Soft tissue and visceral sarcomas: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up

Casali, Paolo G.; Abecassis, N.; Bauer, Sebastian; Biagini, R.; Bielack, Stefan; Bonvalot, Sylvie; Boukovinas, I.; Bovée, Judith; Brodowicz, Thomas; Broto, Javier Martín; Buonadonna, Angela; Álava, Enrique de; Tos, Angelo Paolo Dei; Muro, Xavier García del; Dileo, Palma; Eriksson, Mikael; Fedenko, Alexander N.; Ferraresi, Virginia; Ferrari, Andrea; Ferrari, Stefano; Frezza, Anna Maria; Gasperoni, Silvia; Gelderblom, Hans; Gil, Thierry; Grignani, Giovanni; Gronchi, Alessandro; Haas, Rick L.; Hannu, A.; Hassan, A. Bassim; Hohenberger, Peter; Issels, Rolf D.; Joensuu, Heikki; Jones, Robin L.; Judson, Ian; Jutte, Paul C.; Kaal, Suzanne E. J.; Kasper, Bernd; Kopečková, Kateřina; Krákorová, Dagmar Adámková; Cesne, Axel Le; Ługowska, Iwona; Merimsky, Ofer; Montemurro, Michael; Pantaleo, Maria Abbondanza; Piana, Raimondo; Picci, Piero; Piperno‐Neumann, Sophie; Pousa, Antonio López; Reichardt, Peter; Robinson, Martin; Rutkowski, Piotr; Safwat, Akmal; Schöffski, Patrick; Sleijfer, Stefan; Stacchiotti, Silvia; Hall, Kirsten Sundby; Unk, Mojca; Coevorden, Frits van; Graaf, Winette van der; Whelan, Jeremy; Wardelmann, Eva; Zaikova, Olga; Blay, Jean‐Yves

doi:10.1093/annonc/mdy096

Cited by 764 publications

(856 citation statements)

References 82 publications

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“…Given the positive impact of clinical expertise on patient outcomes including improved survival [24], it is mandatory that systemic therapy be discussed in multidisciplinary tumour boards, especially in early lines of treatment in sarcoma patients [26]. …”

Section: Key Factors Affecting Sts Treatment Outcomesmentioning

confidence: 99%

“… General treatment algorithm in soft tissue sarcoma [26]. CT, chemotherapy; LMS, leiomyosarcoma; LPS, liposarcoma; RT, radiotherapy; SS, synovial sarcoma; UPS, undifferentiated pleomorphic sarcoma.…”

Section: Current Sts Treatment Algorithmmentioning

confidence: 99%

“…In the advanced STS setting, single-agent doxorubicin remains the gold standard for chemotherapy, although multi-agent chemotherapy with adequate-dose anthracycline + ifosfamide may be an option in situations where a tumour response is considered potentially advantageous and the patient has a good performance status [26]. …”

Section: Anthracycline-based Therapymentioning

confidence: 99%

“…This new treatment paradigm is based on results of a phase II trial, which showed that median OS was significantly prolonged with the combination compared with doxorubicin alone (26.5 vs. 14.7 months; hazard ratio 0.46; 95% CI 0.30–0.71; p = 0.0003) [28]. Because tumour overexpression of PDGFRα had no effect on patient outcomes, mechanisms for the added value of this combination are not fully understood [26]. While results of the confirmatory phase III trial (ClinicalTrials.gov identifier: NCT02451943) [21] are awaited, olaratumab is currently available in some countries for use in combination with doxorubicin as first-line treatment of advanced STS.…”

Section: Anthracycline-based Therapymentioning

confidence: 99%

“…At the time of anthracycline failure, several treatment options exist and, increasingly, the choice of therapy is histology driven (Table 2) [26]. Steady improvement in the median OS of patients with metastatic STS [29] can be attributed to the introduction of new agents administered consecutively along multiple treatment lines and to optimising the sequential use of currently available agents.…”

Section: After Anthracycline Failurementioning

confidence: 99%

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Making the Best of Available Options for Optimal Sarcoma Treatment

Cesne¹

2018

Oncology

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For 35 years options for treating advanced soft tissue sarcoma (STS) were limited to doxorubicin, dacarbazine and ifosfamide. In 2007, trabectedin was approved. Since then, several other agents have become available and many more are in development, ushering in a new era in disease management. Considerable scope exists for improving outcomes of advanced STS through better trial design and improved patient care in everyday practice. After anthracycline failure, there are a range of treatment options and, increasingly, the choice of therapy is histology driven. Introduction of newer agents and optimising use of established agents such as trabectedin has led to an increase in overall survival of advanced STS patients. Optimising treatment with trabectedin is being achieved through more extensive experience in drug management, mainly associated with use in earlier lines and uninterrupted use until disease progression. Identification by next-generation sequencing of a significant proportion of cases of actionable mutations among patients with advanced STS suggests a move towards matched therapy in future. As the armamentarium of active agents in advanced sarcoma increases, so too will the challenge of selecting the right drug for the right patient at the right time, in accordance with the patient’s lifestyle and wishes.

