Publications by authors named "Massimiliano Salati"

41 Publications

Association of Obesity With Survival Outcomes in Patients With Cancer: A Systematic Review and Meta-analysis.

JAMA Netw Open 2021 Mar 1;4(3):e213520. Epub 2021 Mar 1.

Oncology Unit, Fondazione Poliambulanza, Brescia, Italy.

Importance: Obesity, defined as a body mass index (BMI) greater than 30, is associated with a significant increase in the risk of many cancers and in overall mortality. However, various studies have suggested that patients with cancer and no obesity (ie, BMI 20-25) have worse outcomes than patients with obesity.

Objective: To assess the association between obesity and outcomes after a diagnosis of cancer.

Data Sources: PubMed, the Cochrane Library, and EMBASE were searched from inception to January 2020.

Study Selection: Studies reporting prognosis of patients with obesity using standard BMI categories and cancer were included. Studies that used nonstandard BMI categories, that were limited to children, or that were limited to patients with hematological malignant neoplasms were excluded. Screening was performed independently by multiple reviewers. Among 1892 retrieved studies, 203 (17%) met inclusion criteria for initial evaluation.

Data Extraction And Synthesis: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were reporting guideline was followed. Data were extracted by multiple independent reviewers. Risk of death, cancer-specific mortality, and recurrence were pooled to provide an adjusted hazard ratio (HR) with a 95% CI . A random-effects model was used for the retrospective nature of studies.

Main Outcomes And Measures: The primary outcome of the study was overall survival (OS) in patients with cancer, with and without obesity. Secondary end points were cancer-specific survival (CSS) and progression-free survival (PFS) or disease-free survival (DFS). The risk of events was reported as HRs with 95% CIs, with an HR greater than 1 associated with a worse outcome among patients with obesity vs those without.

Results: A total of 203 studies with 6 320 365 participants evaluated the association of OS, CSS, and/or PFS or DFS with obesity in patients with cancer. Overall, obesity was associated with a reduced OS (HR, 1.14; 95% CI, 1.09-1.19; P < .001) and CSS (HR, 1.17; 95% CI, 1.12-1.23; P < .001). Patients were also at increased risk of recurrence (HR, 1.13; 95% CI, 1.07-1.19; P < .001). Conversely, patients with obesity and lung cancer, renal cell carcinoma, or melanoma had better survival outcomes compared with patients without obesity and the same cancer (lung: HR, 0.86; 95% CI, 0.76-0.98; P = .02; renal cell: HR, 0.74; 95% CI, 0.53-0.89; P = .02; melanoma: HR, 0.74; 95% CI, 0.57-0.96; P < .001).

Conclusions And Relevance: In this study, obesity was associated with greater mortality overall in patients with cancer. However, patients with obesity and lung cancer, renal cell carcinoma, and melanoma had a lower risk of death than patients with the same cancers without obesity. Weight-reducing strategies may represent effective measures for reducing mortality in these patients.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.3520DOI Listing
March 2021

Integrated Genomics Identifies miR-181/TFAM Pathway as a Critical Driver of Drug Resistance in Melanoma.

Int J Mol Sci 2021 Feb 11;22(4). Epub 2021 Feb 11.

TIGEM, Telethon Institute of Genetics and Medicine, 80078 Naples, Italy.

MicroRNAs (miRNAs) are attractive therapeutic targets and promising candidates as molecular biomarkers for various therapy-resistant tumors. However, the association between miRNAs and drug resistance in melanoma remains to be elucidated. We used an integrative genomic analysis to comprehensively study the miRNA expression profiles of drug-resistant melanoma patients and cell lines. MicroRNA-181a and -181b (miR181a/b) were identified as the most significantly down-regulated miRNAs in resistant melanoma patients and cell lines. Re-establishment of miR-181a/b expression reverses the resistance of melanoma cells to the BRAF inhibitor dabrafenib. Introduction of miR-181 mimics markedly decreases the expression of TFAM in A375 melanoma cells resistant to BRAF inhibitors. Furthermore, melanoma growth was inhibited in A375 and M14 resistant melanoma cells transfected with miR-181a/b mimics, while miR-181a/b depletion enhanced resistance in sensitive cell lines. Collectively, our study demonstrated that miR-181a/b could reverse the resistance to BRAF inhibitors in dabrafenib resistant melanoma cell lines. In addition, miR-181a and -181b are strongly down-regulated in tumor samples from patients before and after the development of resistance to targeted therapies. Finally, melanoma tissues with high miR-181a and -181b expression presented favorable outcomes in terms of Progression Free Survival, suggesting that miR-181 is a clinically relevant candidate for therapeutic development or biomarker-based therapy selection.
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http://dx.doi.org/10.3390/ijms22041801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918089PMC
February 2021

Assessing the impact of COVID-19 on liver cancer management (CERO-19).

JHEP Rep 2021 Feb 23:100260. Epub 2021 Feb 23.

BCLC group, Liver Unit, Hospital Clinic Barcelona, IDIBAPS. CIBERehd. University of Barcelona. Spain.

Background: The coronavirus 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). This project has evaluated if the schedule of LC screening or procedures has been interrupted /delayed because of the COVID-19 pandemic.

Material And Methods: An international survey evaluated the impact of COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave.

Results: Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia and Africa (73.7%, 17.1%, 5.3%, 2.6% and 1.3% per continent, respectively). Eighty-seven per cent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening program, 50% cancelled curative and/or palliative treatments for LC, and 44.0% cancelled the liver transplantation program. Forty-five out 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service prior to COVID-19 pandemic (n=19/37).

Conclusion: The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with LC. Modifications in screening, diagnostic and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision making.
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http://dx.doi.org/10.1016/j.jhepr.2021.100260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901294PMC
February 2021

The Emergence of Immune-checkpoint Inhibitors in Colorectal Cancer Therapy.

Curr Drug Targets 2021 02 4. Epub 2021 Feb 4.

