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新辅助帕唑帕尼治疗非横纹肌肉瘤软组织肉瘤(ARST1321):来自儿童肿瘤学组和 NRG 肿瘤学的主要伤口并发症报告。

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

机构信息

Department of Surgery, K. Hovnanian Children's Hospital at Jersey Shore University Medical Center, Hackensack-Meridian Health Network, Neptune, New Jersey, USA.

Department of Pediatrics, Maine Medical Center, Portland, Maine, USA.

出版信息

J Surg Oncol. 2023 Apr;127(5):871-881. doi: 10.1002/jso.27205. Epub 2023 Feb 13.

Abstract

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.

摘要

背景与目的

当靶向分子疗法被纳入软组织肉瘤的新辅助治疗中时,其对伤口愈合的影响在很大程度上尚不清楚。在这里,我们描述了在软组织肉瘤新辅助放疗(RT)+/-化疗中加入酪氨酸激酶抑制剂(TKI)帕唑帕尼后出现的伤口并发症。

方法

在 ARST1321 的剂量发现和随机臂中评估了伤口并发症,该研究纳入了新辅助 RT、+/-帕唑帕尼、+/-异环磷酰胺/阿霉素(ID)治疗肉瘤。

结果

在 85 例可评估的患者中,有 35 例(41%)发生术后伤口并发症。大多数(57%)为 3 级。与 ID+RT 单独治疗组的 22%(5/23)相比,帕唑帕尼+RT+ID 随机分组的伤口并发症发生率为 50%(17/34,其中 47%为 3 级)。在非化疗研究臂中,与单独接受 RT 的患者(25%)相比,帕唑帕尼+RT 导致 59%的伤口并发症发生率。接受帕唑帕尼治疗的所有患者中有 26%(15/58)发生 3 级伤口并发症。伤口并发症发生于术后中位 35 天。一些并发症发生在诊断性活检和远处手术部位。

结论

在新辅助化疗和 RT 中加入帕唑帕尼后,软组织肉瘤治疗后伤口并发症的发生率更高。3 级并发症的发生率与当代文献报道的相似。

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