Defining the role of neoadjuvant systemic therapy in high-risk retroperitoneal sarcoma: A multi-institutional study from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group.
leiomyosarcoma
liposarcoma
neoadjuvant
retroperitoneal sarcoma
systemic therapy
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
01 03 2021
01 03 2021
Historique:
received:
03
07
2020
revised:
28
08
2020
accepted:
19
10
2020
pubmed:
19
11
2020
medline:
16
10
2021
entrez:
18
11
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
729-738Informations de copyright
© 2020 American Cancer Society.
Références
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
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
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
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
Rutkowski PL, Mullen JT. Management of the “other” retroperitoneal sarcomas. J Surg Oncol. 2018;117:79-86. doi:10.1002/jso.24893
Tseng WW, Pollock RE, Gronchi A. Retroperitoneal sarcomas: big tumors that involve more than just “getting it out”. J Surg Oncol. 2018;117:5-6. doi:10.1002/jso.24886
Bonvalot S, Gronchi A, Le Péchoux C, et al. Preoperative radiotherapy plus surgery versus surgery alone for patients with primary retroperitoneal sarcoma (EORTC-62092: STRASS): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2020;21:1366-1377. doi:10.1016/S1470-2045(20)30446-0
Movva S, von Mehren M, Ross EA, Handorf E. Patterns of chemotherapy administration in high-risk soft tissue sarcoma and impact on overall survival. J Natl Compr Canc Netw. 2015;13:1366-1374. doi:10.6004/jnccn.2015.0165
Linehan DC, Lewis JJ, Leung D, Brennan MF. Influence of biologic factors and anatomic site in completely resected liposarcoma. J Clin Oncol. 2000;18:1637-1643. doi:10.1200/JCO.2000.18.8.1637
Almond LM, Gronchi A, Strauss D, Jafri M, Ford S, Desai A. Neoadjuvant and adjuvant strategies in retroperitoneal sarcoma. Eur J Surg Oncol. 2018;44:571-579. doi:10.1016/j.ejso.2018.02.001
Tseng WW, Pollock RE, Gronchi A. The Trans-Atlantic Retroperitoneal Sarcoma Working Group (TARPSWG): “red wine or white”? Ann Surg Oncol. 2016;23:4418-4420. doi:10.1245/s10434-016-5538-z
van Houdt WJ, Raut CP, Bonvalot S, Swallow CJ, Haas R, Gronchi A. New research strategies in retroperitoneal sarcoma. The case of TARPSWG, STRASS and RESAR: making progress through collaboration. Curr Opin Oncol. 2019;31:310-316. doi:10.1097/CCO.0000000000000535
Trans-Atlantic RPS Working Group. Management of primary retroperitoneal sarcoma (RPS) in the adult: a consensus approach from the Trans-Atlantic RPS Working Group. Ann Surg Oncol. 2015;22:256-263. doi:10.1245/s10434-014-3965-2
Trans-Atlantic RPS Working Group. Management of recurrent retroperitoneal sarcoma (RPS) in the adult: a consensus approach from the Trans-Atlantic RPS Working Group. Ann Surg Oncol. 2016;23:3531-3540. doi:10.1245/s10434-016-5336-7
Trans-Atlantic Retroperitoneal Sarcoma Working Group. Management of metastatic retroperitoneal sarcoma: a consensus approach from the Trans-Atlantic Retroperitoneal Sarcoma Working Group (TARPSWG). Ann Oncol. 2018;29:857-871. doi:10.1093/annonc/mdy052
Eisenhauer EA, Therasse P, Bogaerts J, et al. New Response Evaluation Criteria in Solid Tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228-247. doi:10.1016/j.ejca.2008.10.026
Schemper M, Smith TL. A note on quantifying follow-up in studies of failure time. Control Clin Trials. 1996;17:343-346. doi:10.1016/0197-2456(96)00075-x
Durrleman S, Simon R. Flexible regression models with cubic splines. Stat Med. 1989;8:551-561. doi:10.1002/sim.4780080504