Medical Oncology Unit, Ospedale del Mare, Naples, Italy

Immunotherapy has revolutionized the treatment landscape in a number of solid tumors. In colorectal cancer, evidence suggests that microsatellite high (MSI-H) tumors are the most responsive to immune checkpoint blockade due to increased neo-antigen load and a favorable tumor microenvironment. Indeed, Pembrolizumab now represents a first line option in such patients. However, MSI-H tumors represent the minority and a proportion of patients' progress despite initially responding. Trials are investigating different immunotherapy combinatorial strategies to enhance immune response in less immunogenic colorectal tumors. Such strategies include dual immune checkpoint blockade, combining immune checkpoint inhibitors with other treatment modalities such as radiotherapy, chemotherapy or other biological or targeted agents. Moreover, there is an increasing drive to identify biomarkers to better select patients most likely to respond to immunotherapy and understand intrinsic and acquired resistance mechanisms. Apart from MSI-H tumors, there is a strong rationale to suggest that tumors with alterations in DNA polymerase epsilon and DNA polymerase delta are also likely to respond to immunotherapy and trials in this subpopulation are underway. Other strategies such as priming O6-methylguanineDNA methyltransferase silenced tumors with alkylating agents to make them receptive to immune checkpoint blockade are also being investigated. Here we discuss different colorectal subpopulations together with their likelihood of response to immune checkpoint blockade and strategies to overcome barriers to a successful clinical outcome. We summarize evidence from published clinical trials and provide an overview of trials in progress whilst discussing newer immunotherapy strategies such as adoptive cell therapies and cancer vaccines.
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http://dx.doi.org/10.2174/1389450122666210204204415DOI Listing
February 2021

EGFR amplification and outcome in a randomised phase III trial of chemotherapy alone or chemotherapy plus panitumumab for advanced gastro-oesophageal cancers.

Gut 2020 Nov 16. Epub 2020 Nov 16.

Department of Medicine, Royal Marsden Hospital NHS Trust, London, UK

Objective: Epidermal growth factor receptor (EGFR) inhibition may be effective in biomarker-selected populations of advanced gastro-oesophageal adenocarcinoma (aGEA) patients. Here, we tested the association between outcome and copy number (CN) in pretreatment tissue and plasma cell-free DNA (cfDNA) of patients enrolled in a randomised first-line phase III clinical trial of chemotherapy or chemotherapy plus the anti-EGFR monoclonal antibody panitumumab in aGEA (NCT00824785).

Design: CN by either fluorescence in situ hybridisation (n=114) or digital-droplet PCR in tissues (n=250) and plasma cfDNAs (n=354) was available for 474 (86%) patients in the intention-to-treat (ITT) population. Tissue and plasma low-pass whole-genome sequencing was used to screen for coamplifications in receptor tyrosine kinases. Interaction between chemotherapy and EGFR inhibitors was modelled in patient-derived organoids (PDOs) from aGEA patients.

Results: amplification in cfDNA correlated with poor survival in the ITT population and similar trends were observed when the analysis was conducted in tissue and plasma by treatment arm. EGFR inhibition in combination with chemotherapy did not correlate with improved survival, even in patients with significant CN gains. Addition of anti-EGFR inhibitors to the chemotherapy agent epirubicin in PDOs, resulted in a paradoxical increase in viability and accelerated progression through the cell cycle, associated with p21 and cyclin B1 downregulation and cyclin E1 upregulation, selectively in organoids from -amplified aGEA.

Conclusion: CN can be accurately measured in tissue and liquid biopsies and may be used for the selection of aGEA patients. EGFR inhibitors may antagonise the antitumour effect of anthracyclines with important implications for the design of future combinatorial trials.
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http://dx.doi.org/10.1136/gutjnl-2020-322658DOI Listing
November 2020

IDH Signalling Pathway in Cholangiocarcinoma: From Biological Rationale to Therapeutic Targeting.

Cancers (Basel) 2020 Nov 9;12(11). Epub 2020 Nov 9.

Division of Medical Oncology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy.

Biliary tract cancers are anatomically distinct and genetically diverse tumors, evenly characterized by poor response to standard treatments and a bleak outlook. The advent of comprehensive genomic profiling using next-generation sequencing has unveiled a plethora of potentially actionable aberrations, changing the view of biliary tract cancers from an "orphan" to a "target-rich" disease. Recently, mutations in isocitrate dehydrogenase genes (IDH1/2) and fusions of the fibroblast growth factor receptor have emerged as the most amenable to molecularly targeted inhibition, with several compounds actively investigated in advanced-phase clinical trials. Specifically, the IDH1 inhibitor ivosidenib has been the first targeted agent to show a survival benefit in a randomized phase III trial of cholangiocarcinoma patients harboring IDH1 mutations. In this review article, we will focus on the IDH1/IDH2 pathway, discussing the preclinical rationale of its targeting as well as the promises and challenges of the clinical development of IDH inhibitors in biliary tract cancers.
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http://dx.doi.org/10.3390/cancers12113310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696955PMC
November 2020

Molecular Features and Targeted Therapies in Extrahepatic Cholangiocarcinoma: Promises and Failures.

Cancers (Basel) 2020 Nov 4;12(11). Epub 2020 Nov 4.

Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, 40128 Bologna, Italy.

Biliary tract cancers (BTCs) include a heterogenous group of aggressive malignancies with limited therapeutic options. According to their anatomical location, these hepatobiliary tumors are usually classified into intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma (eCCA), and gallbladder cancer (GBC). Unfortunately, BTCs are often diagnosed when already metastatic, and although the advent of genomic sequencing has led to a deeper understanding of iCCA pathogenesis, very little data are currently available about the molecular landscape of eCCA. Moreover, despite novel systemic treatments emerging in BTC, the grim prognosis of eCCA patients has not changed in the past decade, and no targeted therapies have been approved so far. The aim of the current review is to provide an overview regarding molecular features and potential targeted therapies in eCCA, together with novel therapeutic approaches and future directions of translational and clinical research on this highly aggressive disease that poses many unanswered questions.
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http://dx.doi.org/10.3390/cancers12113256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694193PMC
November 2020

Circulating Tumor DNA as a Biomarker for Outcomes Prediction in Colorectal Cancer Patients.

