Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial

Background: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. Methods: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer. Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely remov…

P1.13-16 The Diagnostic Accuracy of Circulating Tumor DNA for the Detection of EGFR-T790M Mutation in NSCLC: A Systematic Review and Meta-Analysis

The role of polymorphisms occurring in BRCA1/2 genes in determining ovarian cancer risk.

e17551 Background: Ovarian cancer (OC) is the 10th tumor occurring in women, it accounts for 30% of all malignant tumor affecting female genital tract in Italy. There are several factors that contribute to OC development; in 15-25% of cases family history of breast and ovarian cancer represent the main risk factor. It is well known that pathogenic variants (PVs) occurring in BRCA1/2 genes strongly increase the risk of developing OC, ranging from 50% in BRCA1 PVs carriers to 30% in BRCA2 PVs carriers. Recently genetic polymorphism has been shown to increase cancer risk, consequently polymorphisms in BRCA1/2 genes could represent low penetrance susceptibility alleles and contribute to determ…

Reply to: Denosumab for bone health in prostate and breast cancer patients receiving endocrine therapy? A systematic review and a meta-analysis of randomized trials (Galvano et al., J Bone Oncol 2019; 18:100252)

Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer Patients Progressing after Docetaxel: A Prospective Single-Center Study

<b><i>Purpose:</i></b> The present study aims to evaluate the efficacy of cabazitaxel in combination with prednisone treatment in Italian patients affected by hormone-refractory metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel plus prednisone. <b><i>Methods:</i></b> Thirty patients with mCRPC were enrolled between June 2013 and January 2016 (the last follow-up was in January 2016). Cabazitaxel was used according to the summary of product characteristics and administered at a dose of 25 mg/m<sup>2</sup> every 3 weeks plus oral prednisone at a dose of 5-mg tablets twice a day continuously. The…

Advanced breast cancer at presentation (ABC-p) in octogenarian women (OW): Specific elderly-devoted risk tests(SEDRT) (CARG+CRASH) as new tools to prevent serious/irreversible adverse reactions (AR) in frail patients.

e12510 Background: Due to current lengthening of average lifespan and progressive increase of malignant tumors in mankind, more new strategies must be constantly sought especially for thirdage neoplasms. Nevertheless because severe toxicity developed in the majority of frail patients, administration of therapy may cause high risk of life-threatening AIM: We have considered in this paper ABC in frail patients like OW. Purpose of the study is preliminary detection of the overall toxicity (OTox) through the possible use of specifics tests adopted specially in frail patients such as OW, to ensure greater control in drugs administration with good effectiveness. AIM: We have considered in this p…

PROTACs: The Future of Leukemia Therapeutics

The fight to find effective, long-lasting treatments for cancer has led many researchers to consider protein degrading entities. Recent developments in PROteolysis TArgeting Chimeras (PROTACs) have signified their potential as possible cancer therapies. PROTACs are small molecule, protein degraders that function by hijacking the built-in Ubiquitin-Proteasome pathway. This review mainly focuses on the general design and functioning of PROTACs as well as current advancements in the development of PROTACs as anticancer therapies. Particular emphasis is given to PROTACs designed against various types of Leukemia/Blood malignancies.

Moving the target on the optimal adjuvant strategy for resected pancreatic cancers: A systematic review with meta-analysis

Combination regimens have shown superiority over single agents in the adjuvant treatment of resected pancreatic cancer (PC), but there are no data supporting definition of the best regimen. This work aimed to compare the efficacy and safety of mFOLFIRINOX, gemcitabine+capecitabine, and gemcitabine+nab/paclitaxel in PC patients. A meta-analysis was performed for direct comparison between trials comparing combination regimens and gemcitabine monotherapy. Subsequently, an indirect comparison was made between trials investigating the efficacy and safety of mFOLFIRINOX, gemcitabine+capecitabine, and gemcitabine+nab/paclitaxel because of the same control arm (gemcitabine). A total of three studie…

Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses

Background: The addition of PD-L1 inhibitors to platinum-based chemotherapy (CT) has newly received United States Food and Drug Administration (FDA) approval in extensive stage-small cell lung cancer (ES-SCLC). PD-1 agents similarly improved survival rates, even if not yet supported by international regulatory agencies. The current work aims to assess different efficacy and safety profiles among chemoimmunotherapy plus immuno-oncology (CT+IO) approaches according to different immune checkpoint inhibitor (ICI) subtypes. Material & Methods: We included in our meta-analysis six first-line randomised controlled trials (RCTs) comparing the association of single-agent ICI with CT versus CT al…

How to deal with second line dilemma in metastatic colorectal cancer? A systematic review and meta-analysis.

e15006 Background: Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have demonstrated efficacy in combination with chemotherapy as second line for metastatic colorectal cancer (mCRC). However, there is still a paucity of evidence or guidelines suggesting the right sequential treatment in all RAS (KRAS/NRAS) wild type(wt)mCRC. Therefore, we aimed to evaluate the impact of these targeted therapies by reviewing literature data. Methods: We used Cochrane, EMBASE and Medline databases to select phase III clinical trials containing efficacy and safety data about chemotherapy (CT) or CT + targeted agents combination (Anti-VEGF an…

P2.04-10 Early Monitoring of Blood Biomarkers to Predict Nivolumab Efficacy in NSCLC Patients

Numerical, dimensional or mixed progression disease to imatinib as prognostic factor in patients with metastatic GIST.

11040 Background: The majority of GIST patients with advanced disease initially achieves disease control from imatinib treatment. Approximately 10% of patients progresses within 6 months of starting therapy (primary resistance) and also 50-60% of the responding patients develops progression disease within two years (secondary resistance). Progression disease (PD) can be numerical, dimensional or mixed. The known prognostic factors of risk stratification in local disease are tumor size, mitotic activity and anatomic site. In this retrospective analysis we explore several clinical factors affecting survival in metastatic setting. Methods: The population included in this large database of 128…

Body mass index and baseline platelet count as predictive factors in Merkel cell carcinoma patients treated with avelumab

BackgroundMerkel cell carcinoma (MCC) is a rare and aggressive skin cancer, associated with a worse prognosis. The Immune Checkpoint Inhibitors (ICIs) avelumab and pembrolizumab have been recently approved as first-line treatment in metastatic MCC (mMCC). The clinical observation of improved outcomes in obese patients following treatment with ICIs, known as the “obesity paradox”, has been studied across many types of tumors. Probably due to the rarity of this tumor, data on mMMC patients are lacking.Patients and methodsThis is an observational, hospital-based, study to investigate the role of Body Mass Index (BMI) as predictive biomarker of ICI response in mMCC patients treated with aveluma…

sj-docx-14-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-14-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

The prognostic impact of tumor mutational burden (TMB) in the first-line management of advanced non-oncogene addicted non-small-cell lung cancer (NSCLC): a systematic review and meta-analysis of randomized controlled trials

Background The role of tumor mutational burden (TMB) is still debated for selecting advanced non-oncogene addicted non-small-cell lung cancer (NSCLC) patients who might benefit from immune checkpoint inhibitors (ICIs). Of note, TMB failed to predict a benefit in overall survival (OS) among such patients. Materials and methods The purpose of this meta-analysis was to compare efficacy outcomes among first-line immune-oncology (IO) agents versus standard platinum-based chemotherapy (CT) within two subgroups (TMB-low and TMB-high on either tissue or blood). We collected hazard ratios (HRs) to evaluate the association for progression-free survival (PFS) and OS, with the relative 95% confidence i…

Are Long Noncoding RNAs New Potential Biomarkers in Gastrointestinal Stromal Tumors (GISTs)? The Role of H19 and MALAT1

Long noncoding RNAs (lncRNAs) are emerging as key regulators of genetic and epigenetic networks, and their deregulation may underlie complex diseases, such as carcinogenesis. Several studies described lncRNA alterations in patients with solid tumors. In particular, HOTAIR upregulation has been associated with tumor aggressiveness, metastasis, and poor survival in gastrointestinal stromal tumor (GIST) patients. We analyzed expression levels of other lncRNAs, H19 and MALAT1, in FFPE tissue specimens from 40 surgically resected and metastatic GIST patients, using real-time PCR analysis. H19 and MALAT1 were both upregulated in 50% of GIST patients. MALAT1 lncRNA expression levels seem to be cor…

Metastatic site location influences the diagnostic accuracy of ctDNA EGFR- mutation testing in NSCLC patients: a pooled analysis

