Evaluation of the Molecular Landscape in PD-L1 Positive Metastatic NSCLC: Data from Campania, Italy.

BACKGROUND: Immune-checkpoint inhibitors (ICIs) have increased and improved the treatment options for patients with non-oncogene-addicted advanced stage non-small cell lung cancer (NSCLC). However, the role of ICIs in oncogene-addicted advanced stage NSCLC patients is still debated. In this study, in an attempt to fill in the informational gap on the effect of ICIs on other driver mutations, we set out to provide a molecular landscape of clinically relevant oncogenic drivers in programmed death-ligand 1 (PD-L1) positive NSCLC patients. METHODS: We retrospectively reviewed data on 167 advanced stage NSCLC PD-L1 positive patients (≥1%) who were referred to our clinic for molecular evaluation of five driver oncogenes, namely, EGFR, KRAS, BRAF, ALK and ROS1. RESULTS: Interestingly, n = 93 (55.7%) patients showed at least one genomic alteration within the tested genes. Furthermore, analyzing a subset of patients with PD-L1 tumor proportion score (TPS) ≥ 50% and concomitant gene alterations (n = 8), we found that n = 3 (37.5%) of these patients feature clinical benefit with ICIs administration, despite the presence of a concomitant KRAS gene alteration. CONCLUSIONS: In this study, we provide a molecular landscape of clinically relevant biomarkers in NSCLC PD-L1 positive patients, along with data evidencing the clinical benefit of ICIs in patient NSCLC PD-L1 positive alterations.

Pegylated liposomal doxorubicin as second-line therapy in the treatment of patients with advanced classic Kaposi sarcoma: a retrospective study.

BACKGROUND: Classic Kaposi sarcoma (CKS) is a rare neoplasm that predominantly occurs in elderly subjects and has a variable clinical evolution. The clinical course is usually indolent, but occasionally the neoplasm progresses rapidly and spreads to internal organs, necessitating systemic chemotherapy. Because of the rarity of CKS, the best treatment has not been determined to date. To the authors' knowledge, few data exist regarding the use of pegylated liposomal doxorubicin (PLD) as first-line and second-line treatment in advanced CKS. The current retrospective study investigated the activity and toxicity of PLD in pretreated patients with aggressive, nonvisceral CKS. METHODS: Patients were treated with PLD at a dose of 20 mg/m(2) intravenously every 3 weeks until disease progression or the occurrence of intolerable side effects. Objective responses were determined after 3 and 6 cycles; toxicity was assessed every cycle. Secondary endpoints were pain intensity, progression-free survival, and overall survival. RESULTS: Twenty men with pretreated CKS (median age, 67 years) were treated with PLD. All patients received at least 6 cycles of therapy. Complete and partial responses were observed in 2 patients (10%) and 14 patients (70%), respectively. Neutropenia was the most significant grade 3 hematologic toxicity observed (evaluated according to the National Cancer Institute Common Toxicity Criteria for Adverse Events [version 3.0]), occurring in 20% of patients. Only 1 patient (5%) demonstrated grade 4 neutropenia. Fourteen patients (70%) achieved remission of pain and/or edema after 6 cycles. The median progression-free survival was 9 months (95% confidence interval, 5-13 months). At a median follow-up of 36 months, 15 patients (75%) remained alive. CONCLUSIONS: PLD is associated with an improvement in objective response and pain intensity and is well tolerated as a second-line treatment for CKS.

Andrenocortical carcinomas: twelve-year prospective experience.

Adrenocortical carcinoma (AC) is a rare tumor with poor prognosis. Twenty-two patients (14 F, 8 M; age 22 to 59 years; median, 43 years) with AC were evaluated prospectively in a single center: tumor stage was I-II in 12 cases and III-IV in 10. The overall survival in our cohort was 41.6 +/- 42 months; 16 subjects are still alive. Curative surgery was followed by longer survival than debulking or no surgery (p < 0.0001). The first relapse was highly predictive for further recurrences. Recurrent ACs were progressively more aggressive, and they occurred with variable but ever shorter intervals. At diagnosis, 14 patients (63.5%) presented with features of clear adrenocortical hyperactivity. Despite the absence of clinical signs of hormonal excess, all other patients presented some abnormalities of steroid secretion. The most common clinical finding was a recent diagnosis of moderate-to-severe hypertension (68%), poorly controlled by pharmacological treatment, often associated with multiple cardiovascular risk factors. High mitotic rate and undifferentiated polymorph cellular pattern were associated with worse prognosis. Response to treatments other than surgery (mitotane chemotherapy) was better in patients treated early after the first surgery. In conclusion, curative surgery was the most effective treatment. Monitoring arterial pressure, endocrine parameters, and metabolic parameters can be helpful for the early detection of AC recurrences.

Clinicopathologic and immunohistochemical study of surgically treated primary gastric MALT lymphoma.

BACKGROUND AND OBJECTIVES: B-cell MALT lymphoma is a well-recognized entity and its characterization as low-grade (LG) and high-grade (HG) lymphoma has been widely accepted. In the present study we reviewed a series of 95 surgical specimens of primary gastric MALT lymphoma selected between 1979 and 1998. Immunohistochemical expression of p53, bcl-2, and Ki67 and Helicobacter pylori (Hp) infection was evaluated, along with a correlation with clinical outcome. METHODS: A morphologic and immunohistochemical analysis, including p53, bcl-2, and Ki67 expression, was carried out in all cases. A complete follow-up was obtained in 49 patients and in these cases a survival analysis was performed. RESULTS: bcl-2 protein was highly expressed in 25 of 25 assessed LG tumors and in 20 of 24 assessed HG tumors. p53 protein was expressed in 13 of 25 assessed LG tumors and in 21 of 24 assessed HG tumors. High proliferation rate as expressed by Ki67 was detected in 15 of 25 assessed LG tumors and in 23 of 24 assessed HG tumors. Hp infection was detected in 11 of 16 assessed LG tumors and 2 of 10 assessed HG tumors. Median survival rates were 72 months for LG tumors and 24 months for HG tumors. CONCLUSIONS: A significant inverse relationship between Hp infection and histological grade was found. High p53 expression and high-proliferation rate correlated with HG tumors. However, a correlation between p53, bcl-2, and Ki67 expression with clinical outcome was not found.