Curr Drug Targets 2020 Nov 3. Epub 2020 Nov 3.

Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan,. Italy.

Circulating tumour DNA (ctDNA) is a novel tool that has being investigated in several types of tumours, includ-ing colorectal cancer (CRC). In fact, the techniques based on liquid biopsies are proposed as appealing non-invasive alter-natives to tissue biopsy, adding more insights into tumour molecular profile, heterogeneity and for cancer detection and monitoring. Additionally, some analysis showed that in CRC patients ctDNA seems to act as biomarker able to predict the outcome (prognostic role) and the response to treatments (predictive role). In particular, in the early stage CRC (stage I-III) it could represent a time marker of adjuvant therapy benefit as well as a marker of minimal residual disease and recurrence risk in addition to the already recognized risk factors. In metastatic CRC, the analysis of molecular tumour profile by ctDNA has shown to have high concordance with the tissue biopsy at diagnosis. Additionally, some studies demonstrated that ctDNA level during the treatment was linked with early response to treatment and prognosis. Finally, the quantitative anal-ysis of ctDNA and copy number alterations may be useful in order to detect resistance to therapy at the time of progression of disease and to help in finding new therapeutic targets.
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http://dx.doi.org/10.2174/1389450121999201103194248DOI Listing
November 2020

Impact of COVID-19 outbreak on cancer immunotherapy in Italy: a survey of young oncologists.

Authors:
Margaret Ottaviano Marcello Curvietto Pasquale Rescigno Marianna Tortora Giovannella Palmieri Diana Giannarelli Michele Aieta Pasquale Assalone Laura Attademo Antonio Avallone Francesco Bloise Davide Bosso Valentina Borzillo Giuseppe Buono Giuseppe Calderoni Francesca Caputo Giacomo Cartenì Diletta Cavallero Alessia Cavo Fortunato Ciardiello Raffaele Conca Vincenza Conteduca Stefano De Falco Marco De Felice Michelino De Laurentiis Pietro De Placido Sabino De Placido Irene De Santo Alfonso De Stefano Carminia Maria Della Corte Rossella Di Franco Vincenzo Di Lauro Antonietta Fabbrocini Piera Federico Lucia Festino Pasqualina Giordano Mario Giuliano Cesare Gridelli Antonio Maria Grimaldi Michela Lia Antonella Lucia Marretta Valentina Massa Alessia Mennitto Sara Merler Valeria Merz Carlo Messina Marco Messina Monica Milano Alessandro Marco Minisini Vincenzo Montesarchio Alessandro Morabito Floriana Morgillo Brigitta Mucci Lucia Nappi Fabiana Napolitano Immacolata Paciolla Martina Pagliuca Giuseppe Palmieri Sara Parola Stefano Pepe Angelica Petrillo Francovito Piantedosi Luisa Piccin Fernanda Picozzi Erica Pietroluongo Sandro Pignata Veronica Prati Vittorio Riccio Mario Rosanova Alice Rossi Anna Russo Massimiliano Salati Giuseppe Santabarbara Andrea Sbrana Ester Simeone Antonia Silvestri Massimiliano Spada Paolo Tarantino Paola Taveggia Federica Tomei Tortora Vincenzo Dario Trapani Claudia Trojanello Vito Vanella Sabrina Vari Jole Ventriglia Maria Grazia Vitale Fabiana Vitiello Caterina Vivaldi Claudia von Arx Francesca Zacchi Ilaria Zampiva Andrea Zivi Bruno Daniele Paolo Antonio Ascierto

J Immunother Cancer 2020 10;8(2)

Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Campania, Italy

Background: The coronavirus disease 2019 (COVID-19) pandemic has overwhelmed the health systems worldwide. Data regarding the impact of COVID-19 on cancer patients (CPs) undergoing or candidate for immune checkpoint inhibitors (ICIs) are lacking. We depicted the practice and adaptations in the management of patients with solid tumors eligible or receiving ICIs during the COVID-19 pandemic, with a special focus on Campania region.

Methods: This survey (25 questions), promoted by the young section of SCITO (Società Campana di ImmunoTerapia Oncologica) Group, was circulated among Italian young oncologists practicing in regions variously affected by the pandemic: high (group 1), medium (group 2) and low (group 3) prevalence of SARS-CoV-2-positive patients. For Campania region, the physician responders were split into those working in cancer centers (CC), university hospitals (UH) and general hospitals (GH). Percentages of agreement, among High (H) versus Medium (M) and versus Low (L) group for Italy and among CC, UH and GH for Campania region, were compared by using Fisher's exact tests for dichotomous answers and χ test for trends relative to the questions with 3 or more options.

Results: This is the first Italian study to investigate the COVID-19 impact on cancer immunotherapy, unique in its type and very clear in the results. The COVID-19 pandemic seemed not to affect the standard practice in the prescription and delivery of ICIs in Italy. Telemedicine was widely used. There was high consensus to interrupt immunotherapy in SARS-CoV-2-positive patients and to adopt ICIs with longer schedule interval. The majority of the responders tended not to delay the start of ICIs; there were no changes in supportive treatments, but some of the physicians opted for delaying surgeries (if part of patients' planned treatment approach). The results from responders in Campania did not differ significantly from the national ones.

Conclusion: Our study highlights the efforts of Italian oncologists to maintain high standards of care for CPs treated with ICIs, regardless the regional prevalence of COVID-19, suggesting the adoption of similar solutions. Research on patients treated with ICIs and experiencing COVID-19 will clarify the safety profile to continue the treatments, thus informing on the most appropriate clinical conducts.
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http://dx.doi.org/10.1136/jitc-2020-001154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565202PMC
October 2020

PD-1 blockade in deficient mismatch repair mixed adenoneuroendocrine carcinoma of the stomach: new hope for an orphan disease.

Tumori 2020 Dec 2;106(6):NP57-NP62. Epub 2020 Sep 2.

Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy.

