Perivascular epithelioid cell tumors (PEComas) are rare soft-tissue tumors with an extremely heterogeneous clinical behavior. They may arise in different organs and may behave indolently or sometimes ...metastasize with different grades of biological aggressiveness. We report the case of a young woman with a primary inoperable PEComa of the liver with malignant histological features. Since the mTOR pathway is often altered in PEComas and responses have been reported with mTOR-inhibitors such as sirolimus or temsirolimus, we decided to start a neoadjuvant treatment with sirolimus. The patient tolerated the treatment fairly well and after 8 months a favorable tumor shrinkage was obtained. The patient then stopped sirolimus and 2 weeks later underwent partial liver resection, with complete clinical recovery and normal liver function. The histological report confirmed a malignant PEComa with vascular invasion and negative margins. Then 6 additional months of post-operative sirolimus treatment were administered, followed by regular radiological follow-up. For patients with a large and histologically aggressive PEComa, we think that neoadjuvant treatment with mTOR-inhibitor sirolimus may be considered to facilitate surgery and allow early control of a potentially metastatic disease. For selected high-risk patients, the option of adjuvant treatment may be discussed.
stereotactic body radiation therapy (SBRT) use has increased overtime for the management of metastatic renal cell carcinoma (mRCC) patients, with a likely good control of irradiated lesions. We ...planned a retrospective multicenter Italian study, with the aim of investigating the outcome of treatment with SBRT for non-brain secondary lesions in mRCC patients.
all consecutive metastatic non-brain lesions from mRCC that underwent SBRT at nine Italian institutions from January 2015 to June 2017 were considered. The primary endpoint of the study was the lesion-PFS, calculated from SBRT initiation to the local progression of the irradiated lesion.
57 extracranial metastatic lesions from 48 patients with primary mRCC were treated with SBRT. At the median follow-up of 26.4 months, the median lesion-PFS was not reached (43 censored); 72.4% of lesions were progression-free at 40 months, with significantly better lesion-PFS for small metastatic lesions (<14 mm). SBRT was safe and the 1-year local disease control was 87.7%. After SBRT, 18 patients (37.5%) permanently interrupted systemic therapy.
consistently with the previous literature, our findings support the use of SBRT in selected mRCC patients.
BackgroundAvelumab is an anti–PD-L1 monoclonal antibody approved for the treatment of advanced UC after disease progression during or following platinum-based chemotherapy and as maintenance ...treatment in patients whose disease has not progressed with first-line platinum-based chemotherapy.1–3 M9241 is an immunocytokine composed of 2 heterodimers of IL-12 fused to the heavy chains of a human antibody targeting DNA released from necrotic tumor cells.4 During dose-escalation, avelumab + M9241 was well tolerated and showed promising antitumor activity in patients with advanced solid tumors, including 2 objective responses in patients with UC.5 We report on an interim analysis of efficacy and safety from the dose-expansion part of JAVELIN IL-12 (NCT02994953).MethodsEligible patients had locally advanced or metastatic UC that had progressed on first-line therapy, were aged =18 years, had an Eastern Cooperative Oncology Group performance status of 0/1, and were immune checkpoint inhibitor naive. Patients received the recommended phase 2 dose5 of avelumab 800 mg intravenously once weekly (QW) in combination with M9241 16.8 µg/kg subcutaneously Q4W for the first 12 weeks, then continued the combination with avelumab Q2W. The primary endpoints were confirmed best overall response (BOR) per investigator assessment (RECIST 1.1) and safety. The expansion cohort followed a 2-stage design. During stage 1 (single-arm part of the study), 16 patients were enrolled and treated. A futility analysis based on BOR was planned to determine if stage 2 (randomized controlled