Publications by authors named "Marco Tagliamento"

43 Publications

Knowledge, Practice, and Attitudes of Physicians in Low- and Middle-Income Countries on Fertility and Pregnancy-Related Issues in Young Women With Breast Cancer.

JCO Glob Oncol 2022 Jan;8:e2100153

Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

Purpose: Fertility and pregnancy-related issues are highly relevant for young (≤ 40 years) patients with breast cancer. Limited evidence exists on knowledge, practice, and attitudes of physicians from low- and middle-income countries (LMICs) regarding these issues.

Methods: A 19-item questionnaire adapted from an international survey exploring issues about fertility preservation and pregnancy after breast cancer was sent by e-mail between November 2019 and January 2020 to physicians from LMICs involved in breast cancer care. Descriptive analyses were performed.

Results: A total of 288 physicians from Asia, Africa, America, and Europe completed the survey. Median age was 38 years. Responders were mainly medical oncologists (44.4%) working in an academic setting (46.9%). Among responders, 40.2% and 53.8% reported having never consulted the available international guidelines on fertility preservation and pregnancy after breast cancer, respectively. 25.0%, 19.1%, and 24.3% of responders answered to be not at all knowledgeable about embryo, oocyte, or ovarian tissue cryopreservation, respectively; 29.2%, 23.6%, and 31.3% declared that embryo, oocyte, and ovarian tissue cryopreservation were not available in their countries, respectively. 57.6% of responders disagreed or were neutral on the statement that controlled ovarian stimulation can be considered safe in patients with breast cancer. 49.7% and 58.6% of responders agreed or were neutral on the statement that pregnancy in breast cancer survivors may increase the risk of recurrence overall or only in those with hormone receptor-positive disease, respectively.

Conclusion: This survey showed suboptimal knowledge, practice, and attitudes of physicians from LMICs on fertility preservation and pregnancy after treatment completion in young women with breast cancer. Increasing awareness and education on these aspects are needed to improve adherence to available guidelines and to promote patients' oncofertility counseling.
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http://dx.doi.org/10.1200/GO.21.00153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8769103PMC
January 2022

Time-Dependent COVID-19 Mortality in Patients With Cancer: An Updated Analysis of the OnCovid Registry.

JAMA Oncol 2022 Jan;8(1):114-122

Translational Oncology and Urology Research, School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom.

Importance: Whether the severity and mortality of COVID-19 in patients with cancer have improved in terms of disease management and capacity is yet to be defined.

Objective: To test whether severity and mortality from COVID-19 among patients with cancer have improved during the course of the pandemic.

Design, Setting, And Participants: OnCovid is a European registry that collects data on consecutive patients with solid or hematologic cancer and COVID-19. This multicenter case series study included real-world data from 35 institutions across 6 countries (UK, Italy, Spain, France, Belgium, and Germany). This update included patients diagnosed between February 27, 2020, and February, 14, 2021. Inclusion criteria were confirmed diagnosis of SARS-CoV-2 infection and a history of solid or hematologic cancer.

Exposures: SARS-CoV-2 infection.

Main Outcomes And Measures: Deaths were differentiated at 14 days and 3 months as the 2 landmark end points. Patient characteristics and outcomes were compared by stratifying patients across 5 phases (February to March 2020, April to June 2020, July to September 2020, October to December 2020, and January to February 2021) and across 2 major outbreaks (February to June 2020 and July 2020 to February 2021).

Results: At data cutoff, 2795 consecutive patients were included, with 2634 patients eligible for analysis (median [IQR] age, 68 [18-77] years ; 52.8% men). Eligible patients demonstrated significant time-dependent improvement in 14-day case-fatality rate (CFR) with estimates of 29.8% (95% CI, 0.26-0.33) for February to March 2020; 20.3% (95% CI, 0.17-0.23) for April to June 2020; 12.5% (95% CI, 0.06-22.90) for July to September 2020; 17.2% (95% CI, 0.15-0.21) for October to December 2020; and 14.5% (95% CI, 0.09-0.21) for January to February 2021 (all P < .001) across the predefined phases. Compared with the second major outbreak, patients diagnosed in the first outbreak were more likely to be 65 years or older (974 of 1626 [60.3%] vs 564 of 1008 [56.1%]; P = .03), have at least 2 comorbidities (793 of 1626 [48.8%] vs 427 of 1008 [42.4%]; P = .001), and have advanced tumors (708 of 1626 [46.4%] vs 536 of 1008 [56.1%]; P < .001). Complications of COVID-19 were more likely to be seen (738 of 1626 [45.4%] vs 342 of 1008 [33.9%]; P < .001) and require hospitalization (969 of 1626 [59.8%] vs 418 of 1008 [42.1%]; P < .001) and anti-COVID-19 therapy (1004 of 1626 [61.7%] vs 501 of 1008 [49.7%]; P < .001) during the first major outbreak. The 14-day CFRs for the first and second major outbreaks were 25.6% (95% CI, 0.23-0.28) vs 16.2% (95% CI, 0.13-0.19; P < .001), respectively. After adjusting for country, sex, age, comorbidities, tumor stage and status, anti-COVID-19 and anticancer therapy, and COVID-19 complications, patients diagnosed in the first outbreak had an increased risk of death at 14 days (hazard ratio [HR], 1.85; 95% CI, 1.47-2.32) and 3 months (HR, 1.28; 95% CI, 1.08-1.51) compared with those diagnosed in the second outbreak.

Conclusions And Relevance: The findings of this registry-based study suggest that mortality in patients with cancer diagnosed with COVID-19 has improved in Europe; this improvement may be associated with earlier diagnosis, improved management, and dynamic changes in community transmission over time.
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http://dx.doi.org/10.1001/jamaoncol.2021.6199DOI Listing
January 2022

Immunogenicity and risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection after Coronavirus Disease 2019 (COVID-19) vaccination in patients with cancer: a systematic review and meta-analysis.

