ABSTRACT

Oncologic patients are subjected to four major treatment types: surgery, radiotherapy, chemotherapy, and immunotherapy. All nonsurgical forms of cancer management are known to potentially violate the structural and functional integrity of the cardiovascular system. The prevalence and severity of cardiotoxicity and vascular abnormalities led to the emergence of a clinical subdiscipline, called cardiooncology. This relatively new, but rapidly expanding area of knowledge, primarily focuses on clinical observations linking the adverse effects of cancer therapy with deteriorated quality of life of cancer survivors and their increased morbidity and mortality. Cellular and molecular determinants of these relations are far less understood, mainly because of several unsolved paths and contradicting findings in the literature. In this article, we provide a comprehensive view of the cellular and molecular etiology of cardiooncology. We pay particular attention to various intracellular processes that arise in cardiomyocytes, vascular endothelial cells, and smooth muscle cells treated in experimentally-controlled conditions in vitro and in vivo with ionizing radiation and drugs representing diverse modes of anti-cancer activity.

PMID:37221467 | PMC:PMC10207659 | DOI:10.1186/s11658-023-00451-y

20:57

PubMed articles on: Cardio-Oncology

Severe sotorasib-related hepatotoxicity and non-liver adverse events associated with sequential anti-PD(L)1 and sotorasib therapy in KRASG12C-mutant lung cancer

J Thorac Oncol. 2023 May 20:S1556-0864(23)00572-5. doi: 10.1016/j.jtho.2023.05.013. Online ahead of print.

ABSTRACT

INTRODUCTION: Sequential anti-PD-(L)1 followed by small targeted therapy use is associated with increased prevalence of adverse events (AEs) in non-small cell lung cancer (NSCLC). KRASG12C inhibitor sotorasib may trigger severe immune-mediated hepatotoxicity when used in sequence or in combination with anti-PD-(L)1. This study was designed to address whether sequential anti-PD-(L)1 and sotorasib therapy increases the risk of hepatotoxicity and other AEs.

METHODS: This is a multicenter, retrospective study of consecutive advanced KRASG12C-mutant NSCLC treated with sotorasib outside clinical trials in 16 French medical centers. Patient records were reviewed to identify sotorasib-related AEs (NCI-CTCAE v5.0). Grade 3 and higher AE was considered as severe. Sequence group was defined as patients who received an anti-PD-(L)1 as last line of treatment before sotorasib initiation and control group as patients who did not receive an anti-PD-(L)1 as last line of treatment before sotorasib initiation.

RESULTS: We identified 102 patients who received sotorasib, including 48 (47%) in sequence group and 54 (53%) in control group. Patients in control group received an anti-PD-(L)1 followed by at least one treatment regimen before sotorasib in 87% of the cases or did not receive an anti-PD-(L)1 at any time before sotorasib in 13% of the cases. Severe sotorasib-related AEs were significantly more frequent in sequence group compared to control group (50% vs 13%, p<0.001).<0.001).

CONCLUSIONS: Sequential anti-PD-(L)1 and sotorasib therapy is associated with a significantly increased risk of severe sotorasib-related hepatotoxicity and severe non-liver AEs. We suggest avoiding starting sotorasib within 30 days from the last anti-PD-(L)1 infusion.

PMID:37217096 | DOI:10.1016/j.jtho.2023.05.013

20:57

PubMed articles on: Cardio-Oncology

Diastolic function assessment with left atrial strain in long-term survivors of childhood acute lymphoblastic leukemia

Rev Esp Cardiol (Engl Ed). 2023 May 20:S1885-5857(23)00138-X. doi: 10.1016/j.rec.2023.05.001. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Survivors of childhood cancer might be at increased risk of diastolic dysfunction at follow-up due to exposure to cardiotoxic treatment. Although assessment of diastolic function is challenging in this relatively young population, left atrial strain might provide a novel insight in this evaluation. Our aim was to examine diastolic function in a cohort of long-term survivors of childhood acute lymphoblastic leukemia by using left atrial strain and conventional echocardiographic parameters.

METHODS: Long-term survivors who were diagnosed at a single center between 1985 and 2015 and a control group of healthy siblings were recruited. Conventional diastolic function parameters and atrial strain were compared, and the latter was measured during the 3 atrial phases: reservoir (PALS), conduit (LACS) and contraction (PACS). Inverse probability of treatment weighting was used to account for differences between the groups.

RESULTS: We analyzed 90 survivors (age, 24.6 ± 9.7 years, time since diagnosis 18 [11-26] years) and 58 controls. PALS and LACS were significantly reduced compared with the control group: 46.4 ± 11.2 vs 52.1 ± 11.7; P = .003 and 32.5 ± 8.8 vs 38.2 ± 9.3; P = .003, respectively. Conventional diastolic parameters and PACS were similar between the groups. The reductions in PALS and LACS were associated with exposure to cardiotoxic treatment in age- and sex-adjusted analysis (≥ moderate risk, low risk, controls): 45.4 ± 10.5, 49.5 ± 12.9, 52.1 ± 11.7; Padj = .003, and 31.7 ± 9.0, 35.2 ± 7.5, 38.2 ± 9.3; Padj = .001, respectively.

CONCLUSIONS: Long-term childhood leukemia survivors showed a subtle impairment of diastolic function that was detected with atrial strain but not with conventional measurements. This impairment was more pronounced in those with higher exposure to cardiotoxic treatment.

PMID:37217136 | DOI:10.1016/j.rec.2023.05.001

20:57

PubMed articles on: Cardio-Oncology

Correlation between high-resolution computed tomography appearance and histopathological features in the diagnosis of interstitial lung diseases. A real-life study

Minerva Surg. 2023 May 23. doi: 10.23736/S2724-5691.23.09948-3. Online ahead of print.