Introduction: Mixed adenoneuroendocrine carcinoma (MANEC) is an uncommon and aggressive tumor arising throughout the entire gastrointestinal tract. Treatment options are limited, and survival is dismal with conventional therapies.

Case Description: We present the case of a 66-year-old man who was diagnosed with a locally advanced MANEC of the gastroesophageal junction. He was treated with perioperative chemotherapy and total gastrectomy. After anastomotic tumor recurrence was detected, he underwent three systemic regimens, including chemoradiotherapy. The patient was then tested for mismatch repair (MMR) protein status, revealing defective expression of MLH1 and PMS2 proteins. Treatment with anti-programmed death 1 (PD-1) receptor monoclonal antibody pembrolizumab was started and radiologic response is ongoing after 11 months. Clinical benefit was evident, and no immune therapy-related side effect was detected.

Conclusions: To our knowledge, this is the first report of a heavily pretreated and rapidly progressing deficient MMR gastroesophageal MANEC experiencing a durable benefit from anti-PD1 treatment.
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http://dx.doi.org/10.1177/0300891620952845DOI Listing
December 2020

MicroRNAs (miRNAs) and Long Non-Coding RNAs (lncRNAs) as New Tools for Cancer Therapy: First Steps from Bench to Bedside.

Target Oncol 2020 06;15(3):261-278

Division of Molecular Pathology, The Institute of Cancer Research, London, UK.

Non-coding RNAs represent a significant proportion of the human genome. After having been considered as 'junk' for a long time, non-coding RNAs are now well established as playing important roles in maintaining cellular homeostasis and functions. Some non-coding RNAs show cell- and tissue-specific expression patterns and are specifically deregulated under pathological conditions (e.g. cancer). Therefore, non-coding RNAs have been extensively studied as potential biomarkers in the context of different diseases with a focus on microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) for several years. Since their discovery, miRNAs have attracted more attention than lncRNAs in research studies; however, both families of non-coding RNAs have been established to play an important role in gene expression control, either as transcriptional or post-transcriptional regulators. Both miRNAs and lncRNAs can regulate key genes involved in the development of cancer, thus influencing tumour growth, invasion, and metastasis by increasing the activation of oncogenic pathways and limiting the expression of tumour suppressors. Furthermore, miRNAs and lncRNAs are also emerging as important mediators in drug-sensitivity and drug-resistance mechanisms. In the light of these premises, a number of pre-clinical and early clinical studies are exploring the potential of non-coding RNAs as new therapeutics. The aim of this review is to summarise the latest knowledge of the use of miRNAs and lncRNAs as therapeutic tools for cancer treatment.
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http://dx.doi.org/10.1007/s11523-020-00717-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283209PMC
June 2020

Efficacy and Safety of Immune Checkpoint Inhibitors in Patients with Microsatellite Instability-High End-Stage Cancers and Poor Performance Status Related to High Disease Burden.

Oncologist 2020 09 20;25(9):803-809. Epub 2020 May 20.

Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Background: Few real-world series on the efficacy and safety of anti-programmed cell death protein-1(PD-1)/programmed death ligand-1(PD-L1)-based therapy are available in molecularly unselected patients with poor performance status (PS) and specific types of advanced cancers, because such populations are typically excluded from clinical trials due to poor life expectancy and risk of toxicity.

Materials And Methods: This multicenter retrospective case series included patients with microsatellite instability (MSI)-high metastatic cancers with Eastern Cooperative Oncology Group (ECOG) PS of 2 or 3 not related to comorbidities receiving anti-PD-1 with or without anti-CTLA-4 therapy after failure of at least one prior treatment line.

Results: We included 27 patients with six diverse tumor types: colorectal (n = 18), gastric (n = 5), biliary tract, pancreatic, small bowel, and endometrial cancers (n = 1 each). Baseline ECOG PS was 2 (74%) or 3 (26%). Overall response rate was 33%, with six partial and three complete responses. Median time to response was 3.1, months and median duration of response was 16.9 months. Median progression-free survival was 3.4 months (95% CI: 2.3 to not evaluable), and 18-month overall survival was 50.8% (95% confidence interval, 32.7-78.8). Baseline variables were not associated with survival outcomes. ECOG PS 1 was reached by 52% of patients in a median time of 6 weeks, and ECOG PS 0 was reached by 30% of patients in a median time of 10 weeks.

Conclusion: In a high proportion of patients with MSI-high cancers and poor performance status related to end-stage disease, salvage immunotherapy can induce potentially long-lasting "Lazarus responses". Immunotherapy decisions near the end-of-life should be carefully integrated with predictive biomarkers and with palliative care measures in the real-world setting.

Implications For Practice: In this retrospective cohort study of 27 pretreated patients with microsatellite instability (MSI)-high cancers and Eastern Cooperative Oncology Group performance status of 2 or 3 not related to comorbidities, PD-1/PD-L1-based therapy induced a RECIST response in 33% of patients, with a median duration of 16.9 months, and an improvement of performance status in 52% of patients. MSI-high status can be used in clinical practice as a tumor-agnostic predictive biomarker to select critically ill patients with end-stage cancers for salvage immunotherapy.
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http://dx.doi.org/10.1634/theoncologist.2020-0014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485362PMC
September 2020

Multicenter Retrospective Analysis of Second-Line Therapy after Gemcitabine Plus Nab-Paclitaxel in Advanced Pancreatic Cancer Patients.

Cancers (Basel) 2020 Apr 30;12(5). Epub 2020 Apr 30.

Digestive Molecular Clinical Oncology Research Unit, University of Verona, 37134 Verona, Italy.

