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Background: Thymic carcinoma (TC) is a rare tumor with aggressive behavior. Chemotherapy with carboplatin plus paclitaxel represents the treatment of choice for advanced disease. Antiangiogenic drugs, including ramucirumab, have shown activity in previously treated patients. The RELEVENT trial was designed to evaluate the activity and safety of ramucirumab plus chemotherapy as first-line treatment in advanced TC., Patients and Methods: This phase II trial was conducted within the Italian TYME network. Eligible patients had treatment-naïve advanced TC. They received ramucirumab, carboplatin and paclitaxel for six cycles, followed by ramucirumab maintenance until disease progression or intolerable toxicity. Primary endpoint was objective response rate (ORR) according to RECIST v1.1 as assessed by the investigator. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Centralized radiologic review was carried out., Results: From November 2018 to June 2023, 52 patients were screened and 35 were enrolled. Median age was 60.8 years, 71.4% of patients were male and 85.7% had Masaoka-Koga stage IVB. The Eastern Cooperative Oncology Group performance status was 0 in 68.5% and 1 in 31.4% of patients. At the present analysis carried out some months after the interim analysis (earlier than expected) on 35 patients, ORR was 80.0% [95% confidence interval (CI) 63.1% to 91.6%]. At the centralized radiological review of 33/35 assessable patients, ORR was 57.6% (95% CI 39.2% to 74.5%). After a median follow-up of 31.6 months, median PFS was 18.1 months (95% CI 10.8-52.3 months) and median OS was 43.8 months (95% CI 31.9 months-not reached). Thirty-two out of 35 patients (91.4%) experienced at least one treatment-related adverse event (AE), of which 48.6% were AE ≥ grade 3., Conclusions: In previously untreated advanced TC, the addition of ramucirumab to carboplatin and paclitaxel showed the highest activity compared to historical controls, with a manageable safety profile. Despite the small number of patients, given the rarity of the disease, the trial results support the consideration of this combination as first-line treatment in TC., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: We aimed to investigate changes in volume and MRI T2-weighted intensity in desmoid-type fibromatosis (DF) receiving methotrexate plus vinca-alkaloids (MTX-VA) at Istituto Nazionale dei Tumori, Milan., Methods: All cases of sporadic DF treated with MTX-VA from 1999 to 2019 were reviewed. MRIs at baseline, 6 and 12 months of chemotherapy and at treatment withdrawal were retrospectively reviewed, contouring the tumor lesion and measuring diameters, volume, and mean T2-signal intensity (normalized to muscle) changes. These parameters were also evaluated according to clinical variables., Results: Thirty-two DF patients were identified. Best RECIST response was: 25% partial response, 69% stable disease, 6% progression. A ≥65% tumor volume reduction was observed in 38%, <65% reduction in 53%, an increase in 9%. 22% had RECIST stable disease with a ≥65% tumor volume reduction. T2-signal intensity decreased by ≥50% in 47%, <50% in 41% and increased in 12%. In patients with symptomatic improvement while on therapy and in patients maintaining symptomatic improvement during follow-up, median T2-signal intensity showed a reduction along the time points (3.0, 1.9, 1.2, 1.1; 2.9, 2.0, 1.2, 1.2, respectively); in patients without symptomatic improvement and in those clinically progressing during follow-up, a reduction was not observed. High T2-signal intensity at baseline was observed in patients showing RECIST progression during follow-up., Conclusions: In this series, RECIST detected a lower proportion of responses as compared to volumetric and T2-signal changes. T2-signal reduction seemed to better reflect symptomatic improvement. High T2-signal intensity at baseline was related to a higher proportion of further progression., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: The objective of this study was to report on a retrospective series of patients with epithelioid hemangioendothelioma (EHE) who received treatment with sirolimus within the Italian Rare Cancer Network., Methods: From January 2005, 38 adult patients with advanced EHE received continuous-dosing sirolimus, 5 mg daily, until they developed either toxicity or disease progression. Disease progression in the 6 months before the start of treatment was required. Each pathologic diagnosis was reviewed. The daily dose of sirolimus was adjusted based on plasma levels. Response was retrospectively assessed by local investigators using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST). Survival was estimated using the Kaplan-Meier method., Results: All 38 patients (WW Domain Containing Transcription Regulator 1 [WWTR1]-positive, n = 37; transcription factor E3 [TFE3]-positive, n = 1) had disease progression before starting sirolimus (at baseline, 13 of 38 patients had the presence of serosal effusions and systemic symptoms). Thirty-seven patients were evaluable for response (there was 1 early interruption). The best RECIST responses were a partial response in 4 patients (10.8%), stable disease in 28 patients (75.7%), and disease progression in 5 patients (13.5%). At a 41.5-month median follow-up (interquartile range [IQR], 23.9-56.8 months), the median PFS was 13 months (95% CI, 3.7 months to not estimated [NE]), and the median OS was 18.8 months (95% CI, 10.6 months to NE). In patients who had serosal effusions at baseline, the median PFS was 4.8 months (IQR, 3.5-11.7 months), and the median OS was 10.6 months (IQR, 5.1-13.0 months), compared with 47.8 months (IQR, 11.4 months to NE) and 47.8 months (IQR, 15.7 months to NE), respectively, in patients without serosal effusions. Overall, sirolimus was fairly well tolerated, with 10 patients reporting irregular menstruation/ovary disfunction., Conclusions: The current results confirm that sirolimus is active in EHE, leading to prolonged stabilization in most patients who present without serosal effusions. Serosal effusions are confirmed as an unfavorable prognostic sign associated with short survival, and sirolimus displays limited activity in this subgroup., (© 2020 American Cancer Society.)

