PurposeTenosynovial giant cell tumor (TGCT), a rare locally aggressive neoplasm of the synovium of joints and tendon sheaths, is associated with joint destruction, inflammation, pain, and swelling, in part due to colony-stimulating factor 1 receptor–bearing macrophages recruited to the tumor by genetic elevation of colony-stimulating factor 1 activity. The most common treatment is surgery, although promising pharmacologic treatments are in development. Patient-reported outcome (PRO) instruments are critical end points in demonstrating the clinical relevance of standard oncologic outcome measures and the overall impact of novel pharmacologic therapies in nonmalignant neoplastic conditions such as TGCT. The content validity of PROs relevant to patients with TGCT has not been formally investigated, and instruments to evaluate such outcomes do not exist for this condition.MethodsPRO instruments of potential relevance were evaluated by using a literature review and by clinical and PRO experts. Patients with TGCT were recruited through clinical sites and the Internet for participation in qualitative research interviews to identify predominant symptoms and to test the relevance and content validity of several PRO measures. Select PRO measures were included in a Phase I clinical trial, and preliminary results of the PRO end points are reported descriptively.FindingsOf the 22 subjects who participated in qualitative interviews, 73% were female, and their mean age was 42.5 years (range, 27–56 years). The TGCTs (19 diffuse and 3 localized) were located in the knee (n = 15), hip (n = 3), ankle (n = 2), elbow (n= 1), and forearm (n = 1). The most common symptoms cited were pain (82%), swelling (86%), stiffness (73%), reduced range of motion (64%), and joint instability (64%), which were consistent with clinical expert input and with the content of instruments chosen by PRO experts. The worst pain numeric rating scale, Patient Reported Outcomes Measurement Information System physical functioning items, and the Western Ontario and McMaster Universities Osteoarthritis Index, as well as a worst stiffness numeric rating scale developed for TGCT, were confirmed as meaningful measures of TGCT patient symptoms and were well understood in qualitative interviews. Results from the Phase I trial showed trends of improvement in both pain and stiffness over time.ImplicationsThis study is the first to gather information directly from patients with TGCT regarding their symptom experiences. Pain, stiffness, and physical functioning are important treatment outcomes in patients with TGCT. We have identified content-valid PRO measures of these concepts, which are included in an ongoing Phase III TGCT clinical trial with pexidartinib (PLX3397) (NCT02371369).

Background Tenosynovial giant cell tumor (TGCT), a rare, locally aggressive neoplasm of the synovium of joints and tendon sheaths, is associated with joint destruction, pain and swelling. Impacts on physical function (PF) vary depending on tumor size and location. The aim of this study was to identify relevant items, and demonstrate the content validity of custom measures of lower extremity PF from the Patient-Reported Outcomes Measurement Information System Physical Function Physical Function (PROMIS-PF) item bank among patients with TGCT. Methods Patients were recruited for qualitative research interviews to identify predominant TGCT symptoms and impacts. Patients completed a checklist to evaluate the relevance of each PROMIS-PF item. The publicly available PROMIS-PF item response theory (IRT) parameters were used to select items representing the range of the latent PF trait. Results Participants ( n = 20) were 75% female, mean age 42.5 years. TGCTs were located in the knee ( n = 15), hip ( n = 3), and ankle ( n = 2). Fifty-four PROMIS-PF items were identified as relevant by ≥20% of the participants. PF concepts discussed by participants during the qualitative interviews were also used to select relevant items. Selected items ( n = 13) were used to create a physical function subscale specific to lower extremity tumors. Conclusions We describe a novel method of combining qualitative research and IRT-based item information to select a relevant and content valid subset of PROMIS-PF items to assess heterogeneous impacts on PF in TGCT, a rare disease population. Electronic supplementary material The online version of this article (10.1186/s41687-019-0099-0) contains supplementary material, which is available to authorized users.

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11048 Background: TGCT is a locally aggressive neoplasm of joint and tendon sheath synovia that may cause pain, limit joint function and destroy bone and local tissues. Measuring TGCT with RECIST is a challenge due to irregular shape and asymmetrical growth, and local tissue damage is not assessed. We reported earlier results of a longitudinal trial of pexidartinib, a selective CSF1R kinase inhibitor, using RECIST as well as novel TVS, modified RECIST and TDS. Here we examine concordance of these MRI measures with PROs. Methods: Patients (pts) with progressive TGCT in a single-arm, multi-center trial of pexidartinib (1000 mg po daily) were assessed by MRI every 2 months by 2 central radiologists (blind to visit order). For RECIST, longest measurable dimensions of up to 2 tumors per joint or tendon sheath were summed (SLD). Modified RECIST summed short axis dimensions (SSD). TVS was based on 10% increments of the estimated maximally distended normal synovial cavity or tendon sheath. TDS scored bone erosion (ERO), cartilage loss (CAR) and bone marrow edema (BME) in multiple regions of each joint. The relationship with PROs (Worst Pain numerical rating scale [NRS] and Worst Stiffness NRS) was assessed. Results: 15 pts (7 knees, 3 hips, 2 ankles, 1 elbow, 1 wrist, 1 thigh) with PRO data and evaluable MRI scans at baseline and Month 7 were assessed. All SLD, SSD and TVS scores improved with respective median changes of -25%, -39% and -50%. Baseline ERO, CAR, and BME ranged 0-19, 0-34, and 0-15, respectively. Median change for each was 0%: ERO worsened in 1 pt, CAR did not change, and BME improved in 4 and worsened in 2. Worst Pain NRS and Worst Stiffness NRS improved in 11 and 9 pts, respectively. Conclusions: TVS demonstrated the greatest pexidartinib effect size, followed by SSD and then conventional RECIST. All had good concordance with PROs. Clinical trial information: NCT01004861. [Table: see text]