Cardiac dose is associated with immunosuppression and poor survival in locally advanced non-small cell lung cancer

Contreras, J.; Lin, Alexander; Weiner, Ashley A.; Speirs, Christina K.; Samson, Pamela; Mullen, D.; Campian, Jian; Bradley, Jeffrey D.; Roach, Michael C.; Robinson, Clifford G.

doi:10.1016/j.radonc.2018.05.017

Cited by 82 publications

(96 citation statements)

References 31 publications

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“…Recent research suggests that whole-heart dose has an immunosuppressive effect that results in early mortality, where radiation dose affects the circulating immune cells in the blood. [31][32][33] Conversely, higher doses to the certain cardiac substructures can directly affect cardiac function. Such results highlight the multifaceted nature of cardiac toxicity, where it is likely there are multiple mechanisms at play.…”

Section: Discussionmentioning

confidence: 99%

Novel Methodology to Investigate the Effect of Radiation Dose to Heart Substructures on Overall Survival

McWilliam

Khalifa²,

Osorio

et al. 2020

International Journal of Radiation Oncology*Biology*Physics

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This work identifies the cardiac substructures where excess dose is most associated with early mortality. The right atrium, origin of the right coronary artery, and the ascending aorta are identified with a maximum equivalent dose in 2-Gy fractions of 23 Gy presented as a dose limit for future studies. Purpose: For patients with lung cancer treated with radiation therapy, a dose to the heart is associated with excess mortality; however, it is often not feasible to spare the whole heart. Our aim is to define cardiac substructures and dose thresholds that optimally reduce early mortality. Methods and Materials: Fourteen cardiac substructures were delineated on 5 template patients with representative anatomies. One thousand one hundred sixty-one patients with non-small cell lung cancer were registered nonrigidly to these 5 template anatomies, and their radiation therapy doses were mapped. Mean and maximum dose to each substructure were extracted, and the means were evaluated as input to prediction models. The cohort was bootstrapped into 2 variable reduction techniques: elastic net least absolute shrinkage and selection operator and the random survival forest model. Each method was optimized to extract variables contributing most to overall survival, and model coefficients were evaluated to select these substructures. The most important variables common to both models were selected and evaluated in multivariable Cox-proportional hazard models. A threshold dose was defined, and Kaplan-Meier survival curves plotted.

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Section: Discussionmentioning

confidence: 99%

Novel Methodology to Investigate the Effect of Radiation Dose to Heart Substructures on Overall Survival

McWilliam

Khalifa²,

Osorio

et al. 2020

International Journal of Radiation Oncology*Biology*Physics

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“…While RT-induced immune-related adverse events are beyond the scope of this review, it should be mentioned that a body of evidence is emerging for cardiotoxicity from thoracic RT and combined RT with anti-PD-1 immunotherapy or chemotherapy regimens (Contreras et al 2018; Du et al 2018) and highlights the need for greater understanding of the acute and long-term adverse effects of RT/immunotherapy in both tumour and non-tumour tissue compartments. In the preclinical setting, the availability of preclinical irradiators that utilise the clinical technology and treatment planning systems, SARRP ™ by Xstrahl LifeSciences and RAD SmART™ by Precision X-ray, will improve our understanding of RT-induced immune-related adverse events, as well as the accuracy and reproducibility of RT performed but only if radiobiology/radiooncology principles are also applied, such as the radiosensitivity α/β ratio, beam arrangement, and tumour and target volumes.…”

Section: Discussionmentioning

confidence: 99%

Radiation, inflammation and the immune response in cancer

et al. 2018

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Radiation is an important component of cancer treatment with more than half of all patients receive radiotherapy during their cancer experience. While the impact of radiation on tumour morphology is routinely examined in the pre-clinical and clinical setting, the impact of radiation on the tumour microenvironment and more specifically the inflammatory/immune response is less well characterised. Inflammation is a key contributor to short- and long-term cancer eradication, with significant tumour and normal tissue consequences. Therefore, the role of radiation in modulating the inflammatory response is highly topical given the current wave of targeted and immuno-therapeutic treatments for cancer. This review provides a general overview of how radiation modulates the inflammatory and immune response-(i) how radiation induces the inflammatory/immune system, (ii) the cellular changes that take place, (iii) how radiation dose delivery affects the immune response, and (iv) a discussion on research directions to improve patient survival, reduce side effects, improve quality of life, and reduce financial costs in the immediate future. Harnessing the benefits of radiation on the immune response will enhance its maximal therapeutic benefit and reduce radiation-induced toxicity.

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“…Nine studies were included for the relationship between heart dose and overall survival in lung cancer, involving 2823 participants [ 11 – 17 , 26 , 27 ] . The heart dose was analyzed as continuous variable.…”

Section: Resultsmentioning

confidence: 99%

Heart dose linked with cardiac events and overall survival in lung cancer radiotherapy

et al. 2020

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Background: The aim of this study was to investigate the link between heart dose and overall survival, the link between heart dose and cardiac events and whether radiation-induced heart diseases were associated with overall survival in lung cancer radiotherapy. Methods: We performed a literature search by using Pubmed, Embase, China National Knowledge Infrastructure (CNKI) databases. Pairs of reviewers independently screened literature according to the inclusion criteria, extracted data, assessed methodological quality, and publication bias. The primary end points included overall survival and cardiac events. I 2 was calculated in a heterogeneity assessment. Publication bias was evaluated by using Begg funnel plot and Egger test. Results: Ten studies including 1 randomized controlled trial, 3 post hoc analysis of prospective trials, and 6 cohort studies were identified. The meta-analysis showed that heart volume receiving ≥5 Gy (HV5) (hazard ratio [HR] = 1.01; 95% confidence interval [CI]: 1.00–1.01), heart volume receiving ≥30 Gy (HV30) (HR = 1.01; 95% CI: 1.00–1.02), heart volume receiving ≥50 Gy (HV50) (HR = 1.05; 95%CI: 1.00–1.10), and mean heart dose (MHD) (HR = 1.01; 95%CI:1.00–1.02) all were associated with worse overall survival. In addition, the MHD (HR = 1.03; 95% CI: 1.02–1.05), HV5 (HR = 1.02; 95% CI: 1.01–1.03), and HV30 (HR = 1.02; 95% CI: 1.01–1.03) were significantly associated with all grade cardiac events. Meanwhile, compared with those who did not receive radiotherapy, the radiotherapy group experienced a significantly increased risk for cardiac-specific mortality (HR = 1.297; 95% CI: 1.213–1.387). However, the results did not show that cardiac events were associated with overall survival in lung cancer radiotherapy (HR = 1.472; 95% CI: 0.988–2.193). Conclusion: Exposure of the heart to radiation increased the risk of cardiac events during radiotherapy for lung cancer. Meanwhile, heart dose including HV5 and HV30 were predictors of overall survival in lung cancer radiotherapy. It is necessary to constrain the heart dose when perform thoracic radiation therapy to decrease the incidence of cardiac events and improve the overall survival.

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Cardiac dose is associated with immunosuppression and poor survival in locally advanced non-small cell lung cancer

Cited by 82 publications

References 31 publications

Novel Methodology to Investigate the Effect of Radiation Dose to Heart Substructures on Overall Survival

Novel Methodology to Investigate the Effect of Radiation Dose to Heart Substructures on Overall Survival

Radiation, inflammation and the immune response in cancer

Heart dose linked with cardiac events and overall survival in lung cancer radiotherapy

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