Gronchi A, Miceli R, Allard MA, et al. Personalizing the approach to retroperitoneal soft tissue sarcoma: histology-specific patterns of failure and postrelapse outcome after primary extended resection. Ann Surg Oncol. 2015;22:1447-1454. doi:10.1245/s10434-014-4130-7
Pawlik TM, Pisters PW, Mikula L, et al. Long-term results of two prospective trials of preoperative external beam radiotherapy for localized intermediate- or high-grade retroperitoneal soft tissue sarcoma. Ann Surg Oncol. 2006;13:508-517. doi:10.1245/ASO.2006.05.035
Nussbaum DP, Rushing CN, Lane WO, et al. Preoperative or postoperative radiotherapy versus surgery alone for retroperitoneal sarcoma: a case-control, propensity score-matched analysis of a nationwide clinical oncology database. Lancet Oncol. 2016;17:966-975. doi:10.1016/S1470-2045(16)30050-X
Angele MK, Albertsmeier M, Prix NJ, et al. Effectiveness of regional hyperthermia with chemotherapy for high-risk retroperitoneal and abdominal soft-tissue sarcoma after complete surgical resection: a subgroup analysis of a randomized phase-III multicenter study. Ann Surg. 2014;260:749-754; discussion 754-756. doi:10.1097/SLA.0000000000000978
Miura JT, Charlson J, Gamblin TC, et al. Impact of chemotherapy on survival in surgically resected retroperitoneal sarcoma. Eur J Surg Oncol. 2015;41:1386-1392. doi:10.1016/j.ejso.2015.07.014
Bonvalot S, Gaignard E, Stoeckle E, et al. Survival benefit of the surgical management of retroperitoneal sarcoma in a reference center: a nationwide study of the French Sarcoma Group from the NetSarc Database. Ann Surg Oncol. 2019;26:2286-2293. doi:10.1245/s10434-019-07421-9
Tseng WW, Gronchi A, Bonvalot S, Pollock RE. A sommelier to guide wine selection and a specialist to manage the sarcoma patient: barriers to referral and definition of a sarcoma specialist. J Surg Oncol. 2020;121:925-926. doi:10.1002/jso.25863
Constantinidou A, Jones RL. Systemic therapy in retroperitoneal sarcoma management. J Surg Oncol. 2018;117:87-92. doi:10.1002/jso.24933
Italiano A, Toulmonde M, Cioffi A, et al. Advanced well-differentiated/dedifferentiated liposarcomas: role of chemotherapy and survival. Ann Oncol. 2012;23:1601-1607. doi:10.1093/annonc/mdr485
Livingston JA, Bugano D, Barbo A, et al. Role of chemotherapy in dedifferentiated liposarcoma of the retroperitoneum: defining the benefit and challenges of the standard. Sci Rep. 2017;7:11836. doi:10.1038/s41598-017-12132-w
D'Ambrosio L, Touati N, Blay JY, et al. Doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, or doxorubicin alone as a first-line treatment for advanced leiomyosarcoma: a propensity score matching analysis from the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Cancer. 2020;126:2637-2647. doi:10.1002/cncr.32795
Gronchi A, Palmerini E, Quagliuolo V, et al. Neoadjuvant chemotherapy in high-risk soft tissue sarcomas: final results of a randomized trial from Italian (ISG), Spanish (GEIS), French (FSG), and Polish (PSG) sarcoma groups. J Clin Oncol. 2020;38:2178-2186. doi:10.1200/JCO.19.03289
Gronchi A, Frustaci S, Mercuri M, et al. Short, full-dose adjuvant chemotherapy in high-risk adult soft tissue sarcomas: a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group. J Clin Oncol. 2012;30:850-856. doi:10.1200/JCO.2011.37.7218
Gronchi A, Stacchiotti S, Verderio P, et al. Short, full-dose adjuvant chemotherapy (CT) in high-risk adult soft tissue sarcomas (STS): long-term follow-up of a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group. Ann Oncol. 2016;27:2283-2288. doi:10.1093/annonc/mdw430