Eur J Cancer 2022 01 26;160:243-260. Epub 2021 Oct 26.

Breast Cancer Center, Hospital Zambrano Hellion TecSalud, Tecnologico de Monterrey, San Pedro Garza Garcia, Nuevo Leon, Mexico. Electronic address:

Background: Patients with cancer are considered a priority group for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination given their high risk of contracting severe Coronavirus Disease 2019 (COVID-19). However, limited data exist regarding the efficacy of immunisation in this population. In this study, we assess the immunologic response after COVID-19 vaccination of cancer versus non-cancer population.

Methods: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases were searched from 01st March 2020 through 12th August 12 2021. Primary end-points were anti-SARS-CoV-2 spike protein (S) immunoglobulin G (IgG) seroconversion rates, T-cell response, and documented SARS-CoV-2 infection after COVID-19 immunisation. Data were extracted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Overall effects were pooled using random-effects models.

Results: This systematic review and meta-analysis included 35 original studies. Overall, 51% (95% confidence interval [CI], 41-62) and 73% (95% CI, 64-81) of patients with cancer developed anti-S IgG above the threshold level after partial and complete immunisation, respectively. Patients with haematologic malignancies had a significantly lower seroconversion rate than those with solid tumours after complete immunisation (65% vs 94%; P < 0.0001). Compared with non-cancer controls, oncological patients were less likely to attain seroconversion after incomplete (risk ratio [RR] 0.45 [95% CI 0.35-0.58]) and complete (RR 0.69 [95% CI 0.56-0.84]) COVID-19 immunisation schemes. Patients with cancer had a higher likelihood of having a documented SARS-CoV-2 infection after partial (RR 3.21; 95% CI 0.35-29.04) and complete (RR 2.04; 95% CI 0.38-11.10) immunisation.

Conclusions: Patients with cancer have an impaired immune response to COVID-19 vaccination compared with controls. Strategies that endorse the completion of vaccination schemes are warranted. Future studies should aim to evaluate different approaches that enhance oncological patients' immune response.
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http://dx.doi.org/10.1016/j.ejca.2021.10.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548030PMC
January 2022

Prevalence and impact of COVID-19 sequelae on treatment and survival of patients with cancer who recovered from SARS-CoV-2 infection: evidence from the OnCovid retrospective, multicentre registry study.

Lancet Oncol 2021 12 3;22(12):1669-1680. Epub 2021 Nov 3.

Department of Internal Medicine and Medical Therapy, University of Pavia, Pavia, Italy.

Background: The medium-term and long-term impact of COVID-19 in patients with cancer is not yet known. In this study, we aimed to describe the prevalence of COVID-19 sequelae and their impact on the survival of patients with cancer. We also aimed to describe patterns of resumption and modifications of systemic anti-cancer therapy following recovery from SARS-CoV-2 infection.

Methods: OnCovid is an active European registry study enrolling consecutive patients aged 18 years or older with a history of solid or haematological malignancy and who had a diagnosis of RT-PCR confirmed SARS-CoV-2 infection. For this retrospective study, patients were enrolled from 35 institutions across Belgium, France, Germany, Italy, Spain, and the UK. Patients who were diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, and entered into the registry at the point of data lock (March 1, 2021), were eligible for analysis. The present analysis was focused on COVID-19 survivors who underwent clinical reassessment at each participating institution. We documented prevalence of COVID-19 sequelae and described factors associated with their development and their association with post-COVID-19 survival, which was defined as the interval from post-COVID-19 reassessment to the patients' death or last follow-up. We also evaluated resumption of systemic anti-cancer therapy in patients treated within 4 weeks of COVID-19 diagnosis. The OnCovid study is registered in ClinicalTrials.gov, NCT04393974.

Findings: 2795 patients diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, were entered into the study by the time of the data lock on March 1, 2021. After the exclusion of ineligible patients, the final study population consisted of 2634 patients. 1557 COVID-19 survivors underwent a formal clinical reassessment after a median of 22·1 months (IQR 8·4-57·8) from cancer diagnosis and 44 days (28-329) from COVID-19 diagnosis. 234 (15·0%) patients reported COVID-19 sequelae, including respiratory symptoms (116 [49·6%]) and residual fatigue (96 [41·0%]). Sequelae were more common in men (vs women; p=0·041), patients aged 65 years or older (vs other age groups; p=0·048), patients with two or more comorbidities (vs one or none; p=0·0006), and patients with a history of smoking (vs no smoking history; p=0·0004). Sequelae were associated with hospitalisation for COVID-19 (p<0·0001), complicated COVID-19 (p<0·0001), and COVID-19 therapy (p=0·0002). With a median post-COVID-19 follow-up of 128 days (95% CI 113-148), COVID-19 sequelae were associated with an increased risk of death (hazard ratio [HR] 1·80 [95% CI 1·18-2·75]) after adjusting for time to post-COVID-19 reassessment, sex, age, comorbidity burden, tumour characteristics, anticancer therapy, and COVID-19 severity. Among 466 patients on systemic anti-cancer therapy, 70 (15·0%) permanently discontinued therapy, and 178 (38·2%) resumed treatment with a dose or regimen adjustment. Permanent treatment discontinuations were independently associated with an increased risk of death (HR 3·53 [95% CI 1·45-8·59]), but dose or regimen adjustments were not (0·84 [0·35-2·02]).

Interpretation: Sequelae post-COVID-19 affect up to 15% of patients with cancer and adversely affect survival and oncological outcomes after recovery. Adjustments to systemic anti-cancer therapy can be safely pursued in treatment-eligible patients.

Funding: National Institute for Health Research Imperial Biomedical Research Centre and the Cancer Treatment and Research Trust.
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http://dx.doi.org/10.1016/S1470-2045(21)00573-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8565932PMC
December 2021

Safety of systemic hormone replacement therapy in breast cancer survivors: a systematic review and meta-analysis.