Pancreatic cancer is one of the most lethal solid tumors. In many European countries gemcitabine plus nab-paclitaxel is the preferred first-line treatment. An increasing number of patients are eligible for second-line therapy, but the best regimen is still controversial. This study aimed to evaluate the efficacy of oxaliplatin-based compared to irinotecan-based therapies in this setting. 181 advanced pancreatic cancer patients consecutively treated in three centers with a second-line therapy progressed on gemcitabine plus nab-paclitaxel were retrospectively enrolled. OS and PFS were calculated using the Kaplan-Meier method and survival of the two groups was compared using the log-rank test. The median PFS and OS were respectively 3.5 (95%CI 3.2-3.8) and 8.8 months (95%CI 7.9-9.8) from second-line therapy in the overall population. The median PFS and OS were respectively 3.3 (95%CI 3.1-3.5) and 8.2 months (95%CI 7.24-9.34) with an irinotecan-based combination compared to 4.0 (95%CI 2.4-5.7) and 10.3 months (95%CI 8.62-12.02) in patients receiving an oxaliplatin-based combination. We observed a clear trend for longer survival outcomes with platinum-based doublet compared to regimens including irinotecan or nal-IRI. Head-to-head trials are still lacking. The neutrophil-to-lymphocyte ratio and the presence of liver metastases could drive physicians in tailoring the treatment strategy.
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http://dx.doi.org/10.3390/cancers12051131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281137PMC
April 2020

The Role of Anti-Angiogenics in Pre-Treated Metastatic -Mutant Colorectal Cancer: A Pooled Analysis.

Cancers (Basel) 2020 Apr 21;12(4). Epub 2020 Apr 21.

Department of Medical Oncology, Card. G. Panico Hospital of Tricase, 73039 Tricase, Italy.

. FOLFOXIRI plus Bevacizumab is one of the most frequently used first-line treatments for patients with -mutant colorectal cancer (CRC), while second-line treatment requires extensive further research. In this pooled analysis, we evaluate the impact of anti-angiogenics in patients with pre-treated -mutant CRC. We monitored patients in randomized, controlled studies who had advanced CRC and were undergoing second-line chemotherapy in addition to utilizing Bevacizumab, Ramucirumab or Aflibercept treatments. These data were pooled together with the data and results of -mutant patients enrolled in two phase III trials (TRIBE and TRIBE-2 study), who had been treated with second-line treatment both with or without Bevacizumab. Overall survival (OS), in relation to mutational status, was the primary focus. . Pooled analysis included 129 patients. Anti-angiogenics were found to have a significant advantage over the placebo in terms of OS (HR 0.50, 95%CI 0.29-0.85) ( = 0.01). . Our pooled analysis confirms the efficacy of anti-angiogenics in pre-treated -mutant CRC, establishing the combination of chemotherapy plus Bevacizumab or Ramucirumab or Aflibercept as a valid treatment option.
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http://dx.doi.org/10.3390/cancers12041022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226019PMC
April 2020

The Impact of Locoregional Treatment on Response to Nivolumab in Advanced Platinum Refractory Head and Neck Cancer: The Need Trial.

Vaccines (Basel) 2020 Apr 20;8(2). Epub 2020 Apr 20.

Department of Clinical and Molecular Medicine, University of Rome "Sapienza", 00161 Rome, Italy.

Background: Previous locoregional treatment could affect the response to nivolumab in platinum-refractory recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). The aim of this study is to evaluate the impact of the clinicopathological characteristics and previous treatment in predicting early progression to nivolumab in a real-world population.

Methods: This is an observational, multicenter retrospective/prospective study including patients (pts) with platinum refractory R/M HNSCC who received nivolumab 240 mg every 2 weeks from October 2018 to October 2019. We analyzed the association between previous treatment, clinicopathological characteristics, and early progression (within 3 months).

Results: Data from 61 pts were reviewed. Median age was 67 years (30-82). Forty-two pts (69%) received previous locoregional treatment. Early progression to nivolumab occurred in 36 pts (59%), while clinical benefit (stable disease and partial response) was achieved in 25 pts (41%). Early progression to nivolumab was significantly associated to previous locoregional treatment both at univariate and multivariate analysis ( = 0.005 and = 0.048, respectively).

Conclusion: nivolumab in R/M HNSCC is burdened with a high early progression rate. Previous wide neck dissection and high dose radiotherapy may compromise the efficacy of nivolumab, distorting the anatomy of the local lymphatic system and hindering the priming of immune response.
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http://dx.doi.org/10.3390/vaccines8020191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349768PMC
April 2020

Clinical Behavior and Treatment Response of Epstein-Barr Virus-Positive Metastatic Gastric Cancer: Implications for the Development of Future Trials.

Oncologist 2020 09 30;25(9):780-786. Epub 2020 Apr 30.

Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Background: Epstein-Barr virus (EBV)-positive gastric cancers (GCs) have been recently identified as a molecular subgroup showing excellent outcomes after surgery for early-stage disease and responsiveness to immune checkpoint inhibitors (ICIs) for metastatic stage. No data are available on the prevalence, clinical characteristics, and prognosis of this subgroup of GCs in the metastatic setting.

Materials And Methods: In this cohort study, we assessed the impact of EBV status in patients with metastatic GC treated with chemotherapy at two Italian institutions.

Results: Among the 175 cases analyzed, only 7 (4%) were EBV positive and all showed long-lasting and even complete responses to first-line chemotherapy with fluorouracil and platinum and a significantly better survival compared with EBV-negative patients (3-year overall survival: 80% vs. 20.1%; hazard ratio: 0.12).

Conclusion: If confirmed in larger data sets, our results may give a strong rationale for investigating the addition of ICIs to chemotherapy, in order to maximize the chance of achieving durable and complete responses in this uncommon subtype of GC.

Implications For Practice: To date, no data are available on the prevalence and clinical characteristics of patients with Epstein-Barr virus (EBV)-positive metastatic gastric cancer (GC), a specific subtype of GC showing excellent outcomes after radical surgery in early-stage disease and responsiveness to immune checkpoint inhibitors (ICIs). This cohort study showed that patients with EBV-positive GC who did not receive ICIs had exceptional, long-lasting, and even complete responses to first-line chemotherapy with fluorouracil and platinum and a significantly better survival compared with EBV-negative patients. If confirmed in larger series, these results may give a strong rationale for investigating the combination of chemotherapy and ICIs to achieve durable and potentially complete response in this uncommon subtype of GC.
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http://dx.doi.org/10.1634/theoncologist.2020-0037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485344PMC
September 2020

Modulation of Biliary Cancer Chemo-Resistance Through MicroRNA-Mediated Rewiring of the Expansion of CD133+ Cells.

