Severe Cardiac Toxicity Induced by Cancer Therapies Requiring Intensive Care Unit Admission

Montisci, Andrea; Palmieri, Vittorio; Liu, Jennifer E.; Vietri, Maria Teresa; Cirri, Silvia; Donatelli, Francesco; Napoli, Claudio

doi:10.3389/fcvm.2021.713694

Cited by 15 publications

(14 citation statements)

References 146 publications

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“…Moreover, a clinical trial of anti-PD-1 antibody reported a positive response in PDAC patients with MMR alterations, although further studies in a larger patient cohort are needed [ 17 ]. Of note, many novel therapies have cardiac toxicity that need to be considered [ 62 , 63 , 64 , 65 ]…”

Section: Discussionmentioning

confidence: 99%

Pancreatic Cancer with Mutation in BRCA1/2, MLH1, and APC Genes: Phenotype Correlation and Detection of a Novel Germline BRCA2 Mutation

Vietri

Goletti

Caliendo

et al. 2022

Genes

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Pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of cancer death worldwide; most of cases are sporadic, however about 5% to 10% report a hereditary predisposition. Several hereditary syndromes have been associated with familial pancreatic cancer (FPC) onset, including hereditary breast and ovarian cancer syndrome (HBOC), Lynch syndrome (LS), Familial atypical multiple mole melanoma (FAMMM), Familial adenomatous polyposis (FAP), Li–Fraumeni syndrome (LFS),Peutz–Jeghers syndrome (PJS), and Hereditary pancreatitis (HP).The aim of this study was to determine the mutational status of a cohort of 56 HBOC families, 7 LS families, 3 FAP and FAMMM families, and 1 LFS family with at least one case of PDAC. Mutation analysis of BRCA1/2, ATM, CHEK2, PALB2, RAD51C, RAD51D, NBN, CDH1, TP53, MLH1, MSH2, MSH6, and PMS2genes, showedmutation in BRCA1/2, MLH1, and APC genes. We founda high mutation rate in patients belong HBOC and LS families, with a percentage of 28.6% in both syndromes and prevalence in HBOC of BRCA2 mutations with one case of double mutation in BRCA2 gene. In FAP family, we found a pathogenic mutation in APC gene in 1/3 families. We observed an early onset of PDAC and a lower survival in PDAC patients belonging to mutated families, while no evidence of possible pancreatic cancer cluster regions was found. Moreover, we identified a novel BRCA2 germline mutation, c.5511delT (p.Phe1837LeufsX3), not reported in any database, that segregated with disease in HBOC patients. Mutational analysis was extended to family membersof mutated patients, both healthy and cancer affected, which revealed 23 unaffected family members that inherited the proband’s mutation. Although correlative by its nature, the presence of a BRCA mutation in PDAC patients may have benefits in terms of optimized treatment and longer outcome.

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Section: Discussionmentioning

confidence: 99%

Pancreatic Cancer with Mutation in BRCA1/2, MLH1, and APC Genes: Phenotype Correlation and Detection of a Novel Germline BRCA2 Mutation

Vietri

Goletti

Caliendo

et al. 2022

Genes

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“…This led the Food and Drug Administration (FDA) to approve the drug Olaparib for patients with mCRPC who harbor mutation in BRCA1/BRCA2 and/or ATM genes. MMR-mutated patients can benefit from immunotherapy, with the FDA having recently approved PD-L1 inhibitor pembrolizumab (KEYTRUDA) for the treatment of patients with microsatellite instability-high (MSI-H)/MMR-deficient [ 45 , 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Increased Risk of Hereditary Prostate Cancer in Italian Families with Hereditary Breast and Ovarian Cancer Syndrome Harboring Mutations in BRCA and in Other Susceptibility Genes