Breast Cancer Res Treat 2022 Jan 3;191(2):269-275. Epub 2021 Nov 3.

Medical Oncology 2, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

Purpose: Symptoms of treatment-induced menopause negatively affect quality of life and adherence to endocrine therapy of breast cancer (BC) survivors. Nevertheless, the use of systemic hormone replacement therapy (HRT) to mitigate these symptoms may be associated with an increased risk of disease recurrence in these patients. This systematic review and meta-analysis aimed to assess the safety of systemic HRT on risk of disease recurrence in BC survivors.

Methods: A systematic search of PubMed up to April 20, 2021 was conducted to identify randomized controlled trials (RCTs) that investigated the risk of disease recurrence with the use of HRT in BC survivors. A random-effect model was applied to calculate the risk of recurrence, reported as pooled hazard ratio (HR) with 95% confidence intervals (CI). A subgroup analysis was performed to estimate the risk of recurrence according to hormone receptor status.

Results: Four RCTs were included in the meta-analysis (n = 4050 patients). Overall, 2022 patients were randomized to receive HRT (estrogen/progestogen combination or tibolone) and 2023 to the control group with placebo or no HRT. HRT significantly increased the risk of BC recurrence compared to placebo (HR 1.46, 95% CI 1.12-1.91, p = 0.006). At the subgroup analysis, the risk of BC recurrence with the use of HRT was significantly increased in patients with hormone receptor-positive disease (HR 1.8, 95% CI 1.15-2.82, p = 0.010) but not in those with hormone receptor-negative tumors (HR 1.19, 95% CI 0.80-1.77, p = 0.390).

Conclusion: Use of HRT was associated with a detrimental prognostic effect in BC survivors, particularly in those with hormone receptor-positive disease. Alternative interventions to mitigate menopause-related symptoms should be proposed.
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http://dx.doi.org/10.1007/s10549-021-06436-9DOI Listing
January 2022

Serum levels of VCAM-1 are associated with survival in patients treated with nivolumab for NSCLC.

Eur J Clin Invest 2022 Jan 22;52(1):e13668. Epub 2021 Aug 22.

First Clinic of internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.

Background: High circulating levels of cellular adhesion molecules (CAMs) in non-small cell lung cancer (NSCLC) have been supposed to act as a negative prognostic factor. Here, we explored the predictive role of pre-treatment levels of CAMs in previously treated patients receiving nivolumab for NSCLC.

Materials And Methods: Seventy one patients with advanced NSCLC, treated with nivolumab at the dose of 3 mg/kg every 14 days, were enrolled. Maximum follow-up time was 3 years. Serum levels of Vascular Cell Adhesion Molecule-1 (VCAM-1) and Intracellular Adhesion Molecule-1 (ICAM-1) were measured at baseline and before each nivolumab administration. Endpoints of the study were a composite outcome of survival ≥2 years or absence of disease progression at the end of the follow-up, and the overall survival.

Results: Composite outcome and overall survival were positively associated with VCAM-1 baseline levels and with the reduction of VCAM-1 during the treatment. After adjustment for potential confounders, the change in VCAM-1 serum levels during the treatment was an independent predictor of overall survival.

Conclusions: High baseline serum levels of VCAM-1 are associated with a longer survival in patients treated with nivolumab as second line treatment for NSCLC. Surviving patients experience also a significant reduction in CAMs expression during the treatment. Hence, CAMs might be promising prognostic factors in patients with NSCLC underoing immunotherapy.
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http://dx.doi.org/10.1111/eci.13668DOI Listing
January 2022

Heterogeneity of treatment effects in malignant pleural mesothelioma.

Lancet 2021 07;398(10297):301-302

Department of Oncology, University of Genova, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

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http://dx.doi.org/10.1016/S0140-6736(21)00882-5DOI Listing
July 2021

The Role of the Immune Metabolic Prognostic Index in Patients with Non-Small Cell Lung Cancer (NSCLC) in Radiological Progression during Treatment with Nivolumab.

Cancers (Basel) 2021 Jun 22;13(13). Epub 2021 Jun 22.

IRCCS Ospedale Policlinico San Martino, Nuclear Medicine, Largo Rosanna Benzi 10, 16132 Genoa, Italy.

An emerging clinical need is represented by identifying reliable biomarkers able to discriminate between responders and non-responders among patients showing imaging progression during the administration of immune checkpoints inhibitors for advanced non-small cell lung cancer (NSCLC). In the present study, we analyzed the prognostic power of peripheral-blood systemic inflammation indexes and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in this clinical setting. In 45 patients showing radiological progression (defined as RECIST 1.1 progressive disease) during Nivolumab administration, the following lab and imaging parameters were collected: neutrophil-to-lymphocyte ratio (NLR), derived-NLR (dNLR), lymphocyte-to-monocyte ratio (LMR), platelets-to-lymphocyte ratio (PLR), systemic inflammation index (SII), maximum standardized uptake value, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). MTV and SII independently predicted OS. Their combination in the immune metabolic prognostic index (IMPI) allowed the identification of patients who might benefit from immunotherapy continuation, despite radiological progression. The combination of FDG PET/CT volumetric data with SII also approximates the immune-metabolic response with respect to baseline, providing additional independent prognostic insights. In conclusion, the degree of systemic inflammation, the quantification of the metabolically active tumor burden, and their combination might disclose the radiological progression in NSCLC patients receiving Nivolumab.
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http://dx.doi.org/10.3390/cancers13133117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268031PMC
June 2021

VISTA: A Promising Target for Cancer Immunotherapy?

Immunotargets Ther 2021 22;10:185-200. Epub 2021 Jun 22.

Department of Internal Medicine and Medical Specialties (Di.M.I.), University of Genova, Genova, Italy.

