Combining radiation therapy and immunotherapy for lung cancers: a narrative review

Modi, Chirag; Berim, Lyudmyla; Isserow, Lauren; Malhotra, Jyoti; Patel, Malini; Langenfeld, John; Aisner, Joseph; Almeldin, D.S.; Jabbour, Salma K.

doi:10.21037/shc-20-66

Cited by 5 publications

(7 citation statements)

References 67 publications

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Section: Discussionmentioning

confidence: 99%

“…The PACIFIC trial was the first phase III prospective randomized controlled trial to show an increase in progression-free survival (PFS) and overall survival (OS) using consolidation durvalumab following concurrent chemoradiation ( 2 ). The initial analysis showed a significantly improved PFS compared to the placebo (16.8 months compared to 5.6 months, p<0.001), which led to the FDA and EMA approval of duravalumab for use in the consolidative therapy ( 2 ). Upon the success of chemoradiation followed by immunotherapy in treating locally advanced NSCLC, many trials are investigating the incorporation of immunotherapy with concurrent chemoradiotherapy in the definitive management of locally advanced NSCLC.…”

Section: Discussionmentioning

confidence: 99%

“…While surgical resection remains the standard of care for early-stage non-small-cell lung cancer (NSCLC), chemoradiation has been a mainstay of treatment for locally advanced NSCLC. Consolidation immunotherapy has emerged as the new standard with improved survival ( 2 ) in this subset of patients after conventional chemoradiation, with the regimens including CTLA-4, PD-1, and PD-L1 checkpoint inhibitors.…”

Section: Introductionmentioning

confidence: 99%

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Cardiac toxicity in patients with lung cancer receiving thoracic radiotherapy and immunotherapy

Son

Moey²,

Walker³

et al. 2023

Front. Oncol.

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BackgroundImmune checkpoint inhibitors (ICIs) are used to treat locally-advanced and metastatic lung cancer, which can lead to severe immunogenic-related cardiotoxicities. We assessed the risk of cardiotoxicity in ICI-treated lung cancer patients with or without cardiac radiation from thoracic radiotherapy.MethodsRetrospective data was collected on Stage III-IV lung cancer patients who received ICIs between 2015 and 2018. All cardiotoxicities associated with ICI were assessed in correlation with the timing of radiotherapy (RT) in relation to ICI, and the mean RT heart dose. The rate of cardiac events in relation to RT timing and heart dose was compared using multiple logistic regression including the Framingham risk score and steroid use prior to ICI therapy.ResultsOf 194 ICI-treated patients evaluated, 55.2% (n=107/194) patients had received thoracic RT at a median dose of 60.4 Gy (range, 15-75). Cardiotoxicities such as non-ST elevated myocardial infarction and new onset supraventricular tachycardias were observed in 13 (12.2%) of those who had thoracic RT versus 9 (10.3%) who did not (p=0.87). 38 patients who received RT concurrently with ICI did not develop any cardiotoxicity whereas 14.1% (n=22/156) of those who did not receive concurrent RT developed cardiotoxicities (univariate, p=0.030; multivariate, p=0.055). There were no significant differences in the mean heart RT dose, Framingham risk score, and steroid treatment between patients that received concurrent RT with ICI versus non-concurrent RT/ICI.ConclusionICI-related cardiotoxicities were not significantly associated with patients who received concurrent thoracic radiotherapy in this retrospective review. Further validation of prospective studies is needed to confirm these results.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cardiac toxicity in patients with lung cancer receiving thoracic radiotherapy and immunotherapy

Son

Moey²,

Walker³

et al. 2023

Front. Oncol.

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“…According to the AJCC TNM staging 8 th edition ( 45 ), stage III lung cancer describes LA-NSCLC with N1-N3 nodal involvement and/or primary tumor of T3 and T4 classifications, without evidence of distant metastasis ( 34 ). The mainstay of treatment for LA-NSCLC has been CCRT for numerous years, yet even after CCRT, the OS rate was only 15–20%, with disease recurrence as the main contributor to the low OS rate ( 33 , 34 ). Fig.…”

Section: Current Advances In Sbrt and Immunotherapies Synergy In Lung...mentioning

confidence: 99%

The dynamic duo: A narrative review on the synergy between stereotactic body radiotherapy and immunotherapy in lung cancer treatment (Review)

Cheng,

Tu,

Lee

2024

Oncol Rep

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“…Following the destruction of malignant cells by irradiation, a series of products result that trigger reactions of the immune system with both stimulatory and suppressive effects. The presentation of the tumor antigen mediated by irradiation has the effect of activating dendritic cells (DCs), increasing the degree of lymphocyte infiltration of the tumor, but also control cell signaling [ 1 , 5 , 6 ]. Irradiation also has the effect of cross-presentation of the antigen to T cells via DCs and the secretion of inflammatory cytokines.…”

Section: The Effect Of Radiotherapy On the Antitumor Immune Responsementioning

confidence: 99%

Immunotherapy and Radiotherapy as an Antitumoral Long-Range Weapon—A Partnership with Unsolved Challenges: Dose, Fractionation, Volumes, Therapeutic Sequence

Mireștean

Iancu

2022

Current Oncology

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Immunotherapy, the modern oncological treatment with immune checkpoint inhibitors (ICIs), has been part of the clinical practice for malignant melanoma for more than a decade. Anti-cytotoxic T-lymphocyte antigen 4 (CTLA4), anti-programmed cell death Protein 1 (PD-1), or anti programmed death-ligand 1 (PD-L1) agents are currently part of the therapeutic arsenal of metastatic or relapsed disease in numerous cancers; more recently, they have also been evaluated and validated as consolidation therapy in the advanced local stage. The combination with radiotherapy, a treatment historically considered loco-regional, changes the paradigm, offering—via synergistic effects—the potential to increase immune-mediated tumor destruction. However, the fragile balance between the tumoricidal effects through immune mechanisms and the immunosuppression induced by radiotherapy means that, in the absence of ICI, the immune-mediated potentiation effect of radiotherapy at a distance from the site of administration is rare. Through analysis of the preclinical and clinical data, especially the evidence from the PACIFIC clinical trial, we can consider that hypofractionated irradiation and reduction of the irradiated volume, in order to protect the immune-infiltrated tumor microenvironment, performed concurrently with the immunotherapy or a maximum of 2 weeks before the start of ICI treatment, could bring maximum benefits. In addition, avoiding radiation-induced lymphopenia (RILD) by protecting some anatomical lymphoid structures or large blood vessels, as well as the use of irradiation of partial tumor volumes, even in plurimetastatic disease, for the conversion of a "cold" immunological tumor into a “hot” immunological tumor are modern concepts of radiotherapy in the era of immunotherapy. Low-dose radiotherapy could also be proposed in plurimetastatic cases, the effect being different (modeling of the TME) from that of high doses per fraction irradiation (cell death with release of antigens that facilitates immune-mediated cell death).

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Combining radiation therapy and immunotherapy for lung cancers: a narrative review

Cited by 5 publications

References 67 publications

Cardiac toxicity in patients with lung cancer receiving thoracic radiotherapy and immunotherapy

Cardiac toxicity in patients with lung cancer receiving thoracic radiotherapy and immunotherapy

The dynamic duo: A narrative review on the synergy between stereotactic body radiotherapy and immunotherapy in lung cancer treatment (Review)

Immunotherapy and Radiotherapy as an Antitumoral Long-Range Weapon—A Partnership with Unsolved Challenges: Dose, Fractionation, Volumes, Therapeutic Sequence

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