Goletti

Caliendo

Tzioni

et al. 2022

Genes

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Hereditary prostate cancer (HPCa) has the highest heritability of any cancer in men. Interestingly, it occurs in several hereditary syndromes, including breast and ovarian cancer (HBOC) and Lynch syndrome (LS). Several gene mutations related to these syndromes have been identified as biomarkers in HPCa. The goal of this study was to screen for germline mutations in susceptibility genes by using a multigene panel, and to subsequently correlate the results with clinical and laboratory parameters. This was undertaken in 180 HBOC families, which included 217 males with prostate cancer (PCa). Mutational analysis was further extended to 104 family members of mutated patients. Screening of HBOC families revealed that 30.5% harbored germline mutations in susceptibility genes, with 21.6% harboring pathogenic variants (PVs) and 8.9% having variants of uncertain significance (VUS). We found PVs at similar frequency in BRCA1 and BRCA2 genes (8.8% and 9.4%, respectively), while 0.56% of PVs were present in well-established susceptibility genes PALB2, TP53 and RAD51C. Moreover, 0.56% of monoallelic PVs were present in MUTYH, a gene whose function in tumorigenesis in the context of PCa is still unclear. Finally, we reported double heterozygosity (DH) in BRCA1/2 genes in a single family, and found double mutation (DM) present in BRCA2 in a separate family. There was no significant difference between the mean age of onset of PCa in HBOC families with or without germline mutations in susceptibility genes, while the mean survival was highest in mutated patients compared to wild type. Furthermore, PCa is the second most recurrent cancer in our cohort, resulting in 18% of cases in both mutated and non-mutated families. Our investigation shows that PVs were located mostly in the 3′ of BRCA1 and BRCA2 genes, and in BRCA2, most PVs fell in exon 11, suggesting a mutation cluster region relating to risk of HPCa. A total of 65 family members inherited the proband’s mutation; of these, 24 developed cancer, with 41 remaining unaffected.

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“…Among chemotherapy drugs that are most likely to induce cardiotoxicity, anthracyclines (e.g., doxorubicin) have been used since the late 1950s to treat solid and hematologic cancers such as lymphoma, leukemia, sarcoma, and breast cancer. Anthracyclines are associated with several cardiovascular toxicities, including dilated cardiomyopathy with left ventricular systolic dysfunction leading to heart failure ( 59 ). In an Italian prospective study assessing more than 2,600 patients, the overall incidence of anthracycline-induced cardiotoxicity was 9% ( 60 ).…”

Section: Epidemiologymentioning

confidence: 99%

“…Of note, a number of anti-HER2 agents are approved in HER2-positive breast [e.g., monoclonal antibodies, antibody-drug conjugates, and tyrosine kinase inhibitors (TKIs)] and gastric cancer (e.g., monoclonal antibodies, antibody-drug conjugates) ( 67 ). Among them, trastuzumab, a targeted therapy to the HER2 receptor in breast cancer and all its derivatives such as trastuzumab emtansine or trastuzumab deruxtecan, can be responsible for acute cardiac toxicity, which is usually reversible as opposed to the aforementioned anthracyclines ( 59 ). For patients receiving cardiotoxic chemotherapy, such as anthracycline or other anti-HER2 therapy, guidelines recommend a three-monthly left ventricular ejection fraction monitoring ( 68 ).…”

Section: Epidemiologymentioning

confidence: 99%

“…For instance, a full code status should be warranted in CS cases of newly diagnosed malignancies, PE in CPs with good performance status and no frailty, acute cardiac toxicity after complete cancer remission, and clinical response undetermined or still unpredictable ( 59 ). If needed, short-term MCS for refractory CS should be implemented before the onset of multi-organ failure in selected patients as a strategy to buy time for cardiac recovery (bridge-to-recovery strategy) or bridge-to-other therapies (bridge-to-decision strategy) ( 134 ).…”

Section: General Issues For Consideration Regarding Cardiogenic Shock...mentioning

confidence: 99%

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Cardiogenic shock among cancer patients

Curtiaud

Delmas

Gantzer

et al. 2022

Front. Cardiovasc. Med.

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Sophisticated cancer treatments, cardiovascular risk factors, and aging trigger acute cardiovascular diseases in an increasing number of cancer patients. Among acute cardiovascular diseases, cancer treatment, as well as the cancer disease itself, may induce a cardiogenic shock. Although increasing, these cardiogenic shocks are still relatively limited, and their management is a matter of debate in cancer patients. Etiologies that cause cardiogenic shock are slightly different from those of non-cancer patients, and management has some specific features always requiring a multidisciplinary approach. Recent guidelines and extensive data from the scientific literature can provide useful guidance for the management of these critical patients. Even if no etiologic therapy is available, maximal intensive supportive measures can often be justified, as most of these cardiogenic shocks are potentially reversible. In this review, we address the major etiologies that can lead to cardiogenic shock in cancer patients and discuss issues related to its management.

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Severe Cardiac Toxicity Induced by Cancer Therapies Requiring Intensive Care Unit Admission

Abstract: Graphical Abstract

Cited by 15 publications

References 146 publications

Pancreatic Cancer with Mutation in BRCA1/2, MLH1, and APC Genes: Phenotype Correlation and Detection of a Novel Germline BRCA2 Mutation

Pancreatic Cancer with Mutation in BRCA1/2, MLH1, and APC Genes: Phenotype Correlation and Detection of a Novel Germline BRCA2 Mutation

Increased Risk of Hereditary Prostate Cancer in Italian Families with Hereditary Breast and Ovarian Cancer Syndrome Harboring Mutations in BRCA and in Other Susceptibility Genes

Cardiogenic shock among cancer patients

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