Neoadjuvant pazopanib in nonrhabdomyosarcoma soft tissue sarcomas (ARST1321): A report of major wound complications from the Children's Oncology Group and NRG Oncology
- J Surg Oncol. 2023 Apr;127(5):871-881. doi: 10.1002/jso.27205.
- 1. Department of Surgery, K. Hovnanian Children's Hospital at Jersey Shore University Medical Center, Hackensack-Meridian Health Network, Neptune, New Jersey, USA.
- 2. Department of Pediatrics, Maine Medical Center, Portland, Maine, USA.
- 3. Department of Biostatistics, University of Florida, Gainesville, Florida, USA.
- 4. Department of Sarcoma, Moffitt Cancer Center, Tampa, Florida, USA.
- 5. Department of Surgery, Howard University, Washington, District of Columbia, USA.
- 6. Department of Orthopaedic Surgery, University of California Davis, Sacramento, California, USA.
- 7. Department of Orthopedic Surgery, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.
- 8. Department of Pediatrics, University of Washington School of Medicine and Seattle Children's Hospital, Seattle, Washington, USA.
- 9. Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California, USA.
- 10. Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois, USA.
- 11. Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, California, USA.
- 12. Department of Radiation Oncology, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
- 13. Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.
- 14. Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA.
- 15. Department of Pediatrics, Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.
- 16. Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.
- 17. Department of Orthopaedics, James Cancer Hospital and Nationwide Children's Hospital, Columbus, Ohio, USA.
Background and objectives: The impact upon wound healing of targeted molecular therapies, when incorporated into neoadjuvant therapy of soft tissue sarcoma, is largely unknown. Here, we describe wound complications following addition of pazopanib, a tyrosine kinase inhibitor (TKI), to neoadjuvant radiotherapy (RT) +/- chemotherapy for soft tissue sarcoma.
Methods: Wound complications were evaluated on dose-finding and randomized arms of ARST1321, a phase II/III study incorporating neoadjuvant RT, +/- pazopanib, +/- ifosfamide/doxorubicin (ID) for sarcoma therapy.
Results: Of 85 evaluable patients, 35 (41%) experienced postoperative wound complications. Most (57%) were grade III. Randomization to pazopanib + RT + ID carried a 50% wound complication rate (17/34, with 47% grade III), compared to 22% (5/23) with ID + RT alone. In nonchemotherapy study arms, pazopanib + RT resulted in a 59% wound complication rate versus 25% for those receiving RT alone. Grade III wound complications occurred among 26% (15/58) of all patients receiving pazopanib. Wound complications occurred a median of 35 days postoperatively. Some occurred following diagnostic biopsies and at remote surgical sites.
Conclusion: The addition of pazopanib to neoadjuvant chemotherapy and RT resulted in a higher wound complication rate following therapy of soft tissue sarcoma. The rate of grade III complications remained comparable to that reported in contemporary literature.