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Section: Key Factors Affecting Sts Treatment Outcomesmentioning

confidence: 99%

Section: Current Sts Treatment Algorithmmentioning

confidence: 99%

Section: Anthracycline-based Therapymentioning

confidence: 99%

Section: Anthracycline-based Therapymentioning

confidence: 99%

Section: After Anthracycline Failurementioning

confidence: 99%

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Making the Best of Available Options for Optimal Sarcoma Treatment

Cesne¹

2018

Oncology

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Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcoma

et al. 2021

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IMPORTANCE Currently, preoperative radiotherapy for all soft-tissue sarcomas is identical at a 50-Gy dose level, which can be associated with morbidity, particularly wound complications. The observed clinical radiosensitivity of the myxoid liposarcoma subtype might offer the possibility to reduce morbidity. OBJECTIVE To assess whether a dose reduction of preoperative radiotherapy for myxoid liposarcoma would result in comparable oncological outcome with less morbidity. DESIGN, SETTING, AND PARTICIPANTSThe Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcomas (DOREMY) trial is a prospective, single-group, phase 2 nonrandomized controlled trial being conducted in 9 tertiary sarcoma centers in Europe and the US. Participants include adults with nonmetastatic, biopsy-proven and translocation-confirmed myxoid liposarcoma of the extremity or trunk who were enrolled between November 24, 2010, and August 1, 2019. Data analyses, using both per-protocol and intention-to-treat approaches, were conducted from November 24, 2010, to January 31, 2020. INTERVENTIONSThe experimental preoperative radiotherapy regimen consisted of 36 Gy in once-daily 2-Gy fractions, with subsequent definitive surgical resection after an interval of 4 or more weeks. MAIN OUTCOMES AND MEASURESAs a short-term evaluable surrogate for local control, the primary end point was centrally reviewed pathologic treatment response. The experimental regimen was regarded as a success when 70% or more of the resection specimens showed extensive treatment response, defined as 50% or greater of the tumor volume containing treatment effects. Morbidity outcomes consisted of wound complications and late toxic effects. RESULTS Among the 79 eligible patients, 44 (56%) were men and the median (interquartile range) age was 45 (39-56) years. Two patients did not undergo surgical resection because of intercurrent metastatic disease. Extensive pathological treatment response was observed in 70 of 77 patients (91%; posterior mean, 90.4%; 95% highest probability density interval, 83.8%-96.4%). The local control rate was 100%. The rate of wound complication requiring intervention was 17%, and the rate of grade 2 or higher toxic effects was 14%. CONCLUSIONS AND RELEVANCEThe findings of the DOREMY nonrandomized clinical trial suggest that deintensification of preoperative radiotherapy dose is effective and oncologically safe and is associated with less morbidity than historical controls, although differences in radiotherapy techniques and follow-up should be considered. A 36-Gy dose delivered in once-daily 2-Gy fractions is proposed as a dose-fractionation approach for myxoid liposarcoma, given that phase 3 trials are logistically impossible to execute in rare cancers.

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PARP1 expression in soft tissue sarcomas is a poor‐prognosis factor and a new potential therapeutic target

et al. 2019

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Soft tissue sarcomas (STSs) are aggressive tumors with few efficient systemic therapies. Poly(ADP‐ribose) polymerase‐1 (PARP1) inhibitors represent an emerging therapeutic option in tumors with genomic instability. The genomics of STSs is complex in more than half of cases, suggesting a high level of inherent DNA damage and genomic instability. Thus, STSs could be efficiently targeted with PARP inhibitors. Promising preclinical results have been reported, but few data are available regarding PARP1 expression in clinical samples. We examined PARP1 mRNA expression in 1464 clinical samples of STS, including 1432 primary tumors and 32 relapses, and searched for correlations with clinicopathological features, including metastasis‐free survival (MFS). Expression was heterogeneous across the samples, not different between primary and secondary tumors, and was correlated to PARP1 DNA copy number. In the 1432 primary tumors, the ‘PARP1‐high’ samples were associated with younger patients, more frequent locations at the extremities, superficial trunk and head and neck, more leiomyosarcomas and other STSs and less liposarcomas and myxofibrosarcomas, more grade 3, more high‐risk CINSARC tumors, and more ‘chromosomically instable’ tumors. They were associated with shorter MFS, independently of other significant prognostic features, including the CINSARC signature. We found a strong involvement of genes overexpressed in the ‘PARP1‐high’ samples in cell cycle, DNA replication, and DNA repair. PARP1 expression refines the prediction of MFS in STSs, and similar expression exists in secondary and primary tumors, supporting the development of PARP1 inhibitors.

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Soft tissue and visceral sarcomas: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up

Cited by 764 publications

References 82 publications

Making the Best of Available Options for Optimal Sarcoma Treatment

Making the Best of Available Options for Optimal Sarcoma Treatment

Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcoma

PARP1 expression in soft tissue sarcomas is a poor‐prognosis factor and a new potential therapeutic target

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