Summary
Checkpoint inhibitors (CPIs) are routinely employed in relapsed/refractory classical Hodgkin lymphoma. Nonetheless, persistent long‐term responses are uncommon, and one‐third of patients are ...refractory. Several reports have suggested that treatment with CPIs may re‐sensitize patients to chemotherapy, however there is no consensus on the optimal chemotherapy regimen and subsequent consolidation strategy. In this retrospective study we analysed the response to rechallenge with chemotherapy after CPI failure. Furthermore, we exploratively characterized the clonal evolution profile of a small sample of patients (n = 5) by employing the CALDER approach. Among the 28 patients included in the study, 17 (71%) were primary refractory and 26 (92%) were refractory to the last chemotherapy prior to CPIs. Following rechallenge with chemotherapy, response was recorded in 23 (82%) patients experiencing complete remission and 3 (11%) patients experiencing partial remission. The tumour evolution of the patients inferred by CALDER seemingly occurred prior to the first cycle of therapy and was characterized either by linear or branching evolution patterns. Twenty‐five patients proceeded to allogeneic stem cell transplantation. At a median follow‐up of 21 months, median PFS and OS were not reached. In conclusion, patients who fail CPIs can be effectively rescued by salvage chemotherapy and bridged to allo‐SCT/auto‐SCT.
Patients with advanced type B3 thymoma and thymic carcinoma resistant to chemotherapy have few treatment options. We report the efficacy and safety results of the combination of the anti-PD-L1 ...inhibitor avelumab with the anti-angiogenesis drug axitinib in patients with advanced type B3 thymoma and thymic carcinoma.
CAVEATT was a single-arm, multicentre, phase 2 trial, conducted in two Italian centres (the European Instituteof Oncology and the Humanitas Institute, Milan) in patients with histologically confirmed type B3 thymoma or thymic carcinoma, with advanced stage of disease who had progressed after at least one line of platinum-based chemotherapy. Previous treatment with an anti-angiogenesis drug was allowed but not with immune checkpoint inhibitors. Other inclusion criteria were age 18 years or older, an Eastern Cooperative Oncology Group performance status of 0–2, progressive disease, and presence of measurable disease according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. Patients received avelumab 10 mg/kg intravenously every 2 weeks and axitinib 5 mg orally twice daily until disease progression or unacceptable toxicity. The primary endpoint was the centrally assessed overall response rate according to RECIST version 1.1. Patients who received at least one cycle of treatment and had at least one CT scan after treatment start at scheduled time point by protocol were judged assessable for response and were included in efficacy and safety analyses. This study is registered with EUDRACT, 2017–004048–38; enrolment is completed and follow-up is ongoing.
Between April 22, 2019, and June 30, 2021, 32 patients were enrolled. 27 patients had a thymic carcinoma, three a type B3 thymoma, and two a mixed type B3 thymoma and thymic carcinoma. 29 (91%) of 32 patients had stage IVB disease and 13 (41%) of 32 had been pretreated with an anti-angiogenesis drug. 11 of 32 patients had an overall response; thus the overall response rate was 34% (90% CI 21–50); no patients had a complete response, 11 (34%) had a partial response, 18 (56%) had stable disease, and in two patients (6%) progressive disease was the best response. The most common grade 3 or 4 adverse event was hypertension (grade 3 in six 19% of 32 patients). Four (12%) of 32 patients developed serious adverse events that were new-onset immune-related adverse events, including one grade 3 interstitial pneumonitis, one grade 4 polymyositis, and two grade 3 polymyositis. There were no treatment-related deaths.
Avelumab combined with axitinib has promising anti-tumour activity and acceptable toxicity in patients with advanced type B3 thymoma and thymic carcinoma progressing after chemotherapy, and could emerge as a new standard treatment option in this setting.
Pfizer.
Background
We tested for upgrading (Gleason grade group GGG ≥ 4) and/or upstaging to non‐organ‐confined stage (NOC ≥ pT3/pN1) in intermediate unfavorable‐risk (IU) prostate cancer (PCa) patients ...treated with radical prostatectomy, since both change the considerations for dose and/or type of radiotherapy (RT) and duration of androgen deprivation therapy (ADT).
Methods
We relied on Surveillance, Epidemiology, and End Results (2010–2015). Proportions of (a) upgrading, (b) upstaging, or (c) upgrading and/or upstaging were tabulated and tested in multivariable logistic regression models.
Results
We identified 7269 IU PCa patients. Upgrading was recorded in 479 (6.6%) and upstaging in 2398 (33.0%), for a total of 2616 (36.0%) upgraded and/or upstaged patients, who no longer fulfilled the IU grade and stage definition. Prostate‐specific antigen, clinical stage, biopsy GGG, and percentage of positive cores, neither individually nor in multivariable logistic regression models, discriminated between upgraded and/or upstaged patients versus others.