Background: Recent studies evaluated the diagnostic accuracy of circulating tumor DNA (ctDNA) analysis in the detection of epidermal growth factor receptor (EGFR) mutations from plasma of NSCLC patients, overall showing a high concordance as compared to standard tissue genotyping. However it is less clear if the location of metastatic site may influence the ability to identify EGFR mutations. Objective: This pooled analysis aims to evaluate the association between the metastatic site location and the sensitivity of ctDNA analysis in detecting EGFR mutations in NSCLC patients. Methods: Data from all published studies, evaluating the sensitivity of plasma-based EGFRmutation testing, stratifi…

sj-docx-12-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-12-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Analysis of tissue and circulating microRNA expression during metaplastic transformation of the esophagus

Genetic changes involved in the metaplastic progression from squamous esophageal mucosa toward Barrett's metaplasia and adenocarcinoma are almost unknown. Several evidences suggest that some miRNAs are differentially expressed in Barrett's esophagus (BE) and esophageal adenocarcinoma. Among these, miR-143, miR-145, miR-194, miR-203, miR-205, miR-215 appear to have a key role in metaplasia and neoplastic progression. The aim of this study was to analyze deregulated miRNAs in serum and esophageal mucosal tissue biopsies to identify new biomarkers that could be associated with different stages of esophageal disease. Esophageal mucosal tissue biopsies and blood samples were collected and analyz…

Clinical efficacy and safety of Ezetimibe on major cardiovascular endpoints: systematic review and meta-analysis of randomized controlled trials.

Background Randomized clinical trials (RCTs) about Ezetimibe's efficacy on patient-oriented outcomes have given discordant results. The aim of this study was to determine the net effect of Ezetimibe and of the widely marketed combination, Ezetimibe+simvastatin, on mortality and morbidity outcomes. Methods and Findings We searched for RCT on Ezetimibe using MEDLINE, CCTR, EMBASE, ClinicalTrials.gov databases up to December 2013, Merck and Novartis online registers, and personal communications. Two authors independently selected trials fulfilling these criteria: RCTs comparing Ezetimibe±statin or another lipid-lowering drug against placebo, or against the same lipid-lowering drug at the same …

Liquid Biopsy in Colorectal Cancer

Colorectal cancer (CRC) is the third most common cancer worldwide. Oncological CRC treatment is changing gradually replacing ancient drugs with the newest targeted agents (target therapy) and immunotherapy. The correct use of these molecular agents is based on a series of genetic evaluations able to predict treatment response. The tissue evaluation of these predictors is generally fully of serious limitations among which the invasiveness of the tissue biopsy procedure and its non-informative quality compared to the entire neoplastic mass. For these reasons, liquid biopsy could represent an ideal tool to obtain easily and quickly the necessary information to decide the best therapeutic strat…

The significance of epidermal growth factor receptor uncommon mutations in non-small cell lung cancer: A systematic review and critical appraisal

Uncommon epidermal growth factor receptor (EGFR) mutations collectively account for 10% of EGFR mutations, harboring heterogeneous molecular alterations within exons 18-21 with clinically variable responses to EGFR tyrosine kinase inhibitors (TKIs) in advanced Non-Small Cell Lung Cancer (NSCLC) patients. In addition, with the introduction of different NGS gene approach an improvement of EGFR mutations detection was reported. Today, no specific studies have prospectively evaluated uncommon sensitizing mutations in detail and no firm standard of care has been established in the first-line setting. The aim of this comprehensive review is to critically consider the clinical role of uncommon EGF…

Safety and effectiveness of gemcitabine for the treatment of classic Kaposi’s sarcoma without visceral involvement

Background: Classic Kaposi’s sarcoma (CKS) is a rare, multifocal, endothelial cell neoplasm that typically occurs in elderly people with previous infection by human herpes virus-8. Prospective trials are rare, and the choice of drugs relies on prospective trials performed on HIV-associated Kaposi’s sarcoma (KS). Pegylated liposomal anthracyclines and taxanes are considered the standard first- and second-line chemotherapy, respectively. Despite the indolent biologic behavior, the natural history is characterized by recurrent disease. This condition of chronic administration of cytotoxic drugs is often associated with immediate/long-term adverse events. Methods: This was an observational, ret…

Predictive factors of response to Sunitinib in metastatic Gastrointestinal Stromal Tumors (mGISTs): A retrospective analysis

COVID-19 Infection in Cancer Patients: How Can Oncologists Deal With These Patients?

The world is facing a new pandemic caused by a novel beta coronavirus (COVID 19), which causes severe respiratory coronavirus syndrome (SARS-CoV-2). Unfortunately, there are currently no US Food and Drug Administration (FDA) approved medications for the treatment of COVID-19 patients. High mortality rates in frail patients is a notable feature of the virus registered since the onset of COVID-19 pandemic. Above all, elderly patients or those with underlying chronic illnesses and compromised immune system are most at risk (1). Thus, the consideration is that the possible coexistence, in the same individual, of a cancer diagnosis and a COVID-19 infection could generate a synergistic negative p…

1543P Gemcitabine in classic Kaposi’s sarcoma: A pilot study

sj-docx-7-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-7-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Colorectal Cancer: Metastatic Disease

Most patients diagnosed with metastatic colorectal cancer (mCRC) develop metastases during the disease course after resection of the primary locoregional cancer. To date, the liver represents the most common site of metastatic involvement. Although several different biological and clinical hallmarks exist between the colon and rectum (different embryological origin, anatomy, and molecular biology), mCRC requires similar staging procedures and systemic treatment strategies (first and subsequent lines) in terms of a multimodal approach treatment as a part of a “continuum of care.” Patients affected by oligometastatic disease should undergo an upfront evaluation by a multidisciplinary team for…

Cell-free DNA and exoDNA analysis in metastatic colorectal cancer patients (mCRC).

e16093 Background: Liquid biopsy is a growing field in translational cancer research. Two of the most studied liquid biopsy biomarkers are cell-free DNA (cfDNA) and exosomes, nano-sized vesicles that transport protein and nucleic acids including DNA (exoDNA). Therefore, both cfDNA and exoDNA are potentially useful to investigate the molecular landscape of tumor with a minimally invasive approach. Here we investigate the prognostic and predictive role of both cfDNA and exoDNA in mCRC using Next Generation Sequencing (NGS) analysis. Methods: From July 2017 to September 2018, samples of 40 mCRC patients were collected at the Medical Oncology of the AOUP Paolo Giaccone of Palermo. Blood sample…

The Treatment of Medication-Related Osteonecrosis of the Jaw (MRONJ): A Systematic Review with a Pooled Analysis of Only Surgery versus Combined Protocols

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction of antiresorptive and antiangiogenic agents, and it is also a potentially painful and debilitating condition. To date, no specific studies have prospectively evaluated the efficacy of its treatment and no robust standard of care has been established. Therefore, a systematic review (2007–2020) with a pooled analysis was performed in order to compare MRONJ surgical techniques (conservative or aggressive) versus combined surgical procedures (surgery plus a non-invasive procedure), where 1137 patients were included in the pooled analysis. A statistically significant difference in the 6-month improvement rate, comp…

sj-docx-3-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-3-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

1281P The prognostic impact of tissue tumour mutational burden (TMB) in the first-line treatment of advanced non-oncogene addicted non-small cell lung cancer (NSCLC): A systematic review and meta-analysis of randomized controlled trials

Ramucirumab and its use in gastric cancer treatment

Abstract: The inhibition of the mechanisms of tumor neo-angiogenesis represents a milestone that in the last 10 years has seen the advent of numerous molecules to target action against the vascular endothelial growth factor (VEGF). More recently, new molecules have been developed that inhibit tumor spread by the blockade of specific VEGF receptors (VEGFRs), thereby preventing the binding of a ligand to its receptor and the cascade of proliferative events downstream. Ramucirumab is a fully humanized IgG1 monoclonal antibody that performs its action by blocking the isoform 2 of the VEGF receptor (VEGFR-2). Numerous preclinical and clinical studies have demonstrated its activity in several sol…

Analysis of systemic inflammatory biomarkers in neuroendocrine carcinomas of the lung: prognostic and predictive significance of NLR, LDH, ALI, and LIPI score

Background: Lung neuroendocrine carcinoma (NEC) is characterized by aggressive clinical behavior and lack of treatment advances. We evaluate the prognostic and the predictive roles of systemic inflammatory biomarkers in patient circulating blood: neutrophil–lymphocyte ratio (NLR), lactate dehydrogenase (LDH), advanced lung cancer inflammation index (ALI), and the Lung Immune Prognostic Index (LIPI) score. Methods: A total of 120 patients with small-cell lung cancer (SCLC) ( n = 110) and large cell neuroendocrine carcinoma (LCNEC) ( n = 10) were enrolled. Overall survival (OS) was evaluated by Kaplan–Meier estimator and univariate and multivariate Cox proportional hazard analyses were perfor…

