Yttrium-90 transarterial radioembolization (TARE) is a microembolic procedure that minimizes alterations to hepatic arterial flow, and thus can be safely performed in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). In this study, we retrospectively evaluated the independent predictors of long-term outcomes in patients with HCC and PVTT treated with TARE. Bilirubin level, extension of PVTT and tumor burden were independently related to post-treatment survival: the combination of these factors allowed us to build a prognostic stratification that may help to better identify good candidates for the treatment, and those for whom TARE may be futile.

DEBDOX/M1 TACE is an effective procedure with a favorable safety profile and promising results in terms of objective response rate, tumor downstaging, and necrosis.

Cristina Marenghi and Maria Francesca Alvisi contributed equally to this work as co-first authors. Nicola Nicolai and Riccardo Valdagni contributed equally to this work. ABSTRACT Purpose:To evaluate the outcomes of active surveillance (AS) on patients with low-risk prostate cancer (PCa) and to identify predictors of disease reclassification. Methods: In 2005, we defined an institutional AS protocol (Sorveglianza Attiva Istituto Nazionale Tumori [SAINT]), and we joined the Prostate Cancer Research International: Active Surveillance (PRIAS) study in 2007. Eligibility criteria included clinical stage ≤T2a, initial prostate-specific antigen (PSA) <10 ng/mL, and Gleason Pattern Score (GPS) ≤3 + 3 (both protocols); ≤25% positive cores with a maximum core length containing cancer ≤50% (SAINT); and ≤2 positive cores and PSA density <0.2 ng/mL/cm 3 (PRIAS). Switching to active treatment was advised for a worsening of GPS, increased positive cores, or PSA doubling time <3 years. Active treatment-free survival (ATFS) was assessed using the Kaplan-Meier method. Factors associated with ATFS were evaluated with a multivariate Cox proportional hazards model. Results: A total of 818 patients were included: 200 in SAINT, 530 in PRIAS, and 88 in personalized AS monitoring. Active treatment-free survival was 50% after a median follow-up of 60 months. A total of 404/818 patients (49.4%) discontinued AS: 274 for biopsy-related reclassification, 121/404 (30%) for off-protocol reasons, 9/404 (2.2%) because of anxiety. Biopsy reclassification was associated with PSA density (hazard ratio [HR] 1.8), maximum percentage of core involvement (HR 1.5), positive cores at diagnostic biopsy (HR 1.6), older age (HR 1.5), and prostate volume (HR 0.6) (all p<0.01). Patients from SAINT were significantly more likely to discontinue AS than were the patients from PRIAS (HR 1.65, p<0.0001). Conclusions: Five years after diagnosis, 50% of patients with early PCa were spared from active treatment. Wide inclusion criteria are associated with lower ATFS. However, at preliminary analysis, this does not seem to affect the probability of unfavorable pathology.

AIMTo assess the safety and efficacy of transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) using a new generation of 40 μm drug eluting beads in patients not eligible for curative treatment.METHODSDrug eluting bead TACE (DEB-TACE) using a new generation of microspheres (embozene tandem, 40 μm) preloaded with 100 mg of doxorubicin was performed on 48 early or intermediate HCC patients with compensated cirrhosis. Response to therapy was assessed with Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST) guidelines applied to computed tomography or magnetic resonance imaging. Eleven out of the 48 treated patients treated progressed on to receive liver orthotopic transplantation (OLT). This allowed for histological analysis on the treated explanted nodules.RESULTSDEB-TACE with 40 μm showed a good safety profile without major complications or 30-d mortality. The objective response rate of treated tumors was 72.6% and 26.7% according to mRECIST and RECIST respectively. Histological examination in 11 patients assigned to OLT showed a necrosis degree > 90% in 78.6% of cases. The overall time to progression was 13 mo (11-21).CONCLUSIONDEB-TACE with 40 μm particles is an effective treatment for the treatment of HCC in early-intermediate patients (Barcelona Clinic Liver Cancer stage A/B) with a good safety profile and good results in term of objective response rate and necrosis.

BackgroundImmune checkpoint inhibitors (ICIs) are the new standard of care in microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC). Since tumor response dynamic parameters already shown a strong association with survival outcomes in patients with mCRC treated with first-line therapy, we investigated the association of early tumor shrinkage (ETS) and depth of response (DoR) in patients with MSI-H/dMMR mCRC treated with ICIs.MethodsThis is a retrospective, multicenter, cohort study in patients with dMMR and/or MSI-high mCRC treated with ICIs (anti-PD-1/PD-L1 with or without anti-CTLA-4 agents) with measurable disease and at least one post-baseline radiological disease reassessment. The Kaplan-Meier method and Cox proportional-hazards regression models were used for survival analyses. A maximally selected statistics method in a Cox regression model for progression-free survival (PFS) was used to determine the optimal cut-offs for ETS and DoR.ResultsWe included a total of 169 patients: 116 (68.6%) were treated with anti-PD-1 monotherapy, whereas 53 (31.4%) with anti-PD-1 plus anti-CTLA-4 agents. Patients with primary progressive disease (N=37, 21.9%), experienced an extremely poor overall survival (OS) and were evaluated separately. In patients with clinical benefit, we observed a significant association between ETS and DoR with both OS and PFS, and we identified a relative reduction of at least 1% as the optimal cut-off for ETS and a relative reduction of at least 50% as the optimal cut-off for DoR.ConclusionsETS and DoR are important prognostic factors in patients with MSI-high mCRC treated with ICIs that might be useful to design treatment intensification/deintensification strategies. A prospective validation of both is warranted.

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 þ 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 PRESS-ING 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 Z 0.010 and p < 0.001) and mOS (p Z 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 PRESS-ING 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 Z 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 decisionmaking on upfront treatment duration and intensity.

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