Clinical utility of Next Generation Sequencing of plasma cell-free DNA for the molecular profiling of patients with NSCLC at diagnosis and disease progression.

Background: The present study evaluates the utility of NGS analysis of circulating free DNA (cfDNA), which incorporates small amounts of tumor DNA (ctDNA), at diagnosis or at disease progression (PD) in NSCLC patients.

Methods: Comprehensive genomic profiling on cfDNA by NGS were performed in NSCLC patients at diagnosis (if tissue was unavailable/insufficient) or at PD to investigate potential druggable molecular aberrations. Blood samples were collected as routinary diagnostic procedures, DNA was extracted, and the NextSeq 550 Illumina platform was used to run the Roche Avenio ctDNA Expanded Kit for molecular analyses.

Non-pegylated liposomal doxorubicin in older adjuvant early breast cancer patients: cardiac safety analysis and final results of the COLTONE study.

Aims: To explore the cardiac safety of adjuvant Non-Pegylated Liposomal Doxorubicin (NPL-DOX) plus Cyclophosphamide (CTX) followed by weekly Paclitaxel, in elderly women (≥ 65 years) with high-risk breast cancer. Previously, we described no symptomatic cardiac events within the first 12 months from starting treatment. We now reported the updated results after a median follow-up 76 months.

Pembrolizumab for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer: Analysis of Prognostic Factors of Outcomes.

Background: In advanced non-small-cell lung cancer, without activating mutations and with PD-L1≥50%, Pembrolizumab monotherapy is the therapeutic standard in Europe.

Objective: To evaluate retrospectively the safety and efficacy of this drug and to investigate potential prognostic factors in daily clinical practice.

Methods: From September 2017 to September 2019, 205 consecutive patients from 14 Italian Medical Oncology Units were enrolled in the study.

Endothelial nitric oxide synthase c.-813C>T predicts for proteinuria in metastatic breast cancer patients treated with bevacizumab-based chemotherapy.

Purpose: To investigate the association between single nucleotide polymorphisms (SNPs) in endothelial nitric oxide synthase (eNOS) and interleukin-8 (IL-8) genes and risk of developing bevacizumab-related adverse events in metastatic breast cancer (mBC) patients.

Patients And Methods: mBC patients candidate to receive bevacizumab-based chemotherapy were enrolled in this pharmacogenetic study. eNOS c.

Second generation tyrosine kinase inhibitors for the treatment of metastatic non-small-cell lung cancer.

Backgruond: Since their first description, activating epidermal growth factor receptor (EGFR) mutations identify a distinct clinical entity of patients with non-small-cell lung cancer (NSCLC).

Findings: New targeted therapies for molecularly selected NSCLC are changing the natural history of the disease, with results superior to standard chemotherapy as demonstrated in large phase III studies with first generation EGFR tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib. However, after an initial response, all patients inevitably progress and several mechanisms including a secondary mutation in exon 20 of the EGFR gene (T790M) or MET or HER2 amplifications are responsible for acquired resistance (AR).

Profile of bavituximab and its potential in the treatment of non-small-cell lung cancer.

Bavituximab is a an unconjugated, chimeric immunoglobulin G1 (IgG1) monoclonal antibody directed against the phosphatidylserine (PS) expressed on tumor endothelium, with a specific mechanism of action. PS is an anionic membrane phospholipid, physiologically restricted to the internal membrane leaflet; various pathophysiologic processes cause the exposure of PS on the external membrane leaflet. Bavituximab, once bound, starts up host effector activities, such as antibody dependent cellular cytotoxicity, causing vessel destruction and enhancing antitumor immunity.

Randomized trial of two induction chemotherapy regimens in metastatic colorectal cancer: an updated analysis.

Background: In a randomized trial with a median follow-up of 18.4 months, 6 months of induction chemotherapy with a three-drug regimen comprising 5-fluorouracil (by continuous infusion)-leucovorin, irinotecan, and oxaliplatin (FOLFOXIRI) demonstrated statistically significant improvements in response rate, radical surgical resection of metastases, progression-free survival, and overall survival compared with 6 months of induction chemotherapy with fluorouracil-leucovorin and irinotecan (FOLFIRI).

Methods: From November 14, 2001, to April 22, 2005, we enrolled 244 patients with metastatic colorectal cancer.

Cetuximab plus irinotecan after irinotecan failure in elderly metastatic colorectal cancer patients: clinical outcome according to KRAS and BRAF mutational status.

Background: Scarce data are available about safety and efficacy of cetuximab in elderly metastatic colorectal cancer (mCRC) patients.

Patients And Methods: We retrospectively analysed 54 irinotecan-refractory mCRC patients aged≥70 years treated with cetuximab plus irinotecan and evaluated clinical outcome according to KRAS and BRAF mutational status.

Results: Median age was 73 years (70-82).

Beyond KRAS: perspectives on new potential markers of intrinsic and acquired resistance to epidermal growth factor receptor inhibitors in metastatic colorectal cancer.

The monoclonal antibodies cetuximab and panitumumab, directed against the epidermal growth factor receptor (EGFR), are licensed for the treatment of KRAS wild-type metastatic colorectal cancer (mCRC). Such 'molecular restriction' derived from post-hoc analyses of randomized trials and from other retrospective series all indicate how tumors bearing KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutations are resistant to EGFR inhibition. Even if highly sensitive for nonresponse, KRAS testing is not very specific.

Refractory neuroendocrine tumor-response to liposomal doxorubicin and capecitabine.

Background: A 61-year-old patient with no relevant medical or family history presented with a 2 month history of refractory dry cough that led to the diagnosis of typical carcinoid tumor of the lung metastatic to the mediastinal lymph nodes and liver. She initially received a long-acting somatostatin analog (octreotide) and chemotherapy with cisplatin and etoposide, which was ineffective.

Investigations: Physical examination, laboratory test, chromogranin A test, CT scan, (111)In-diethylenetriaminepentaacetic acid (DTPA)-octreotide scan, (18)F-FDG-PET scan, fine-needle and tissue core liver biopsies.

PTEN expression and KRAS mutations on primary tumors and metastases in the prediction of benefit from cetuximab plus irinotecan for patients with metastatic colorectal cancer.

Purpose: PTEN, AKT, and KRAS are epidermal growth factor receptor (EGFR) downstream regulators. KRAS mutations confer resistance to cetuximab. This retrospective study investigated the role of PTEN loss, AKT phosphorylation, and KRAS mutations on the activity of cetuximab plus irinotecan in patients with metastatic colorectal cancer (mCRC).

High concordance of KRAS status between primary colorectal tumors and related metastatic sites: implications for clinical practice.

Purpose: Several studies have suggested that KRAS somatic mutations may predict resistance to cetuximab- and panitumumab-based treatments in metastatic colorectal cancer (CRC) patients. Nevertheless, most experiences were conducted on samples from primaries. The aim of this study was to evaluate the grade of concordance in terms of KRAS status between primaries and related metastases.