part of the study) would be initiated.ResultsAt data cut-off (Jun 3, 2020), 16 patients had received avelumab + M9241 for a median duration of 8 weeks (range, 4.0–25.0 weeks). No complete or partial responses were observed; the study failed to meet the criterion (>2 responders) to initiate stage 2. Two patients (12.5%) had stable disease, 13 (81.3%) had progressive disease, and 1 (6.3%) was not evaluable. Any-grade treatment-related adverse events (TRAEs) occurred in 15 patients (93.8%); the most common (in =4 patients) were pyrexia (50.0%), nausea (37.5%), asthenia (31.3%), anemia (25.0%), and hyperthermia (25.0%); grade 4 gamma-glutamyltransferase increased occurred in 1 patient (6.3%). No TRAEs led to death. Pharmacodynamic effects on the peripheral immune system and results of pharmacokinetic and biomarker analyses will also be reported.ConclusionsThe predefined efficacy criterion to proceed to stage 2 was not met. The combination was well tolerated; no new safety signals emerged and the profile was consistent with the dose-escalation part of the study.5 Trial RegistrationNCT02994953Ethics ApprovalThe study was approved by each site’s independent ethics committee.ConsentN/AReferencesBavencio(avelumab) injection package insert. Rockland, MA: EMD Serono, Inc; New York, NY: Pfizer Inc; 2020.Health Canada. https://www.canada.ca/en/health-canada.html. Accessed July 31, 2020.US Food and Drug Administration. FDA approves avelumab for urothelial carcinoma maintenance treatment. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-avelumab-urothelial-carcinoma-maintenance-treatment. Accessed July 31, 2020.Fallon J, Tighe R, Kradjian G, et al. The immunocytokine NHS-IL12 as a potential cancer therapeutic. Oncotarget. 2014;5:1869–1884.Strauss J, Vugmeyster Y, Sznol M, et al. Phase 1b, open-label, dose escalation study of M9241 (NHS-IL12) plus avelumab in patients (pts) with advanced solid tumours. Ann Oncol. 2019;30(5 Suppl):Abstract 4062.
In patients with advanced renal-cell carcinoma, treatment with cabozantinib plus nivolumab and ipilimumab resulted in longer progression-free survival than treatment with nivolumab and ipilimumab ...alone.
•This review analyses the evidence on high dose chemotherapy as salvage therapy for metastatic germ cell tumors.•It focuses on the 2-year overall survival, complications, and the quality of life of ...survivors.•The review is integrated by our retrospective real-world experience, with survival and quality of life outcomes.
Evidence for the choice of second line, standard vs high dose chemotherapy, (SDCT, HDCT) for patients with relapsed germ cell tumors (GCTs) comes mainly from retrospective studies.
: relevant literature was reviewed, considering as endpoints both survival and long term quality of life (QoL). Patients with metastatic GCT progressing after first-line treatment at our Institution were retrospectively evaluated.
HDCT seems to achieve a higher rate of long-term remissions. QoL data for this group of patients are lacking. Our experience on 29 patients was in line with these results. Two-year OS for the 18 patients treated with one or two HDCT/PBSCT procedures was 47.5 %, while 2-year PFS was 44 %. For the 11 receiving SDCT 2-year OS was 36.4 %, and 2-year PFS was 32.7 %.
HDCT/PBSCT confirmed to be effective in treating patients with relapsed GCT, but prospective studies are needed.
Tyrosine kinase inhibitors (TKI) have revolutionized the treatment of gastrointestinal stromal tumors (GIST) although most patients develop resistance to first and second-line therapies. Regorafenib, ...an oral multi-targeted TKI, has demonstrated benefit in previously treated GIST patients.
We assessed safety and activity of regorafenib in patients treated within the Managed Access Program (MAP). All consecutive patients with advanced GIST who had progressed on or were intolerant to imatinib and sunitinib were recruited from the Royal Marsden and University College Hospitals. We retrospectively reviewed the data for response, toxicity, treatment duration and survival. Response was assessed by RECIST and Choi criteria. Toxicity was graded according to CTCAE v4.0 criteria.