Agents targeting the B7 family co-inhibitory receptors cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein-1 (PD-1), or its ligand (PD-L1), have a pivotal role in clinical practice. V-domain Ig suppressor of T-cell activation (VISTA) is a protein highly conserved between species, with a similar amino acid sequence to the B7 family members, characterized by a particularly structural homology to PD-1. It has been counted as an emerging target within the list of novel targetable immune checkpoints in oncology. Physiologically, VISTA exerts a regulatory function on the immune system at several levels, particularly by modulating T cells activation. Its altered activity plays a role in many autoimmune diseases, and its expression has been found to be prognostically implicated in different cancer types in preclinical models. We hereby present the main evidence on the value of VISTA as an immune checkpoint in solid and hematological malignancies. We also review its value as a potential target for cancer immunotherapy, by reporting the results of Phase I and II clinical trials assessing the use of drugs targeting VISTA. The complexity of its pathway, along with some unclear biological aspects concerning its molecular interactions, currently represent a limit to the applicability of VISTA as an effective biomarker for immunotherapy in oncology. A deeper characterization of this immune checkpoint may help defining its value within immune signatures of solid and hematological malignancies, and to design future therapeutic strategies.
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http://dx.doi.org/10.2147/ITT.S260429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235942PMC
June 2021

Emerging issues related to COVID-19 vaccination in patients with cancer.

Oncol Ther 2021 Jun 16:1-11. Epub 2021 Jun 16.

Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy.

Coronavirus disease 2019 (COVID-19) has resulted in millions of deaths globally. The pandemic has had a severe impact on oncology care and research. Patients with underlying cancer are more vulnerable to contracting COVID-19, and also have a more severe clinical course following the infection. The rollout of COVID-19 vaccines in many parts of the world has raised hopes of controlling the pandemic. In this editorial, the authors outline key characteristics of the currently approved COVID-19 vaccines, provide a brief overview of key emerging issues such as vaccine-induced immune thrombotic thrombocytopenia and SARS-CoV-2 variants of concern, and review the available data related to the efficacy and side effects of vaccinating patients with cancer.
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http://dx.doi.org/10.1007/s40487-021-00157-1DOI Listing
June 2021

Emerging issues related to COVID-19 vaccination in patients with cancer.

Oncol Ther 2021 Dec 16;9(2):255-265. Epub 2021 Jun 16.

Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy.

Coronavirus disease 2019 (COVID-19) has resulted in millions of deaths globally. The pandemic has had a severe impact on oncology care and research. Patients with underlying cancer are more vulnerable to contracting COVID-19, and also have a more severe clinical course following the infection. The rollout of COVID-19 vaccines in many parts of the world has raised hopes of controlling the pandemic. In this editorial, the authors outline key characteristics of the currently approved COVID-19 vaccines, provide a brief overview of key emerging issues such as vaccine-induced immune thrombotic thrombocytopenia and SARS-CoV-2 variants of concern, and review the available data related to the efficacy and side effects of vaccinating patients with cancer.
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http://dx.doi.org/10.1007/s40487-021-00157-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208766PMC
December 2021

Comparing the Gonadotoxicity of Multiple Breast Cancer Regimens: Important Understanding for Managing Breast Cancer in Pre-Menopausal Women.

Breast Cancer (Dove Med Press) 2021 24;13:341-351. Epub 2021 May 24.

Department of Medical Oncology, U.O.C Clinica Di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

Over the last several decades, improvements in breast cancer treatment have contributed to increased cure rates for women diagnosed with this malignancy. Consequently, great importance should be paid to the long-term side effects of systemic therapies. For young women (defined as per guideline ≤40 years at diagnosis) who undergo chemotherapy, one of the most impactful side effects on their quality of life is premature ovarian insufficiency (POI) leading to fertility-related problems and the side effects of early menopause. Regimens, type, and doses of chemotherapy, as well as the age of patients and their ovarian reserve at the time of treatment are major risk factors for treatment-induced POI. For these reasons, childbearing desire and preservation of ovarian function and/or fertility should be discussed with all premenopausal patients before planning the treatments. This manuscript summarizes the available fertility preservation techniques in breast cancer patients, the risk of treatment-induced POI with different anticancer treatments, and the possible procedures to prevent it. A special focus is paid to the role of oncofertility counseling, as a central part of the visit in this setting, during which the patient should receive all the information about the potential consequences of the disease and of the proposed treatment on her future life.
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http://dx.doi.org/10.2147/BCTT.S274283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164347PMC
May 2021

Mortality in adult patients with solid or hematological malignancies and SARS-CoV-2 infection with a specific focus on lung and breast cancers: A systematic review and meta-analysis.

Crit Rev Oncol Hematol 2021 Jul 27;163:103365. Epub 2021 May 27.

Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, Genova, Italy; Department of Medical Oncology, UOC Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy. Electronic address:

Background: A systematic review and meta-analysis was performed to estimate mortality in adult patients with solid or hematological malignancies and SARS-CoV-2 infection.

Methods: A systematic search of PubMed, up to 31 January 2021, identified publications reporting the case-fatality rate (CFR) among adult patients with solid or hematological malignancies and SARS-CoV-2 infection. The CFR, defined as the rate of death in this population, was assessed with a random effect model; 95% confidence intervals (CI) were calculated.

Results: Among 135 selected studies (N = 33,879 patients), the CFR was 25.4% (95% CI 22.9%-28.2%). At a sensitivity analysis including studies with at least 100 patients, the CFR was 21.9% (95% CI 19.1%-25.1%). Among COVID-19 patients with lung (N = 1,135) and breast (N = 1,296) cancers, CFR were 32.4% (95% CI 26.5%-39.6%) and 14.2% (95% CI 9.3%-21.8%), respectively.

Conclusions: Patients with solid or hematological malignancies and SARS-CoV-2 infection have a high probability of mortality, with comparatively higher and lower CFRs in patients with lung and breast cancers, respectively.
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http://dx.doi.org/10.1016/j.critrevonc.2021.103365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156831PMC
July 2021

Novel Emerging Molecular Targets in Non-Small Cell Lung Cancer.

