEL OF EVIDENCE: 4.

Back to Bayesian: A strategy to enhance prognostication of metastatic spine disease.

AIMS: Clinicians must consider prognosis when offering treatment to patients with spine metastases. Although several prognostic indices have been developed and validated for this purpose, they may not be applicable in the current era of targeted systemic therapies. Even before the introduction of targeted therapies, these prognostic indices should not have been directly used for individual patient decision making without contextualising with other sources of data. By contextualising, we mean that prognostic estimates should not be based on these scores alone and formally incorporate clinically relevant factors not part of prognostic indices. Contextualisation requires the use of Bayesian statistics which may be unfamiliar to many readers. In this paper we show readers how to correctly apply prognostic scores to individual patients using Bayesian statistics. Through Bayesian analysis, we explore the impact of new targeted therapies on prognostic estimates obtained using the Tokuhashi score. METHODS: We provide a worked calculation for the probability of a patient surviving up to 6 months using dichotomous prognostication. We then demonstrate how to calculate a patient's expected survival using continuous prognostication. Sensitivity of the posterior distribution to prior assumptions is illustrated through effective sample size adjustment. RESULTS: When the predicted prognosis from the Tokuhashi score is contextualised with data on contemporary systemic treatments, patients previously deemed non-surgical candidates may be eligible for surgery. CONCLUSIONS: Bayesian prognostication generates intuitive results and allows multiple data points to be synthesised transparently. These techniques can extend the usefulness of existing prognostic scores in the era of targeted systemic therapies.

The Psychometric Properties of a Self-Administered, Open-Source Module for Valuing Metastatic Epidural Spinal Cord Compression Utilities.

INTRODUCTION: Web surveys are often used for utility valuation. Typically, custom utility valuation tools that have not undergone psychometric evaluation are used. OBJECTIVES: This study aimed to determine the psychometric properties of a metastatic epidural spinal cord compression (MESCC) module run on a customizable open-source, internet-based, self-directed utility valuation platform (Self-directed Online Assessment of Preferences [SOAP]). METHODS: Individuals accompanying patients to the emergency department waiting room in Ottawa, Canada, were recruited. Participants made SOAP MESCC health state valuations in the waiting room and 48 h later at home. Validity, agreement reliability, and responsiveness were measured by logical consistency of responses, smallest detectable change, the interclass correlation coefficient, and Guyatt's responsiveness index, respectively. RESULTS: Of 285 participants who completed utility valuations, only 113 (39.6%) completed the re-test. Of these 113 participants, 92 (81.4%) provided valid responses on the first test and 75 (66.4%) provided valid responses on the test and re-test. Agreement for all groups of health states was adequate, since their smallest detectable change was less than the minimal clinically important difference. The mean interclass correlation coefficients for all health states were > 0.8, indicating at least substantial reliability. Guyatt's responsiveness indices all exceeded 0.80, indicating a high level of responsiveness. CONCLUSIONS: To our knowledge, this is the first validated open-source, web-based, self-directed utility valuation module. We have demonstrated the SOAP MESCC module is valid, reproducible, and responsive for obtaining ex ante utilities. Considering the successful psychometric validation of the SOAP MESCC module, other investigators can consider developing modules for other diseases where direct utility valuation is needed.