TITLE: A Collaborative Multidisciplinary Approach May Lead to Enhanced Clinical Outcomes and Quality of Care for Patients with Diffuse TGCT

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Authors: John Abraham MD  , Gerhard Maale MD  , Atrayee Basu Mallick MD  , Arianna Mixon BS  , Ryan Paul BS  , R. Lor Randall MD  , Matthew H. Wayne  , Lauren Zeitlinger DO

  Rothman Institute: Philadelphia, Pennsylvania

  Dallas Fort Worth Sarcoma Group: Plano, Texas

  Thomas Jefferson University: Philadelphia, Pennsylvania

  Dallas Forth Worth Sarcoma Group: Plano, Texas

  Thomas Jefferson University: Philadelphia, Pennsylvania

  University of California Davis: Sacramento, California

  Medical Impact Ventures: Austin, Texas

  University of California Davis: Sacramento, California

 

Objective: Diffuse Tenosynovial giant cell tumor (D-TGCT) is a rare tumor of joint synovium which causes significant pain and limitations to daily living. Historically, management has been surgical excision. Recently in August 2019, a CSF1R inhibitor Pexidartinib was approved by the Food and Drug Administration (FDA) for use in patients who are not surgical candidates. Little information exists on the optimal approach of utilization of CSF1R inhibitors and surgery in treatment of TGCT. Therefore, we sought to assess the management approach used in a consortium of high-volume musculoskeletal oncology centers across the country, in order to suggest treatment guidelines that can be used as a model for academic and community health care centers.

 

Methods: Three high volume musculoskeletal oncology centers collaborated in a consortium-type format to gather information on how diffuse TGCT not amenable to surgery is treated, in order to understand the care pathways at each center. The combined data demonstrated a total of 12 patients (mean age: 44 years; 3 males, 9 females) with a mean follow-up of approximately 1 year. A multi-site chart review was conducted to collect clinical information on demographics, changes in tumor volume, recurrence of tumor growth, drug tolerance and complications, any patient reported outcomes, and future surgeries, in order to understand the impact of the care pathway on the outcomes.

 

Results:

All three centers presented all D-TGCT patients in a multidisciplinary tumor board format prior to initiating treatment plan. Both CSF1R inhibition and surgery were considered for all cases. Cases in whom an operation was not felt to be the best first option by the experienced tumor board surgeon were treated with pexidartinib in all cases, given its accessibility due to FDA-approved status. 12 patients were identified in whom the decision had been made to treat with pexidartinib. The disease was in the following locations: 6 knee, 3 foot, 2 shoulder, and 1 ankle. 8 of these patients were first seen at the study sites with recurrent disease after having initial treatment elsewhere. After starting the drug, 5 patients (42%) had reduction of tumor volume on MRI after starting drug, with an average of 50% reduction in tumor volume in those patients. No patient in this series had disease progression while on the drug. In all three centers, patient reported outcomes (PROs) were felt to be critical for decision making and were incorporated into the management, but none of the centers had PROs adequately recorded at the time of the study. Regarding adverse effects, 42% of patients (n=5) experienced some hypopigmentation and fatigue. 8% reported a rash (n=1). More concerning side effects of cognitive impairment and liver toxicity were seen in 17% (n=2) and 8% (n=1), respectively. Two patients needed to stop taking the drug for adverse effects: Grade 3 liver toxicity 1.5 weeks after starting drug, and cognitive impairments affecting their work as a medical doctor. Two patients went on to surgery after initiation of drug: One experienced liver toxicity which resolved after stopping the drug, but due to continued pain and difficulty with ambulation from the disease site required surgical resection. This patient received at total of 1.5 weeks of the drug and no histologic changes were seen at resection. The second patient took the drug for 6.5 months but continued to have symptoms in the knee and went on to surgical resection. Concurrent osteoarthritis may have been a confounding factor in this case.

 

Conclusion: In all three high-volume centers, a multidisciplinary tumor board approach to all patients with D-TGCT was utilized. Utilizing this approach, highly favorable response in our series was seen, with moderate to high rates of MRI response, histologic response, and symptomatic response. Based on the assessment of the results of our three centers, we conclude that this collaborative multispecialty approach is necessary and optimal for management of this tumor. It is likely that some of these patients may have become better surgical candidates after medical treatment, and therefore continued multidisciplinary input is needed throughout treatment course, not just at the initiation of treatment. In our combined series, two patients did go on to have surgery after drug, suggesting that surgery should not be ruled out for patients receiving drug, and consideration should be given to both the use of CSF1-R inhibition and surgery as treatment options in all patients. Other approaches, such as use of CSF-1 inhibition both before and after surgery may demonstrate additional benefits. In most patients, the adverse events profile did not require change in management. Given that D-TGCT is primarily a quality-of-life condition, We did feel that none of our centers, in spite of being high-volume research institutions, kept adequate records of patient reported outcomes, and wwe strongly would suggest incorporation of PROMsthis into the care pathway of any institution treating a number of these tumors. Based on the current lack of a clear clinical guideline for treatment of this condition, we believe that additional education on optimal care pathways is needed. To this end, we aim to disseminate educational materials and lessons learned from this assessment among consortium institutions and beyond. The impact of this education on perceptions and practices, along with ongoing educational needs, will be measured and reported in future studies.