Imatinib mesylate inhibits the growth of metastatic lung lesions in a patient with dermatofibrosarcoma protuberans

Mizutani, Koya; Tamada, Yasuhiko; Hara, Kazuo; Tsuzuki, T.; Saeki, Hidehisa; Tamaki, Kunihiko; Matsumoto, Yoshinari

doi:10.1111/j.1365-2133.2004.06024.x

Cited by 55 publications

(44 citation statements)

References 6 publications

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“…[10][11][12][13][14][15][16][17] Imatinib has been used successfully to treat unresectable and metastatic lesions as well as locally advanced primary and recurrent DFSP. 1,6,18,19 This study adds to a growing body of literature showing that the use of imatinib can reduce the tumor burden of DFSP.…”

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confidence: 80%

“…Five groups have described a total of 7 patients with metastatic DFSP, 5 of whom had partial or complete remission. 6,18,[24][25][26] The 2 patients with metastatic DFSP who did not to respond to imatinib therapy were found to be without r(17;22) or t(17;22) chromosomal rearrangements. One imatinib-treated case of recurrent DFSP achieved a good response, 22 and a total of 11 patients with locally advanced primary DFSP also had some degree of success.…”

Section: Commentmentioning

confidence: 99%

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Neoadjuvant Imatinib Therapy for Dermatofibrosarcoma Protuberans

Han¹,

Chen²,

Niedt³

et al. 2009

Arch Dermatol

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Background: Dermatofibrosarcoma protuberans (DFSP) is an unusual soft-tissue tumor with a propensity for subclinical extension and local recurrence. Surgical excision, even with tissue-sparing techniques, may cause significant deformity or disability because of the infiltrative nature of DFSP. In this study, we evaluate retrospective data obtained from 4 patients with locally advanced or recurrent DFSP who received neoadjuvant imatinib mesylate therapy before undergoing Mohs micrographic surgery.Observations: Patients treated with neoadjuvant imatinib therapy had an average tumor size reduction of 36.9%. This clinical response was paralleled by histopathologic changes, including decreased cellularity in 100% of the total area as well as significant hyalinization. Imatinib therapy for DFSP before Mohs micrographic surgery was associated with 100% local control at a maximum follow-up of 4 years.Conclusions: Neoadjuvant imatinib therapy is a welltolerated, novel approach to DFSP that reduces tumor burden and facilitates resection. Larger prospective studies are needed to confirm and expand on these results.

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confidence: 80%

Section: Commentmentioning

confidence: 99%

Neoadjuvant Imatinib Therapy for Dermatofibrosarcoma Protuberans

Han¹,

Chen²,

Niedt³

et al. 2009

Arch Dermatol

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“…The use of IM has also been reported in 20 isolated cases outside of clinical trials (4,5,(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). Among these, seven patients had fibrosarcoma on DFSP (4,15,16,24) and six patients had metastatic sarcoma (4,5,15,16,18).…”

Section: Discussionmentioning

confidence: 99%

“…Among these, seven patients had fibrosarcoma on DFSP (4,15,16,24) and six patients had metastatic sarcoma (4,5,15,16,18). Cytogenetic analysis showed the COL1A-PDGFB fusion gene in eight out of nine patients studied (4,5,15,17,24,25).…”

Section: Discussionmentioning

confidence: 99%

Imatinib Mesylate as a Preoperative Therapy in Dermatofibrosarcoma: Results of a Multicenter Phase II Study on 25 Patients

