A nonrandom association of breast implants and the formation of desmoid tumors.

BACKGROUND: Studies suggest that surgical breast augmentation with implants is a risk factor for breast desmoid tumors. The statistical strength of this correlation is unknown, as evidence is limited to anecdotal reports. METHODS: Patients with breast desmoid tumors and a history of breast implants seen at a single center between 2000 and 2021 were identified via radiology, breast, and sarcoma databases. The standardized incidence ratio (SIR) was calculated to assess the correlation between breast desmoid tumors and breast implants. The cases were pooled with published cases for analyses. Progression-free survival curves and hazard ratios were estimated using the Kaplan-Meier method and Cox proportional-hazards modeling. RESULTS: Fourteen patients from one institution and 66 cases in the literature were identified. All patients were female, and the mean age was 38 years old (range 20-66). 63 patients (82%) underwent resection, 9 (12%) received chemotherapy, 3 (4%) received sorafenib, 11 (14%) received hormonal therapy, and 3 (4%) underwent active surveillance. After resection, the 2-year recurrence-free survival rate was 77% (95% CI 65%-89%). The recurrence risk was lower for resection with no residual tumor (R0) compared to microscopic (R1) or macroscopic (R2) residual tumor (HR: 0.15; 95% CI 0.02-0.8; p < 0.05). The SIR was 482 (95% CI 259-775) to 823 (95% CI 442-1322), suggesting a 482-823 times higher risk of developing a breast desmoid tumor after breast augmentation than the general population. CONCLUSION: We present a nonrandom association between breast implants and desmoid tumors. Whether the tumors arise from the surgical trauma or the implant's biomaterial is unknown. When surgery is indicated, negative margins reduce the risk of recurrence.

Phase II study of the mammalian target of rapamycin inhibitor ridaforolimus in patients with advanced bone and soft tissue sarcomas.

PURPOSE: Ridaforolimus is an inhibitor of mammalian target of rapamycin, an integral component of the phosphatidyl 3-kinase/AKT signaling pathway, with early evidence of activity in sarcomas. This multicenter, open-label, single-arm, phase II trial was conducted to assess the antitumor activity of ridaforolimus in patients with distinct subtypes of advanced sarcomas. PATIENTS AND METHODS: Patients with metastatic or unresectable soft tissue or bone sarcomas received ridaforolimus 12.5 mg administered as a 30-minute intravenous infusion once daily for 5 days every 2 weeks. The primary end point was clinical benefit response (CBR) rate (complete response or partial response [PR] or stable disease ≥ 16 weeks). Safety, progression-free survival (PFS), overall survival (OS), time to progression, and duration of response were also evaluated. RESULTS: A total of 212 patients were treated in four separate histologic cohorts. In this heavily pretreated population, 61 patients (28.8%) achieved CBR. Median PFS was 15.3 weeks; median OS was 40 weeks. Response Evaluation Criteria in Solid Tumors (RECIST) confirmed response rate was 1.9%, with four patients achieving confirmed PR (two with osteosarcoma, one with spindle cell sarcoma, and one with malignant fibrous histiocytoma). Archival tumor protein markers analyzed were not correlated with CBR. Related adverse events were generally mild or moderate and consisted primarily of stomatitis, mucosal inflammation, mouth ulceration, rash, and fatigue. CONCLUSION: Single-agent ridaforolimus in patients with advanced and pretreated sarcomas led to PFS results that compare favorably with historical metrics. A phase III trial based on these data will further define ridaforolimus activity in sarcomas.

Sunitinib treatment in pediatric patients with advanced GIST following failure of imatinib.

BACKGROUND: Sunitinib inhibits KIT and other members of the split-kinase-domain family of receptor tyrosine kinases. Sunitinib prolongs survival in adult patients with imatinib-resistant gastrointestinal stromal tumor (GIST). We report the experience with sunitinib in pediatric patients with advanced GIST following failure of imatinib. PROCEDURE: Sunitinib therapy was provided through a treatment-use protocol. Patients were 10-17 years old at enrollment. All patients had GIST resistant to imatinib therapy. Sunitinib was administered daily for 4 weeks in 6-week treatment cycles. KIT and platelet-derived growth factor receptor alpha (PDGFRA) genotyping of tumor tissue were performed. RESULTS: One patient achieved a partial response, five patients had stable disease and one patient had progressive disease on sunitinib. The duration of disease stabilization was between 7 and 21+ months, with a mean of 15 months. Time to tumor progression was longer on sunitinib than on prior imatinib treatment for five of six patients. Two patients experienced grade 3 adverse events. All other adverse events were grade 1-2. None of the five patients tested had mutations in KIT or PDGFRA. CONCLUSION: Sunitinib treatment was associated with substantial initial antitumor activity and acceptable tolerability in this group of pediatric patients with imatinib-resistant GIST.

Therapeutic potential of directed tyrosine kinase inhibitor therapy in sarcomas.

BACKGROUND: Sarcomas are rare mesenchymally derived tumors for which there are limited treatment options. This paper discusses the current therapeutic potential of directed tyrosine kinase inhibitors (TKIs) in sarcoma. METHODS: The authors review antibody-based strategies and small molecular inhibitors of TKIs, with specific emphasis placed on the potential use of these targeted agents as therapeutic options for the treatment of sarcomas that are not gastrointestinal stromal tumors. RESULTS: Many TKs have been shown to be mutated or overexpressed in human sarcoma tumors and cell lines and may serve as potential targets for promising new sarcoma therapies. Furthermore, the novel mechanism of targeting TKs may complement the antitumor activity of existing sarcoma treatment options. CONCLUSIONS: TKIs such as imatinib, sunitinib, and sorefanib are promising new therapeutic options for the management of patients with soft tissue sarcoma.