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TPS4148 Background: Cancer stem cells are considered to be fundamentally important for resistance to therapy, recurrence and metastasis. Napabucasin is a first-in-class cancer stemness inhibitor identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al, PNAS 112(6):1839, 2015). Preclinical studies suggest that napabucasin sensitizes heterogeneous cancer cells to chemotherapeutic agents, including nab-PTX and gem. Encouraging anticancer activity in mPDAC was observed in a phase Ib (El-Rayes et al, ASCO 2016) study of 37 pts, reporting 93% (28/30) disease control rate (DCR) and 50% (15/30) overall response rate (ORR), with 1 complete and 14 partial responses and prolonged disease control ( > 24 wks) in 57% (17/30) of pts who have had a RECIST evaluation. On the basis of these data, a phase III trial is being conducted in North America, Europe, Australia and Asia. Methods: This study (ClinicalTrials.gov NCT02993731) will assess the efficacy of napabucasin+nab-PTX+gem vs nab-PTX+gem in pts with mPDAC (n = 1132). Pts must have been diagnosed with mPDAC < 6 weeks prior to randomization and not have received treatment for metastatic disease. Pts are randomized in a 1:1 ratio to receive napabucasin 240 mg PO twice daily continuously plus nab-PTX+gem IV weekly for 3 out every 4 weeks, or nab-PTX+gem IV weekly for 3 out every 4 weeks. Pts will be stratified by geography, performance status and presence of liver metastases. Treatment will continue until disease progression, death, intolerability or patient/investigator decision to stop. Primary endpoint is overall survival (OS) in the general study population (HR 0.80 for OS improvement from 8.5 to 10.63 months); secondary endpoints include progression free survival (PFS), OS and PFS in the biomarker positive sub-population, ORR and DCR, safety and quality of life. In addition, blood and tumor archival tissue will be assessed for pharmacokinetic and biomarker analyses. Global enrollment is underway. Clinical trial information: NCT02993731.

Background: The minimum clinically important difference (MCID) attempts to define the patient’s experience of treatment outcomes. Efforts at calculating the MCID have yielded multiple and inconsistent MCID values. The purposes of this review were to describe the usage of the MCID in the most recent orthopaedic literature, to explain the limitations of its current uses, and to clarify the underpinnings of the MCID calculation, so as to help practitioners to understand and utilize the MCID and to guide future efforts to calculate the MCID. In Part I of this review, we sampled the orthopaedic literature in relation to the upper extremity. In this part, Part II, of the review, we will focus on the lower-extremity literature. Methods: A review was conducted of the 2014 to 2016 MCID-related publications in The Journal of Arthroplasty, The Journal of Bone & Joint Surgery, The American Journal of Sports Medicine, Foot & Ankle International, Journal of Orthopaedic Trauma, Journal of Pediatric Orthopaedics, and Journal of Shoulder and Elbow Surgery. Only clinical science articles utilizing patient-reported outcome measures (PROMs) were included in the analysis. A keyword search was then performed to identify articles that used the MCID. Articles were then further categorized into upper-extremity and lower-extremity publications. The MCID utilization in the selected articles was characterized and was recorded. Results: The MCID was referenced in 129 (7.5%) of 1,709 clinical science articles that utilized PROMs: 79 (61.2%) of the 129 articles were related to the lower extremity; of these, 11 (13.9%) independently calculated the MCID values and 68 (86.1%) used previously published MCID values as a gauge of their own results. The MCID values were calculated or were considered for 31 PROMs, of which 24 were specific to the lower extremity. Eleven different methods were used to calculate the MCID. The MCID had a wide range of values for the same questionnaires, for instance, 5.8 to 31.3 points for the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Conclusions: There are more than twice as many PROMs for the lower extremity (24) than for the upper extremity (11), confirming that the determination of useful MCID values is, in part, hampered by the proliferation of PROMs in the field of orthopaedics. The difference between significance and clinical importance needs to be further clarified. For instance, the common use of determining sample size with the MCID and comparing group means with the MCID implies that a significant result will also be clinically important. Further, the study of the MCID would benefit from consensus agreement on relevant terminology and the appropriate usage of the MCID determining equations. Clinical Relevance: MCID is increasingly used as a measure of patients’ improvement. However, MCID does not yet adequately capture the clinical importance of patients’ improvement.

