Partial response of a rare malignant metastatic diffuse tenosynovial giant cell tumor with benign histologic features, treated with SCH 717–454, an insulin growth factor receptor inhibitor, in combination with everolimus, an MTOR inhibitor

Sikaria, Swati; Heim-Hall, Josefine; Diaz, Elizabeth; Williams, Ronald; Sankhala, Kamelesh; Laabs, Brenda; Mita, Monica

doi:10.1007/s11523-013-0267-8

Cited by 8 publications

(4 citation statements)

References 20 publications

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“…As shown by the case reported by Sikaria et al 5 and the present case, histologically benign metastatic TS-GCT can be potentially fatal. Pulmonary metastatic spread in the present case was not promoted by surgical manipulation and must have been caused by an active multi-step process rather than passive implantation of tumor cells.…”

Section: Discussionsupporting

confidence: 69%

“…Asano et al 6 speculated that these metastases from histologically benign lesions were an “implantation phenomenon” without potentially fatal malignancy and could be managed conservatively. In contrast, Sikaria et al 5 reported a patient with histologically benign but clinically malignant metastatic TS-GCT. The patient was treated with molecularly targeted agents (an IGFR inhibitor, an mTOR inhibitor, and imatinib); however, he died of pulmonary metastases.…”

Section: Discussionmentioning

confidence: 92%

“…The development of metastatic spread from a histologically benign, diffuse TS-GCT is extremely exceptional and as far as we know, only five cases have been previously reported in the English literature (Table 1). 3 –7 Metastases usually follow several local recurrences, with the duration from primary surgery ranging from 5 to 49 years. The present patient noticed a golf-ball-sized lump in the buttock 12 years prior to presentation, but she had not undergone any surgical treatment for the tumor.…”

Section: Discussionmentioning

confidence: 99%

“…2 Development of metastases from histologically benign TS-GCT is extremely rare; to our knowledge, only five cases have been described in the English literature. [3][4][5][6][7] Herein, we report a 41-year-old woman who developed fatal multiple pulmonary metastases from extra-articular diffuse TS-GCT without obvious histologically malignant findings. The patient was informed that data concerning her case would be submitted for publication, and she provided consent.…”

Section: Introductionmentioning

confidence: 99%

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Extra-articular diffuse-type tenosynovial giant cell tumor with benign histological features resulting in fatal pulmonary metastases

Osanai

Suzuki

Hiraga

et al. 2017

J Orthop Surg (Hong Kong)

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Diffuse-type tenosynovial giant cell tumor (TS-GCT) is categorized as a locally aggressive but non-metastasizing neoplasm according to the WHO classification. Herein, we report an extremely rare case of a 41-year-old woman who developed multiple metastases from diffuse TS-GCT with benign histological features. The patient complained of a painful buttock mass and imaging studies revealed a soft tissue tumor of the buttock and multiple pulmonary nodules. The buttock tumor was excised and the final diagnosis was extra-articular diffuse-type TS-GCT. By video-assisted thoracic surgery, pulmonary nodules were pathologically identical to the primary tumor. Residual pulmonary nodules progressively grew, and she developed a muscle metastasis and a subcutis metastasis. She died of respiratory dysfunction due to multiple pulmonary metastases 1 year after primary surgery. Very few reports on histologically benign metastases from TS-GCT have been published, and the natural course of this rare condition remains unclarified. This rare case could provide important information for further clinical evaluation of this tumor.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Extra-articular diffuse-type tenosynovial giant cell tumor with benign histological features resulting in fatal pulmonary metastases

Osanai

Suzuki

Hiraga

et al. 2017

J Orthop Surg (Hong Kong)

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Current Systemic Treatment Options for Tenosynovial Giant Cell Tumor/Pigmented Villonodular Synovitis: Targeting the CSF1/CSF1R Axis

Brahmi

Vinceneux

Cassier

2016

Curr. Treat. Options in Oncol.

