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Systemic Treatments and Molecular Biomarkers for Perivascular Epithelioid Cell Tumors: A Single-institution Retrospective Analysis.

ABSTRACT: Perivascular epithelioid cell tumors (PEComa) are a large family of mesenchymal neoplasms, with variable clinical course. Evidence regarding treatment of advanced PEComas is scarce, with only one FDA-approved treatment available. The goals of this study were to provide data regarding systemic treatments for advanced PEComas and to identify biomarkers of prognostic relevance. This is a single-institution retrospective study of patients with advanced PEComas requiring systemic treatment, including malignant PEComa, angiomyolipoma (including the epithelioid variant), and lymphangioleiomyomatosis. Outcomes measured were overall survival (OS), first-line and combined progression-free survival (PFS), and tumor response. Kaplan-Meier, univariable, and multivariable Cox proportional hazards analysis were performed. A total of 29 patients were included, most with malignant PEComa (n = 17). Median OS was 204.9 months, while median PFS was 92.4 months from first-line, and 15.8 months for all lines combined. TFE3 overexpression correlated with higher risk of death (HR: 11.8, P = 0.04), and shorter median OS (P = 0.001). Chemotherapy and mTOR inhibitors showed similar OS (P = 0.84), and first-line PFS (P = 0.67). Combined PFS was similar between individual mTOR inhibitors, chemotherapy, immune checkpoint inhibitors and other treatments (P = 0.19). Different mTOR inhibitors demonstrated similar efficacy, making cost and availability important considerations when choosing a specific agent. mTOR inhibitors showed similar outcomes as chemotherapy, suggesting that these should be preferred whenever possible for patients with PEComas given the morbidity associated with chemotherapy. TFE3 overexpression highlighted a subgroup of PEComas with worse prognosis and more aggressive behavior.

Significance

This study examines systemic treatments for advanced PEComas, a rare group of sarcomas, and identifies molecular biomarkers of prognosis. Our results show that mTOR inhibitors have similar efficacy as chemotherapy, and that TFE3 overexpression, on IHC or FISH, correlates with a more aggressive disease course.

SUBMITTER: Testa S

PROVIDER: S-EPMC10335919 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Systemic Treatments and Molecular Biomarkers for Perivascular Epithelioid Cell Tumors: A Single-institution Retrospective Analysis.

Testa Stefano S Bui Nam Q NQ Ganjoo Kristen N KN

Cancer research communications 20230712 7

Perivascular epithelioid cell tumors (PEComa) are a large family of mesenchymal neoplasms, with variable clinical course. Evidence regarding treatment of advanced PEComas is scarce, with only one FDA-approved treatment available. The goals of this study were to provide data regarding systemic treatments for advanced PEComas and to identify biomarkers of prognostic relevance. This is a single-institution retrospective study of patients with advanced PEComas requiring systemic treatment, including ...[more]

PMID: 37448552

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Project description:PurposeMalignant perivascular epithelioid cell tumor (PEComa) is a rare aggressive sarcoma, with no approved treatment. To our knowledge, this phase II, single-arm, registration trial is the first prospective clinical trial in this disease, investigating the safety and efficacy of the mammalian target of rapamycin inhibitor nab-sirolimus (AMPECT, NCT02494570).Patients and methodsPatients with malignant PEComa were treated with nab-sirolimus 100 mg/m2 intravenously once weekly for 2 weeks in 3-week cycles. The primary end point was objective response rate evaluated by independent radiology review. Key secondary end points included duration of response, progression-free survival, and safety. A key exploratory end point was tumor biomarker analysis.ResultsThirty-four patients were treated (safety evaluable), and 31 were evaluable for efficacy. The overall response rate was 39% (12 of 31; 95% CI, 22 to 58) with one complete and 11 partial responses, 52% (16 of 31) of patients had stable disease, and 10% (3 of 31) had progressive disease. Responses were of rapid onset (67% by week 6) and durable. Median duration of response was not reached after a median follow-up for response of 2.5 years, with 7 of 12 responders with treatment ongoing (range, 5.6-47.2+ months). Twenty-five of 31 patients had tumor mutation profiling: 8 of 9 (89%) patients with a TSC2 mutation achieved a confirmed response versus 2 of 16 (13%) without TSC2 mutation (P < .001). The median progression-free survival was 10.6 months (95% CI, 5.5 months to not reached), and the median overall survival was 40.8 months (95% CI, 22.2 months to not reached). Most treatment-related adverse events were grade 1 or 2 and were manageable for long-term treatment. No grade ≥ 4 treatment-related events occurred.Conclusionnab-Sirolimus is active in patients with malignant PEComa. The response rate, durability of response, disease control rate, and safety profile support that nab-sirolimus represents an important new treatment option for this disease.