Triple negative breast cancer: shedding light onto the role of pi3k/akt/mtor pathway

// Daniela Massihnia 1,* , Antonio Galvano 1,* , Daniele Fanale 1 , Alessandro Perez 1 , Marta Castiglia 1 , Lorena Incorvaia 1 , Angela Listi 1 , Sergio Rizzo 1 , Giuseppe Cicero 1 , Viviana Bazan 1 , Sergio Castorina 2,3,** and Antonio Russo 1,** 1 Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy 2 Fondazione Mediterranea “G.B. Morgagni”, Catania, Italy 3 Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy * These authors have contributed equally to this work ** Both the authors are last name Correspondence to: Antonio Russo, email: // Keywords : ER, HER2, PI3K/AKT/mTOR inhib…

Clinical parameters to guide decision-making in elderly metastatic colorectal CANCER patients treated with intensive cytotoxic and anti-angiogenic therapy

// Gemma Bruera 1, 2 , Antonio Russo 3 , Antonio Galvano 3 , Sergio Rizzo 3 and Enrico Ricevuto 1, 2 1 Oncology Territorial Care, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L’Aquila, L’Aquila, Italy 2 Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy 3 Medical Oncology, Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy Correspondence to: Antonio Russo, email: antonio.russo@usa.net Keywords: elderly, intensive treatment, metastatic colorectal cancer, triplet chemotherapy plus bevacizumab, unfit Received: June 07, 2016     Accepted: November 24, 2016     Published:…

Metastatic site location may influence the diagnostic accuracy of plasma EGFR-mutation testing in NSCLC: A pooled analysis

sj-docx-12-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-12-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Survival of patients treated with sorafenib for hepatocellular carcinoma recurrence after liver transplantation: A systematic review and meta-analysis

Background: Data on survival and safety of sorafenib for hepatocellular carcinoma recurrence after liver transplant are still equivocal. Aim: We performed a meta-analysis of published studies, with the aim of estimating the 1-year rates of survival, analysing the variability in survival rates and, finally, identifying the factors associated with a longer survival. Methods: Data from 8 of the 17 selected studies were pooled, while the other 9 were excluded because survival rates were missing. All included studies were retrospective. Results: Overall, the 1-year survival ranged from 18% to 90%. Tumour progression was the main cause of death. The second cause was bleeding, reported only in pat…

sj-docx-10-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-10-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

sj-docx-14-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-14-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

sj-docx-8-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-8-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

KRAS and BRAF as prognostic biomarkers in patients undergoing surgical resection of colorectal cancer liver metastasis: A systematic review and meta-analysis.

3565Background: Clinical trials investigated the potential role of both KRAS and BRAF mutations, as prognostic biomarkers, in colorectal cancer (CRC) patients who underwent surgical treatment of li...

P33.15 TMB in the First-Line Setting of NSCLC: A Systematic Review with Indirect Comparisons Between PD-1 and PD-L1 Inhibitors

Targeted Therapies for Colorectal Cancer

In the last decades, the standard chemotherapeutic approach for the metastatic colorectal cancer (mCRC) treatment was represented by a 5-FU-based regimen with the addition of either oxaliplatin or irinotecan. Recent discoveries in the molecular biology field led to the spread of so-called targeted agents whose mechanism of action is based on the binding with specific target molecules (cellular receptors or soluble proteins) responsible for the activation of many transduction pathways required for malignant cell growth and survival. Among these, the most important consist of monoclonal antibodies (mAbs) and the tyrosine kinase inhibitors (TKIs). As a consequence, the different mechanism of a…

sj-pdf-3-tam-10.1177_17588359211018018 – Supplemental material for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses

Supplemental material, sj-pdf-3-tam-10.1177_17588359211018018 for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses by Valerio Gristina, Antonio Galvano, Luisa Castellana, Lavinia Insalaco, Stefania Cusenza, Giuseppa Graceffa, Federica Iacono, Nadia Barraco, Marta Castiglia, Alessandro Perez, Sergio Rizzo, Antonio Russo and Viviana Bazan in Therapeutic Advances in Medical Oncology

Is there any place for PD-1/CTLA-4 inhibitors combination in the first-line treatment of advanced NSCLC?—A trial-level meta-analysis in PD-L1 selected subgroups

BACKGROUND: The advent of immuno-oncology (IO) represented a breakthrough in non-small cell lung cancer (NSCLC) therapy over the last few years. However, establishing the optimal therapeutic options among programmed death-ligand 1 (PD-L1) selected subgroups still addresses an unmet need in the clinical setting. METHODS: We performed a systematic review and finally included eleven first-line randomized controlled trials to compare efficacy and safety outcomes among first-line IO treatment strategies versus standard platinum-based chemotherapy (CT) according to PD-L1 expression level (<1%, 1–49%, ≥50%). Pooled hazard ratios (HRs) and risk ratios (RRs) for progression-free survival (PFS), over…

Dietary restriction: could it be considered as speed bump on tumor progression road?

Dietary restrictions, including fasting (or long-term starvation), calorie restriction (CR), and short-term starvation (STS), are considered a strong rationale that may protect against various diseases, including age-related diseases and cancer. Among dietary approaches, STS, in which food is not consumed during designed fasting periods but is typically not restricted during designated feeding periods, seems to be more suitable, because other dietary regimens involving prolonged fasting periods could worsen the health conditions of cancer patients, being they already naturally prone to weight loss. Until now, the limited amount of available data does not point to a single gene, pathway, or …

The use of pegylated liposomal doxorubicin (PLD) in association with weekly paclitaxel as second line therapy in metastatic bladder carcinoma: final results

sj-docx-3-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-3-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Nintedanib in NSCLC: evidence to date and place in therapy

The treatment of advanced non-small cell lung cancer (NSCLC) is currently driven by the detection of targetable oncogenic drivers, i.e. epidermal growth factor receptor, echinoderm microtubule-associated protein-like 4–anaplastic lymphoma kinase, etc. Those patients who are wildtype for known and valuable oncogenes can receive standard chemotherapy as first-line treatment, with the possibility of adding bevacizumab. With regard to second-line treatment, nintedanib can improve the efficacy of docetaxel. Nintedanib is a tyrosine kinase inhibitor targeting three angiogenesis-related transmembrane receptors. The usefulness of nintedanib as an anticancer agent for NSCLC has been proved by both …

Predictive Factors of Response to Sunitinib in Imatinib-Resistant Gastrointestinal Stromal Tumors (GISTs): A Multi-Institutional Study

Imatinib 400 mg is the standard of care for medical treatment of advanced GISTs. In the majority of cases, however, GISTs eventually develop resistance to imatinib. The optimal second line treatment has not been established yet and imatinib dose escalation (800 mg) or sunitinib represent two feasible options. The objective of this retrospective, multi-institutional, study is to analyze the validity of several parameters as possible predictive factors of response to sunitinib after imatinib failure. We reviewed 128 metastatic GISTs treated with sunitinib between January 2007 to June 2017. Primary tumour site, metastatic site, c-KIT/PDGFR-&amp;alpha; mutational status, PET-FDG status and type…

sj-docx-10-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-10-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

sj-docx-11-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-11-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

sj-docx-6-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-6-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Farletuzumab for NSCLC: Exploiting a well-known metabolic pathway for a new therapeutic strategy

Abstract: Introduction: The therapeutic options for NSCLC are limited barring targeted drugs, such as EGFR tyrosine-kinase inhibitors and anaplastic lymphoma kinase inhibitors, for patients bearing oncogenic mutations. Platinum-based chemotherapy remains the best strategy for most patients. New targeted drugs, including mAbs and small molecules, are currently under clinical investigation for treating NSCLC patients. Areas covered: The authors of this article focus on farletuzumab, a mAb targeting folate receptor, which has been studied in ovarian cancer and various other malignancies. In this review, the authors review its potential as therapy for NSCLC, because of the biological rationale …

Cancer of Exocrine Pancreas

Pancreatic adenocarcinoma represents today a real challenge for oncologists all around the world: it is the 11th most common cancer worldwide, and the 7th deadliest, with a steadily increasing number of new cases every year. Many risk factors, both environmental and genetic, have been identified, the most important of which are excessive body weight, diabetes, and smoking; also, new diagnostic techniques, such as spiral TC, MRCP, and EUS, have improved the ability to diagnose this disease at an early stage. Nevertheless, pancreatic cancer is a silent disease, with few or no symptoms and signs until late stages: the vast majority of patients are inoperable at the time of diagnosis, with eith…

An update on the conquests and perspectives of cardio-oncology in the field of tumor angiogenesis-targeting TKI-based therapy.

