Gonadal Function in Male Patients With Metastatic Renal Cell Cancer Treated With Sunitinib

Background/aim: Single-agent tyrosine kinase inhibitors are still prescribed as first-line treatment to a relevant subgroup of patients with metastatic renal cell carcinoma (mRCC). These agents are known to cause disfunction of many endocrine glands (e.g., thyroid). In this two-step trial, we aimed to assess gonadal function among male patients with mRCC treated with sunitinib. Patients and methods: We enrolled a first cross-sectional cohort of pre-treated (>6 months) patients and a subsequent cohort of treatment-naïve patients who were prospectively followed-up. All patients were screened for hypogonadism and received a Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire at study entry and after 6 months of therapy. Patients who were candidates for testosterone replacement therapy (TRT) also received a FACT-G questionnaire at baseline and 3 months after supplementation. Results: Among the 30 enrolled patients, the prevalence of hypogonadism was found to be higher in those receiving sunitinib for a longer period (27.3% at baseline, 41.7% in the first 6 months, and 68.4% after 9 months of therapy). The testosterone level of patients correlated with quality of life (R=0.32). A total of six patients received TRT, with a significant improvement in their global quality of life after the first 3 months of treatment. Conclusion: An increasing prevalence of hypogonadism was seen among male patients who received long-term treatment with sunitinib. TRT was associated with relevant improvements in quality of life. These findings corroborate similar published observations and encourage the assessment of gonadal function in male patients with mRCC under treatment with sunitinib

Pathological Complete Response to Pembrolizumab plus Axitinib Combination following Serious Immune-Related Adverse Events in an Advanced Renal Cell Carcinoma Patient with a History of Rheumatoid Arthritis

Immune checkpoint inhibitors (ICIs)-based combinations have improved survival outcomes of advanced renal cell carcinoma (RCC) patients and are currently recommended as first-line treatment options. Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD) of unknown etiology characterized by a chronic inflammatory process involving joints and extra-articular organs. Patients with AD are usually excluded from large randomized clinical trials investigating immunotherapeutic drugs. Therefore, little is known about clinical outcomes of patients with a history of RA treated with ICIs in real-world practice. In the present study, we report the clinical outcome of an advanced RCC patient with a history of RA treated with pembrolizumab in combination with axitinib. The patient experienced serious immune-related adverse events (irAEs) and achieved pathological complete response following only one ICI administration. Our case report shows that ICI-based combinations can be administered efficaciously in advanced RCC patients with a history of AD. However, a close monitoring of these patients is required, given the risk of irAEs and clinical exacerbations of symptoms associated with the preexisting AD. Moreover, prospective clinical data are needed to assess the hypothesis of a correlation between the onset of irAEs and AD flares and responses and survival outcomes to ICIs

Maintenance of androgen deprivation therapy or testosterone supplementation in the management of castration-resistant prostate cancer: that is the question

Purpose Whether or not androgen receptor (AR) axis could still be targetable in castration resistant prostate cancer (CRPC) patients with disease progression to next generation hormonal agents (NGHAs) is a controversial issue. Results Serum testosterone in CRPC patients has a positive prognostic role and increasing testosterone levels after androgen deprivation therapy (ADT) withdrawal or testosterone supplementation, as part of a bipolar androgen therapy (BAT) strategy, has been shown to potentially restore sensitivity to previous lines of NGHAs. Conclusion These data suggest that maintenance of ADT in CRPC patients receiving further lines of treatment, as recommended by current international guidelines, could be questionable. Conversely, testosterone supplementation aimed to re-sensitize CRPC to further hormonal manipulation is a strategy worth to be explored in future clinical trials

Response Assessment by Volumetric Iodine Uptake Measurement: Preliminary Experience in Patients with Intermediate-Advanced Hepatocellular Carcinoma Treated with Yttrium-90 Radioembolization

