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

Gronchi, Alessandro; Stacchiotti, Silvia; Verderio, Paolo; Ferrari, Stefano; Martin‐Broto, Javier; Pousa, Antonio López; Llombart‐Bosch, Antonio; Tos, Angelo Paolo Dei; Collini, Paola; Jurado, Josefina Cruz; Paoli, Antonino De; Donati, Davide María; Poveda, Andrés; Quagliuolo, Vittorio; Comandone, Alessandro; Grignani, Giovanni; Morosi, Carlo; Messina, A.; Sanctis, Rita De; Bottelli, Stefano; Palassini, Elena; Casali, Paolo G.; Picci, Piero

doi:10.1093/annonc/mdw430

Cited by 99 publications

(60 citation statements)

References 15 publications

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“…The concept of high‐risk is important (high grade, tumor larger than 5 cm, and deep tumors), as well as the selection of highest dose intensity for the two most active drugs: doxorubicin/epirubicin and ifosfamide. Taking into account these two crucial concepts, two randomized trials have obtained similar survival curves above 65% , and this outcome was maintained in the long term . More recently, the standard three courses of full‐dose epirubicin and ifosfamide were demonstrated to be significantly better than the experimental arm, in terms of disease‐free survival and overall survival, when compared with histotype‐tailored schemes .…”

Section: Discussionmentioning

confidence: 89%

Relevance of Reference Centers in Sarcoma Care and Quality Item Evaluation: Results from the Prospective Registry of the Spanish Group for Research in Sarcoma (GEIS)

et al. 2018

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Background Reference centers (RCs) are a key point for improving the survival of patients with soft‐tissue sarcomas (STS). The aim of this study was to evaluate selected items in the management of patients with STS, comparing results between RC and local hospitals (LHs). Materials and Methods Diagnostic and therapeutic data from patients diagnosed between January 2004 and December 2011 were collected. Correlation with outcome was performed. Results A total of 622 sarcomas were analyzed, with a median follow‐up of 40 months. Imaging of primary tumor preoperatively (yes vs. no) correlated with a higher probability of free surgical margins (77.4% versus 53.7%; p = .006). The provenance of the biopsy (RC vs. LH) significantly affected relapse‐free survival (RFS; 3‐year RFS 66% vs. 46%, respectively; p = .019). Likewise, 3‐year RFS was significantly worse in cases with infiltrated (55.6%) or unknown (43.4%) microscopic surgical margins compared with free margins (63.6%; p < .001). Patients managed by RCs had a better 3‐year overall survival compared with those managed by LHs (82% vs. 70.4%, respectively; p = .003). Perioperative chemotherapy in high‐risk STS, more frequently administered in RCs than in LHs, resulted in significantly better 3‐year RFS (66% vs. 44%; p = .011). In addition, patients with stage IV disease treated in RCs survived significantly longer compared with those in LHs (30.4 months vs. 18.5 months; p = .036). Conclusion Our series indicate that selected quality‐of‐care items were accomplished better by RCs over LHs, all with significant prognostic value in patients with STS. Early referral to an RC should be mandatory if the aim is to improve the survival of patients with STS. Implications for Practice This prospective study in patients diagnosed with soft‐tissue sarcoma shows the prognostic impact of reference centers in the management of these patients. The magnitude of this impact encompasses all steps of the process, from the initial management (performing diagnostic biopsy) to the advanced disease setting. This is the first prospective evidence showing improvement in outcomes of patients with metastatic disease when they are managed in centers with expertise. This study provides extra data supporting referral of patients with sarcoma to reference centers.

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Section: Discussionmentioning

confidence: 89%

Relevance of Reference Centers in Sarcoma Care and Quality Item Evaluation: Results from the Prospective Registry of the Spanish Group for Research in Sarcoma (GEIS)

et al. 2018

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“…In light of these considerations, a new study was designed comparing three cycles of epirubicin (120 mg/m 2 ) plus ifosfamide (9 g/m 2 ) given preoperatively with five cycles of the same drugs given perioperatively (three neoadjuvant cycles followed by surgery and two further adjuvant cycles). 42,43 This study did not identify any survival difference between these two treatment modalities and three chemotherapy cycles given preoperatively were deemed as effective as five cycles. These results were criticized for the lack of a control arm in which patients would have been treated with surgery alone.…”

Section: Studymentioning

confidence: 82%

Neoadjuvant chemotherapy in soft tissue sarcomas: latest evidence and clinical implications

2017

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Soft tissue sarcomas are a rare and multifaceted group of solid tumours. Neoadjuvant chemotherapy is increasingly used to limit loss of function after wide surgical excision with the ultimate aim of improving patient survival. Recently, advances in the identification of effective treatment strategies and improvements in patient risk stratification have been reached. A randomized trial demonstrated that neoadjuvant epirubicin and ifosfamide improves survival of patients affected by five high-risk soft tissue sarcoma histologies of trunk and extremities, including undifferentiated pleomorphic sarcoma, myxoid liposarcoma, synovial sarcoma, malignant peripheral nerve sheath tumours, and leiomyosarcoma. Selection of patients for these treatments is expected to be improved by the eighth edition of the American Joint Committee on Cancer (AJCC) TNM staging system, as it tailors T-stage categories on primary tumour site and considers a prognostic nomogram for retroperitoneal sarcoma, which also includes soft tissue sarcoma histology and other patient and tumour features not directly included in the TNM staging. Within this framework, this article will present neoadjuvant treatment strategies for high-risk soft tissue sarcoma, emphasizing the most recent advances and discussing the need for further research to improve the effectiveness of neoadjuvant treatments.

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“…At longer follow‐up of the Italian and Spanish Sarcoma Group study, noninferiority of three cycles of a full‐dose conventional preoperative chemotherapy in comparison with five cycles (three preoperative and two postoperative) was confirmed . Response to therapy was demonstrated to be associated with better survival.…”

Section: Discussionmentioning

confidence: 93%

Pre- and Postoperative Chemotherapy in Localized Extremity Soft Tissue Sarcoma: A European Organization for Research and Treatment of Cancer Expert Survey

et al. 2017

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The management of localized extremity soft tissue sarcomas (STS) is challenging and the role of pre- and postoperative chemotherapy is unclear and debated among experts. This study analyzed the decision-making process among 12 European experts on systemic therapy for STS. A wide range of recommendations among experts regarding the use of perioperative chemotherapy was discovered. Discrepancies in the use of decision criteria were also uncovered, including the definition of what constitutes high-risk cancer, which is a basis for many to recommend chemotherapy. Before any standardization is possible, a common use of decision criteria is necessary.

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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

Cited by 99 publications

References 15 publications

Relevance of Reference Centers in Sarcoma Care and Quality Item Evaluation: Results from the Prospective Registry of the Spanish Group for Research in Sarcoma (GEIS)

Relevance of Reference Centers in Sarcoma Care and Quality Item Evaluation: Results from the Prospective Registry of the Spanish Group for Research in Sarcoma (GEIS)

Neoadjuvant chemotherapy in soft tissue sarcomas: latest evidence and clinical implications

Pre- and Postoperative Chemotherapy in Localized Extremity Soft Tissue Sarcoma: A European Organization for Research and Treatment of Cancer Expert Survey

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