Adherence to treatment guidelines for primary sarcomas affects patient survival: a side study of the European CONnective TIssue CAncer NETwork (CONTICANET)

Róssi, Carlo; Vecchiato, Antonella; Mastrangelo, Giuseppe; Montesco, Maria Cristina; Russano, Francesco; Mocellin, Simone; Pasquali, Sandro; Scarzello, Giovanni; Basso, Umberto; Frasson, Alvise; Pilati, Pierluigi; Nitti, D.; Lurkin, Antoine; Ray‐Coquard, Isabelle

doi:10.1093/annonc/mdt031

Cited by 65 publications

(44 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Chemotherapy is still a matter of debate and must be discussed in a dedicated multidisciplinary committee with an individual approach basis 28. For all adult sarcoma in a localized phase, R0 surgery remains the cornerstone of treatment 29, 30, 31, 32, 33, 34, 35. The present study underlines the heterogeneity of adult RMS management.…”

Section: Discussionmentioning

confidence: 75%

Outcome of 449 adult patients with rhabdomyosarcoma: an observational ambispective nationwide study

et al. 2018

View full text Add to dashboard Cite

Five‐year overall survival (OS) of localized RMS exceeds 70% in children (<18) but is very poor in adult patients. We analyzed the outcome and prognostic factors (PF) of a national series of adult patients with RMS in a large study. The study population consisted of two different cohorts: a retrospective cohort (157 adult patients treated in 13 reference centers between 05/1981 and 02/2010) and the prospective cohort (292 patients with RMS diagnosed and treated between 01/2010 and 12/2014 in France) included in the NetSarc database. A descriptive analysis of patients’ characteristics and prognostic factors was conducted on both series which were compared. In the retrospective series, histological subtypes were embryonal (E‐RMS) for 21% of patients, alveolar (A‐RMS) for 35% of patients, and “adult‐type” P‐RMS (pleomorphic, spindle cell RMS, not otherwise specified) (P) for 44% patients. This distribution significantly differed in the prospective cohort: A‐RMS: 18%; E‐RMS: 17%; and P‐RMS 65%. With a median follow‐up of 8.5 years, 5‐year OS for localized RMS and advanced RMS (with nodes and/or metastases) was 43% and 5%, respectively, (P < 0.0001), and median OS was 51, 33, and 16 months for E‐RMS, A‐RMS, and P‐RMS, respectively, in the retrospective cohort. The median OS was less than 40 months for the prospective nationwide cohort for the entire population. In a multivariate analysis of the retrospective study, independent prognostic factors for OS were A‐RMS, R0 resection, and adjuvant radiotherapy (RT). For localized RMS, age and use of pediatric chemotherapy (CT) regimen are independent prognostic factors. Adult patients with RMS have a poorer overall survival than pediatric patients, and survival varies considerably across histological subtypes.

show abstract

Section: Discussionmentioning

confidence: 75%

Outcome of 449 adult patients with rhabdomyosarcoma: an observational ambispective nationwide study

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Sarcoma is a rare cancer with many subtypes that are genetically and biologically distinct (28)(29)(30). Molecular heterogeneity and resistance to chemotherapy make sarcoma a rather useful model to study mechanisms of tumorigenesis and drug resistance (31,32). Surgery is the only curative method for resectable disease and chemotherapy and radiation have only limited ability to control inoperable or metastatic disease (33).…”

Section: Introductionmentioning

confidence: 99%

Selinexor (KPT-330) Induces Tumor Suppression through Nuclear Sequestration of IκB and Downregulation of Survivin

Nair

Musi

Schwartz

2017

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Selinexor, a small molecule that inhibits nuclear export protein XPO1, has demonstrated efficacy in solid tumors and hematologic malignancies with the evidence of clinical activity in sarcoma as a single agent. Treatment options available are very few, and hence the need to identify novel targets and strategic therapies is of utmost importance.Experimental Design: The mechanistic effects of selinexor in sarcomas as a monotherapy and in combination with proteasome inhibitor, carfilzomib, across a panel of cell lines in vitro and few in xenograft mouse models were investigated.Results: Selinexor induced IkB nuclear localization as a single agent, and the effect was enhanced by stabilization of IkB when pretreated with the proteasome inhibitor carfilzomib. This stabilization and retention of IkB in the nucleus resulted in inhibition of NFkB and transcriptional suppression of the critical antiapoptotic protein, survivin. Treatment of carfilzomib followed by selinexor caused selinexor-sensitive and selinexor-resistant cell lines to be more sensitive to selinexor as determined by an increase in apoptosis. This was successfully demonstrated in the MPNST xenograft model with enhanced tumor suppression.Conclusions: The subcellular distributions of IkB and NFkB are indicative of carcinogenesis. Inhibition of XPO1 results in intranuclear retention of IkB, which inhibits NFkB and thereby provides a novel mechanism for drug therapy in sarcoma. This effect can be further enhanced in relatively selinexor-resistant sarcoma cell lines by pretreatment with the proteasome inhibitor carfilzomib. Because of these results, a human clinical trial with selinexor in combination with a proteasome inhibitor is planned for the treatment of sarcoma.

show abstract

“…Recent literature has emphasized on the need to centralize the management of these patients in highly specialized centers, showing how the different experience of various centers can significantly change the outcome of these patients (10). This is because these are rare neoplasms, not easy to handle in either the diagnostic framework or oncosurgical management, and possible neoadjuvant therapy and choice of surgical intervention most likely to ensure radicality need to be considered.…”

mentioning

confidence: 99%

Magnetic Resonance Imaging Assessment of Lipomatous Soft-tissue Tumors

Coran

Ortolan

Attar

et al. 2017

View full text Add to dashboard Cite

show abstract

Adherence to treatment guidelines for primary sarcomas affects patient survival: a side study of the European CONnective TIssue CAncer NETwork (CONTICANET)

Abstract: Incomplete adherence to CPGs for loco-regional treatment of sarcomas was associated with worse prognosis in patients with non-metastatic tumors.

Cited by 65 publications

References 31 publications

Outcome of 449 adult patients with rhabdomyosarcoma: an observational ambispective nationwide study

Outcome of 449 adult patients with rhabdomyosarcoma: an observational ambispective nationwide study

Selinexor (KPT-330) Induces Tumor Suppression through Nuclear Sequestration of IκB and Downregulation of Survivin

Magnetic Resonance Imaging Assessment of Lipomatous Soft-tissue Tumors

Contact Info

Product

Resources

About