Activity of sunitinib in extraskeletal myxoid chondrosarcoma

S. Stacchiotti, M. A. Pantaleo, A. Astolfi, G. P. Dagrada, T. Negri, A. P. Dei Tos, V. Indio, C. Morosi, A. Gronchi, C. Colombo, E. Conca, L. Toffolatti, M. Tazzari, F. Crippa, R. Maestro, S. Pilotti, P. G. Casali

Research output: Contribution to journalArticle

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Abstract

Background Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma, marked by NR4A3 rearrangement. Herein we report on the activity of sunitinib in a series of 10 patients, strengthening what initially observed in two cases. Patients and methods From July 2011, 10 patients with progressive metastatic translocated EMC have been consecutively treated with sunitinib 37.5 mg/day, on a named-use basis. In an attempt to interpret the activity of sunitinib in EMC, genotype/phenotype correlations were carried out by fluorescence in situ hybridization (FISH) analyses. Moreover, transcriptome, immunohistochemical and biochemical analyses of a limited set of samples were performed focusing on some putative targets of sunitinib. Results Eight of 10 patients are still on therapy. Six patients had a Response Evaluation Criteria in Solid Tumours (RECIST) partial response (PR), two were stable, two progressed. Positron emission tomography (PET) was consistent in 6/6 evaluable cases. One patient underwent surgery after sunitinib, with evidence of a pathologic response. At a median follow-up of 8.5 months (range 2-28), no secondary resistance was detected. Median progression free survival (PFS) has not been reached. Interestingly, all responsive cases turned out to express the typical EWSR1-NR4A3 fusion, while refractory cases carried the alternative TAF15-NR4A3 fusion. Among putative sunitinib targets, only RET was expressed and activated in analysed samples. Conclusions This report confirms the therapeutic activity of sunitinib in EMC. Genotype/phenotype analyses support a correlation between response and EWSR1-NR4A3 fusion. Involvement of RET deserves further investigation.

Original languageEnglish
Pages (from-to)1657-1664
Number of pages8
JournalEuropean Journal of Cancer
Volume50
Issue number9
DOIs
Publication statusPublished - 2014

Fingerprint

Genetic Association Studies
Extraskeletal Myxoid Chondrosarcoma
sunitinib
Fluorescence In Situ Hybridization
Transcriptome
Sarcoma
Positron-Emission Tomography
Disease-Free Survival
Genotype
Phenotype
Therapeutics
Response Evaluation Criteria in Solid Tumors

Keywords

  • Antiangiogenic
  • Chemotherapy
  • Chondrosarcoma
  • Extraskeletal myxoid chondrosarcoma
  • Sarcoma
  • Sunitinib

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Activity of sunitinib in extraskeletal myxoid chondrosarcoma. / Stacchiotti, S.; Pantaleo, M. A.; Astolfi, A.; Dagrada, G. P.; Negri, T.; Dei Tos, A. P.; Indio, V.; Morosi, C.; Gronchi, A.; Colombo, C.; Conca, E.; Toffolatti, L.; Tazzari, M.; Crippa, F.; Maestro, R.; Pilotti, S.; Casali, P. G.

In: European Journal of Cancer, Vol. 50, No. 9, 2014, p. 1657-1664.

Research output: Contribution to journalArticle

Stacchiotti, S, Pantaleo, MA, Astolfi, A, Dagrada, GP, Negri, T, Dei Tos, AP, Indio, V, Morosi, C, Gronchi, A, Colombo, C, Conca, E, Toffolatti, L, Tazzari, M, Crippa, F, Maestro, R, Pilotti, S & Casali, PG 2014, 'Activity of sunitinib in extraskeletal myxoid chondrosarcoma', European Journal of Cancer, vol. 50, no. 9, pp. 1657-1664. https://doi.org/10.1016/j.ejca.2014.03.013
Stacchiotti, S. ; Pantaleo, M. A. ; Astolfi, A. ; Dagrada, G. P. ; Negri, T. ; Dei Tos, A. P. ; Indio, V. ; Morosi, C. ; Gronchi, A. ; Colombo, C. ; Conca, E. ; Toffolatti, L. ; Tazzari, M. ; Crippa, F. ; Maestro, R. ; Pilotti, S. ; Casali, P. G. / Activity of sunitinib in extraskeletal myxoid chondrosarcoma. In: European Journal of Cancer. 2014 ; Vol. 50, No. 9. pp. 1657-1664.
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abstract = "Background Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma, marked by NR4A3 rearrangement. Herein we report on the activity of sunitinib in a series of 10 patients, strengthening what initially observed in two cases. Patients and methods From July 2011, 10 patients with progressive metastatic translocated EMC have been consecutively treated with sunitinib 37.5 mg/day, on a named-use basis. In an attempt to interpret the activity of sunitinib in EMC, genotype/phenotype correlations were carried out by fluorescence in situ hybridization (FISH) analyses. Moreover, transcriptome, immunohistochemical and biochemical analyses of a limited set of samples were performed focusing on some putative targets of sunitinib. Results Eight of 10 patients are still on therapy. Six patients had a Response Evaluation Criteria in Solid Tumours (RECIST) partial response (PR), two were stable, two progressed. Positron emission tomography (PET) was consistent in 6/6 evaluable cases. One patient underwent surgery after sunitinib, with evidence of a pathologic response. At a median follow-up of 8.5 months (range 2-28), no secondary resistance was detected. Median progression free survival (PFS) has not been reached. Interestingly, all responsive cases turned out to express the typical EWSR1-NR4A3 fusion, while refractory cases carried the alternative TAF15-NR4A3 fusion. Among putative sunitinib targets, only RET was expressed and activated in analysed samples. Conclusions This report confirms the therapeutic activity of sunitinib in EMC. Genotype/phenotype analyses support a correlation between response and EWSR1-NR4A3 fusion. Involvement of RET deserves further investigation.",
keywords = "Antiangiogenic, Chemotherapy, Chondrosarcoma, Extraskeletal myxoid chondrosarcoma, Sarcoma, Sunitinib",
author = "S. Stacchiotti and Pantaleo, {M. A.} and A. Astolfi and Dagrada, {G. P.} and T. Negri and {Dei Tos}, {A. P.} and V. Indio and C. Morosi and A. Gronchi and C. Colombo and E. Conca and L. Toffolatti and M. Tazzari and F. Crippa and R. Maestro and S. Pilotti and Casali, {P. G.}",
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T1 - Activity of sunitinib in extraskeletal myxoid chondrosarcoma