Background: In patients with metastatic colorectal cancer (mCRC) receiving highly active first-line combination treatments, early tumor shrinkage (ETS) and depth of response (DoR) are associated with survival, but their influence on outcomes during maintenance therapy is unknown. The Valentino study showed inferior PFS in 229 RAS wild-type mCRC patients randomized to panitumumab plus FOLFOX followed by maintenance with panitumumab vs. panitumumab + 5-FU/LV., Patients and Methods: After blinded independent central review of ETS (≥20% reduction of the sum of target lesions) and DoR in patients enrolled in Valentino, the prognostic and predictive role of such parameters was investigated, along with their combination with PRESSING panel (uncommon genomic alterations associated with anti-EGFRs resistance beyond RAS and BRAF)., Results: One hundred and ninety-six patients were included (ETS in 132 [67.3%], median DoR: 44.1%). Both ETS and DoR ≥34% were associated with longer mPFS (p = 0.010 and p < 0.001) and mOS (p = 0.006 and p < 0.001). The PFS benefit of 5-FU/LV added to panitumumab maintenance, reported in the study, was independent from ETS and DoR status (interaction tests NS for both PFS and OS). However, outcomes were extremely poor in patients who received single-agent panitumumab and had no-ETS (mPFS and mOS: 7.7 and 18.7 months) or DoR < 34% (mPFS and mOS: 6.5 and 18 months). Combining PRESSING panel ('molecular hyperselection') and response dynamics allowed to stratify both PFS (p < 0.001 and p < 0.001 for ETS and DoR, respectively) and OS (p < 0.001 and p = 0.017 for ETS and DoR, respectively)., Conclusions: ETS and DoR allow on-treatment anticipation of outcomes following an anti-EGFR-based strategy planning de-escalation, and poor radiological response may guide enrolment in crossover strategy trials. As in vivo markers of drug sensitivity, ETS and DoR may be integrated with several patient- and tumor-related factors to wisely drive decision-making on upfront treatment duration and intensity., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Declaration of interests: FP has received honoraria for speaker activities and participation in advisory boards from Sanofi, Amgen, Bayer, Merck-Serono, Lilly, Roche, Servier, and research grants from BMS. SL has received honoraria for speaker activities and participation in advisory boards from Amgen, Bayer, Merck-Serono, Roche, Servier, Bristol-Myers Squibb. CC has received honoraria for speaker activities and participation in advisory boards from Roche, Amgen, Bayer, Servier, Merck-Serono and research grants from Merck Serono. LR has received honoraria for speaker activities and participation in advisory boards from AstraZeneca, AbbVie, Amgen, ArQule, Basilea, Bayer, Celgene, Eisai, Exelixis, Gilead, Hengrui Therapeutics, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Nerviano Medical Sciences, Roche, Sanofi, and research grants to her Institution from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Lilly, Exelixis, FibroGen, Incyte, Ipsen, Merck Sharp & Dohme. AZ has received honoraria for speaker activities and participation in advisory boards from Sanofi, Amgen, Bayer, Merck-Serono, Roche. PR has received honoraria for speaker activities and participation in advisory boards from Servier, Amgen, Roche and Merck. MDB has received honoraria for speaker activities and participation in advisory boards from Amgen, Roche, Lilly, Servier, MSD. FM has received honoraria for speaker activities from Servier. FDB has received honoraria for speaker activities and participation in advisory boards from Amgen, Roche, Novartis, Incyte, Celgene. All other authors declared no disclosures., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)