Hepatology 2020 09 10;72(3):982-996. Epub 2020 Sep 10.

Division of Cancer Therapeutics, Institute of Cancer Research, London, United Kingdom.

Background And Aims: Changes in single microRNA (miRNA) expression have been associated with chemo-resistance in biliary tract cancers (BTCs). However, a global assessment of the dynamic role of the microRNome has never been performed to identify potential therapeutic targets that are functionally relevant in the BTC cell response to chemotherapy.

Approach And Results: High-throughput screening (HTS) of 997 locked nucleic acid miRNA inhibitors was performed in six cholangiocarcinoma cell lines treated with cisplatin and gemcitabine (CG) seeking changes in cell viability. Validation experiments were performed with mirVana probes. MicroRNA and gene expression was assessed by TaqMan assay, RNA-sequencing, and in situ hybridization in four independent cohorts of human BTCs. Knockout of microRNA was achieved by CRISPR-CAS9 in CCLP cells (MIR1249KO) and tested for effects on chemotherapy sensitivity in vitro and in vivo. HTS revealed that MIR1249 inhibition enhanced chemotherapy sensitivity across all cell lines. MIR1249 expression was increased in 41% of cases in human BTCs. In validation experiments, MIR1249 inhibition did not alter cell viability in untreated or dimethyl sulfoxide-treated cells; however, it did increase the CG effect. MIR1249 expression was increased in CD133+ biliary cancer cells freshly isolated from the stem cell niche of human BTCs as well as in CD133+ chemo-resistant CCLP cells. MIR1249 modulated the chemotherapy-induced enrichment of CD133+ cells by controlling their clonal expansion through the Wnt-regulator FZD8. MIR1249KO cells had impaired expansion of the CD133+ subclone and its enrichment after chemotherapy, reduced expression of cancer stem cell markers, and increased chemosensitivity. MIR1249KO xenograft BTC models showed tumor shrinkage after exposure to weekly CG, whereas wild-type models showed only stable disease over treatment.

Conclusions: MIR1249 mediates resistance to CG in BTCs and may be tested as a target for therapeutics.
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http://dx.doi.org/10.1002/hep.31094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590111PMC
September 2020

The prognostic nutritional index predicts survival and response to first-line chemotherapy in advanced biliary cancer.

Liver Int 2020 03 11;40(3):704-711. Epub 2019 Dec 11.

Department of Oncology and Hematology, Division of Oncology, University of Modena and Reggio Emilia, Modena, Italy.

Background: An accurate risk-stratification is key to optimize the benefit-to-risk ratio of palliative treatment in advanced biliary cancer. We aimed at assessing the impact of the prognostic nutritional index (PNI) on survival and treatment response in advanced biliary cancer (ABC) receiving first-line chemotherapy.

Methods: Medical records of ABC treated with standard chemotherapy at the Modena Cancer Centre were retrospectively reviewed for variables deemed of potential interest, including the PNI. Univariate and multivariate analyses were performed to investigate the association between the covariates and overall survival (OS).

Results: 114 ABC fulfilled the inclusion criteria and made up the training cohort. A PNI cut-off value of 36.7 was established using the receiver operating characteristic (ROC) analysis. At both the univariate and the multivariate analysis, low PNI value (<36.7) was associated with shorter OS (P = .0011), together with increased NLR (P = .0046) and ECOG >1 (P < .0001). The median OS was 5.4 vs 12.1 months in the low- vs high PNI-group. Moreover, a PNI value >36.7 resulted in a higher disease control in patients treated with gemcitabine/platinum combination (61.4% vs 34.3%). These results were validated in an independent cohort of 253 ABC.

Conclusions: We demonstrated and externally validated a prognostic role for the PNI in ABC treated with first-line chemotherapy. Although the PNI turned out to be predictive in the subset of patients receiving platinum/gemcitabine combination, future prospective confirmation is needed.
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http://dx.doi.org/10.1111/liv.14314DOI Listing
March 2020

NUT midline carcinoma: Current concepts and future perspectives of a novel tumour entity.

Crit Rev Oncol Hematol 2019 Dec 1;144:102826. Epub 2019 Nov 1.

Medical Oncology Department, Sant'Andrea Hospital, Rome, Italy; Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Rome, Italy.

NMC is a recently recognized cancer type hallmarked by chromosomal translocation involving the NUT gene, a catastrophic event leading to fusion oncoprotein responsible for malignant transformation and tumor progression. The aggressiveness of disease together with a poor response to conventional treatment make NMC one of the most lethal cancer. Moreover, although until recently NMC has been poorly understood and largely neglected, the number of reported cases is steadily rising. Recently, in addition to its pathogenetic and diagnostic role, NUT-fusion oncoprotein has been shown to be amenable to targeted inhibition using BET inhibitors. Future clinical trials are warranted with the aim of investigate the incorporation of targeted agent into multimodal therapeutic strategy. Since new promising NUT-targeting drugs are emerging that may affect the clinical course, the correct and prompt recognition of NMC is key to improve patients' outcome.
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http://dx.doi.org/10.1016/j.critrevonc.2019.102826DOI Listing
December 2019

Adjuvant chemotherapy in resected bile duct cancer: A systematic review and meta-analysis of randomized trials.

Crit Rev Oncol Hematol 2019 Nov 9;143:124-129. Epub 2019 Sep 9.

Department of Medical Oncology, Santa Chiara Hospital, Trento, Italy.

Background: The role of adjuvant chemotherapy (ACT) for resected biliary tract cancer (BTC) is still unclear and there is no specific recommendation by international guidelines.

Aim: To perform a meta-analysis of randomized clinical trials (RCTs) to better define the clinical benefit and risks of ACT or observation in resected BTC.

