Hepatotoxicity in Patients with Hepatocellular Carcinoma on Treatment with Immune Checkpoint Inhibitors.

Risk factors for hepatic immune-related adverse events (HIRAEs) in patients with advanced/unresectable hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICIs) are unclear. We investigated: (i) clinical and morpho-pathological predictors of HIRAEs in 27 pretreatment tumor specimens, including surrogate biomarkers of the HCC immune class (based on intratumoral tertiary lymphoid structures, and glutamine synthase, CD3, and CD79 expression); and (ii) the relationship between HIRAE onset and subsequent treatment outcomes. Fifty-eight patients were included-20 (34%) received ICIs alone, and 38 (66%) received ICIs plus targeted agents as first- or further-line treatment. After a median time of 0.9 months (range, 0.4-2.7), nine patients (15.5%) developed grade ≥ 3 hepatitis, which was significantly associated with higher baseline ALT levels (p = 0.037), and an infectious HCC etiology (p = 0.023). ICIs were safely resumed in six out of nine patients. Time to treatment failure (TTF) was not significantly different in patients developing grade ≥ 3 hepatitis vs. lower grades (3.25 vs. 3.91 months, respectively; p = 0.81). Biomarker surrogates for the HCC immune class were not detected in patients developing grade ≥ 3 hepatitis. Grade ≥ 3 hepatitis has a benign course that does not preclude safe ICI reintroduction, without any detrimental effect on TTF.

Cerebral Air Embolism After CT-guided Lung Biopsy: A Case of Early Diagnosis and Successful Treatment / Embolismo aéreo cerebral tras una biopsia pulmonar guiada por CT: un caso de diagnóstico temprano y tratamiento exitoso

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Pilot study on use of home telephoning to identify and recruit high-risk individuals for lung cancer screening.

Widespread lung cancer screening with low-dose computed tomography is urgently needed in Europe to identify lung cancers early and reduce lung cancer deaths. The most effective method of identifying high-risk individuals and recruiting them for screening has not been determined. In the present pilot study we investigated direct telephoning to families as a way of identifying high risk individuals and recruiting them to a screening/smoking cessation program, that avoided the selection bias of voluntary screening. Families in the province of Milan, Italy, were contacted by telephone at their homes and asked about family members over 50 years who were heavy smokers (30 or more pack-years). Persons meeting these criteria were contacted and asked to participate in the program. Those who agreed were given an appointment to undergo screening and receive smoking cessation counseling. Among the 1000 contacted families, involving 2300 persons, 44 (1.9%) were eligible for LDCT screening, and 12 (27%) of these participated in the program. The cost of this recruitment strategy pilot study was around 150 euro per screened subject. We obtained useful information on the proportion of the general population eligible for lung cancer screening and the proportion of those who responded. However the cost of home telephone calling is probably too high to be practicable as a method of recruiting high risk persons for screening. Alternative recruitment methods, possibly involving family physicians practitioners, need to be investigated.

Non-pegylated liposomal doxorubicin plus ifosfamide in metastatic soft tissue sarcoma: results from a phase-II trial.

BACKGROUND/AIM: Non-pegylated liposomal doxorubicin (NPLD) has demonstrated antitumour activity equivalent to conventional doxorubicin and a significantly lower risk of cardiotoxicity. This phase II trial was performed to evaluate the activity and the safety of NPLD and ifosfamide combination in patients with metastatic soft tissue sarcoma. PATIENTS AND METHODS: Thirty-four patients received NPLD 40 mg/m(2) (d1) and ifosfamide 3 g/m(2)/day (d1-3) every three weeks as first-line therapy of metastatic soft tissue sarcoma. The treatment was planned for a maximum of six cycles. RESULTS: The objective response (OR) rate among response-assessable patients was 55.9%. The median progression-free survival (PFS) was 4.2 months and the median overall survival (OS) was 11.2 months. Symptomatic grade 3 cardiotoxicity occurred in one patient (3%). CONCLUSION: The combination of NPLD and ifosfamide reported in a population of metastatic soft tissue sarcoma patients at risk for developing heart failure encourage antitumour activity, similar to that of classical doxorubicin.

Phase I study of non-pegylated liposomal doxorubicin in combination with ifosfamide in adult patients with metastatic soft tissue sarcomas.

OBJECTIVE: The aim of this study was to evaluate the maximum tolerated dose (MTD) and safety of the combination of non- pegylated liposomal doxorubicin (Myocet) and ifosfamide in patients with metastatic soft tissue sarcomas. METHODS: Cohorts of four patients with metastatic soft tissue sarcomas received up to five cycles of intravenous ifosfamide 3000 mg/m2 on days 1- 3 in combination with escalating doses of intravenous Myocet on day 1 every 3 weeks until dose limiting toxicity (DLT) in at least one patient. Starting dose of Myocet was 40 mg/m2 to be escalated through 10 mg/m2 increase up to 80 mg/m2. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria v3.0 (NCI-CTC v3.0). RESULTS: Ten patients were enrolled in the study and 8 of them received the treatment. Median age was 45 years, 3 patients were male and 5 were female. DLT, consisting of neutropenic fever, was reached in one patient at dose level 2 (Myocet 50 mg/m2). Therefore, the MTD and the recommended phase II dose is 40 mg/m2. CONCLUSIONS: The combination of intravenous Myocet 40 mg/m2 on day 1 and ifosfamide 3,000 mg/m2 on days 1-3 every 3 weeks is safe and feasible; a phase II study is ongoing.