Early palliative care and quality of life of advanced cancer patients-a multicenter randomized clinical trial.

BACKGROUND: To compare quality of life (QoL) of patients receiving early palliative care (EPC) vs. standard oncologic care (SOC). METHODS: Pragmatic, multicenter, randomized trial at five University and Community Hospital Cancer Centers in Northern Italy. Advanced non-small cell lung, gastric, pancreatic and biliary tract cancer patients diagnosed within the previous 8 weeks. In the EPC arm, visits were performed systematically by a dedicated physician/nurse palliative care (PC) team, who assessed physical and psychosocial symptoms, and enacted the necessary services. In the SOC arm, PC visits were only carried out if requested. The primary outcome was the difference in the change of QoL [Functional Assessment of Cancer Therapy-General measure (FACT-G)] from baseline to 12 weeks in the two groups. RESULTS: From November 2014 to March 2016, 281 patients were enrolled (142 EPC, 139 SOC); 218 completed FACT-G at 12 weeks. Baseline demographic and clinical characteristics were similar for the two groups. Values of FACT-G at baseline and 12 weeks were 72.3 (SD 12.6) and 70.1 (SD 15.5) for patients enrolled in the EPC arm, vs. 71.7 (SD 14.7) and 69.6 (SD 15.5) for the SOC arm, but the change scores did not differ significantly between groups. In the multivariable analysis, adjusting for QoL at baseline, two potential prospective prognostic factors were statistically significant: lung cancer (P=0.03) and interaction of living without a partner and intervention arm (P=0.01). Dying within 6 months (P<0.001) was also statistically significant. CONCLUSIONS: In this study, EPC did not improve QoL in advanced cancer patients, but our findings highlight aspects which may guide future research on EPC.

The Relationships between HER2 Overexpression and DCIS Characteristics.

The aim of this study was to demonstrate the correlation between human epidermal growth factor receptor 2 (HER2) overexpression and some poor prognosis factors in patients affected by ductal carcinoma in situ (DCIS). We evaluated 48 cases of DCIS, divided into two groups according to HER2 amplification status. Nuclear grade and "cancerization of lobules" were determined within primary DCIS and Ki67, estrogen receptor (ER), PR, and HER2 expression was established using immunohistochemistry. The histopathological variables in HER2-positive and in HER2-negative patients were compared to determine the recurrence risk. We also considered the median age at the time of surgery according to HER2 status. There were 11 recurrences (23%), 6 DCIS (55%), and 5 invasive cancer (45%). In an 8-year-long median follow-up, we hypothesized high risk of recurrence in HER2-positive DCIS. Patients with HER2-positive DCIS were younger than HER2-negative ones (p = 0.002). HER2-positive DCIS was also related to histopathological predictors of recurrence such as high nuclear grade (p < 0.001), high Ki67 expression (p = 0.003), low ER and PgR levels (p < 0.001), and the presence of "cancerization of lobules" (p < 0.049). Our trial suggests that HER2 amplification in primary DCIS is identified more frequently in younger patients and hypothesizes high risk of recurrence in HER2-positive DCIS related to histopathological predictors of overall relapse as high nuclear grade, high Ki67 expression, low ER and PgR levels, and the presence of "cancerization of lobules." In HER2-positive DCIS, other variables of recurrence risk are compared to HER2-negative lesions, without statistical significance. Our results show that HER2 testing might suggest clinicians the optimal treatment of patients with DCIS.

Good tolerability, long-term survival and easy management of side effects in a patient with metastatic renal cell carcinoma treated with pazopanib.

In recent years many new agents have been introduced into clinical practice to treat metastatic renal cell carcinoma. Some of these agents are tyrosine kinase inhibitors, which have different adverse events compared to chemotherapy or immunotherapy. We describe the case of a man treated with pazopanib as first-line therapy for metastatic disease, demonstrating the efficacy, good tolerability and easy management of some side effects of this tyrosine kinase inhibitor. The patient, who presented with lung metastases, started therapy in November 2012 and was alive and in continuous response at the time of writing (November 2014). We controlled the elevation of transaminase levels with low-dose corticosteroid administration. The patient had no other significant adverse events (apart from dysgeusia and grade 1 diarrhea), he had good quality of life, and his performance status throughout the treatment was very good (ECOG 0).

Microwave ablation of hepatocellular carcinoma using a new percutaneous device: preliminary results.