Purpose: To retrospectively compare early response to yttrium-90 radioembolization (Y90) according to volumetric iodine uptake (VIU) changes, Response Evaluation Criteria In Solid Tumor 1.1 (RECIST 1.1) and modified RECIST (mRECIST) in patients with intermediate-advanced hepatocellular carcinoma (HCC) and to explore their association with survival. Materials and Methods: Twenty-four patients treated with Y90 and evaluated with dual-energy computed tomography before and 6 weeks after treatment were included. VIU was measured on late arterial phase spectral images; 6-week VIU response was defined as: complete response (CR, absence of enhancing tumor), partial response (PR, ≥ 15% VIU reduction), progressive disease (PD, ≥ 10% VIU increase) and stable disease (criteria of CR/PR/PD not met). RECIST 1.1 and mRECIST were evaluated at 6 weeks and 6 months. Responders included CR and PR. Overall survival (OS) was evaluated by Kaplan–Meier analysis and compared by Cox regression analysis. Results: High intraobserver and interobserver agreements were observed in VIU measurements (k > 0.98). VIU identified a higher number of responders (18 patients, 75%), compared to RECIST 1.1 (12.5% at 6 weeks and 23.8% at 6 months) and mRECIST (29.2% at 6 weeks and 61.9% at 6 months). There was no significant correlation between OS and RECIST 1.1 (P = 0.45 at 6 weeks; P = 0.21 at 6 months) or mRECIST (P = 0.38 at 6 weeks; P = 0.79 at 6 months); median OS was significantly higher in VIU responders (17.2 months) compared to non-responders (7.4 months) (P = 0.0022; HR 8.85; 95% CI 1.29–88.1). Conclusion: VIU is highly reproducible; as opposite to mRECIST and RECIST 1.1, early VIU response correlates with OS after Y90 in intermediate-advanced HCC patients

Monitoring of Thermal-Induced Changes in Liver Stiffness During Controlled Hyperthermia and Microwave Ablation in an Ex Vivo Bovine Model Using Point Shear Wave Elastography

To investigate liver stiffness changes-evaluated by point shear wave elastography (pSWE)-in controlled hyperthermia and microwave ablation (MWA) in an ex vivo animal model

Case Report: 18F-PSMA PET/CT Scan in Castration Resistant Prostate Cancer With Aggressive Neuroendocrine Differentiation

The development of a neuroendocrine phenotype as a mechanism of resistance to hormonal treatment is observed in up to 20% of advanced prostate cancer patients. High grade neuroendocrine prostate cancer (NEPC) is associated to poor prognosis and the therapeutic armamentarium is restricted to platinum-based chemotherapy. Prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET)/computed tomography (CT) imaging has recently emerged as a potential new standard for the staging of prostate cancer and PSMA-based radioligand therapy (RLT) as a therapeutic option in advanced metastatic castration resistant prostate cancer (mCRPC). PSMA-based theranostic is not currently applied in the staging and treatment of NEPC since PSMA expression on neuroendocrine differentiated cells was shown to be lost. In this case series, we present 3 consecutive mCRPC patients with histologically proven high grade neuroendocrine differentiation who underwent PSMA-PET/CT and surprisingly showed high tracer uptake. This observation stimulates further research on the use of PSMA-based theranostic in the management of NEPC

Feasibility of Percutaneous Intrahepatic Split by Microwave Ablation (PISA) After Portal Vein Embolization for Hypertrophy of Future Liver Remnant: The Radiological Stage-1 ALPPS

Purpose: To assess the feasibility of radiological stage-1 ALPPS, associating liver partition and portal vein ligation for staged hepatectomy, by combining portal vein embolization (PVE) with percutaneous intrahepatic split by ablation (PISA). Materials and Methods: Three patients (mean age 65.0 ± 7.3 years) underwent PVE and PISA. PISA was performed 21 days after PVE by microwave ablation to create a continuous intrahepatic cutting plane. Abdominal CT examinations were performed before and after PVE and PISA. The future liver remnant (FLR) volume was calculated by semiautomatic segmentation, and increase was reported as a percentage of the pre-procedural volume. The FLR/body weight (FLR/BW) ratio was calculated; a ratio greater than 0.8% was considered sufficient for guaranteeing adequate liver function after surgery. The liver function before and after PISA was also evaluated by 99mTc-mebrofenin hepatobiliary scintigraphy. Patientsâ\u80\u99 laboratory tests, performance status, ability to walk were assessed before and after PVE and PISA procedures. Results: No procedure-related complications were recorded. The FLR volume increase in each patient was 42.0, 33.1 and 30.4% within 21 days of PVE and 109.3, 68.1 and 71.7% within 10 days after PISA. The FLR/BW ratios were 0.76, 0.66, 0.63% and 1.13, 0.83, 0.83% after PVE and PISA procedures, respectively. Two patients underwent successful right hepatectomy; in one patient, despite 1.13% FLR/BW, surgery was not performed because of the absolute rejection of blood transfusion due to the patientâ\u80\u99s religious convictions. Conclusion: Radiological stage-1 ALPPS is a feasible, minimally invasive option to be further investigated to become an effective alternative to surgical stage-1 ALPPS