Introduction: The angiogenesis mechanism is considered a crucial point in neoplastic development. A growing number of multi-targeted tyrosine kinase inhibitors (TKI) has been developed and approved for cancer treatment during the last few years. Cardiac side effects still remain an issue to manage nowadays. These drugs mechanisms and toxicities have already been discussed, hence the authors will report updates on these already available drugs. Area covered: This manuscript provides an updated review on the new mechanisms involved in angiogenesis and cardiotoxicity that are TKI-related. Here is reported an overview of the already available and the most recent TKIs under investigation in the …

1535P Exploring the dynamic crosstalk between immune system and genetics in a cohort of 116 completely resected gastrointestinal stromal tumors (GISTs)

sj-docx-7-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-7-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

P07.02 Detection of Molecular Residual Disease (MRD) using ctDNA in NSCLC: A Systematic Review and Meta-Analysis

Clinical Potential of Circulating Cell-Free DNA (cfDNA) for Longitudinally Monitoring Clinical Outcomes in the First-Line Setting of Non-Small-Cell Lung Cancer (NSCLC): A Real-World Prospective Study

Background: Despite the increasing implementation of targeted and immunotherapy-based treatments, the prognosis of patients with advanced NSCLC remains dismal. We prospectively evaluated longitudinal plasma cfDNA kinetics as an early marker of therapeutic efficacy in patients with advanced NSCLC undergoing standard first-line treatments. Methods: From February 2020 to May 2022, treatment-na&iuml;ve patients with advanced NSCLC were consecutively enrolled at the Medical Oncology Unit of the Paolo Giaccone University Hospital, Palermo (Italy). We quantified cfDNA in terms of ng/&mu;L using a QubitTM dsDNA HS Assay Kit. The agreement between the cfDNA and radiologic response was evaluated from…

A narrative review on the implementation of liquid biopsy as a diagnostic tool in thoracic tumors during the COVID-19 pandemic.

Objective: In this review, we evaluate the role of liquid biopsy in managing lung cancer patients during the still ongoing coronavirus disease 2019 (COVID-19) healthcare emergency. Background: The novel influenza coronavirus (severe acute respiratory syndrome coronavirus or SARSCoV-2) has upended several aspects of our lives, including medical activities. In this setting, many routine cancer diagnostic and therapeutic procedures have been suspended, leading to delays in diagnosis, treatments, and, ultimately, increases in cancer mortality rates. Equally drastic has been the impact of COVID-19 on clinical trials, many of which have been stalled or have never begun. This has left many patient…

Not all KIT 557/558 codons mutations have the same prognostic influence on recurrence-free survival: breaking the exon 11 mutations in gastrointestinal stromal tumors (GISTs)

Background: Although the gastrointestinal stromal tumor (GIST) genotype is not currently included in risk-stratification systems, a growing body of evidence shows that the pathogenic variant (PV) type and codon location hold a strong prognostic influence on recurrence-free survival (RFS). This information has particular relevance in the adjuvant setting, where an accurate prognostication could help to better identify high-risk tumors and guide clinical decision-making. Materials and Methods: Between January 2005 and December 2020, 96 patients with completely resected GISTs harboring a KIT proto-oncogene receptor tyrosine kinase ( KIT) exon 11 PV were included in the study. We analyzed the t…

P48.10 Chemo-Immunotherapy in the Frontline of Extensive-Stage Small Cell Lung Cancer: A Systematic Review and Indirect Comparisons

Gastric Cancer: Locoregional Disease

Gastric cancer (GC) is still a worldwide major leading cause of cancer death which shows large geographical differences. Despite an overall decline in incidence and mortality over the last decades, GC remains a poor prognosis disease since patients often present with advanced stage of disease. A large number of risk factors have been associated with GC. Thus, prevention (environment and lifestyle factors) and early diagnosis may be the most promising strategies for cancer control and key strategies to reduce mortality. Surgical resection remains the main form of curative treatment whenever feasible. Endoscopic approaches have been used as valid alternatives to surgery for selected patients.…

sj-docx-4-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-4-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Monoclonal antibodies for the treatment of non-haematological tumours: update of an expanding scenario.

Abstract: Introduction: The identification of cell membrane-bound molecules with a relevant role in cancer cell survival prompted the development of moAbs to block the related pathways. In the last few years, the number of approved moAbs for cancer treatment has constantly increased. Many of these drugs significantly improved the survival outcomes in patients with solid tumours. Areas covered: In this review, all the FDA-approved moAbs in solid tumours have been described. This is an update of moAbs available for cancer treatment nowadays in comparison with the moAbs approved until few years ago. The moAbs under development are also discussed here. Expert opinion: The research on cancer ant…

sj-docx-9-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-9-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Detection of RAS mutations in circulating tumor DNA: a new weapon in an old war against colorectal cancer. A systematic review of literature and meta-analysis

Background: Tissue evaluation for RAS (KRAS or NRAS) gene status in metastatic colorectal cancer (mCRC) patients represent the standard of care to establish the optimal therapeutic strategy. Unfortunately, tissue biopsy is hampered by several critical limitations due to its invasiveness, difficulty to access to disease site, patient’s compliance and, more recently, neoplastic tissue spatial and temporal heterogeneity. Methods: The authors performed a systematic literature review to identify available trials with paired matched tissue and ctDNA RAS gene status evaluation. The authors searched EMBASE, MEDLINE, Cochrane, www.ClinicalTrials.gov , and abstracts from international meetings. In to…

Prognostic role of soluble PD-1 and BTN2A1 in overweight melanoma patients treated with nivolumab or pembrolizumab: finding the missing links in the symbiotic immune-metabolic interplay

Individual response to immune checkpoint inhibitors (ICIs) is currently unpredictable in patients with melanoma. Recent findings highlight a striking improvement in the clinical outcomes of overweight/obese patients treated with ICIs, which seems driven, at least in part, by programmed cell death protein 1 (PD-1)-mediated T-cell dysfunction. A putative role of butyrophilins (BTNs) is under investigation as a novel mechanism of cancer immune evasion and obesity-associated inflammation. This study investigates the role of baseline plasma levels of soluble PD-1 (sPD-1), soluble programmed cell death ligand 1 (sPD-L1), BTN2A1 (sBTN2A1), BTN3A1 (sBTN3A1), along with body mass index (BMI), as pr…

The prognostic role of KRAS and BRAF in patients undergoing surgical resection of colorectal cancer liver metastasis: a systematic review and meta-analysis

Background: Clinical trials investigated the potential role of both KRAS and BRAF mutations, as prognostic biomarkers, in colorectal cancer (CRC) patients who underwent surgical treatment of liver metastasis (CLM), showing conflicting results. This meta-analysis aims to review all the studies reporting survival outcomes (recurrence free survival (RFS), and/or overall survival (OS)) of patients undergoing resection of CLM, stratified according to KRAS and/or BRAF mutation status. Materials and Methods: Data from all published studies reporting survival outcomes (RFS and/or OS) of CRC patients who received resection of CLM, stratified by KRAS and/or BRAF mutation status were collected by sear…

sj-docx-8-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-8-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Second medical opinion in oncological setting

Oncological patients increasingly require second medical opinions to feel more likely confident with their oncologists and treatments, although this could lead to wrong opinions and delay in the start of treatments. Second opinions can be required also by physicians to obtain advices, especially in case of rare tumors. The request of new opinions is documented in radiology and pathology settings too, with not negligible discrepancy rate. Conversely, the role in general medical/surgical conditions has not been well established. Literature is poor of studies relative to second opinions or they are more focused on patient's motivations. For these reasons, AIOM (Italian Association of Medical O…

The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Background: The circulating tumor DNA (ctDNA) diagnostic accuracy for detecting phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha ( PIK3CA) mutations in breast cancer (BC) is under discussion. We aimed to compare plasma and tissue PIK3CA alterations, encompassing factors that could affect the results. Methods: Two reviewers selected studies from different databases until December 2020. We considered BC patients with matched tumor tissue and plasma ctDNA. We performed meta-regression and subgroup analyses to explore sources of heterogeneity concerning tumor burden, diagnostic technique, sample size, sampling time, biological subtype, and hotspot mutation. Pooled sensitiv…

“Back to a false normality”: new intriguing mechanisms of resistance to PARP inhibitors

Several evidences have shown that BRCA mutations increased tumor-cells sensitivity to PARP inhibitors by synthetic lethality leading to an accelerated development of several compounds targeting the PARP enzymes system as anticancer agents for clinical setting. Most of such compounds have been investigated in ovarian and breast cancer, showing promising efficacy in BRCA-mutated patients. Recently clinical studies of PARP-inhibitors have been extended across different tumor types harboring BRCA-mutations, including also "BRCA-like" sporadic tumors with homologous recombination deficiency (HRD). This review summarizes the biological background underlying PARP-inhibition, reporting the results …

Anti-angiogenic drugs for second-line treatment of NSCLC patients: just new pawns on the chessboard?