AU - Stacchiotti, S.

AU - Pantaleo, M. A.

AU - Astolfi, A.

AU - Dagrada, G. P.

AU - Negri, T.

AU - Dei Tos, A. P.

AU - Indio, V.

AU - Morosi, C.

AU - Gronchi, A.

AU - Colombo, C.

AU - Conca, E.

AU - Toffolatti, L.

AU - Tazzari, M.

AU - Crippa, F.

AU - Maestro, R.

AU - Pilotti, S.

AU - Casali, P. G.

PY - 2014

Y1 - 2014

N2 - Background Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma, marked by NR4A3 rearrangement. Herein we report on the activity of sunitinib in a series of 10 patients, strengthening what initially observed in two cases. Patients and methods From July 2011, 10 patients with progressive metastatic translocated EMC have been consecutively treated with sunitinib 37.5 mg/day, on a named-use basis. In an attempt to interpret the activity of sunitinib in EMC, genotype/phenotype correlations were carried out by fluorescence in situ hybridization (FISH) analyses. Moreover, transcriptome, immunohistochemical and biochemical analyses of a limited set of samples were performed focusing on some putative targets of sunitinib. Results Eight of 10 patients are still on therapy. Six patients had a Response Evaluation Criteria in Solid Tumours (RECIST) partial response (PR), two were stable, two progressed. Positron emission tomography (PET) was consistent in 6/6 evaluable cases. One patient underwent surgery after sunitinib, with evidence of a pathologic response. At a median follow-up of 8.5 months (range 2-28), no secondary resistance was detected. Median progression free survival (PFS) has not been reached. Interestingly, all responsive cases turned out to express the typical EWSR1-NR4A3 fusion, while refractory cases carried the alternative TAF15-NR4A3 fusion. Among putative sunitinib targets, only RET was expressed and activated in analysed samples. Conclusions This report confirms the therapeutic activity of sunitinib in EMC. Genotype/phenotype analyses support a correlation between response and EWSR1-NR4A3 fusion. Involvement of RET deserves further investigation.

AB - Background Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma, marked by NR4A3 rearrangement. Herein we report on the activity of sunitinib in a series of 10 patients, strengthening what initially observed in two cases. Patients and methods From July 2011, 10 patients with progressive metastatic translocated EMC have been consecutively treated with sunitinib 37.5 mg/day, on a named-use basis. In an attempt to interpret the activity of sunitinib in EMC, genotype/phenotype correlations were carried out by fluorescence in situ hybridization (FISH) analyses. Moreover, transcriptome, immunohistochemical and biochemical analyses of a limited set of samples were performed focusing on some putative targets of sunitinib. Results Eight of 10 patients are still on therapy. Six patients had a Response Evaluation Criteria in Solid Tumours (RECIST) partial response (PR), two were stable, two progressed. Positron emission tomography (PET) was consistent in 6/6 evaluable cases. One patient underwent surgery after sunitinib, with evidence of a pathologic response. At a median follow-up of 8.5 months (range 2-28), no secondary resistance was detected. Median progression free survival (PFS) has not been reached. Interestingly, all responsive cases turned out to express the typical EWSR1-NR4A3 fusion, while refractory cases carried the alternative TAF15-NR4A3 fusion. Among putative sunitinib targets, only RET was expressed and activated in analysed samples. Conclusions This report confirms the therapeutic activity of sunitinib in EMC. Genotype/phenotype analyses support a correlation between response and EWSR1-NR4A3 fusion. Involvement of RET deserves further investigation.

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KW - Chemotherapy

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KW - Extraskeletal myxoid chondrosarcoma

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KW - Sunitinib

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