Perivascular epithelioid cell tumor (PEComa) is a family of mesenchymal tumors. Conventional chemotherapy has little activity in this disease, but case reports are available on the activity of ...mammalian target of rapamycin inhibitors (e.g. sirolimus and temsirolimus). Pharmacokinetic assays of sirolimus are available as this drug has a precise therapeutic window and blood levels might be influenced by CYP3A4 polymorphisms and drug interactions. We report on a case of a patient with metastatic, progressive PEComa who started sirolimus at a dose of 5 mg/day with evidence of grade (G) 3 mucositis, G2 thrombocytopenia, and G1 leucopenia 10 days after the treatment started, in absence of concomitant medications or prohibited food assumption. Elevated sirolimus blood levels were detected (156.8 ng/ml). Sirolimus was stopped, and toxicity resolved in 5 weeks. Computed tomography scan 2 months after the treatment started showed a partial response (RECIST). After toxicity resolution, the patient restarted sirolimus at a dose of 1 mg/day, with blood levels in the range of 10–20 ng/ml. Tumor response was confirmed and maintained, and the patient is still under treatment 18 months later, with no additional adverse effects. Genetic analysis of five selected polymorphisms (rs2740574, rs776746, rs1128503, rs2032582, and rs1045642) in drug metabolism enzymes and transporters did not provide a clear explanation of the observed unusual pharmacokinetic. This case confirms the activity of mammalian target of rapamycin inhibitors in PEComa and strengthens the importance of pharmacokinetic drug blood levels monitoring in patients treated with sirolimus. In our patient, after dose adjustment, sirolimus could be restarted with a prolonged clinical benefit and no additional toxicity.
Gastrointestinal stromal tumor (GIST) follow-up is recommended by international guidelines, but data on the role of follow-up in patients with low relapse risk are missing. For these patients, the ...potential benefit of anticipating recurrence detection should be weighed against psychological burden and radiologic examination loads in terms of costs and radiation exposure.
To evaluate the outcomes of guideline-based follow-up in low-risk GIST.
This multi-institutional retrospective cohort study involving Italian Sarcoma Group reference institutions evaluated patients with GIST who underwent surgery between January 2001 and June 2019. Median follow-up time was 69.2 months. Data analysis was performed from December 15, 2022, to March 20, 2023. Patients with GIST at low risk according to Armed Forces Institute of Pathology criteria were included provided adequate clinical information was available: primary site, size, mitotic index, surgical margins, and 2 or more years of follow-up.
All patients underwent follow-up according to European Society for Medical Oncology (ESMO) guidelines.
The primary outcome was the number of tests needed to identify a relapse according to ESMO guidelines follow-up plan. Secondary outcomes included relapse rate, relapse timing, disease-free survival (DFS), overall survival (OS), GIST-specific survival (GIST-SS), postrelapse OS, secondary tumor rates, and theoretical ionizing radiation exposure. An exploratory end point, new follow-up schedule proposal for patients with low-risk GIST according to the observed results, was also assessed.
A total of 737 patients (377 men 51.2%; median age at diagnosis, 63 range, 18-86 years) with low-risk GIST were included. Estimated 5-year survival rates were 95.5% for DFS, 99.8% for GIST-SS, and 96.1% for OS. Estimated 10-year survival rates were 93.4% for DFS, 98.1% for GIST-SS, and 91.0% for OS. Forty-two patients (5.7%) experienced disease relapse during follow-up (9 local, 31 distant, 2 both), of which 9 were detected after 10 or more years. This translated into approximately 1 relapse detected for every 170 computed tomography scans performed, with a median radiation exposure of 80 (IQR, 32-112) mSv per patient. Nongastric primary tumor (hazard ratio HR, 2.09; 95% CI, 1.14-3.83; P = .02), and KIT mutation (HR, 2.77; 95% CI, 1.05-7.27; P = .04) were associated with a higher risk of relapse. Second tumors affected 187 of 737 patients (25%), of which 56 were detected during follow-up and represented the primary cause of death in these patients.
In this cohort study on patients affected by low-risk GISTs, the risk of relapse was low despite a follow-up across 10 or more years. These data suggest the need to revise follow-up schedules to reduce the anxiety, costs, and radiation exposure of currently recommended follow-up strategy.
Lapatinib in advanced chordoma: A phase II study Stacchiotti, Silvia; Tamborini, Elena; Palassini, Elena ...
Journal of clinical oncology,
05/2012, Letnik:
30, Številka:
15_suppl
Journal Article
Recenzirano
Odprti dostop
Abstract only
10026
Background: To report on a prospective Phase II, investigator-driven, collaborative study to explore the activity of lapatinib, a dual EGFR and ErbB2 inhibitor, in EGFR-positive ...advanced chordomas. Methods: From December 2009 to December 2011, 19 advanced progressing chordoma patients entered this study (mean age: 59 yrs – range = 35-75; PS: 0-3 - ≥2 = 52%; site: sacrum = 68%, spine = 21%, skull base = 11%; disease extent: metastatic = 68%, locally advanced = 32%). EGFR expression was evaluated by immunohistochemistry in all patients. EGFR activation was detected in 15 of 17 evaluable cases by phospho-arrays and/or real-time PCR and/or fluorescence immunostaining. EGFR FISH analysis showed high level of gene gain in 4. HerB2 status is under evaluation. Patients received lapatinib 1500 mg/day (dose intensity in excess of 1250 mg/day), until progression or toxicity. The primary study end-point was response rate (RR) as for Choi criteria extended to MRI. Secondary end-points were RR by RECIST, PFS by Choi, OS, clinical benefit rate (CBR) (CR+PR+SD≥6mos), correlation between EGFR status and response. Results: 16 pts are evaluable for response (3 too early); 4 patients are still on treatment. 3 patients (19%) had a partial response (PR) and 8 (50%) a stable disease (SD) as their best Choi response, corresponding to RECIST SD in all cases. The 3 cases with a PR by Choi had a minor decrease in size; another patient had a mixed response. The CBR was 19%. Median PFS as for Choi was 5.5 (range = 2-12+) months, with 1 patient being progression-free at 18 months. Toxicity was as expected. In one case treatment was interrupted due to side effects. No correlation was observed between EGFR expression/activation and response. Conclusions: This Phase II study showed a modest activity of lapatinib in chordoma. EGFR expression was not predictive of response. The clinical relevance of EGFR targeting in chordoma needs to be further investigated.