Project description:Perivascular epithelioid cell tumor (PEComa) is a rare entity with distinctive morphology and of expressing myomelanocytic markers. Gastrointestinal tract (GI) is one of the most common anatomic sites of origin and counts for 20% to 25% of all reported cases of perivascular epithelioid cell tumors not otherwise specified (PEComas-NOS). However, the biologic behavior of perivascular epithelioid cell tumors of gastrointestinal tract (GI PEComas-NOS) is still unclear. The aim of conducting this systematic review is to sum up what is known so far of the epidemiology, natural history, management and prognosis of GI PEComas-NOS.A systematic research was performed on PubMed and EMBASE using the following terms: ("perivascular epithelioid cell tumor" or "PEComa") and ("gastrointestinal tract" or "GI" or "oral " or "mouth" or "esophagus" or "gullet" or "gastric" or "stomach" or "duodenum" or "jejunum" or "ileum" or "cecum" or "colon" or "colorectal" or "sigmoid" or "rectum" or "anus" or "mesentery") up to December 1, 2015. Retrieved GI PEComas-NOS publications, which included these terms, contains case reports, case series to case characteristic researches.A total of 168 articles were reviewed, 41 GI PEComa-NOS English studies among which were retrieved for analysis. We reviewed epidemiology, natural history, management and prognosis of GI PEComa-NOS. Generally GI PEComa-NOS is believed to have women predomination. The most frequently involved location is colon with non-specific clinical signs. Pathologically, GI PEComas-NOS shows epithelioid predominance (70%), meanwhile coexpresses melanocytic and muscle markers characteristically, while immunohistochemistry is a useful tool for identify, which indicates that HMB-45 is regarded as the most sensitive reagent. Complete resection served as mainstay of treatment, while chemotherapy should be unanimously considered to apply in malignant cases. Eventually, it is necessary for closed and long-term follow-up with endoscope and imaging for ruling out local recurrence or distant metastasis of this tumor.GI PEComas-NOS lives with unclear behavior. There are still many unverified clinicopathological issues of GI PEComas-NOS that needs to be clarified. Further studies and analyses concerning this rare entity should be brought out. Thus, the randomized clinical researches (RCTs) are required to be conducted.

Project description:BACKGROUND:In the perioperative period, intravenous lidocaine has been used as an opioid-sparing systemic analgesic with additional anti-inflammatory and anti-hyperalgesic properties. OBJECTIVE:The aim of this retrospective study was to review the utilization, efficacy, and safety of intravenous lidocaine on our Acute Pain Service (APS) and identify surgical and patient populations where this intervention was found to be useful. PATIENTS AND METHODS:This retrospective study was designed to assess acute pain management in patients who received an intravenous lidocaine infusion between February 2013 and December 2017. Data collected included demographics, surgery type, infusion duration, pain scores, analgesic consumption, and adverse effects. Pain scores included rest and active pain scores and were analyzed by surgical model and subgroups. Clinically important differences (CIDs) in pain were determined by changes in pain score difference of???2 (11-point scale) or???30% reduction in pain intensity. A patient was considered to have a true CID if a CID was observed with rest and/or active pain scores at both first to second (4-24 h) and first to final time point (4 h to infusion end) comparisons. RESULTS:In total, 544 patients received intravenous lidocaine during this period, and 394 were included in the final analysis. The average (±?standard deviation) duration of infusion was 68.60?±?49.52 h. Surgical specialties included gastrointestinal surgery (41%), orthopedics (28%), neurosurgery (15%), vascular surgery (10%), and others (6%). Overall, 56.1% of the study population experienced a CID, with reduced pain scores at rest and/or with activity. CIDs were also observed in patients with chronic pain (53.5%) and when intravenous lidocaine was used as a rescue technique (69.6%). Within the rescue cohort, opioid-dependent and opioid-naïve patients experienced 23.0% and 45.6% reductions, respectively, in their 8-h intravenous opioid consumption. In total, 37 patients in the study experienced transient signs of mild local anesthetic toxicity, which resolved with infusion titration (conservative) management. One serious adverse event required intervention, and the patient was successfully resuscitated. CONCLUSIONS:This retrospective study at a single institution with an APS policy for intravenous lidocaine in the postoperative period identifies benefits of intravenous lidocaine in certain surgical and patient populations. The findings need to be confirmed with further research.

Dataset Information

Systemic Treatments and Molecular Biomarkers for Perivascular Epithelioid Cell Tumors: A Single-institution Retrospective Analysis.

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Publications

Systemic Treatments and Molecular Biomarkers for Perivascular Epithelioid Cell Tumors: A Single-institution Retrospective Analysis.

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