Defining the role of neoadjuvant systemic therapy in high-risk retroperitoneal sarcoma: A multi-institutional study from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group

William W Tseng¹, Francesco Barretta², Lorenzo Conti³, Giovanni Grignani⁴, Francesco Tolomeo⁴, Markus Albertsmeier⁵, Martin K Angele⁵, Piotr Rutkowski⁶, Jacek Skoczylas⁶, Antonino De Paoli⁷, Federico Navarria⁷, Chandrajit P Raut^{8

9}, Mark Fairweather^{8

9}, Jeffrey M Farma^{10

11}, Carolyn Nessim¹², Neha Goel^{13

14}, Valerie P Grignol¹⁵, Samuel J Ford¹⁶, Kenneth Cardona¹⁷, Ty Subhawong^{13

14}, Hannah L Tattersall¹⁶, Rachel M Lee¹⁷, James S Hu¹⁸, Margaret von Mehren^{10

11}, Roberta Sanfilippo³, Alessandro Gronchi³

Affiliations

¹ Division of Breast, Endocrine, and Soft Tissue Surgery, Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California.
² Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
³ Sarcoma Service, Departments of Surgery and Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
⁴ Division of Medical Oncology, Candiolo Cancer Institute, Fondazione del Piemonte per l'Oncologia-IRCCS, Candiolo, Italy.
⁵ Department of General, Visceral, and Transplantation Surgery, University Hospital Großhadern, Ludwig Maximilian University of Munich, Munich, Germany.
⁶ Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska Curie National Research Institute of Oncology, Warsaw, Poland.
⁷ Radiation Oncology Department, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.
⁸ Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
⁹ Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
¹⁰ Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
¹¹ Department of Hematology/Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
¹² Department of Surgery, University of Ottawa-Ottawa General Hospital, Ottawa, Ontario, Canada.
¹³ Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida.
¹⁴ Department of Radiology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida.
¹⁵ Division of Surgical Oncology, Department of Surgery, James Comprehensive Cancer Center, Ohio State University, Columbus, Ohio.
¹⁶ Department of Sarcoma Surgery, University Hospitals Birmingham, Birmingham, United Kingdom.
¹⁷ Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia.
¹⁸ Division of Oncology, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California.

PMID: 33206381
DOI: 10.1002/cncr.33323

Multicenter Study

Defining the role of neoadjuvant systemic therapy in high-risk retroperitoneal sarcoma: A multi-institutional study from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group

William W Tseng et al. Cancer. 2021.

. 2021 Mar 1;127(5):729-738.

doi: 10.1002/cncr.33323. Epub 2020 Nov 18.

Authors

Affiliations

¹ Division of Breast, Endocrine, and Soft Tissue Surgery, Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California.
² Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
³ Sarcoma Service, Departments of Surgery and Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
⁴ Division of Medical Oncology, Candiolo Cancer Institute, Fondazione del Piemonte per l'Oncologia-IRCCS, Candiolo, Italy.
⁵ Department of General, Visceral, and Transplantation Surgery, University Hospital Großhadern, Ludwig Maximilian University of Munich, Munich, Germany.
⁶ Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska Curie National Research Institute of Oncology, Warsaw, Poland.
⁷ Radiation Oncology Department, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.
⁸ Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
⁹ Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
¹⁰ Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
¹¹ Department of Hematology/Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
¹² Department of Surgery, University of Ottawa-Ottawa General Hospital, Ottawa, Ontario, Canada.
¹³ Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida.
¹⁴ Department of Radiology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida.
¹⁵ Division of Surgical Oncology, Department of Surgery, James Comprehensive Cancer Center, Ohio State University, Columbus, Ohio.
¹⁶ Department of Sarcoma Surgery, University Hospitals Birmingham, Birmingham, United Kingdom.
¹⁷ Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia.
¹⁸ Division of Oncology, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California.

PMID: 33206381
DOI: 10.1002/cncr.33323

Abstract

Background: In patients with retroperitoneal sarcoma (RPS), the incidence of recurrence after surgery remains high. Novel treatment approaches are needed. This retrospective study evaluated patients with primary, high-risk RPS who received neoadjuvant systemic therapy followed by surgery to 1) determine the frequency and potential predictors of radiologic tumor responses and 2) assess clinical outcomes.

Methods: Clinicopathologic data were collected for eligible patients treated at 13 sarcoma referral centers from 2008 to 2018. Univariable and multivariable logistic models were performed to assess the association between clinical predictors and response. Overall survival (OS) and crude cumulative incidences of local recurrence and distant metastasis were compared.

Results: Data on 158 patients were analyzed. A median of 3 cycles of neoadjuvant systemic therapy (interquartile range, 2-4 cycles) were given. The regimens were mostly anthracycline based; however, there was significant heterogeneity. No patients demonstrated a complete response, 37 (23%) demonstrated a partial response (PR), 88 (56%) demonstrated stable disease, and 33 (21%) demonstrated progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Only a higher number of cycles given was positively associated with PR (P = .005). All patients underwent complete resection, regardless of the tumor response. Overall, patients whose tumors demonstrated PD before surgery showed markedly worse OS (P = .005). An indication of a better clinical outcome was seen in specific regimens given for grade 3 dedifferentiated liposarcoma and leiomyosarcoma.

Conclusions: In patients with high-risk RPS, the response to neoadjuvant systemic therapy is fair overall. Disease progression on therapy may be used to predict survival after surgery. Subtype-specific regimens should be further validated.

Keywords: leiomyosarcoma; liposarcoma; neoadjuvant; retroperitoneal sarcoma; systemic therapy.

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References

1. van Houdt WJ, Zaidi S, Messiou C, Thway K, Strauss DC, Jones RL. Treatment of retroperitoneal sarcoma: current standards and new developments. Curr Opin Oncol. 2017;29:260-267. doi:10.1097/CCO.0000000000000377
1. Dingley B, Fiore M, Gronchi A. Personalizing surgical margins in retroperitoneal sarcomas: an update. Expert Rev Anticancer Ther. 2019;19:613-631. doi:10.1080/14737140.2019.1625774
1. Gronchi A, Strauss DC, Miceli R, et al. Variability in patterns of recurrence after resection of primary retroperitoneal sarcoma (RPS): a report on 1007 patients from the multi-institutional collaborative RPS working group. Ann Surg. 2016;263:1002-1009. doi:10.1097/SLA.0000000000001447
1. Tan MC, Brennan MF, Kuk D, et al. Histology-based classification predicts pattern of recurrence and improves risk stratification in primary retroperitoneal sarcoma. Ann Surg. 2016;263:593-600. doi:10.1097/SLA.0000000000001149
1. Rutkowski PL, Mullen JT. Management of the “other” retroperitoneal sarcomas. J Surg Oncol. 2018;117:79-86. doi:10.1002/jso.24893

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Defining the role of neoadjuvant systemic therapy in high-risk retroperitoneal sarcoma: A multi-institutional study from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group

Affiliations

Defining the role of neoadjuvant systemic therapy in high-risk retroperitoneal sarcoma: A multi-institutional study from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group

Authors

Affiliations

Abstract

References

Publication types

MeSH terms

LinkOut - more resources

Research Materials