Kérob

Porcher

Vérola

et al. 2010

Clinical Cancer Research

129

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Aims: The treatment of dermatofibrosarcoma protuberans (DFSP) involves wide local excision with frequent need for reconstructive surgery. A t(17;22) translocation resulting in COL1A1-PDGFB fusion is present in >95% of cases. Certain patient observations and a report on nine patients suggest that imatinib mesylate, targeting platelet-derived growth factor receptor β, has clinical potential in DFSP. The primary aim of this phase II multicenter study was to define the percentage of clinical responders (Response Evaluation Criteria in Solid Tumors) to a 2-month preoperative daily administration of 600 mg of imatinib mesylate before wide local excision. The secondary aims were to determine tolerance, objective response from imaging results (ultrasound and magnetic resonance imaging), and pathologic responses observed in sequential tissue specimens.Patients and Methods: A two-stage flexible design was used with interim analysis after the recruitment of six patients. Twenty-five adults suffering from primary or recurrent DFSP were included from July 2004 to May 2006.Results: The COL1A1-PDGFB fusion gene was detected in 21 out of 25 patients following fluorescence in situ hybridization analysis (two cases were noninformative). A clinical response was achieved in nine (36%) patients (95% confidence interval, 18.9-57.5). The median relative tumoral decrease was 20.0% (range, −12.5 to 100). Apart from expected grade 1 or 2 side effects, we observed one grade 3 neutropenia, one grade 3 maculopapular rash, and one grade 4 transient transaminitis.Conclusion: Our results support the use of imatinib in a neoadjuvant setting in nonresectable DFSP, or when surgery is difficult or mutilating. These results will be useful for setting hypotheses in the evaluation of new drugs to treat primary or secondary resistance to imatinib. Clin Cancer Res; 16(12); 3288-95. ©2010 AACR.Dermatofibrosarcoma protuberans (DFSP) is a rare soft-tissue sarcoma characterized by progressive local growth of CD34+ spindle cells with a highly infiltrative pattern (1). Approximately 85% to 90% of tumors are low-grade, whereas others contain a high-grade fibrosarcomatous component (1). Wide excision is the standard therapy, but it can be difficult and mutilating (2). In less than 2% of cases, DFSP metastasizes and becomes lifethreatening.More than 95% of DFSP present anomalies on the 17q22 and 22q13 chromosomal regions leading to fusion of COL1A1 and PDGFB genes. Transfection studies suggest that PDGFB could act as a mitogen for tumor cells, leading to platelet-derived growth factor (PDGF) receptor activation (3), which thus constitutes a therapeutic target. Indeed, three cases of DFSP with a spectacular response to imatinib mesylate (IM) were reported in 2002 (4, 5). In approximately 5% of cases, COL1A1-PDGFB fusion was not found, suggesting that other genes might be involved in DFSP pathogenesis (6).

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“…There have been a couple of reports (6,7) on the role of 18 F-FDG PET/CT in detecting distant metastasis of dermatofibrosarcoma protuberans, highlighting the fact that metastasis of this entity, though rare, is possible. Two reports (8,9) have also illustrated a possible role for 18 F-FDG PET/CT in monitoring the response of dermatofibrosarcoma protuberans to treatment with imatinib mesylate. However, to our knowledge there has been no specific literature on its role in predicting aggressive biology in individuals showing high uptake at the diseased sites.…”

Section: Discussionmentioning

confidence: 99%

¹⁸F-FDG PET/CT Prediction of an Aggressive Clinical Course for Dermatofibrosarcoma Protuberans

Basu¹,

Goliwale²

2015

J. Nucl. Med. Technol.

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The ability to assess tumor biology is a benefit of molecular imaging with 18 F-FDG PET/CT, which performs better than anatomic imaging in evaluating malignancies. We present an unusual case of fatal dermatofibrosarcoma protuberans, a usually indolent entity for which high-grade 18 F-FDG uptake was predictive of an aggressive clinical course unabated by tyrosine kinase inhibitor imatinib mesylate, to which the patient showed a poor response.

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Imatinib mesylate inhibits the growth of metastatic lung lesions in a patient with dermatofibrosarcoma protuberans

Cited by 55 publications

References 6 publications

Neoadjuvant Imatinib Therapy for Dermatofibrosarcoma Protuberans

Neoadjuvant Imatinib Therapy for Dermatofibrosarcoma Protuberans

Imatinib Mesylate as a Preoperative Therapy in Dermatofibrosarcoma: Results of a Multicenter Phase II Study on 25 Patients

¹⁸F-FDG PET/CT Prediction of an Aggressive Clinical Course for Dermatofibrosarcoma Protuberans

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Imatinib mesylate inhibits the growth of metastatic lung lesions in a patient with dermatofibrosarcoma protuberans

Cited by 55 publications

References 6 publications

Neoadjuvant Imatinib Therapy for Dermatofibrosarcoma Protuberans

Neoadjuvant Imatinib Therapy for Dermatofibrosarcoma Protuberans

Imatinib Mesylate as a Preoperative Therapy in Dermatofibrosarcoma: Results of a Multicenter Phase II Study on 25 Patients

18F-FDG PET/CT Prediction of an Aggressive Clinical Course for Dermatofibrosarcoma Protuberans

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¹⁸F-FDG PET/CT Prediction of an Aggressive Clinical Course for Dermatofibrosarcoma Protuberans