The Molecular Tumor Board of the Regina Elena National Cancer Institute: from accrual to treatment in real-world.

Background: Molecular Tumor Boards (MTB) operating in real-world have generated limited consensus on good practices for accrual, actionable alteration mapping, and outcome metrics. These topics are addressed herein in 124 MTB patients, all real-world accrued at progression, and lacking approved therapy options.

Methods: Actionable genomic alterations identified by tumor DNA (tDNA) and circulating tumor DNA (ctDNA) profiling were mapped by customized OncoKB criteria to reflect diagnostic/therapeutic indications as approved in Europe.

Interleukin-8 in Colorectal Cancer: A Systematic Review and Meta-Analysis of Its Potential Role as a Prognostic Biomarker.

Among soluble actors that have emerged as druggable factors, the chemokine interleukin-8 (IL-8) has emerged as a possible determinant of response to immunotherapy and targeted treatment in several cancer types; however, its prognostic/predictive role in colorectal cancer (CRC) remains to be established. We: (i) conducted a systematic review of published literature on IL-8 expression in CRC; (ii) searched public transcriptomics databases; (iii) investigated IL-8 expression, by tumor and infiltrating cells, in a series of CRC samples; and (iv) carried out a meta-analysis of published literature correlating IL-8 expression and CRC prognosis. IL-8 possesses an important role as a mediator of the bidirectional crosstalk between tumor/stromal cells.

A multicentre study with real-world data of the use of palbociclib in the treatment of breast cancer: Treatment duration correlates with dose reductions.

Objective: Palbociclib, a highly selective reversible CDK4-6 kinase inhibitor, is indicated in combination with an aromatase inhibitor or in combination with fulvestrant in women who had received prior endocrine treatment. Studies have demonstrated the efficacy of palbociclib in combination with fulvestrant in increasing progression-free survival in patients who relapsed or progressed on previous endocrine therapy, or in combination with aromatase inhibitor in patients who had not received previous treatments. We analysed the prescribing patterns of palbociclib in real practice correlating it with the evidence of treatment-related toxicity management and to time-to-treatment discontinuation and treatment adherence.

Fibroblast-Induced Paradoxical PI3K Pathway Activation in PTEN-Competent Colorectal Cancer: Implications for Therapeutic PI3K/mTOR Inhibition.

Purpose: Tumor-microenvironment interactions are important determinants of drug resistance in colorectal cancer (CRC). We, therefore, set out to understand how interactions between genetically characterized CRC cells and stromal fibroblasts might influence response to molecularly targeted inhibitors.

Techniques: Sensitivity to PI3K/AKT/mTOR pathway inhibitors of CRC cell lines, with known genetic background, was investigated under different culture conditions [serum-free medium, fibroblasts' conditioned medium (CM), direct co-culture].

Radiotherapy and Immunotherapy: The Power of the Teamwork for the Treatment of NSCLC.

Immune checkpoint inhibitors (ICPi) targeting programmed cell death 1(PD-1)/programmed cell death ligand-1 (PD-L1) have revolutionized the treatment of patients with advanced non-small cell lung cancer (NSCLC). Despite impressive success, only a small proportion of patients benefit from PD1/PDL1 inhibitors. Radiotherapy (RT) can induce a systemic anti-tumor immune response on local and distant tumors.

Cross-sectional analysis of circulating tumor DNA in primary colorectal cancer at surgery and during post-surgery follow-up by liquid biopsy.

Background: Liquid biopsy (LB) in early-stage, non-metastatic colorectal cancer (CRC) must be sensitive enough to detect extremely low circulating tumor DNA (ctDNA) levels. This challenge has been seldom and non-systematically investigated.

Methods: Next generation sequencing (NGS) and digital PCR (dPCR) were combined to test tumor DNAs (tDNAs) and paired ctDNAs collected at surgery from 39 patients, 12 of whom were also monitored during the immediate post-surgery follow up.

Gender effects of single nucleotide polymorphisms and miRNAs targeting clock-genes in metastatic colorectal cancer patients (mCRC).

The circadian system is composed of a set of clock-genes including PERIOD, CLOCK, BMAL1 and CRY. Disrupting this system promotes cancer development and progression. The expression levels of miR-206, miR-219, miR-192, miR-194 and miR-132 regulating clock-genes and three functional polymorphisms rs11133373 C/G, rs1801260 T/C, rs11133391 T/C in CLOCK sequence were associated with the survival of 83 mCRC patients (50 males and 33 females).

Epidermal growth factor receptor gene copy number in 101 advanced colorectal cancer patients treated with chemotherapy plus cetuximab.

Background: Responsiveness to Cetuximab alone can be mediated by an increase of Epidermal Growth factor Receptor (EGFR) Gene Copy Number (GCN). Aim of this study was to assess the role of EGFR-GCN in advanced colorectal cancer (CRC) patients receiving chemotherapy plus Cetuximab.

Methods: One hundred and one advanced CRC patients (43 untreated- and 58 pre-treated) were retrospectively studied by fluorescence in situ hybridization (FISH) to assess EGFR-GCN and by immunohistochemistry (IHC) to determine EGFR expression.

Chordoma: clinical characteristics, management and prognosis of a case series of 25 patients.

Background: Adequate surgery still remains the only curative treatment of chordoma. Interesting clinical data on advanced disease with molecularly targeted therapies were reported.

