PD-1/PDL-1 Inhibitors and Cardiotoxicity; Molecular, Etiological and Management Outlines

Safi, Mohammed; Ahmed, Hyat; Al‐Azab, Mahmoud; Xia, Yunlong; Shan, Xin; Alradhi, Mohammed; Al-Danakh, Abdullah; Shopit, Abdullah; Liu, Jiwei

doi:10.1016/j.jare.2020.09.006

Cited by 37 publications

(32 citation statements)

References 97 publications

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“… 34 The effects of checkpoint inhibitors and genetic research provide a reason for optimism in the treatment of bladder cancer, and these have not yet been thoroughly investigated. 35 Extramural vascular invasion and obstruction/occlusion status, as well as microsatellite stability/instability (MSS/MSI) status, are all missing from the SEER database. Although further details would be preferable, we assumed that the currently available SEER database data would be adequate for our research.…”

Section: Discussionmentioning

confidence: 99%

Surgery improves survival in bladder signet-ring cell carcinoma-a population-based study

Alradhi

Safi

Tao

et al. 2022

Therapeutic Advances in Urology

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Objectives: The purpose of this study is to determine the therapeutic value of surgery in individuals with urinary bladder signet ring cell carcinoma (SRCC). Surgery has not been examined as a prognostic factor for urinary bladder cancer (SRCC). Materials and Methods: Using the Surveillance, Epidemiology, and End Results program (SEER), patients with urinary bladder SRCC who presented from 1975 to 2018 were included in a retrospective study. The effect of surgical therapy on cause-specific survival (CSS) and overall survival (OS) was examined using univariate and multivariate Cox regression models. We subdivided 595 patients with SRCC into 2 groups, as follows: 496 who underwent surgery; and 99 who did not undergo surgery. Results: Males had high predominance in all cases in both groups ( p = 0.04). Moderate and poor differentiation (III–IV) were observed in the majority of patients who underwent surgery (77.2 vs 58.6, p ⩽ 0.001) and had no insurance ( p ⩽ 0.001). By using KM, the OS and CSS of the surgery group were found to be significantly better than those of the non-surgery group ( p = 0.001,%) after adjusting for the variables of age, race, sex, primary site, grade, stage, lymph node removal, chemotherapy record, radiotherapy record, insurance, and marital status in the multivariate Cox proportional hazard model (hazard ratio [HR]= 0. 592; 95% confidence interval [CI] = 0.449–0.782; p = 0.0001). In comparison with chemotherapy and radiation, which resulted in poorer survival rates, surgery considerably improved survival outcomes in urinary bladder SRCC. The nomogram prediction model was built with C-index values of 0.70 and 73 for OS and CSS prediction, respectively. AUC in OS values were 0.77, 0.76, and 0.74, whereas AUC in CSS were 0.83, 0.80, and 0.79 for the 1-, 3-, and 5-year survival nomograms, respectively. Conclusion: Surgery was a significant independent predictor of bladder SRCC survival. Patients who underwent surgery had higher CSS and OS than people who did not undergo surgery. Surgery also led to better survival than the combination of the different treatment modalities.

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Section: Discussionmentioning

confidence: 99%

Surgery improves survival in bladder signet-ring cell carcinoma-a population-based study

Alradhi

Safi

Tao

et al. 2022

Therapeutic Advances in Urology

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“…However, in general immunotherapy-related cardiotoxicity symptoms, several studies suggest an increase in patients with end organ failure compared with those without organ dysfunction (in both cases of myocarditis or controls without myocarditis) (10). The median time to the presentation of cardiotoxicity-related immunotherapy ranged from 2 to 454 days (23 months), and the majority occurred within the first four cycles of immunotherapy (1st month) (11). To the best knowledge of the authors, the present study was a large unique study that detected the OS of patients who died from heart diseases in the contemporary eras of immunotherapy and nonimmunotherapy NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Overall Survival in Heart Disease–Related Death in Non-Small Cell Lung Cancer Patients: Nonimmunotherapy Versus Immunotherapy Era: Population-Based Study

