Association of Left Anterior Descending Coronary Artery Radiation Dose With Major Adverse Cardiac Events and Mortality in Patients With Non–Small Cell Lung Cancer

Atkins, Katelyn M.; Chaunzwa, Tafadzwa L.; Lamba, Nayan; Bitterman, Danielle S.; Rawal, Bhupendra; Bredfeldt, Jeremy S.; Williams, Christopher; Kozono, David; Baldini, Elizabeth H.; Nohria, Anju; Hoffmann, Udo; Aerts, Hugo J.W.L.; Mak, Raymond H.

doi:10.1001/jamaoncol.2020.6332

Cited by 110 publications

(131 citation statements)

References 49 publications

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“…Overall, this study provides the most robust data to date on the impact of durvalumab on local-regional disease outcomes and in KEAP1-NFE2L2-mutant tumors. With a growing understanding of both the toxicity of radiotherapy on thoracic organs and the heterogeneity of radiation sensitivity among tumors and patients, 24,29,30 appreciating the role of durvalumab on local-regional control can aide future trial development investigating radiation dose and volume personalization in stage III NSCLC.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Durvalumab on Local-Regional Control in Stage III NSCLCs Treated With Chemoradiation and on KEAP1-NFE2L2-Mutant Tumors

Shaverdian

Offin

Shepherd

et al. 2021

Journal of Thoracic Oncology

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Introduction: KEAP1-NFE2L2-mutant NSCLCs are chemoradiation resistant and at high risk for local-regional failure (LRF) after concurrent chemoradiation (cCRT). To elucidate the impact of durvalumab on local-regional control, we evaluated LRF in patients with NSCLC treated with cCRT with and without durvalumab.Methods: Patients with stage III NSCLC treated with cCRT or cCRT and durvalumab who underwent tumor genomic profiling were evaluated. The incidence of LRF and outcomes of patients with and without KEAP1-NFE2L2-mutant tumors were evaluated.Results: We analyzed 120 consecutive patients (cCRT alone, n ¼ 54; cCRT and durvalumab, n ¼ 66). Patients treated with cCRT alone had significantly more LRF events compared with those treated with cCRT and durvalumab, with 12-month LRF incidence of 39% (95% confidence interval [CI]: 24%-54%) and 18% (95% CI: 8%-28%), respectively (p ¼ 0.002). Among patients treated with cCRT alone and cCRT and durvalumab, 20 patients (37%) and 18 patients (27%), respectively, had KEAP1-NFE2L2mutant tumors. In patients treated with cCRT alone, those with KEAP1-NFE2L2-mutant tumors had worse localregional control (p ¼ 0.015), and on multivariate analysis, KEAP1-NFE2L2 mutation predicted for LRF (hazard ratio ¼ 3.9, 95% CI: 1.6-9.8, p ¼ 0.003). Nevertheless, patients with and without KEAP1-NFE2L2-mutant tumors had similar LRF outcomes (p ¼ 0.541) when treated with cCRT and durvalumab, and mutational status did not predict for LRF (p ¼ 0.545). Among those with KEAP1-NFE2L2-mutant tumors, cCRT and durvalumab significantly reduced the incidence of LRF compared with cCRT alone: 12-month LRF incidence of 62% (95% CI: 40%-*Corresponding author. Disclosure: Dr. Shaverdian reports receiving research funding from Novartis. Dr. Offin reports having advisory role for PharMar, Novartis, and Targeted Oncology and receiving honoraria from Bristol-Myers Squibb and Merck Sharp & Dohme. Dr. Shepherd reports receiving honoraria from ASCO. Dr. Simone II reports receiving honoraria from Varian Medical Systems. Dr. Wu reports receiving research support from CivaTech Oncology, Inc., nonfinancial support from AlphaTau Medical, personal fees from MoreHealth, and personal fees from AstraZeneca. Dr. Hellmann reports receiving personal fees from Genentech, Mirati, Syndax, Nektar, Blueprint Medicines, and Merck; grants, personal fees, and nonfinancial support from Bristol-Myers Squibb; personal fees and nonfinancial support from AstraZeneca; and personal fees and equity from Shattuck Labs and Immunai;

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Section: Discussionmentioning

confidence: 99%

The Impact of Durvalumab on Local-Regional Control in Stage III NSCLCs Treated With Chemoradiation and on KEAP1-NFE2L2-Mutant Tumors

Shaverdian

Offin

Shepherd

et al. 2021

Journal of Thoracic Oncology

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“…In the coronary circulation the typical pattern associated with radiation-induced coronary artery disease (RICAD) is ostial stenosis with a significantly higher incidence of severe left main disease, followed by ostial right coronary artery and left anterior descending artery stenoses ( 17 ). The location and severity directly correlate with the direction and dose of radiation beam ( 28 – 30 ) ( Figure 3 ). Extensive mantle radiation such as for Hodgkin's lymphoma, breast cancer, and esophageal cancer is more likely to cause ostial and multivessel stenoses ( 23 , 28 ).…”

Section: Pathogenic Mechanismsmentioning

confidence: 99%

Radiation-Induced Vascular Disease—A State-of-the-Art Review

Yang

Marmagkiolis

Balanescu

et al. 2021

Front. Cardiovasc. Med.

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Since the 1990s, there has been a steady increase in the number of cancer survivors to an estimated 17 million in 2019 in the US alone. Radiation therapy today is applied to a variety of malignancies and over 50% of cancer patients. The effects of ionizing radiation on cardiac structure and function, so-called radiation-induced heart disease (RIHD), have been extensively studied. We review the available published data on the mechanisms and manifestations of RIHD, with a focus on vascular disease, as well as proposed strategies for its prevention, screening, diagnosis, and management.

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“…Firstly, the tumor itself can invade the adjacent heart and great vessels. Secondly, the surgical procedure and radiotherapy can also exert a harmful impact on the heart (70,71). Thirdly, cardiotoxicity can be caused by anthracycline treatment (72).…”

Section: Discussionmentioning

confidence: 99%

Induction Strategy for Locally Advanced Thymoma

Zhang

Chen

et al. 2021

Front. Oncol.

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Surgery remains cornerstone for the management of thymoma. Complete surgical resection (R0), is recognized as the constant and significant factor for prognosis. However, in locally advanced (Masaoka-Koga stages III-IVa) thymomas, achieving R0 resection remains challenging due to local-regional invasion of the disease. Induction treatment, with the aim of reducing bulky tumor mass, offers new strategy to facilitate totally surgical resection. Herein, we reviewed recent progress and provided a comprehensive overview of induction strategy in locally advance thymoma.

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Association of Left Anterior Descending Coronary Artery Radiation Dose With Major Adverse Cardiac Events and Mortality in Patients With Non–Small Cell Lung Cancer

Cited by 110 publications

References 49 publications

The Impact of Durvalumab on Local-Regional Control in Stage III NSCLCs Treated With Chemoradiation and on KEAP1-NFE2L2-Mutant Tumors

The Impact of Durvalumab on Local-Regional Control in Stage III NSCLCs Treated With Chemoradiation and on KEAP1-NFE2L2-Mutant Tumors

Radiation-Induced Vascular Disease—A State-of-the-Art Review

Induction Strategy for Locally Advanced Thymoma

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