Conclusions
IU PCa patients showed very high (36%) upgrading and/or upstaging proportion. Interestingly, the overwhelming majority of those were upstaged to NOC. Conversely, very few were upgraded to GGG ≥ 4. In consequence, more than one‐third of IU PCa patients treated with RT may be exposed to suboptimal dose and/or type of RT and to insufficient duration of ADT, since their true grade and stage corresponded to high‐risk PCa definition, instead of IU PCa. Data about magnetic resonance imaging were not available but may potentially help with better stage discrimination.
Moyamoya syndrome (MMS) is the most common cerebral vasculopathy among children with neurofibromatosis type 1 (NF1). In this study, we clinically, radiologically, and genetically examined a cohort ...that was not previously described, comprising European children with NF1 and MMS. The NF1 genotyping had been registered. This study included 18 children. The mean age was 2.93 ± 3.03 years at the NF1 diagnosis and 7.43 ± 4.27 years at the MMS diagnosis. In seven patients, MMS was diagnosed before or at the same time as NF1. Neuroimaging was performed in 10 patients due to clinical symptoms, including headache (n = 6), cerebral infarction (n = 2), and complex partial seizures (n = 2). The remaining eight children (47%) had MMS diagnosed incidentally. Sixteen children were characterized molecularly. The features of MMS were similar between patients with and without NF1. Additionally, the NF1 phenotype and genotype were similar between children with and without MMS. Interestingly, three children experienced tumors with malignant histology or behavior. The presence of two first cousins in our cohort suggested that there may be potential genetic factors, not linked to NF1, with an additional role respect of NF1 might play a role in MMS pathogenesis. The incidental diagnosis of MMS, and the observation that, among children with NF1, those with MMS were clinically indistinguishable from those without MMS, suggested that it might be worthwhile to add an angiographic sequence to brain MRIs requested for children with NF1. A MMS diagnosis may assist in properly addressing an NF1 diagnosis in very young children who do not fulfill diagnostic criteria.
•Functional feed with olive extract improves plasma fatty acid profile in dairy cows.•Phenolic compounds in PhenoFeed Dry are hydroxytyrosol, tyrosol and verbascoside.•High total polyphenols content ...and antioxidant activity in the functional feed.•Close relationship between the diet fatty acid composition and plasma lipid content.•PUFA are the fatty acids most influenced by the phenolic composition of cows’ diet.
This study evaluated the effects of supplementing with natural functional feed on the plasma fatty acid profile of lactating Italian Holstein-Friesian dairy cows. Thirty cows in mid-lactation received the natural olive extract PHENOFEED DRY (500 mg/cow/day) which mainly comprises hydroxytyrosol, tyrosol and verbascoside. The total content of polyphenols and the antioxidant power of standard feed, enriched feed and pure extract was evaluated respectively by Folin-Ciocalteu and DPPH assay, and a characterization in HPLC-UV (High-Performance Liquid Chromatography-Ultraviolet) of bioactive molecules present in the extract PHENOFEED DRY was performed. PHENOFEED DRY was provided for 60 days, and the plasma profile of fatty acids was determined by Gas Chromatography. The administration of enriched feed resulted in an increase in the ratio of Omega-6 to Omega-3 polyunsaturated fatty acids from 3:1 to 4:1 (p<0.001). This was not influenced by the calving order. The addition of polyphenols helped to keep monounsaturated (MUFA) and saturated (SFA) levels constant and results in a significant increase in polyunsaturated (PUFA) fatty acid after 15 days of administration. The Omega-6/Omega-3 ratio was in the optimal range. The findings show that inclusion of natural functional food such as plant polyphenols helps to maintain a healthy blood fatty acid profile in lactating dairy cows.
Purpose
To describe the macroscopic characteristics of the subretinal fluid (SRF) and its spilling modality during evacuative puncture in scleral buckling (SB) surgery for rhegmatogenous retinal ...detachment.
Methods
We retrospective reviewed all the SB surgeries performed over a period of 26 months at the University Eye Clinic of Trieste, Italy. We selected a cohort of 102 patients in which SRF drainage by means of evacuative puncture was performed. A high-definition video was recorded during the whole duration of the procedures, and the macroscopic characteristics of the SRF leakage were assessed.
Results
Pigmented dark-brownish deposits spilling in the fluid outcoming from the evacuative puncture was observed during the surgeries. In all cases, this macroscopic feature was detected during the late phases of the drainage. Moreover, indirect ophthalmoscopic evaluation showed the almost complete SRF drainage and a flattened retina at that moment.
Conclusions
The pigment stream sign, easily detectable by the surgeon, allows to understand, during the evacuative puncture, when the SRF has been drained almost completely and that the drainage procedure is therefore close to the end.