Methods: We described the clinical outcome of a series of chordoma patients followed at Regina Elena National Cancer Centre of Rome from 2004 to 2008.

A phase II study of cetuximab/irinotecan in patients with heavily pretreated metastatic colorectal cancer: predictive value of early specific toxicities.

Background: This study was designed to evaluate the predictive value of early specific toxicities on efficacy of weekly irinotecan/cetuximab administered as salvage therapy in patients with metastatic colorectal cancer (CRC) refractory to oxaliplatin and irinotecan.

Patients And Methods: Seventy patients received a regimen composed of weekly irinotecan 125 mg/m2 as a 1-hour intravenous infusion and cetuximab 400 mg/m2 infused over 2 hours as the initial dose and 250 mg/m2 infused over 1 hour for subsequent administrations. A single treatment cycle was composed of 4 weekly irinotecan infusions followed by 2 weeks of rest.

Unexpected clinical outcome in a patient with liver and brain metastasis from melanoma.

The treatment of disseminated melanoma is inadequate. The most active single agents provide brief objective response in 20% of patients, while the combination chemotherapy improves response rates without any apparent survival benefit. Median overall survival is, in fact, 7-9 months and 5 year survival is approximately 6%.

Gemcitabine at fixed dose-rate in patients with advanced soft-tissue sarcomas: a mono-institutional phase II study.

Purpose: To explore the clinical activity and toxicity of gemcitabine infused at the fixed dose of 10 mg/m(2)/min over 100 min in patients with soft tissue sarcomas (STSs).

Patients And Methods: Fourteen patients with advanced locally unresectable and/or metastatic, pretreated STSs (seven leiomyosarcoma, three malignant schwannoma, one synovialsarcoma, one malignant fibrous histiocytoma, one endometrial stromal cell sarcoma, one undifferentiated) were treated with gemcitabine 10 mg/m(2)/min/week over 100 min given for 3 weeks out of 4. The median age was 52 years (range 27-77), male/female ratio was 3/11, and the median WHO performance status was 0 (range 0-1).

A phase II trial of gefitinib in combination with capecitabine and oxaliplatin as first-line chemotherapy in patients with advanced colorectal cancer.

Objective: This study was designed as a multicentre phase II trial to assess the efficacy and safety of gefitinib in association with capecitabine and oxaliplatin in patients with untreated metastatic colorectal cancer.

Research Design And Methods: Patients with metastatic colorectal cancer that had received no prior chemotherapy for advanced disease were treated with oral gefitinib (250 mg daily) plus oral capecitabine (1000 mg/m2 twice a day on Days 1-14) and intravenous oxaliplatin (120 mg/m2 on Day 1 of each 3-week cycle).

Results: Thirty-five patients were enrolled.

Nonmyeloablative allogeneic blood stem cell transplantation in patients with metastatic solid tumors.

Background: The aim of the study was to evaluate the feasibility and efficacy of a non-myeloablative regimen to achieve complete donor chimerism after stem cell transplantation (SCT) in patients with metastatic solid tumors.

Patients And Methods: Seven patients with renal cell carcinoma (RCC), 3 with colorectal carcinoma and 1 with soft tissue sarcoma received an allogeneic SCT after fludarabine (90 mg/m2) and TBI 200 cGy.

Results: At day 30, median donor chimerism was 94%.

Severe skin reaction in a patient with gastrointestinal stromal tumor treated with imatinib mesylate.

Imatinib mesylate is a selective protein kinase inhibitor, highly active in patients with chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GISTs). Cutaneous toxicity, a well-recognized, dose-related side-effect of imatinib mesylate, has been reported in 18 to 69% of patients with GIST treated with doses ranging from 400 to 800 mg once a day. In this case-report a severe skin reaction observed in a patient with GIST treated with imatinib mesylate, in an adjuvant setting and whose severity led to definitive drug discontinuation, is described.

Central nervous system as exclusive site of disease in patients with melanoma: treatment and clinical outcome of two cases.

The central nervous system (CNS) is a favourite site of metastasis in advanced melanoma and, despite the improvement obtained in the control of brain metastasis, most patients die as a result of extracranial progression of the disease. CNS primary malignant melanoma is a rare entity and the diagnosis is generally made after the exclusion of a primary cutaneous or mucosal/retinal malignant melanoma, as differential histological diagnosis between primary and metastatic origins is often difficult. From a review of the literature, patients with primary brain melanoma or exclusive (and limited) brain metastasis in the absence of extracranial melanoma present a relatively good prognosis if adequately treated with aggressive locoregional treatments (neurosurgery and/or radiotherapy) and, later, with drugs able to cross the blood-brain barrier (i.

PET scanning evaluation of response to imatinib mesylate therapy in gastrointestinal stromal tumor (GIST) patients.

Background: Unresectable or metastatic gastrointestinal stromal tumors (GISTs) exhibit a dynamic clinical course, with no evidence of benefit from any standard cytotoxic chemotherapy and an inevitably fatal outcome. With the introduction of Imatinib, an oral drug able to inhibit the KIT receptor tyrosine kinase, new questions arise regarding our ability to monitor treatment response with conventional methods and optimally manage such patients on treatment with new agents.

Materials And Methods: Herein we report two cases of patients with a history of GIST in treatment with Imatinib.