103

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Adequate surgical resection remains the treatment of choice for tenosyovial giant cell tumor (TGCT). However, diffuse type TGCT (D-TGCT) is more difficult to resect and has a higher rate of recurrence (up to 50 %), which is often multiple. D-TGCT is rarely lethal and only rare cases of metastases have been described. Nevertheless, patients might have a significant decline in their quality of life due to multiple operations, which may sometimes result in a partial loss of function of the affected joint and may also be associated with perioperative morbidity and secondary arthrosis. As of today, no systemic treatment is approved for this rare disease. The aims of systemic therapy in the context of a non-lethal tumor are to reduce surgical morbidity and to preserve function and patient quality of life. Because TGCT is associated with characteristic cytogenetic abnormalities resulting in the overexpression of CSF1, systemic therapies targeting the CSF1/CSF1R axis (imatinib, nilotinib, emactuzumab, and PLX3397) have been tested in patients with locally advanced or relapsed D-TGCT. The more recent and more specific CSF1R inhibitors have shown a very interesting clinical activity with acceptable toxicity in early phase trials. These results will need to be confirmed in larger, ideally randomized, trials. But the high rate of clinical and functional improvement seen in some patients with advanced D-TGCT, often after multiple operations, suggests that these inhibitors will likely have a role in the management of patients with an inoperable disease; the definition of "inoperable TGCT" still requires refinement to reach a consensus. Another point that will need to be addressed is that of "the optimal duration of therapy" for these patients. Indeed, we and others have observed often prolonged clinical benefit and symptomatic relief even after treatment was stopped, with both monoclonal antibodies and tyrosine kinase inhibitors. Responses were observed very early on with emactuzumab and PLX3397, and patients experienced significant symptom improvement within a few weeks of starting therapy (2-4 weeks). Another possible application of CSF1R inhibitors could be used either as a preoperative or postoperative therapy for patients with operable TGCT. However, we currently lack sufficient follow-up to adequately address these questions which will each require specific trial designs. Overall, the striking clinical activity of CSF1R specific inhibitors in TGCT has created great enthusiasm among clinicians, and further development of these agents is clearly medically needed. Nevertheless, further investigations are necessary to validate those treatments and assess how to best incorporate them among other treatment modalities into the overall therapeutic strategy for a given patient.

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mTOR inhibitors in urinary bladder cancer

et al. 2016

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Despite the great scientific advances that have been made in cancer treatment, there is still much to do, particularly with regard to urinary bladder cancer. Some of the drugs used in urinary bladder cancer treatment have been in use for more than 30 years and show reduced effectiveness and high recurrence rates. There have been several attempts to find new and more effective drugs, to be used alone or in combination with the drugs already in use, in order to overcome this situation.The biologically important mammalian target of rapamycin (mTOR) pathway is altered in cancer and mTOR inhibitors have raised many expectations as potentially important anticancer drugs. In this article, the authors will review the mTOR pathway and present their experiences of the use of some mTOR inhibitors, sirolimus, everolimus and temsirolimus, in isolation and in conjunction with non-mTOR inhibitors cisplatin and gemcitabine, on urinary bladder tumour cell lines. The non-muscle-invasive cell line, 5637, is the only one that exhibits a small alteration in the mTOR and AKT phosphorylation after rapalogs exposure. Also, there was a small inhibition of cell proliferation. With gemcitabine plus everolimus or temsirolimus, the results were encouraging as a more effective response was noticed with both combinations, especially in the 5637 and T24 cell lines. Cisplatin associated with everolimus or temsirolimus also gave promising results, as an antiproliferative effect was observed when the drugs were associated, in particular on the 5637 and HT1376 cell lines. Everolimus or temsirolimus in conjunction with gemcitabine or cisplatin could have an important role to play in urinary bladder cancer treatment, depending on the tumour grading.

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Partial response of a rare malignant metastatic diffuse tenosynovial giant cell tumor with benign histologic features, treated with SCH 717–454, an insulin growth factor receptor inhibitor, in combination with everolimus, an MTOR inhibitor

Cited by 8 publications

References 20 publications

Extra-articular diffuse-type tenosynovial giant cell tumor with benign histological features resulting in fatal pulmonary metastases

Extra-articular diffuse-type tenosynovial giant cell tumor with benign histological features resulting in fatal pulmonary metastases

Current Systemic Treatment Options for Tenosynovial Giant Cell Tumor/Pigmented Villonodular Synovitis: Targeting the CSF1/CSF1R Axis

mTOR inhibitors in urinary bladder cancer

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