BACKGROUND: Thermal ablative techniques have gained increasing popularity as safe and effective options for patients with unresectable solid malignancies. Microwave ablation has emerged as a relatively new technique with the promise of larger and faster ablation areas without some of the limitations of radiofrequency thermal ablation. Herein, we report our preliminary results on the feasibility and efficacy of thermal ablation for hepatocellular carcinoma (HCC) with a new 2.45-MHz microwave generator. PATIENTS AND METHODS: Under ultrasound guidance 194 HCCs in 144 patients were treated through a percutaneous approach. The median diameter of lesions was 2.7 cm (range=2.0-11.0 cm); 68 lesions had a diameter greater than 30 mm. We used a microwave generator (AMICA-GEM, Apparatus for MICrowave Ablation) connected to a 14- or 16-gauge coaxial antenna endowed with a miniaturized sleeve choke to reduce back heating effects and increase the sphericity of the ablated area. Contrast-enhanced computed tomography scan was carried out one month after treatment, and then every three months to assess efficacy. RESULTS: Complete ablation was achieved in 94.3% of the lesions after a mean of 1.03 percutaneous sessions. For small HCCs (diameter <3 cm) complete necrosis was obtained in 100%. Local tumor progressions were found in 10 treated lesions (5.1%) a median of 19.5 months after ablation. Minor complications occurred in 5.1% procedures. No deaths, or other major complications occurred. CONCLUSION: In our experience, the new device for microwave ablation proved to provide an effective and safe percutaneous ablative method, capable of producing large areas of necrosis.

Serum pharmacokinetics in patients treated with transarterial chemoembolization (TACE) using two types of epirubicin-loaded microspheres.

AIM: The purpose of this study was the pharmacokinetic (PK) profile assessment in the serum of patients affected by hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) with drug-eluting beads. PATIENTS AND METHODS: This study included 20 patients, 12 treated with DC Bead® and 8 with HepaSphere Microsphere®, preloaded with epirubicin. No patient randomization was used for the inclusion in one group or in the other. Peripheral blood samples were obtained from all patients after the treatment, until 24 hours past the procedure. RESULTS: The pharmacokinetic study showed low peak serum epirubicin concentrations with greater drug exposure for the DC Bead® group (p<0.05). The highest drug concentration after microsphere injection was observed at 5 minutes in all 20 patients. In the time interval between 1 and 24 hours after TACE, persisting levels of epirubicin were detected in peripheral blood samples. CONCLUSION: A persistent and sustained drug elution for both types of microparticles was found.

Hepatic intra-arterial cetuximab in combination with 5-fluorouracil and cisplatin as salvage treatment for sorafenib-refractory hepatocellular carcinoma.

BACKGROUND: Sorafenib is the only therapy approved for advanced hepatocellular carcinoma no longer eligible for transcatheter arterial chemoembolization. Hepatic intra-arterial chemotherapy has been shown to be an effective and safe therapy for advanced hepatocellular carcinoma. Cetuximab has been administered intravenously to patients with advanced hepatocellular carcinoma, showing encouraging results in terms of its safety and toxicity profile. AIM: Our purpose was to evaluate the safety and feasibility of hepatic arterial chemotherapy with cetuximab, cisplatin and 5-fluoruracil for patients with advanced hepatocellular carcinoma, not responsive or not eligible for sorafenib therapy. PATIENTS AND METHODS: From January 2010 to January 2011, 12 patients received a 2-day course of chemotherapy consisting of repeated daily hepatic arterial administration of 20 mg of cisplatin as 2-h infusion, 5-fluorouracil at 500 mg/m(2) as 5-h infusion and cetuximab 500 mg/m(2) as 12-h infusion. Cycles were repeated every 14 days. RESULTS: After a mean of four months of therapy, computed tomography revealed five partial responses, five cases of stable disease and two of progressive disease. The toxicity profile was favourable, with no G4 gastrointestinal, hematologic or skin side-effects, or severe deterioration of liver function. CONCLUSION: Hepatic intra-arterial chemotherapy with cetuximab is a safe and feasible treatment for advanced hepatocellular carcinoma, with promising results in patients with initial poor prognosis.

Use of sorafenib in two metastatic renal cell cancer patients with end-stage renal impairment undergoing replacement hemodialysis.

Patients with renal cell carcinoma (RCC) may exhibit renal impairment as a more or less direct consequence of their primary disease. Renal impairment may become a severe complication and alter the normal pharmacokinetic and pharmacodynamic behavior of treatment drugs, thus increasing the risk of side effects. We will discuss the cases of two advanced RCC patients with end-stage renal impairment submitted to dialysis who were treated with sorafenib tosylate in our center. Our experience confirms the scarce literature data available so far that indicate that sorafenib can be used in patients undergoing dialysis. Dialysis cannot be considered per se a contraindication to sorafenib therapy, which can be effective. However, patients must be carefully selected and monitored, since sorafenib administration unquestionably increases the risk of side effects in patients affected by several conditions.