Neoadjuvant pazopanib in nonrhabdomyosarcoma soft tissue sarcomas (ARST1321): A report of major wound complications from the Children's Oncology Group and NRG Oncology

TY - JOUR

T1 - Neoadjuvant pazopanib in nonrhabdomyosarcoma soft tissue sarcomas (ARST1321)

T2 - A report of major wound complications from the Children's Oncology Group and NRG Oncology

AU - Kayton, Mark L.

AU - Weiss, Aaron R.

AU - Xue, Wei

AU - Binitie, Odion

AU - Hayes Dixon, Andrea

AU - Randall, R. Lor

AU - Sorger, Joel I.

AU - Hawkins, Douglas S.

AU - Spunt, Sheri L.

AU - Wang, Dian

AU - Million, Lynn

AU - Terezakis, Stephanie

AU - Choy, Edwin

AU - Okuno, Scott H.

AU - Venkatramani, Rajkumar

AU - Chen, Yen Lin

AU - Scharschmidt, Thomas J.

N1 - Publisher Copyright: © 2023 Wiley Periodicals LLC.

PY - 2023/4

Y1 - 2023/4

N2 - 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.

AB - 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.

KW - neoadjuvant

KW - pazopanib

KW - sarcoma

KW - wound complications

KW - wound healing

UR - https://www.scopus.com/pages/publications/85148025383

U2 - 10.1002/jso.27205

DO - 10.1002/jso.27205

M3 - Article

C2 - 36779385

SN - 0022-4790

VL - 127

SP - 871

EP - 881

JO - Journal of Surgical Oncology

JF - Journal of Surgical Oncology

IS - 5

ER -