Int J Mol Sci 2021 Mar 5;22(5). Epub 2021 Mar 5.

Department of Internal Medicine and Medical Specialties (Di.M.I.), University of Genoa, 16132 Genoa, Italy.

In the scenario of systemic treatment for advanced non-small cell lung cancer (NSCLC) patients, one of the most relevant breakthroughs is represented by targeted therapies. Throughout the last years, inhibitors of the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-Ros oncogene 1 (ROS1), and V-raf murine sarcoma viral oncogene homolog B (BRAF) have been approved and are currently used in clinical practice. However, other promising molecular drivers are rapidly emerging as therapeutic targets. This review aims to cover the molecular alterations with a potential clinical impact in NSCLC, including amplifications or mutations of the mesenchymal-epithelial transition factor (MET), fusions of rearranged during transfection (RET), rearrangements of the neurotrophic tyrosine kinase (NTRK) genes, mutations of the Kirsten rat sarcoma viral oncogene (KRAS) and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), as well as amplifications or mutations of human epidermal growth factor receptor 2 (HER2). Additionally, we summarized the current status of targeted agents under investigation for such alterations. This revision of the current literature on emerging molecular targets is needed as the evolving knowledge on novel actionable oncogenic drivers and targeted agents is expected to increase the proportion of patients who will benefit from tailored therapeutic approaches.
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http://dx.doi.org/10.3390/ijms22052625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961376PMC
March 2021

Safety and efficacy of immune checkpoint inhibitors in non-small-cell lung cancer: focus on challenging populations.

Immunotherapy 2021 04 25;13(6):509-525. Epub 2021 Feb 25.

UOC Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, 16100 Genova, Italy.

In recent years, immune-checkpoint inhibitors (ICIs) have represented one of the major breakthroughs in advanced non-small cell lung cancer treatment scenario. However, enrollment in registering clinical trials is usually restricted, since frail patients (i.e., elderly, individuals with poor performance status and/or active brain metastases), as well as patients with chronic infections or who take concurrent medications, such as steroids, are routinely excluded. Thus, safety and efficacy of ICIs for these subgroups have not been adequately assessed in clinical trials, although these populations often occur in clinical practice. We reviewed the available data regarding the use of ICIs in these 'special' populations, including a focus on the issues raised by the administration of immunotherapy in lung cancer patients infected with Sars-Cov-2.
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http://dx.doi.org/10.2217/imt-2020-0226DOI Listing
April 2021

Expected Medium- and Long-Term Impact of the COVID-19 Outbreak in Oncology.

JCO Glob Oncol 2021 02;7:162-172

Medical Oncology, CHU Sart Tilman Liège and University of Liège, Liège, Belgium.

Purpose: The COVID-19 pandemic has affected healthcare systems globally, leading to reorganization of medical activities. We performed an international survey aimed to investigate the medium- and long-term impact on oncology units.

Materials And Methods: An 82-item survey was distributed from June 17 to July 14, 2020 among medical oncologists worldwide.

Results: One hundred nine medical oncologists from 18 countries in Europe (n = 93), United States (n = 5), and Latin America (n = 11) answered the survey. A systematic tracing of COVID-19-positive patients was continued in the postacute phase by 77.1% of the centers; 64.2% of the respondents participated in a local registry and 56% in international or national registries of infected patients. Treatment adaptations were introduced, and surgery was the most affected modality being delayed or canceled in more than 10% of patients in 34% of the centers, whereas early cessation of palliative treatment was reported in 32.1% of the centers; 64.2% of respondents reported paying attention to avoid undertreatments. The use of telemedicine has been largely increased. Similarly, virtual tools are increasingly used particularly for medical education and international or national or multidisciplinary meetings. 60.6% of the participants reduced clinical activity, and 28.4% compensated by increasing their research activity. Significant reduction of clinical trial activities is expected in 37% of centers this year. The well-being of healthcare staff would not recover by the end of the year according to 18% of the participants.

Conclusion: The COVID-19 outbreak has had a major impact on oncologic activity, which will persist in the future, irrespective of geographical areas.
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http://dx.doi.org/10.1200/GO.20.00589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081548PMC
February 2021

Update on the Management of Breast Cancer during Pregnancy.

Cancers (Basel) 2020 Dec 3;12(12). Epub 2020 Dec 3.

Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, 16132 Genova, Italy.

The diagnosis of breast cancer during pregnancy represents a challenging situation for the patient, her caregivers and physicians. Pregnancy adds complexity to oncological treatment planning, as many therapies can be potentially dangerous to the fetus. Therefore, a multidisciplinary approach is needed to offer a proper care for obtaining the best possible outcomes for the mother and the future child. Breast surgery is feasible throughout the pregnancy while radiotherapy should be postponed after delivery. Administration of chemotherapy is considered safe and can be given during the second and third trimesters, while it is contraindicated in the first trimester due to the high risk of fetal malformations. Endocrine therapy and targeted agents are not recommended during the whole pregnancy period; however, limited data are available on the use of the majority of new anticancer drugs in this context. The aim of the current review is to provide an update on the current state of art about the management of women diagnosed with breast cancer during pregnancy.
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http://dx.doi.org/10.3390/cancers12123616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761659PMC
December 2020

Radiomic Detection of EGFR Mutations in NSCLC.

Cancer Res 2021 02 4;81(3):724-731. Epub 2020 Nov 4.