Tumor angiogenesis is one of the main pathways targeted to treat cancer. Bevacizumab added survival benefit when combined with platinum-based chemotherapy in NSCLC. Recently, Phase III trials showed survival benefit when anti-angiogenic drugs are added to docetaxel as second-line treatment for NSCLC. These anti-angiogenic agents include nintedanib and ramucirumab, a tyrosine-kinase inhibitor and a monoclonal antibody, respectively, which target receptors involved in angiogenesis. These studies have some similarities and differences. We propose a new algorithm for treatment sequences in performance status 0-1 patients with non-oncogene-addicted NSCLC type adenocarcinoma. Indeed clearer scien…

sj-docx-2-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-2-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Liquid Biopsy in Prostate Cancer

Chemotherapy is no longer the only therapeutic option for the treatment of advanced prostate cancer. The understanding of the pathophysiological mechanisms and its dynamic changes has divided neoplastic progression into different moments. Indeed prostate cancer changes over time from a state where cell proliferation is hormone-dependent to a stage where cell growth is hormone-independent (castration resistant disease, mCRPC). This knowledge has allowed the development of new generation hormonal agents that, along with the advent of new chemotherapeutic agents, have changed the long-term prognosis of this disease. As a result, the progression of prostate disease is dynamic over time and its …

Prognostic clinical factors in patients affected by non-small-cell lung cancer receiving Nivolumab

Background: Immune-checkpoint inhibitors have radically changed the treatment landscape of Non-Small-Cell Lung Cancer (NSCLC). It is still unclear whether specific clinical characteristics might identify those patients benefiting from immunotherapy more than others. The aim of this study was to identify clinical characteristics associated with disease-specific survival (DSS), time-to-treatment failure (TTF), objective responses (OR) and progressive disease (PD) in NSCLC patients treated with Nivolumab. Methods: This was a multicenter retrospective study conducted on 294 patients treated with Nivolumab for advanced NSCLC. Results: Of the more than 50 variables analyzed, five showed a signifi…

sj-pdf-1-tam-10.1177_17588359211018018 – Supplemental material for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses

Supplemental material, sj-pdf-1-tam-10.1177_17588359211018018 for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses by Valerio Gristina, Antonio Galvano, Luisa Castellana, Lavinia Insalaco, Stefania Cusenza, Giuseppa Graceffa, Federica Iacono, Nadia Barraco, Marta Castiglia, Alessandro Perez, Sergio Rizzo, Antonio Russo and Viviana Bazan in Therapeutic Advances in Medical Oncology

Denosumab for bone health in prostate and breast cancer patients receiving endocrine therapy? A systematic review and a meta-analysis of randomized trials

Highlights • Hormonal receptors positive breast tumor and prostate cancer are managed with endocrine therapies. • Endocrine therapies designed for breast and prostate cancer are often associated to serious adverse skeletal related events, such fractures. • Denosumab is a monoclonal anti-body binding RANKL which acts as inhibitor of osteoclasts activity, thus increasing bone mass. • Denosumab was showed to strongly prevent hormonal therapies-related skeletal issues. • Denosumab administration results safe in bone mass increase and reduction of fractures risk.

Next generation diagnostic algorithm in non-small cell lung cancer predictive molecular pathology: The KWAY Italian multicenter cost evaluation study

Abstract Aims The KWAY project aims to investigate the economic sustainability of the up-front NGS technologies adoption in the analysis of clinically relevant molecular alterations in NSCLC patients. Methods The diagnostic workflow and the related sustained costs of five Italian referral centers were assessed in four different evolving scenarios were analyzed. For each scenario, two alternative testing strategies were evaluated: the Maximized Standard strategy and the Maximized NGS strategy. Results For each center, the robustness of obtained results was verified through a deterministic sensitivity analysis, observing the variation of total costs based on a variation of ±20 % of the input …

sj-docx-13-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-13-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

How do skeletal morbidity rate and special toxicities affect 12-week versus 4-week schedule zoledronic acid efficacy? A systematic review and a meta-analysis of randomized trials

Abstract Background Zoledronic Acid is a bisphosphonate used in a 4-week schedule for the treatment of bone metastases. Some randomized trials supported its role also when administered every 12 weeks. Methods we performed a systematic review and a meta-analysis in order to evaluate the two different schedules in terms of skeletal morbidity rate (SMR), skeletal related events (SRE) and adverse events (AEs). Results our results showed a clinical difference favouring the 12-week schedule in terms of AEs (RR 1.17, 95% CI 1.06–1.29). No signifcant differences were found for SMR (RR 0.97, 95% CI 0.84–1.13) and SRE (RR 1.02, 95% CI 0.89–1.16). Conclusions Our findings support in clinical practice …

sj-docx-5-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-5-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Non-Small Cell Lung Cancer Harboring Concurrent EGFR Genomic Alterations: A Systematic Review and Critical Appraisal of the Double Dilemma

The molecular pathways which promote lung cancer cell features have been broadly explored, leading to significant improvement in prognostic and diagnostic strategies. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have dramatically altered the treatment approach for patients with metastatic non-small cell lung cancer (NSCLC). Latest investigations by using next-generation sequencing (NGS) have shown that other oncogenic driver mutations, believed mutually exclusive for decades, could coexist in EGFR-mutated NSCLC patients. However, the exact clinical and pathological role of concomitant genomic aberrations needs to be investigated. In this systematic review, we ai…

Monitoring blood biomarkers to predict nivolumab effectiveness in NSCLC patients

Background: We investigated whether early dynamic changes of circulating free (cfDNA) levels as well as the neutrophil to lymphocyte ratio (NLR) could predict nivolumab effectiveness in pretreated patients with advanced non-small cell lung cancer (NSCLC). Methods: A total of 45 patients receiving nivolumab 3 mg/kg every 2 weeks were enrolled. Patients underwent a computed tomography scan and responses were evaluated by the response evaluation criteria in solid tumors. Peripheral blood samples were obtained from the patients and the cfDNA level as well as the NLR were assessed. Time to progression (TTP) and overall survival (OS) were determined. Results: Patients with increased cfDNA &gt;20%…

The diagnostic accuracy of circulating tumor DNA for the detection of EGFR-T790M mutation in NSCLC: a systematic review and meta-analysis

AbstractThis pooled analysis aims at evaluating the diagnostic accuracy of circulating tumor (ct) DNA for the detection of EGFR-T790M mutation in NSCLC patients who progressed after EGFR-TKIs. Data from all published studies, reporting both sensitivity and specificity of plasma-based EGFR-T790M mutation testing by ctDNA were collected by searching in PubMed, Cochrane Library, American Society of Clinical Oncology, European Society of Medical Oncology and World Conference of Lung Cancer meeting proceedings. A total of twenty-one studies, with 1639 patients, were eligible. The pooled sensitivity of ctDNA analysis was 0.67 (95% CI: 0.64–0.70) and the pooled specificity was 0.80 (95% CI: 0.77–0…

Indications for Locoregional Tumor Therapies: CRC Liver Metastases

The liver represents the most affected site in patients affected by colorectal carcinoma (mCRC) [1]. More than half cases develop colorectal liver metastases (CLMs) during the evolution of the disease, and about one-quarter occur at the disease onset [1, 2]. To date, the standard treatment of CLM is represented by liver surgery, which has allowed to achieve interesting long-term survival rates (40-60%) [3] in reported series, while it is less than 25% for patients who do not undergo surgery [4]. Unfortunately, most patients (80%), however, are not immediately eligible for surgery [5, 6]. For these patients, surgical treatment may be administered in combination with chemotherapy regimens (+/…

Potential miRNAs involved in molecular pathways mediating the anticancer effects of short term starvation in breast cancer cells treated with doxorubicin

Background: In recent years, increasing evidences showed that several types of dietary approaches restricting food intake, including Short Term Starvation (STS), may exert a protective role against aging and other age-related pathologies as well as cancer. Interestingly, the dietary restriction showed significant anticancer effects able to prevent cancer onset, slow its progression and improve therapy response. Since recent studies showed that miRNAs may modulate sensibility/resistance to antiblastic therapy, the aim of our study was to investigate the STS-induced molecular changes in breast cancer cells treated with doxorubicin, focusing our attention on miRNA expression profile. Materials…

sj-pdf-4-tam-10.1177_17588359211018018 – Supplemental material for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses

