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All the changes regarding BP and cfPWV appear early after treatment initiation and seem to be reversible if treatment is stopped, instead diastolic and systolic left ventricular function are persistently altered by anti-VEGFR drugs.

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Ketoconazole is an inhibitor of adrenal androgen synthesis which carries on the anti‐tumour activity by interfering with different enzymes, cytochrome P450 14‐α‐demethylase, C 17,20 lyase and C 17 α‐hydroxylase. Some studies have shown an anti‐tumour activity of ketoconazole employed at different dose levels following the failure of androgen‐suppressive therapies. Patients refractory to pharmacological castration and/or chemotherapy could have an additional benefit in terms of disease control from the use of low dose of ketoconazole. The safety profile was good. OBJECTIVE To assess the efficacy of ketoconazole in patients with castration‐resistant prostate cancer (CRPC). PATIENTS AND METHODS From April 2008 to November 2009, 37 patients with CRPC have been treated with ketoconazole. The primary endpoint was the prostate‐specific antigen (PSA) response; the secondary endpoints were progression‐free survival and safety profile. Ketoconazole was administered by oral route at a dose of 200 mg every 8 h continuous dosing until the onset of serious adverse events or disease progression. The study was based on a two‐step design with an interim efficacy analysis carried out on the first 12 patients accrued. RESULTS Main characteristics of population were: median age 75 years (range 60–88); baseline mean PSA 28.8 ng/mL (4.3–1000); 30 patients previously challenged with at least two lines of hormone therapy; 15 patients previously treated with chemotherapy. Biochemical responses accounted for: two complete responses (5%), six partial responses (16%), 13 patients with stable disease (35%), and 14 with progressive disease (38%). Of 15 patients resistant to chemotherapy, overall disease control (complete plus partial responses plus stable disease) was recorded in seven of them. Treatment was feasible without inducing grade 3–4 adverse events. The most common grade 1–2 adverse events were asthenia (27%), vomiting (8%) and abdominal pain (8%). CONCLUSION Treatment with low‐dose ketoconazole is feasible and well tolerated. The efficacy was satisfactory in patients previously treated with chemotherapy.

We aimed to overcome intratumoral heterogeneity in clear cell renal cell carcinoma (clearRCC). One hundred cases of clearRCC were sampled. First, usual standard sampling was applied (1 block/cm of tumor); second, the whole tumor was sampled, and 0.6 mm cores were taken from each block to construct a tissue microarray; third, the residual tissue, mapped by taking pieces 0.5 × 0.5 cm, reconstructed the entire tumor mass. Precisely, six randomly derived pieces of tissues were placed in each cassette, with the number of cassettes being based on the diameter of the tumor (called multisite 3D fusion). Angiogenic and immune markers were tested. Routine 5231 tissue blocks were obtained. Multisite 3D fusion sections showed pattern A, homogeneous high vascular density (10%), pattern B, homogeneous low vascular density (8%) and pattern C, heterogeneous angiogenic signatures (82%). PD-L1 expression was seen as diffuse (7%), low (33%) and absent (60%). Tumor-infiltrating CD8 scored high in 25% (pattern hot), low in 65% (pattern weak) and zero in 10% of cases (pattern desert). Grading was upgraded in 26% of cases (G3–G4), necrosis and sarcomatoid/rhabdoid characters were observed in, respectively, 11 and 7% of cases after 3D fusion (p = 0.03). CD8 and PD-L1 immune expressions were higher in the undifferentiated G4/rhabdoid/sarcomatoid clearRCC subtypes (p = 0.03). Again, 22% of cases were set to intermediate to high risk of clinical recurrence due to new morphological findings of all aggressive G4, sarcomatoid/rhabdoid features by using 3D fusion compared to standard methods (p = 0.04). In conclusion, we propose an easy-to-apply multisite 3D fusion sampling that negates bias due to tumor heterogeneity.