UOC Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

Radiomics is defined as the use of automated or semi-automated post-processing and analysis of multiple features derived from imaging exams. Extracted features might generate models able to predict the molecular profile of solid tumors. The aim of this study was to develop a predictive algorithm to define the mutational status of EGFR in treatment-naïve patients with advanced non-small cell lung cancer (NSCLC). CT scans from 109 treatment-naïve patients with NSCLC (21 -mutant and 88 -wild type) underwent radiomics analysis to develop a machine learning model able to recognize -mutant from -WT patients via CT scans. A "test-retest" approach was used to identify stable radiomics features. The accuracy of the model was tested on an external validation set from another institution and on a dataset from the Cancer Imaging Archive (TCIA). The machine learning model that considered both radiomic and clinical features (gender and smoking status) reached a diagnostic accuracy of 88.1% in our dataset with an AUC at the ROC curve of 0.85, whereas the accuracy values in the datasets from TCIA and the external institution were 76.6% and 83.3%, respectively. Furthermore, 17 distinct radiomics features detected at baseline CT scan were associated with subsequent development of T790M during treatment with an EGFR inhibitor. In conclusion, our machine learning model was able to identify -mutant patients in multiple validation sets with globally good accuracy, especially after data optimization. More comprehensive training sets might result in further improvement of radiomics-based algorithms. SIGNIFICANCE: These findings demonstrate that data normalization and "test-retest" methods might improve the performance of machine learning models on radiomics images and increase their reliability when used on external validation datasets.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-0999DOI Listing
February 2021

Mortality in patients with cancer and coronavirus disease 2019: A systematic review and pooled analysis of 52 studies.

Eur J Cancer 2020 11 2;139:43-50. Epub 2020 Sep 2.

Institut Jules Bordet, Brussels, Belgium; Université Libre de Bruxelles (U.L.B.), Brussels, Belgium. Electronic address:

Background: Patients with coronavirus disease 2019 (COVID-19) who have underlying malignancy have a higher mortality rate compared with those without cancer, although the magnitude of such excess risk is not clearly defined. We performed a systematic review and pooled analysis to provide precise estimates of the mortality rate among patients with both cancer and COVID-19.

Methods: A systematic literature search involving peer-reviewed publications, preprints and conference proceedings up to July 16, 2020, was performed. The primary end-point was the case fatality rate (CFR), defined as the rate of death among patients with cancer and COVID-19. The CFR was assessed with a random effects model, which was used to derive a pooled CFR and its 95% confidence interval (CI).

Results: Fifty-two studies, involving a total of 18,650 patients with both COVID-19 and cancer, were selected for the pooled analysis. A total of 4243 deaths were recorded in this population. The probability of death was 25.6% (95% CI: 22.0%-29.5%; I = 48.9%) in this patient population.

Conclusions: Patients with cancer who develop COVID-19 have high probability of mortality. Appropriate and aggressive preventive measures must be taken to reduce the risk of COVID-19 in patients with cancer and to optimally manage those who do contract the infection.
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http://dx.doi.org/10.1016/j.ejca.2020.08.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467090PMC
November 2020

Burning Questions in the Oncofertility Counseling of Young Breast Cancer Patients.

Breast Cancer (Auckl) 2020 4;14:1178223420954179. Epub 2020 Sep 4.

Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy.

The improved prognosis of breast cancer patients makes survivorship issues an area of crucial importance. In this regard, an increased attention is needed toward the development of potential anticancer treatment-related long-term side-effects, including gonadal failure and infertility in young women. Therefore, fertility preservation and family planning are crucial issues to be addressed in all young women of reproductive age with newly diagnosed cancer. Despite a growing availability of data on the efficacy and safety of fertility preservation options and the fact that conceiving after prior history of breast cancer has become more accepted over time, there are still several gray zones in this field so that many physicians remain uncomfortable to deal with these topics. The purpose of this review is to answer some of the most controversial questions frequently asked by patients during their oncofertility counseling, in order to provide a detailed and up-to-date overview on the evidence available in this field to physicians involved in the care of young women with breast cancer.
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http://dx.doi.org/10.1177/1178223420954179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476336PMC
September 2020

Oncological care organisation during COVID-19 outbreak.

ESMO Open 2020 08;5(4)

Department of Medical Oncology, CHU de Liège, Liege, Belgium.

Background: COVID-19 appeared in late 2019, causing a pandemic spread. This led to a reorganisation of oncology care in order to reduce the risk of spreading infection between patients and healthcare staff. Here we analysed measures taken in major oncological units in Europe and the USA.

Methods: A 46-item survey was sent by email to representatives of 30 oncological centres in 12 of the most affected countries. The survey inquired about preventive measures established to reduce virus spread, patient education and processes employed for risk reduction in each oncological unit.

Results: Investigators from 21 centres in 10 countries answered the survey between 10 April and 6 May 2020. A triage for patients with cancer before hospital or clinic visits was conducted by 90.5% of centres before consultations, 95.2% before day care admissions and in 100% of the cases before overnight hospitalisation by means of phone calls, interactive online platforms, swab test and/or chest CT scan. Permission for caregivers to attend clinic visits was limited in many centres, with some exceptions (ie, for non-autonomous patients, in the case of a new diagnosis, when bad news was expected and for terminally ill patients). With a variable delay period, the use of personal protective equipment was unanimously mandatory, and in many centres, only targeted clinical and instrumental examinations were performed. Telemedicine was implemented in 76.2% of the centres. Separated pathways for COVID-19-positive and COVID-19-negative patients were organised, with separate inpatient units and day care areas. Self-isolation was required for COVID-19-positive or symptomatic staff, while return to work policies required a negative swab test in 76.2% of the centres.

Conclusion: Many pragmatic measures have been quickly implemented to deal with the health emergency linked to COVID-19, although the relative efficacy of each intervention should be further analysed in large observational studies.
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http://dx.doi.org/10.1136/esmoopen-2020-000853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451457PMC
August 2020

Current State of the Art in the Adjuvant Systemic Treatment of Premenopausal Patients With Early Breast Cancer.

Clin Med Insights Oncol 2020 29;14:1179554920931816. Epub 2020 Jun 29.