Supplemental material, sj-pdf-4-tam-10.1177_17588359211018018 for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses by Valerio Gristina, Antonio Galvano, Luisa Castellana, Lavinia Insalaco, Stefania Cusenza, Giuseppa Graceffa, Federica Iacono, Nadia Barraco, Marta Castiglia, Alessandro Perez, Sergio Rizzo, Antonio Russo and Viviana Bazan in Therapeutic Advances in Medical Oncology

2020 Reply to: Denosumab for bone health in prostate and breast cancer patients receiving endocrine therapy? A systematic review and a meta-analysis of randomized trials

Cardiovascular Damage Induced by Radiotherapy

Radiotherapy is a fundamental therapeutic aid that in recent years has contributed significantly to improve the prognosis of cancer patients. Despite its great effectiveness, it can cause a wide spectrum of toxic effects. Among these, cardiovascular toxicity is very relevant, and it can occur even many years after the termination of treatment. The concomitant use of radiotherapy with other antineoplastic drugs, including new-generation tyrosine-kinase inhibitors or immunotherapy, can enhance its cardiotoxic effects. It is fundamental to know the cardiovascular toxic effects that are potentially linked to radiotherapy (RIHD: radiation-induced heart damage), to monitor patients who underwent …

The prognostic role of KRAS and BRAF in patients undergoing surgical resection of colorectal cancer liver metastasis: a systematic review and meta-analysis

sj-docx-6-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-6-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

The use of same in chemotherapy-induced liver injury

Drug-induced liver injury (DILI) remains the most common cause of acute liver failure in the Western world. Chemotherapy is one of the major class of drugs most frequently associated with idiosyncratic DILI. For this reason, patients who receive chemotherapy require careful assessment of liver function prior to treatment to determine which drugs may not be appropriate and which drug doses should be modified. S-adenosylmethionine (SAMe) is an endogenous agent derived from methionine. Its supplementation is effective in the treatment of liver disease, in particular intrahepatic cholestasis (IHC). The target of this review is to analyze the mechanisms of hepatotoxicity of the principal antican…

Can KRAS and BRAF mutations limit the benefit of liver resection in metastatic colorectal cancer patients? A systematic review and meta-analysis.

Clinical trials investigated the potential role of both KRAS and BRAF mutations, as prognostic biomarkers, in colorectal cancer (CRC) patients who underwent surgical treatment of CRC-related liver metastases (CLM), showing conflicting results. This meta-analysis aims to review all the studies reporting survival outcomes (recurrence free survival (RFS), and/or overall survival (OS)) of patients undergoing resection of CLM, stratified according to KRAS and/or BRAF mutation status. Background: Clinical trials investigated the potential role of both KRAS and BRAF mutations, as prognostic biomarkers, in colorectal cancer (CRC) patients who underwent surgical treatment of CRC-related liver metast…

The resistance related to targeted therapy in malignant pleural mesothelioma: Why has not the target been hit yet?

Abstract: Malignant pleural mesothelioma (MPM) is an aggressive tumor of the pleura with a poor prognosis. The most active first-line regimens are platinum compounds and pemetrexed. There is no standard second-line treatment in MPM. Advances in the understanding of tumor molecular biology have led to the development of several targeted treatments, which have been evaluated in clinical trials. Unfortunately none of the explored targeted treatments can currently be recommended as routine treatment in MPM. We reviewed the biological pathways involved in MPM, the clinical trials about targeted therapy, and possible related mechanisms of resistance. We suggest that specific genetic markers are n…

Search_strategy_-_Supplemental_Material_1_final – Supplemental material for Detection of RAS mutations in circulating tumor DNA: a new weapon in an old war against colorectal cancer. A systematic review of literature and meta-analysis

Supplemental material, Search_strategy_-_Supplemental_Material_1_final for Detection of RAS mutations in circulating tumor DNA: a new weapon in an old war against colorectal cancer. A systematic review of literature and meta-analysis by Antonio Galvano, Simona Taverna, Giuseppe Badalamenti, Lorena Incorvaia, Marta Castiglia, Nadia Barraco, Francesco Passiglia, Fabio Fulfaro, Giordano Beretta, Giovanni Duro, Bruno Vincenzi, Pierosandro Tagliaferri, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

1818P Body mass index (BMI) is not a cancer risk factor for BRCA1/2 carriers: A systematic review and meta-analysis of case-control studies

Cardiotoxic Effects of Anti-VEGFR Tyrosine Kinase Inhibitors

Angiogenesis is a key moment in tumor development and proliferation. Until recently oncologists did not know the mechanisms that were behind this phenomenon, but following the discoveries of Folkman and coworkers, they have gradually created and developed a series of drugs that act against angiogenesis by interacting with molecules belonging to the vascular endothelial growth factor (VEGFs) class and its receptors (VEGFRs) giving rise to anticancer effects. Tyrosine kinase inhibitors (TKIs) are a major class of these new anticancer agents, demonstrating high antitumor activity in a variety of "orphan" neoplasms (such as hepatocellular carcinoma, kidney cancer, sarcomas, etc.). The mechanism…

The challenge of the Molecular Tumor Board empowerment in clinical oncology practice: A Position Paper on behalf of the AIOM- SIAPEC/IAP-SIBioC-SIC-SIF-SIGU-SIRM Italian Scientific Societies

The development of innovative technologies and the advances in the genetics and genomics, have offered new opportunities for personalized treatment in oncology. Although the selection of the patient based on the molecular characteristics of the neoplasm has the potential to revolutionize the therapeutic scenario of oncology, this approach is extremely challenging. The access, homogeneity, and economic sustainability of the required genomic tests should be warranted in the clinical practice, as well as the specific scientific and clinical expertise for the choice of medical therapies. All these elements make essential the collaboration of different specialists within the Molecular Tumor Boar…

Dose-finding study of oxaliplatin associated to capecitabinebased preoperative chemoradiotherapy in locally advanced rectal cancer

// Gemma Bruera 1, 2 , Mario Di Staso 3 , Pierluigi Bonfili 3 , Antonio Galvano 4 , Rosa Manetta 5 , Gino Coletti 6 , Roberto Vicentini 7 , Stefano Guadagni 2, 8 , Corrado Ficorella 2, 9 , Ernesto Di Cesare 2, 3 , Antonio Russo 4 and Enrico Ricevuto 1, 2 1 Oncology Territorial Care, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L'Aquila, L'Aquila, Italy 2 Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy 3 Radiotherapy, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L’Aquila, L’Aquila, Italy 4 Medical Oncology, Department of Surgical, Oncological and Stomatological Sciences, University of Palermo,…

sj-docx-13-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-13-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Programmed Death Ligand 1 (PD-L1) as a Predictive Biomarker for Pembrolizumab Therapy in Patients with Advanced Non-Small-Cell Lung Cancer (NSCLC).

Recently, immunotherapy has been shown to be an effective and helpful therapeutic option for the treatment of advanced non-small-cell lung cancer (NSCLC). The activity of antitumor T cells may be restored through the checkpoint blockade using anti-programmed death 1 or anti-programmed death ligand 1 (PD-L1) antibodies, showing, in several cancer patients, an increased progression-free survival and overall survival compared with classical chemotherapy. As recently shown by several studies, the PD-L1 expression levels in tumors may offer a selection criterion for patients to predict their immunotherapy response. In particular, NSCLC patients with high tumor PD-L1 levels (proportional score ≥ …

sj-pdf-2-tam-10.1177_17588359211018018 – Supplemental material for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses

Supplemental material, sj-pdf-2-tam-10.1177_17588359211018018 for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses by Valerio Gristina, Antonio Galvano, Luisa Castellana, Lavinia Insalaco, Stefania Cusenza, Giuseppa Graceffa, Federica Iacono, Nadia Barraco, Marta Castiglia, Alessandro Perez, Sergio Rizzo, Antonio Russo and Viviana Bazan in Therapeutic Advances in Medical Oncology

sj-pdf-3-tam-10.1177_17588359211018018 – Supplemental material for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses

Supplemental material, sj-pdf-3-tam-10.1177_17588359211018018 for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses by Valerio Gristina, Antonio Galvano, Luisa Castellana, Lavinia Insalaco, Stefania Cusenza, Giuseppa Graceffa, Federica Iacono, Nadia Barraco, Marta Castiglia, Alessandro Perez, Sergio Rizzo, Antonio Russo and Viviana Bazan in Therapeutic Advances in Medical Oncology

sj-docx-1-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-1-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Exploring the Dynamic Crosstalk between the Immune System and Genetics in Gastrointestinal Stromal Tumors