20 patients were included in the MAP in the UK between 3/2013 and 9/2013. Median age was 68 (range 45-87), 65% of patients were male. Performance Status was 0-1 for 18 patients (90%), 2 for 2 patients (10%). The median treatment duration was 9.25 months (range 0.1-15.33). 18 patients were assessable for response and all patients attained a best response of at least stable disease. At a median follow-up of 12.6 months, there were 2 partial responses (11%) by RECIST and 7 partial responses (39%) according to Choi criteria. 7 patients remain on regorafenib. 3 patients discontinued treatment due to unacceptable adverse events; fistulation, myalgia and fatigue. 10 (50%) patients had grade 3 toxicities and 11 (55%) patients required a dose reduction. Median PFS was 9.4 months (95% Cl: 6.2-not calculable) and median OS was 12.2 months (95% Cl: 10.5-not calculable). Notably, prolonged stable disease was seen in 1 patient with exon 9 mutation and 1 patient with PDGFR D842V mutation.
These data demonstrate encouraging activity and tolerability of regorafenib in routine clinical practice. The documented adverse events are in line with previous trial data.
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Background: At least 75% of bladder cancer (BC) are diagnosed in adults aged ≥65 years, with a median of 72 years. Older adults have poor outcomes but are also an heterogeneous population in ...which the functional status often does not reflect the chronological age. ASCO and SIOG recommend the use of geriatric assessment (GA) to guide management of these patients (pts) but very few data are present to date. Methods: We investigated the role of GA and an oncological version of MPI in pts ≥70 years old affected by advanced/metastatic urothelial carcinoma. Data were retrieved from a prospectively maintained database from 2010 to 2022. Comprehensive GA (CGA) is a multidimensional tool used to classify pts as fit, vulnerable and frail according to Balducci’s criteria. Onco-MPI was calculated by a validated algorithm derived from different GA domains and tumour characteristics. We also collected characteristics of pts, tumors and treatment regimens. Correlation between GA and treatments used and oncological outcomes were analysed. Results: Complete data and follow up were available for 181 patients. Pts characteristics are reported in Table 1. According to Onco-MPI all the pts but 7 were at high risk. The mFU was 46.2 months, while mOS was 8.2 months. Balducci’s CGA and Bellmunt groups had a concordance of 58%, p<0.01. Strong correlations between these scores and type of treatment received were found (pts fit or 0 score received more often a platinum-based treatment without reduction dose while frail or 2-3 score received more often treatment with a reduced dose or no treatment at all, p<0.01). The two scores have a strong prognostic value (18.5 vs 10.8 vs 3.8 months, p<0.01; 21.9 vs 8.5 vs 4.1 months, p<0.01, respectively for CGA and Bellmunt subgroups). At univariate analysis also timing of mets, number of sites, type of treatment and dose were good prognostic variables. All these variables retained their prognostic value at a multivariate analysis incorporating each of the two scores separately. Conclusions: CGA has a great prognostic value in older adults with metastatic urothelial cancer. This tool could help in decision making and patients stratification but validation in prospective cohort is needed. Onco-MPI could also be useful but new cut offs must be set in this specific population.Table: see text
Introduction:
Evaluation of tumor response according only to dimensional criteria may underestimate treatment benefit in patients treated for metastatic renal cell carcinoma (RCC). In this study we ...evaluated the role of lesion enhancement modifications and Choi criteria in patients affected by renal cell carcinoma treated with immunotherapy.
Methods:
We collected data of 60 consecutive patients (with a total of 154 measurable lesions) treated with immunotherapy (nivolumab or ipilimumab plus nivolumab) at a single Institution. We evaluated tumour response using both RECIST1.1 criteria and Choi criteria at the first radiological assessment; we subsequently associated response with progression free survival and overall survival.
Results:
Choi criteria found a higher rate of objective response compared to RECIST criteria (38.3% vs 18.3%). An objective response according to both criteria was associated with longer progression free survival and overall survival. Response rate for Choi did not vary according to lesion site.
Conclusion:
Choi criteria seemed to be able to predict clinical benefit in a higher proportion of patients with renal cell carcinoma treated with immunotherapy than RECIST criteria. Partial response according to RECIST was confirmed as a predictor of longer progression-free survival and overall survival.
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