Method: A systematic literature search of Pubmed, Embase, and the Cochrane Library was performed up to April 2019. A meta-analysis was carried out using the random effects model.

Results: ACT provided a mild improvement in recurrence free survival (RFS) (HR:0.83, 95%CI 0.69-0.99) and no effect on overall survival (OS) (HR:0.91, 95%CI 0.75-1.09). Similarly, ACT showed no effect on OS in lymph-node positive subgroup (HR:0.84, 95% CI 0.65-1.08) and surgical margin positive subgroup (HR:0.95, 95%CI 0.69-1.31). Moreover, ACT led to a substantial increase of chemotherapy-associated adverse events (RR:3.03, 95%CI 2.22-4.15).

Conclusion: ACT for resected BTC patients modestly improved RFS with no effect on OS and a substantial increase in chemotherapy associated AEs.
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http://dx.doi.org/10.1016/j.critrevonc.2019.09.002DOI Listing
November 2019

Gastric cancer: Translating novels concepts into clinical practice.

Cancer Treat Rev 2019 09 14;79:101889. Epub 2019 Aug 14.

Department of Medical Oncology, Universita' di Modena e Reggio Emilia, Modena, Italy.

The overall 5-year survival of gastric cancer (GC) has change only little in the last decades and it remains the fifth leading cause of cancer-related death worldwide. However, in the past few years a more effective combination chemotherapy has raised the bar of curability of about 10% in resectable disease. Morever, a deeper knowledge of GC biology have unveiled biomarkers to help personalize adjunctive treatments in patients candidate to surgery. Despite a plateau in efficacy of fist-line treatment, incremental survival advantages have been recorded in unresectable advanced disease. The growing number of effective drugs in second and later lines along with a more judicious delivery of cytotoxics and early supportive interventions have enabled more patients to proceed beyond first-line. The continuum of care has become a reality in a considerable proportion of patients that offer opportunities to improve outcomes. Finally, the advent of the immune checkpoint inhibitors has brought great expectations in molecularly-defined subset of patients. This Review summarizes the state-of-the art in the management of GC together with novel concepts that have entered clinical development with the potential of change practice in the foreseeable future.
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http://dx.doi.org/10.1016/j.ctrv.2019.101889DOI Listing
September 2019

Surgery or Locoregional Approaches for Hepatic Oligometastatic Pancreatic Cancer: Myth, Hope, or Reality?

Cancers (Basel) 2019 Aug 1;11(8). Epub 2019 Aug 1.

Oncology Unit, Oncology Department, ASST Bergamo Ovest, 24047 Treviglio (BG), Italy.

Despite extensive research, pancreatic ductal adenocarcinoma (PDAC) remains a difficult-to-treat cancer associated with poor survival. Due to the known aggressive disease biology, palliative chemotherapy is the only routinely recommended treatment in the metastatic setting in patients with adequate performance status. However, in a subset of patients with oligometastatic disease, multimodality treatment with surgery and/or locoregional approaches may provide long-term disease control and prolong survival. In fact, in highly selected cases, median overall survival has been reported to extend to 56 months in patients treated with surgery. In particular, liver and extraregional nodal resections may provide long-term tumor control with acceptable morbidity. Current guidelines do not recommend surgery for patients with metastatic PDAC and, in the case of PDAC with oligometastases, there are no published randomized controlled trials regarding locoregional or surgical approaches. Here we review the literature on surgical and locoregional approaches including radiofrequency ablation, irreversible electroporation, and stereotactic body radiation, and focus on patients with hepatic oligometastatic pancreatic cancer. We provide a summary regarding survival outcomes, morbidity and mortality and discuss selection criteria that may be useful to predict the best outcomes for such strategies.
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http://dx.doi.org/10.3390/cancers11081095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721290PMC
August 2019

The A.L.A.N. score identifies prognostic classes in advanced biliary cancer patients receiving first-line chemotherapy.

Eur J Cancer 2019 08 2;117:84-90. Epub 2019 Jul 2.

Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK; Gastrointestinal Unit, The Royal Marsden NHS Trust, London and Surrey, UK; Institute of Cancer Sciences, University of Glasgow, Glasgow, UK. Electronic address:

Background: Chemotherapy is the mainstay treatment for advanced biliary cancer (ABC). Best supportive care and clinical trials are currently alternative options. The identification of a prognostic score that can be widely applied to daily practice has the potential to better inform clinical management of ABC patients.

Methods: A cohort of 123 ABC patients undergoing first-line chemotherapy was used as an exploratory cohort to define the prognostic value of laboratory tests routinely performed in clinical practice. Kaplan-Meier analysis was used to investigate the association between the variables and overall survival (OS). Those variables that were statistically significant at the multivariate analysis were combined in a multiplex score. Performance of the novel prognostic score was confirmed in a validation cohort of 60 ABC patients.

Results: Baseline actual neutrophil count, lymphocytes-monocytes ratio, neutrophil-lymphocytes ratio and albumin (A.L.A.N.) correlated with OS at the multivariate analysis in the exploratory cohort. When combined in the multiplex, A.L.A.N. score was able to identify three classes of ABC patients with significantly different OS (high-risk: median OS, 5 months; intermediate-risk: median OS, 12 months and low-risk: median OS, 22 months; p:<0.001). The score performed well in the different subtypes of ABC and was independent of stage, performance status and chemotherapy regimen. The performance of the A.L.A.N. score was confirmed in a validation cohort of cholangiocarcinoma patients (high-risk: median OS, 4.3 months; intermediate-risk: median OS 9.3 months, low-risk: median OS 13 months; p:0.005).

Conclusions: The A.L.A.N score can be derived by variables routinely recorded in clinical practice and can provide prognostic assessment of ABC patients considered for first-line treatment.
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http://dx.doi.org/10.1016/j.ejca.2019.05.030DOI Listing
August 2019

A nomogram to predict survival in non-small cell lung cancer patients treated with nivolumab.

J Transl Med 2019 03 27;17(1):99. Epub 2019 Mar 27.

Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.