Department of Medical Oncology, U.O.C Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

Breast cancer is the most frequent malignancy diagnosed in premenopausal women. In this age group, breast tumors tend to be diagnosed at more advanced stages and to harbor more aggressive biological features. In addition, specific age-related issues including genetic counseling, fertility preservation, impact on social and couple relationships, working life, and management of long-term side effects should be considered highly relevant when managing early breast cancer in premenopausal women. Therefore, the care of these patients is particularly complex and a multidisciplinary approach is mandatory. The present review summarizes the current state of art in the adjuvant systemic treatment of premenopausal women with early breast cancer focusing on the optimal chemotherapy, endocrine therapy, and targeted therapy approaches in this specific patient population.
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http://dx.doi.org/10.1177/1179554920931816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325453PMC
June 2020

Assessing the Impact of the COVID-19 Outbreak on the Attitudes and Practice of Italian Oncologists Toward Breast Cancer Care and Related Research Activities.

JCO Oncol Pract 2020 11 23;16(11):e1304-e1314. Epub 2020 Jun 23.

Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy.

Purpose: To investigate the impact of the COVID-19 outbreak on the attitudes and practice of Italian oncologists toward breast cancer care and related research activities.

Methods: A 29-question anonymous online survey was sent by e-mail to members of the Italian Association of Medical Oncology and the Italian Breast Cancer Study Group on April 3, 2020. Only medical oncologists (both those in training and specialists) were invited to complete the questionnaire.

Results: Out of 165 responding oncologists, 121 (73.3.%) worked in breast units. In the (neo)adjuvant setting, compared with before the emergency, fewer oncologists adopted weekly paclitaxel (68.5% 93.9%) and a dose-dense schedule for anthracycline-based chemotherapy (43% 58.8%) during the COVID-19 outbreak. In the metastatic setting, compared with before the emergency, fewer oncologists adopted first-line weekly paclitaxel for HER2-positive disease (41.8% 53.9%) or CDK4/6 inhibitors for luminal tumors with less-aggressive characteristics (55.8% 80.0%) during the COVID-19 outbreak. A significant change was also observed in delaying the timing for monitoring therapy with CDK4/6 inhibitors, assessing treatment response with imaging tests, and flushing central venous devices. Clinical research and scientific activities were reduced in 80.3% and 80.1% of respondents previously implicated in these activities, respectively.

Conclusion: Medical oncologists face many challenges in providing cancer care during the COVID-19 outbreak. Although most of the changes in their attitudes and practice were reasonable responses to the current health care emergency without expected major negative impact on patient outcomes, some potentially alarming signals of undertreatment were observed.
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http://dx.doi.org/10.1200/OP.20.00297DOI Listing
November 2020

New emerging targets in cancer immunotherapy: the role of VISTA.

ESMO Open 2020 06;4(Suppl 3):e000683

Oncology Department, Thoracic Oncology, University of Turin & San Luigi Hospital, Orbassano (Turin), Italy.

The immune surveillance system is complex and regulated by different actors. Programmed death protein-ligand 1 (PD-L1), the only approved biomarker in clinical practice, has proven to be imperfect in selecting patients to immune checkpoint inhibitors treatment. Therefore, new biomarkers, and new therapeutic targets, are needed to maximise the efficacy of immunotherapy. V-domain Ig Suppressor of T-cell Activation (VISTA) is a programmed death protein-1 (PD-1) homolog expressed on T cells and on antigen-presenting cells, which regulates processes of activation and repression of the immune system with not yet completely clarified mechanisms. Its blockage has demonstrated in vitro and in vivo antitumour activity. The clinical research of VISTA antagonists is ongoing. Particularly, CA-170, an orally delivered dual inhibitor of VISTA and PD-L1, has shown to have clinical efficacy in phase I and II clinical trials in different advanced solid tumour types. Further data are needed to define whether this drug class can become a new therapeutic option for patients with VISTA expressing cancers.
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http://dx.doi.org/10.1136/esmoopen-2020-000683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305420PMC
June 2020

Italian survey on managing immune checkpoint inhibitors in oncology during COVID-19 outbreak.

Eur J Clin Invest 2020 Sep 5;50(9):e13315. Epub 2020 Jul 5.

Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy.

Background: During COVID-19 outbreak, oncological care has been reorganized. Patients with cancer have been reported to experience a more severe COVID-19 syndrome; moreover, there are concerns of a potential interference between immune checkpoint inhibitors (ICIs) and SARS-CoV-2 pathogenesis.

Materials And Methods: Between 6 and 16 May 2020, a 22-item survey was sent to Italian physicians involved in administering ICIs. It aimed at exploring the perception about SARS-CoV-2-related risks in cancer patients receiving ICIs, and the attitudes towards their management.

Results: The 104 respondents had a median age of 35.5 years, 58.7% were females and 71.2% worked in Northern Italy. 47.1% of respondents argued a synergism between ICIs and SARS-CoV-2 pathogenesis leading to worse outcomes, but 97.1% would not deny an ICI only for the risk of infection. During COVID-19 outbreak, to reduce hospital visits, 55.8% and 30.8% opted for the highest labelled dose of each ICI and/or, among different ICIs for the same indication, for the one with the longer interval between cycles, respectively. 53.8% of respondents suggested testing for SARS-CoV-2 every cancer patient candidate to ICIs. 71.2% declared to manage patients with onset of dyspnoea and cough as infected by SARS-CoV-2 until otherwise proven; however, 96.2% did not reduce the use of steroids to manage immune-related toxicities. The administration of ICIs in specific situations for different cancer types has not been drastically conditioned.

Conclusions: These results highlight the uncertainties around the perception of a potential interference between ICIs and COVID-19, supporting the need of focused studies on this topic.
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http://dx.doi.org/10.1111/eci.13315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323025PMC
September 2020

Call for ensuring cancer care continuity during COVID-19 pandemic.

ESMO Open 2020 05;5(3):e000783

Department of Internal Medicine and Medical Specialties (Di.M.I.), School of Medicine, University of Genoa, Genoa, Italy; Department of Medical Oncology, U.O.C. Oncologia Medica 2, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

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http://dx.doi.org/10.1136/esmoopen-2020-000783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228560PMC
May 2020

Precision Medicine for NSCLC in the Era of Immunotherapy: New Biomarkers to Select the Most Suitable Treatment or the Most Suitable Patient.