Gastrointestinal Stromal Tumors (GISTs) represent a paradigmatic model of oncogene addiction. Despite the well-known impact of the mutational status on clinical outcomes, we need to expand our knowledge to other factors that influence behavior heterogeneity in GIST patients. A growing body of studies has revealed that the tumor microenvironment (TME), mostly populated by tumor-associated macrophages (TAMs) and lymphocytes (TILs), and stromal differentiation (SD) have a significant impact on prognosis and response to treatment. Interestingly, even though the current knowledge of the role of immune response in this setting is still limited, recent pre-clinical and clinical data have highlight…

Liquid biopsy in colorectal carcinoma: the search for potential prognostic and predictive biomarkers

Background: Liquid biopsy is considered a repeatable, non-invasive and dynamic tool. It could be able to recover from liquid samples (expecially blood)) cancer-specific informations (miRNAs, circulating-free DNA (cfDNA), circulating tumor DNA (ctDNA) and exosomes) by overcoming the limitations associated with traditional tissue biopsy. Aim: to investigate the potential prognostic and predictive role of blood cancer-related biomarkers such as cfDNA or ctDNA and exosomal DNA in colorectal cancer (CRC) patients. Results: cfDNA or ctDNA and exosomal DNA could have a potential applicability in CRC management. New generation technologies are able to identify clinically relevant genomic alteration…

A novel predictive biomarker of immunotherapy response in metastatic renal cell carcinoma (mRCC): The lymphocyte microRNA expression profile.

e16109 Background: Predicting which patient with metastatic renal cell carcinoma (mRCC) will benefit from immune checkpoints inhibitors (ICPIs) still remain an issue. Biological factors particular to certain individuals have a clear effect on variation in response. Emerging evidence suggests that small non-coding RNA, such as microRNAs (miRNAs), are critical modulators of numerous cellular processes, including immune surveillance. The main aim of this study was to analyze the lymphocyte miRNA expression profile in mRCC patients and dynamic changes after the treatment with ICPI, in order to investigate the molecular mechanisms and signaling pathways involved in ICPI response and their poten…

How to Deal with Second Line Dilemma in Metastatic Colorectal Cancer? A Systematic Review and Meta-Analysis

Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have demonstrated efficacy with chemotherapy (CT) as second line treatment for metastatic colorectal cancer (mCRC). The right sequence of the treatments in all RAS (KRAS/NRAS) wild type (wt) patients has not precisely defined. We evaluated the impact of aforementioned targeted therapies in second line setting, analyzing efficacy and safety data from phase III clinical trials. We performed both direct and indirect comparisons between anti-EGFR and anti-VEGF. Outcomes included disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), overall su…

Dose-finding study of intensive weekly alternating schedule of docetaxel, 5-fluorouracil, and oxaliplatin, FD/FOx regimen, in metastatic gastric cancer.

// Gemma Bruera 1, 2 , Silvia Massacese 3 , Antonio Galvano 4 , Antonella Dal Mas 5 , Stefano Guadagni 6, 2 , Giuseppe Calvisi 5 , Eugenio Ciacco 3 , Antonio Russo 4 , Enrico Ricevuto 1, 2 , on behalf of Oncology Network ASL1 Abruzzo, Italy 1 Oncology Territorial Care, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L'Aquila, L'Aquila, Italy 2 Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy 3 Pharmacy Unit, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, L’Aquila, Italy 4 Medical Oncology, Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy 5 Pathology, S. Salva…

sj-pdf-1-tam-10.1177_17588359211018018 – Supplemental material for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses

Supplemental material, sj-pdf-1-tam-10.1177_17588359211018018 for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses by Valerio Gristina, Antonio Galvano, Luisa Castellana, Lavinia Insalaco, Stefania Cusenza, Giuseppa Graceffa, Federica Iacono, Nadia Barraco, Marta Castiglia, Alessandro Perez, Sergio Rizzo, Antonio Russo and Viviana Bazan in Therapeutic Advances in Medical Oncology

Analysis of miRNA expression profile induced by short term starvation in breast cancer cells treated with doxorubicin

// Sergio Rizzo 1, * , Antonina Cangemi 1, * , Antonio Galvano 1, * , Daniele Fanale 1 , Silvio Buscemi 2 , Marcello Ciaccio 3 , Antonio Russo 1 , Sergio Castorina 4, 5, # and Viviana Bazan 1, # 1 Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy 2 Department of Internal and Specialistic Medicine (DIBIMIS), Laboratory of Clinical Nutrition, University of Palermo, Palermo, Italy 3 Section of Clinical Biochemistry and Clinical Molecular Medicine, Department of Biopathology and Medical Biotechnology, University of Palermo, U.O.C. Laboratory Medicine, Policlinico University Hospital, Palermo, Italy 4 Fondazione Mediterranea…

Impact of phospho-Akt expression on the clinical outcome and activity of gemcitabine and Akt inhibitors in pancreatic ductal adenocarcinoma

Background: Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal solid tumors. Despite extensive preclinical and clinical research, the prognosis of this disease has not significantly improved, with a 5-year survival rate around 7%. There is an urgent need to better understand the molecular pathology of PDAC in order to improve patient selection for current treatment options and to develop novel therapeutic strategies. The PI3K/AKT/mTOR pathway plays a crucial role in PDAC: activation of Akt is a frequent event and has been correlated to poor prognosis and resistance to chemotherapy. Against this background, effective blockage of Akt signaling can lead to programmed cell death a…

sj-pdf-2-tam-10.1177_17588359211018018 – Supplemental material for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses

Supplemental material, sj-pdf-2-tam-10.1177_17588359211018018 for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses by Valerio Gristina, Antonio Galvano, Luisa Castellana, Lavinia Insalaco, Stefania Cusenza, Giuseppa Graceffa, Federica Iacono, Nadia Barraco, Marta Castiglia, Alessandro Perez, Sergio Rizzo, Antonio Russo and Viviana Bazan in Therapeutic Advances in Medical Oncology

Monoclonal antibodies in gastrointestinal cancers

Introduction: Among gastrointestinal cancers, colorectal and gastric neoplasms are the most frequent. The development of new targeted drugs improved the efficacy of systemic therapy in advanced stages of those malignancies. Areas covered: This review highlights the main biological processes implicated in gastrointestinal cancer development and progression, such as angiogenesis and epidermal growth factor receptor (EGFR) signaling pathway. On these bases, anti-EGFR and anti-vascular endothelial growth factor (VEGF) monoclonal antibodies in colorectal and gastric cancer are discussed. Data about further monoclonal antibodies in development are also reported. Expert opinion: The use of monoclo…

PD-L1 expression as predictive biomarker in patients with NSCLC: a pooled analysis

// Francesco Passiglia 1, * , Giuseppe Bronte 1, * , Viviana Bazan 1, * , Clara Natoli 2 , Sergio Rizzo 1 , Antonio Galvano 1 , Angela Listi 1 , Giuseppe Cicero 1 , Christian Rolfo 3 , Daniele Santini 4 , Antonio Russo 1 1 Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy 2 Department of Medical, Oral and Biotechnological Sciences, University “G. D’Annunzio”, Chieti, Italy 3 Phase I- Early Clinical Trials Unit, Oncology Department and Multidisciplinary Oncology Center Antwerp (MOCA), Antwerp University Hospital, Edegem, Belgium 4 Medical Oncology Department, Campus Biomedico, University of Rome, Rome, Italy * These auth…

LncRNA H19, HOTAIR and MALAT1 as prognostic molecular biomarkers in GIST

sj-docx-1-tam-10.1177_17588359231151845 – Supplemental material for Prognostic role of soluble PD-1 and BTN2A1 in overweight melanoma patients treated with nivolumab or pembrolizumab: finding the missing links in the symbiotic immune-metabolic interplay

Supplemental material, sj-docx-1-tam-10.1177_17588359231151845 for Prognostic role of soluble PD-1 and BTN2A1 in overweight melanoma patients treated with nivolumab or pembrolizumab: finding the missing links in the symbiotic immune-metabolic interplay by Lorena Incorvaia, Gaetana Rinaldi, Giuseppe Badalamenti, Alessandra Cucinella, Chiara Brando, Giorgio Madonia, Alessia Fiorino, Angela Pipitone, Alessandro Perez, Federica Li Pomi, Antonio Galvano, Valerio Gristina, Nadia Barraco, Marco Bono, Tancredi Didier Bazan Russo, Francesca Toia, Adriana Cordova, Daniele Fanale, Antonio Russo and Viviana Bazan in Therapeutic Advances in Medical Oncology

New findings on primary and acquired resistance to anti-EGFR therapy in metastatic colorectal cancer: Do all roads lead to RAS?