Background: The advent of immune checkpoint inhibitors (ICIs) has considerably expanded the armamentarium against non-small cell lung cancer (NSCLC) contributing to reshaping treatment paradigms in the advanced disease setting. While promising tissue- and plasma-based biomarkers are under investigation, no reliable predictive factor is currently available to aid in treatment selection.

Methods: Patients with stage IIIB-IV NSCLC receiving nivolumab at Sant'Andrea Hospital and Regina Elena National Cancer Institute from June 2016 to July 2017 were enrolled onto this study. Major clinicopathological parameters were retrieved and correlated with patients' survival outcomes in order to assess their prognostic value and build a useful tool to assist in the decision making process.

Results: A total of 102 patients were included in this study. The median age was 69 years (range 44-85 years), 69 (68%) were male and 52% had ECOG PS 0. Loco-regional/distant lymph nodes were the most commonly involved site of metastasis (71%), followed by lung parenchyma (67%) and bone (26%). Overall survival (OS) in the whole patients' population was 83.6%, 63.2% and 46.9% at 3, 6 and 12 months, respectively; while progression-free survival (PFS) was 66.5%, 44.4% and 26.4% at 3, 6 and 12 months, respectively. At univariate analysis, age ≥ 69 years (P = 0.057), ECOG PS (P < 0.001), the presence of liver (P < 0.001), lung (P = 0.017) metastases, lymph nodes only involvement (P = 0.0145) were significantly associated with OS and ECOG PS (P < 0.001) and liver metastases (P < 0.001), retained statistical significance at multivariate analysis. A prognostic nomogram based on three variables (liver and lung metastases and ECOG PS) was built to assign survival probability at 3, 6, and 12 months after nivolumab treatment commencement.

Conclusion: We developed a nomogram based on easily available and inexpensive clinical factors showing a good performance in predicting individual OS probability among NSCLC patients treated with nivolumab. This prognostic device could be valuable to clinicians in more accurately driving treatment decision in daily practice as well as enrollment onto clinical trials.
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http://dx.doi.org/10.1186/s12967-019-1847-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437908PMC
March 2019

Noncoding RNA in Cholangiocarcinoma.

Semin Liver Dis 2019 02 7;39(1):13-25. Epub 2018 Dec 7.

Division of Cancer Therapeutics, The Institute of Cancer Research, London, United Kingdom.

Cholangiocarcinomas (CCAs) are tumors with a dismal prognosis. Early diagnosis is a key challenge because of the lack of specific symptoms, and the curability rate is low due to the difficulty in achieving a radical resection and the intrinsic chemoresistance of CCA cells. Noncoding RNAs (ncRNAs) are transcripts that are not translated into proteins but exert their functional role by regulating the transcription and translation of other genes. The discovery of the first ncRNA dates back to 1993 when the microRNA (miRNA) was discovered in . Only 10 years later, miRNAs were shown to play an oncogenic role in cancer cells and within 20 years miRNA therapeutics were tested in humans. Here, the authors review the latest evidence for a role for ncRNAs in CCA and discuss the promise and challenges associated with the introduction of ncRNAs into clinical practice.
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http://dx.doi.org/10.1055/s-0038-1676097DOI Listing
February 2019

Oligometastatic gastric cancer: An emerging clinical entity with distinct therapeutic implications.

Eur J Surg Oncol 2019 Aug 10;45(8):1479-1482. Epub 2018 Nov 10.

Department of Oncology, University Hospital of Modena and Reggio Emilia, Modena, Italy.

Gastric cancer (GC) remains responsible for a high burden worldwide being the third leading cause of cancer-related mortality. Most of patients present at an advanced stage at diagnosis and are thus candidates to standard chemotherapy resulting in median survival of less than 1 year. Oligometastatic gastric cancer is an increasingly recognized clinical entity characterized by limited metastatic spread that has been showing to benefit from aggressive multimodality strategies encompassing chemotherapy and surgery. The ongoing RENAISSANCE/AIO-FLOT5 (NCT02578368) phase III trial is aimed at evaluating if perioperative chemotherapy with FLOT in combination with surgical resection of the primary tumour and metastases could become the new standard of care for oligometastatic GC. In the meantime, in addition to currently available clinical parameters, the emerging predictive/prognostic role of biomarkers such mismatch repair deficiency/microsatellite instability high status needs to be specifically addressed also in this subgroup of GC to assist in patient selection.
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http://dx.doi.org/10.1016/j.ejso.2018.11.006DOI Listing
August 2019

Nivolumab-Induced Impressive Response of Refractory Pulmonary Sarcomatoid Carcinoma with Brain Metastasis.

Case Rep Oncol 2018 Sep-Dec;11(3):615-621. Epub 2018 Sep 7.

Department of Oncology, University of Modena and Reggio Emilia - Policlinico of Modena, Modena, Italy.

Background: Pulmonary sarcomatoid carcinoma is a rare, poorly differentiated, and highly aggressive type of non-small cell lung cancer. High tumor mutational burden and PD-L1 overexpression make it an excellent candidate for immunotherapy.

Objectives And Method: We presented the case of a patient who underwent left inferior lobectomy with concurrent right paravertebral muscular metastasectomy for an infiltrative neoplastic mass, whose final diagnosis was consistent with stage IV pulmonary sarcomatoid carcinoma. He received first- and second-line chemotherapy without any benefit. Since March 2016, he has been treated with the anti-PD1 agent nivolumab with a dramatic improvement of symptoms, disappearance of a brain lesion, and partial response on other metastatic sites. He tolerated the treatment well and is still responding after 22 months from the beginning.

Results And Conclusions: In very lethal non-small cell lung cancer subtypes such as the sarcomatoid variants, high tumor burden and deteriorated general conditions should not preclude, at least in some cases, the use of immunotherapy. Anti-PD1 may also have a reliable role in disease control in the brain. Lastly, the strong rationale behind sarcomatoid histology should further prompt trials exploring immunotherapeutic approaches in this subset of non-small cell lung cancer.
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http://dx.doi.org/10.1159/000492666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180262PMC
September 2018