Background: The minimum clinically important difference (MCID) attempts to define the patient’s experience of treatment outcomes. Efforts at calculating the MCID have yielded multiple and inconsistent MCID values. The purposes of this review were to describe the usage of the MCID in the most recent orthopaedic literature, to explain the limitations of its current uses, and to clarify the underpinnings of MCID calculation. Subsequently, we hope that the information presented here will help practitioners to better understand the MCID and to serve as a guide for future efforts to calculate the MCID. The first part of this review focuses on the upper-extremity orthopaedic literature. Part II will focus on the lower-extremity orthopaedic literature. Methods: A review was conducted of the 2014 to 2016 publications in The Journal of Arthroplasty, The Journal of Bone & Joint Surgery, The American Journal of Sports Medicine, Foot & Ankle International, Journal of Orthopaedic Trauma, Journal of Pediatric Orthopaedics, and Journal of Shoulder and Elbow Surgery . Only clinical science articles utilizing patient-reported outcome measure (PROM) scores were included in the analysis. A keyword search was then performed to identify articles that calculated or referenced the MCID. Articles were then further categorized into upper-extremity and lower-extremity publications. MCID utilization in the selected articles was subsequently characterized and recorded. Results: The MCID was referenced in 129 (7.5%) of 1,709 clinical science articles that utilized PROMs: 52 (40.3%) of 129 were related to the upper extremity, 5 (9.6%) of 52 independently calculated MCID values, and 47 (90.4%) of 52 used previously published MCID values as a gauge of their own results. MCID values were considered or calculated for 16 PROMs; 12 of these were specific to the upper extremity. Six different methods were used to calculate the MCID. Calculated MCIDs had a wide range of values for the same PROM (e.g., 8 to 36 points for Constant-Murley scores and 6.4 to 17 points for American Shoulder and Elbow Surgeons [ASES] scores). Conclusions: Determining useful MCID values remains elusive and is compounded by the proliferation of PROMs in the field of orthopaedics. The fundamentals of MCID calculation methods should be critically evaluated. If necessary, these methods should be corrected or abandoned. Furthermore, the type of change intended to be measured should be clarified: beneficial, detrimental, or small or large changes. There should also be assurance that the calculation method actually measures the intended change. Finally, the measurement error should consistently be reported. Clinical Relevance: The MCID is increasingly used as a measure of patients’ improvement. However, the MCID does not yet adequately capture the clinical importance of patients’ improvement.

AbstractBackgroundSeveral factors affect the level of difficulty of laparoscopic distal pancreatectomy (LDP). The purpose of this study was to develop a difficulty scoring (DS) system to quantify the degree of difficulty in LDP.MethodsWe collected clinical data for 80 patients who underwent LDP. A 10‐level difficulty index was developed and subcategorized into a three‐level difficulty index; 1–3 as low, 4–6 as intermediate, and 7–10 as high index. The automatic linear modeling (LINEAR) statistical tool was used to identify factors that significantly increase level of difficulty in LDP.ResultsThe operator's 10‐level DS concordance between the 10‐level DS by the reviewers, LINEAR index DS, and clinical index DS systems were analyzed, and the weighted Cohen's kappa statistic were at 0.869, 0.729, and 0.648, respectively, showing good to excellent inter‐rater agreement. We identified five factors significantly affecting level of difficulty in LDP; type of operation, resection line, proximity of tumor to major vessel, tumor extension to peripancreatic tissue, and left‐sided portal hypertension/splenomegaly.ConclusionsThis novel DS for LDP adequately quantified the degree of difficulty, and can be useful for selecting patients for LDP, in conjunction with fitness for surgery and prognosis.

Linked ContentThis article is linked to Tse et al and Ma and Kotze paper. To view these articles visit https://doi.org/10.1111/apt.14829 and https://doi.org/10.1111/apt.14858.