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

Lung Cancer Unit, Medical Oncology 2, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy.

In recent years, the evolution of treatments has made it possible to significantly improve the outcomes of patients with non-small cell lung cancer (NSCLC). In particular, while molecular targeted therapies are effective in specific patient sub-groups, immune checkpoint inhibitors (ICIs) have greatly influenced the outcomes of a large proportion of NSCLC patients. While nivolumab activity was initially assessed irrespective of predictive biomarkers, subsequent pivotal studies involving other PD-1/PD-L1 inhibitors in pre-treated advanced NSCLC (atezolizumab within the OAK study and pembrolizumab in the Keynote 010 study) reported the first correlations between clinical outcomes and PD-L1 expression. However, PD-L1 could not be sufficient on its own to select patients who may benefit from immunotherapy. Many studies have tried to discover more precise markers that are derived from tumor tissue or from peripheral blood. This review aims to analyze any characteristics of the immunogram that could be used as a predictive biomarker for response to ICIs. Furthermore, we describe the most important genetic alteration that might predict the activity of immunotherapy.
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http://dx.doi.org/10.3390/cancers12051125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281184PMC
April 2020

Association Between Response to Nivolumab Treatment and Peripheral Blood Lymphocyte Subsets in Patients With Non-small Cell Lung Cancer.

Front Immunol 2020 7;11:125. Epub 2020 Feb 7.

Department of Experimental Medicine (DiMES) and Center of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy.

Immune checkpoint blockade represents a major breakthrough in advanced non-small cell lung cancer (NSCLC) therapy. However, success is limited to a subset of patients and there is a critical need to identify robust biomarkers associated with clinical response. In this study, we assessed whether pre-existing immunological characteristics, as well as immune parameters measured during treatment, might provide such clinical guidance. We studied blood samples collected at baseline and during treatment in a cohort of advanced NSCLC patients ( = 74) treated with nivolumab. Several lymphocyte subsets and biomarkers were then correlated with overall survival (OS) as well as clinical response, assessed using RECIST criteria. We found that patients characterized by longer OS had higher levels of CD3, CD4, and CD8 T cells but lower levels of NK cells at baseline. Moreover, that they displayed a statistically significant lower expression of PD-1 on both CD3 and CD8 T cells ( = 0.013 and = 0.033, respectively). The pre-treatment level of exhausted T cells (CD8PD1Eomes) was significantly lower in patients with controlled disease (CD), defined as partial response (PR), and stable disease (SD), compared to those with progressive disease (PD) ( = 0.046). In CD patients, the frequency of exhausted CD8 T cells further decreased during treatment cycles ( = <0.0001, = 0.0032, and = 0.0239, respectively). In conclusion, our results suggest that the distribution of lymphocyte subsets and expression of PD-1 on T cells before treatment may help predict the outcome of anti-PD-1 treatment in NSCLC patients. In addition, assessing the initial levels of exhausted T cells as well as their decrease upon treatment may also predict response and clinical outcome.
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http://dx.doi.org/10.3389/fimmu.2020.00125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018763PMC
March 2021

ADP ribose polymerase inhibitors for treating non-small cell lung cancer: new additions to the pharmacotherapeutic armamentarium.

Expert Opin Pharmacother 2020 Apr 19;21(6):679-686. Epub 2020 Feb 19.

Lung Cancer Unit, IRCCS Ospedale Policlinico San Martino , Genoa, Italy.

Introduction: Poly (ADP-ribose) polymerase inhibitors (PARPi) are already part of the armamentarium of drugs available against ovarian and breast cancer. There is less data available on the efficacy of these drugs in the treatment of non-small cell lung cancer (NSCLC).

Areas Covered: The authors have analyzed the preclinical studies that justified the use of PARPi in NSCLC. They then evaluate the in vivo efficacy of the combination of these drugs with chemotherapy, radiotherapy, and immunotherapy.

Expert Opinion: Data from clinical trials available to date have discouraged the use of PARPi in association with chemotherapy or radiotherapy in NSCLC. The knowledge available to date opens the door to the use of PARPi in association with immunotherapy. In fact, the activity of these drugs would not be based only on direct cytotoxic action, but also on the modification of the intra-tumor microenvironment, in particular by increasing the expression of PD-L1 on tumor cells. This action might potentially enhance available treatments with a modest increase in toxicity.
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http://dx.doi.org/10.1080/14656566.2020.1724283DOI Listing
April 2020

Targeted therapy of oncogenic-driven advanced non-small cell lung cancer: recent advances and new perspectives.

Expert Rev Respir Med 2020 04 17;14(4):367-383. Epub 2020 Jan 17.

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

: The discovery of new actionable oncogenic drivers has led to the development of effective antineoplastic targeted agents in advanced non-small cell lung cancer (NSCLC). While the role of inhibitors of the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1 (ROS1) is widely acknowledged, other oncogenic drivers can be exploited as therapeutic targets.: Our aim is to explore the therapeutic role of actionable oncogenic drivers, including well-established targets, such as EGFR, ALK, and ROS1, as well as less frequent drivers for which specific agents are at different stages of clinical development, such as MET, RET, BRAF, and NTRK.: Targeted agents have revolutionized the management of advanced NSCLC; in particular, novel agents and combinations targeting EGFR, ALK, ROS1, BRAF, and NTRK have become available and others are on their way. The molecularly driven approach to advanced NSCLC requires adequate tumor samples, as well as increasingly complex technologies designed to assess multiple targets on limited available tissue in an acceptable time-span. Furthermore, the role of other novel antineoplastic approaches, such as immunotherapy with immune checkpoint inhibitors, needs to be elucidated in the case of patients with oncogenic-driven NSCLC.
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http://dx.doi.org/10.1080/17476348.2020.1714441DOI Listing
April 2020
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