Neoadjuvant hypofractionated radiotherapy and chemotherapy for extremity soft tissue sarcomas: Safety, feasibility, and early oncologic outcomes of a phase 2 trial

Maria Leticia Gobo Silva; Celso Abdon Lopes de Mello; Samuel Aguiar Junior; Felipe D'Almeida Costa; Paulo Roberto Stevanato Filho; Tiago Santoro Bezerra; Suely Akiko Nakagawa; Antonio Geraldo Nascimento; Isabela Werneck da Cunha; Ranyell Matheus Spencer Sobreira Batista; Ulisses Ribaldo Nicolau Daher; Maria Nirvana Da Cruz Formiga; Janaina Naiara Germano; Bruna Elisa Catin Kupper; Antonio Cassio De Assis Pellizzon; Ademar Lopes

doi:10.1016/j.radonc.2021.03.033

Neoadjuvant hypofractionated radiotherapy and chemotherapy for extremity soft tissue sarcomas: Safety, feasibility, and early oncologic outcomes of a phase 2 trial

Radiother Oncol. 2021 Jun:159:161-167. doi: 10.1016/j.radonc.2021.03.033. Epub 2021 Mar 31.

Authors

Maria Leticia Gobo Silva¹, Celso Abdon Lopes de Mello², Samuel Aguiar Junior³, Felipe D'Almeida Costa⁴, Paulo Roberto Stevanato Filho⁵, Tiago Santoro Bezerra⁶, Suely Akiko Nakagawa⁷, Antonio Geraldo Nascimento⁸, Isabela Werneck da Cunha⁹, Ranyell Matheus Spencer Sobreira Batista¹⁰, Ulisses Ribaldo Nicolau Daher¹¹, Maria Nirvana Da Cruz Formiga¹², Janaina Naiara Germano¹³, Bruna Elisa Catin Kupper¹⁴, Antonio Cassio De Assis Pellizzon¹⁵, Ademar Lopes¹⁶

Affiliations

¹ Department of Radiation Oncology, A C Camargo Cancer Center, São Paulo, Brazil. Electronic address: [email protected].
² Department of Clinical Oncology, A C Camargo Cancer Center, São Paulo, Brazil. Electronic address: [email protected].
³ Division of Surgery, Department of Sarcoma, A C Camargo Cancer Center, São Paulo, Brazil. Electronic address: [email protected].
⁴ Department of Anatomic Pathology, A C Camargo Cancer Center, São Paulo, Brazil. Electronic address: [email protected].
⁵ Division of Surgery, Department of Sarcoma, A C Camargo Cancer Center, São Paulo, Brazil. Electronic address: [email protected].
⁶ Division of Surgery, Department of Sarcoma, A C Camargo Cancer Center, São Paulo, Brazil. Electronic address: [email protected].
⁷ Division of Surgery, Department of Orthopedics, A C Camargo Cancer Center, São Paulo, Brazil. Electronic address: [email protected].
⁸ Department of Anatomic Pathology, A C Camargo Cancer Center, São Paulo, Brazil. Electronic address: [email protected].
⁹ Department of Anatomic Pathology, A C Camargo Cancer Center, São Paulo, Brazil. Electronic address: [email protected].
¹⁰ Division of Surgery, Department of Sarcoma, A C Camargo Cancer Center, São Paulo, Brazil. Electronic address: [email protected].
¹¹ Department of Clinical Oncology, A C Camargo Cancer Center, São Paulo, Brazil. Electronic address: [email protected].
¹² Department of Clinical Oncology, A C Camargo Cancer Center, São Paulo, Brazil. Electronic address: [email protected].
¹³ Department of Statistics, A C Camargo Cancer Center, São Paulo, Brazil. Electronic address: [email protected].
¹⁴ Division of Surgery, Department of Sarcoma, A C Camargo Cancer Center, São Paulo, Brazil. Electronic address: [email protected].
¹⁵ Department of Radiation Oncology, A C Camargo Cancer Center, São Paulo, Brazil. Electronic address: [email protected].
¹⁶ Division of Surgery, Department of Sarcoma, A C Camargo Cancer Center, São Paulo, Brazil. Electronic address: [email protected].

PMID: 33798613
DOI: 10.1016/j.radonc.2021.03.033

Abstract

Background and purpose: Optimal treatment of extremity soft tissue sarcomas (ESTS) is controversial. The aim of this study was to evaluate neoadjuvant chemotherapy (ChT) plus concomitant hypofractionated RT (hypo-RT) in local and distant disease relapse. Here we report safety, feasibility and early outcomes.

Materials and methods: This was a prospective, single arm study with a goal accrual of 70 patients. Between 2015 and 2018, 18 patients with histologically confirmed nonmetastatic ESTS were assigned to receive doxorubicin and ifosfamide for three neoadjuvant cycles, concomitant with hypo-RT (25 Gy in 5 fractions) followed by surgery. The primary endpoint was disease-free survival (DFS). Secondary outcomes were pathologic response, wound complications (WC), and morbidity rates.

Results: Median follow-up was 29 months. At last follow-up, 13/18 patients were alive without evidence of local or systemic disease (DFS 72%), 1 had died due to metastatic disease, and 3 were alive with distant metastasis. One patient presented with local relapse within the irradiated field. Mean DFS time was 48.6 months (95% CI: 37.3-59.9). Six patients (33%) had no residual viable tumor detected in pathologic specimens (3 of these myxoid liposarcomas). There was a significant difference in WC among patients with acute RT skin toxicity. Six patients (33%) developed major WC. No grade 3 or 4 ChT adverse events were reported.

Conclusion: Despite the limited sample size, these early outcomes demonstrate that this treatment regimen is feasible and well tolerated with high rates of limb preservation, local control, and pathologic complete response, supporting further investigation in a multi-institutional setting.

Trial registration: ClinicalTrials.gov NCT02812654; https://clinicaltrials.gov/ct2/show/NCT02812654.

Keywords: Combined modality treatment; Extremity soft tissue sarcoma; Hypofractionated radiotherapy; Neoadjuvant chemotherapy and radiotherapy; Pathologic response; Wound complications.

Publication types

Clinical Trial, Phase II

MeSH terms

Antineoplastic Combined Chemotherapy Protocols
Extremities
Feasibility Studies
Humans
Neoadjuvant Therapy*
Neoplasm Recurrence, Local
Prospective Studies
Sarcoma* / drug therapy
Treatment Outcome

Associated data

ClinicalTrials.gov/NCT02812654