Abstract: Anti-epidermal growth factor receptor therapy with the monoclonal antibodies cetuximab and panitumumab is the main targeted treatment to combine with standard chemotherapy for metastatic colorectal cancer. Many clinical studies have shown the benefit of the addition of these agents for patients without mutations in the EGFR pathway. Many biomarkers, including KRAS and NRAS mutations, BRAF mutations, PIK3CA mutations, PTEN loss, AREG and EREG expression, and HER-2 amplification have already been identified to select responders to anti-EGFR agents. Among these alterations KRAS and NRAS mutations are currently recognized as the best predictive factors for primary resistance. Liquid b…

Molecular profiling of pancreatic neuroendocrine tumors (pNETS) and the clinical potential

Abstract: Introduction: Pancreatic neuroendocrine tumors (pNETs) represent a small part of pancreatic neoplasms, and the knowledge about their indolent clinical course remains a subject of investigation. They occur sporadically or as part of familial cancer syndromes and are classified by WHO in 3 categories. There is ongoing research to understand their molecular profiling and leading mutations.Areas covered: The aim of this review is to clarify the overall aspects of tumorigenesis, to expose the latest developments in understanding the course of the disease and the possible therapeutic implications of these. The review also discusses functional and non-functional pNETs and associated inhe…

Effects of the number of removed lymph nodes on survival outcome in patients with sentinel node-negative breast cancer.

Abstract Background Sentinel lymph node biopsy is the gold standard surgical technique for axillary staging in patients with clinically node-negative. However, it is still uncertain what is the optimal number of sentinel lymph nodes (SLNs) to be removed to reduce the false-negative rate. The aim of this study was to investigate whether patients with a single negative SLN have a worse prognosis than those with two or more negative SLNs. Methods A retrospective review was conducted on a large series of SLN-negative breast cancer patients. Survival outcomes and regional recurrence rate were evaluated according to the number of removed SLNs. Secondly, the contribution of different adjuvant ther…

Navigating the liquid biopsy Minimal Residual Disease (MRD) in Non-Small Cell Lung Cancer: Making the Invisible Visible.

Liquid biopsy has gained increasing interest in the growing era of precision medicine as minimally invasive technique. Recent findings demonstrated that detecting minimal or molecular residual disease (MRD) in NSCLC is a challenging matter of debate that need multidisciplinary competencies, avoiding the overtreatment risk along with achieving a significant survival improvement. This review aims to provide practical consideration for solving data interpretation questions about MRD in NSCLC thanks to the close cooperation between biologists and oncology clinicians. We discussed with a translational approach the critical point of view from benchside, bedside and bunchside to facilitate the fut…

sj-docx-9-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-9-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

20P Is evaluation of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutational status on circulating tumour DNA (ctDNA) by liquid biopsy ready for prime-time? A systematic review and an individual patient meta-analysis

Real life triplet FIr/FOx chemotherapy in first-line metastatic pancreatic ductal adenocarcinoma patients: Recommended schedule for expected activity and safety and phase II study

// Gemma Bruera 1, 2 , Silvia Massacese 3 , Stefania Candria 1 , Antonio Galvano 4 , Rosa Manetta 5 , Aldo Victor Giordano 5 , Sergio Carducci 5 , Alessandra Di Sibio 5 , Eugenio Ciacco 3 , Antonio Russo 4 , Enrico Ricevuto 1, 2 and on behalf of Oncology Network ASL1 Abruzzo, Italy 1 Oncology Territorial Care Unit, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L’Aquila, L’Aquila, Italy 2 Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy 3 Pharmacy Unit, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, L’Aquila, Italy 4 Medical Oncology Unit, Department of Surgical, Oncological and Stomatological Sciences, Univers…

The effects of enzalutamide and abiraterone on skeletal related events and bone radiological progression free survival in castration resistant prostate cancer patients: An indirect comparison of randomized controlled trials.

Two new drugs, the CYP17 inhibitor abiraterone acetate and the androgen receptor (AR) antagonist enzalutamide, have recently shown to prolong OS prior chemotherapy or in docetaxel treated mCRPC patients, using steroidal therapy or placebo as control group. Updated analyses underlined the role of these new agents on two prostate-specific endpoints as radiographic progression-free survival (rPFS) and time to first skeletal-related event (tSRE). On the basis of these reports, we made an indirect comparison between abiraterone and enzalutamide. We obtained a clinically but not significant difference favouring enzalutamide over abiraterone in terms of rPFS (HR 0.48, 95% CI 0.22–1.02). No signi…

Impact of BMI on Preoperative Axillary Ultrasound Assessment in Patients With Early Breast Cancer

Background The accuracy of axillary ultrasound (AUS) with fine-needle aspiration with varying patient body mass index (BMI) is still unclear. The aim of our study was to evaluate whether the US features of axillary lymph nodes changes with BMI of patients. Patients and methods A retrospective review was performed involving 144 out of 270 patients with early breast cancer who underwent breast surgery with sentinel lymph node biopsy. Diagnostic efficacy of AUS in preoperative axillary nodal staging was assessed in relation to BMI. Results Negative predictive values of AUS for the overweight and obese groups were statistically significantly lower compared to the normal/underweight group (p=0.0…

Immunological Aspects of Von Hippel-Lindau Disease: A Focus on Neuro-Oncology and Myasthenia Gravis

Von Hippel-Lindau (VHL) disease is an autosomal dominant condition that predisposes affected individuals to a variety of malignant and benign neoplasms. The pathogenetic turning point of this illness is the accumulation of hypoxia-inducible factor (HIF)-1α, a transcription factor of several genes involved in oncogenesis, angiogenesis, tissue regeneration, metabolic regulation, hematopoiesis, and inflammatory responses. From an oncological perspective, increased awareness of the molecular pathways underlying this disease is bringing us closer to the development of specific and targeted therapies. Meanwhile, on the surgical side, improved understanding can help to better identify the patients…

sj-docx-4-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-4-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

The Emerging Therapeutic Landscape of ALK Inhibitors in Non-Small Cell Lung Cancer.

The treatment of metastatic non-small cell lung cancer (NSCLC) has undergone a paradigm shift over the last decade. Better molecular characterization of the disease has led to the rapid improvement of personalized medicine and the prompt delivery of targeted therapies to patients with NSCLC. The discovery of the EML4-ALK fusion gene in a limited subset of patients affected by NSCLC and the subsequent clinical development of crizotinib in 2011 has been an impressive milestone in lung cancer research. Unfortunately, acquired resistances regularly develop, hence disease progression occurs. Afterward, modern tyrosine kinase inhibitors (TKIs), such as ceritinib, alectinib, brigatinib, and lorlat…

sj-docx-2-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-2-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

sj-pdf-4-tam-10.1177_17588359211018018 – Supplemental material for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses

Supplemental material, sj-pdf-4-tam-10.1177_17588359211018018 for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses by Valerio Gristina, Antonio Galvano, Luisa Castellana, Lavinia Insalaco, Stefania Cusenza, Giuseppa Graceffa, Federica Iacono, Nadia Barraco, Marta Castiglia, Alessandro Perez, Sergio Rizzo, Antonio Russo and Viviana Bazan in Therapeutic Advances in Medical Oncology

sj-docx-1-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-1-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Outcomes with Nivolumab in Pretreated Non-Small Cell Lung Cancer (NSCLC): A Large Retrospective Multicenter Study

Introduction: Immune checkpoint inhibitors have provided substantial benefit in non-small cell lung cancer (NSCLC) with unprecedented results in terms of survival. However, the identification of reliable predictive biomarkers to these agents is lacking and multiple clinicopathological factors have been evaluated. The aim of this study was to analyze the potential role of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lactate dehydrogenase (LDH) levels in patients with pretreated NSCLC receiving nivolumab. Methods: This was a retrospective multicenter study involving 14 Italian centers, evaluating the role of some laboratory results in patients with NSCLC treat…

sj-docx-11-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-11-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

sj-docx-5-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-5-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Neutrophil-To-Lymphocyte Ratio (NLR) Platelet-To-Lymphocyte Ratio (PLR), and Outcomes With Nivolumab in Pretreated Non-Small Cell Lung Cancer (NSCLC): A Large Retrospective Multicenter Study

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