et al. 2020

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The cardiotoxicity during immunotherapy administration leads to mortality by more than 42% and heart disease-related mortality among immunotherapy-linked cancers is still considered to be underestimated. In this study, the advanced stage of non-small cell lung cancer (NSCLC) with heart disease-related death was selected in accordance with immunotherapy approval time. NSCLC was searched on the Surveillance, Epidemiology, and End Results (SEER) program. Results show that 538 advanced NSCLC cases, those dominated by men and elderly people aged more than 70 years, had a high percentage of heart disease-related death in both eras. The difference between contemporary groups was fairly nonsignificant (P = > 0.05). The overall survival (OS) of allcause mortality difference showed improved survival in the immunotherapy group (P = 0.0001). In the study of heart disease-related death survival with adjusted data, the NSCLC patients show significant lower survival in the immunotherapy era compared with the nonimmunotherapy era (P = 0.003; hazard ratio [HR] = 1.31; 95% CI = 1.099-1.57). In the multivariate analysis of NSCLC-related immunotherapy, histology revealed that the non-squamous cell type had an independent risk for lower OS than the squamous cell type (P = 0.04; HR= 0.74; CI = 0, 55-0.99). The results demonstrate the survival benefits for NSCLC in immunotherapy; however, in heart disease-related death, immunotherapy in patients with NSCLC shows decreased OS. This study highlights that NSCLC patients should be highly monitored during immunotherapy administration, and further assessment is needed.

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“…It is postulated that myocarditis, pre-existing cardiovascular diseases, past cardiotoxic chemotherapy, myocardial metastases, old age, and systemic inflammatory conditions could all contribute to arrhythmias in cancer patients treated with PD-1/PDL-1 inhibitors. 42 Lyon et al hypothesized that ventricular myocarditis, inflammation of the His-Purkinje conduction system, either via direct T-cell-Purkinje interactions or via activation of local macrophages resident in the Purkinje system, increased systemic inflammatory state (without myocarditis), left ventricular impairment due to noninflammatory functional cardiotoxicity, or inflammation of myocardial metastases (if present) could all be at the origin of arrhythmias in the context of ICIs use. 43 In murine models, the deletion of PD-1 leads to autoimmune dilated cardiomyopathy.…”

Section: Case 2: Chb With Pembrolizumabmentioning

confidence: 99%

Bradyarrhythmias in Cardio-Oncology

Fonseca

Cheng

et al. 2021

South Asian J Cancer

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The relationship between bradyarrhythmias and cancer therapies has not been well described but is increasingly recognized. There have been extensive advances in oncological pharmacotherapy, with several new classes of drugs available including targeted agents, immune checkpoint inhibitors and CAR T cell therapy. This increasing repertoire of available drugs has revolutionized overall prognosis and survival of cancer patients but the true extent of their cardiovascular toxicity is only beginning to be understood. Previous studies and published reviews have traditionally focused on conventional chemotherapies and in arrhythmias in general, particularly tachyarrhythmias. The number of patients with both cancer and cardiovascular problems is increasing globally and oncologists and cardiologists need to be adept at managing arrythmia based scenarios. Greater collaboration between the two specialties including studies with prospective data collection in Cardio-Oncology are much needed to fill in knowledge gaps in this arena. This case-based review summarizes current available evidence of cancer treatment-related bradyarrhythmia incidence (including its different subtypes), possible mechanisms and outcomes. Furthermore, we propose a stepwise surveillance and management protocol for patients with suspected bradyarrhythmia related to cancer treatment.

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PD-1/PDL-1 Inhibitors and Cardiotoxicity; Molecular, Etiological and Management Outlines

Abstract: Graphical abstract PD-1/PDL-1 inhibitors and cardiotoxicity; molecular, etiological and management outlines.

Cited by 37 publications

References 97 publications

Surgery improves survival in bladder signet-ring cell carcinoma-a population-based study

Surgery improves survival in bladder signet-ring cell carcinoma-a population-based study

Overall Survival in Heart Disease–Related Death in Non-Small Cell Lung Cancer Patients: Nonimmunotherapy Versus Immunotherapy Era: Population-Based Study

Bradyarrhythmias in Cardio-Oncology

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