Relationship Between Prior Radiotherapy and Checkpoint-Inhibitor Pneumonitis in Patients With Advanced Non–Small-Cell Lung Cancer

Voong, Khinh Ranh; Hazell, Sarah Z.; Fu, Wei; Hu, Chen; Lin, Cheng Ting; Ding, Kai; Suresh, Karthik; Hayman, James A.; Hales, Russell K.; Al-Faifi, Salem M.; Marrone, Kristen A.; Levy, Benjamin; Hann, Christine L.; Ettinger, David S.; Feliciano, Josephine; Peterson, Valerie; Kelly, Ronan J.; Brahmer, Julie R.; Forde, Patrick M.; Naidoo, Jarushka

doi:10.1016/j.cllc.2019.02.018

Cited by 84 publications

(77 citation statements)

References 22 publications

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“…48,61,62 Interestingly, smoking history has not been found to be a significant risk factor for the development of ICI pneumonitis. 49,52 In addition, Voong et al 63 found that no specific RT parameter, either total dose or timing of RT, was associated with increased risk of ICI pneumonitis, although it was numerically more common in patients who received curative-intent RT compared with palliative RT.…”

Section: Risk Factorsmentioning

confidence: 99%

Pulmonary toxicity of systemic lung cancer therapy

Long

Suresh

2020

Respirology

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Lung cancer is the leading cause of cancer-related deaths worldwide. As new therapies are developed, it is important to understand the pulmonary toxicities associated with systemic lung cancer therapies. Cytotoxic chemotherapy regimens for NSCLC often include taxanes. Pulmonary toxicity from taxanes presents as an ILD-type reaction characterized by increasing dyspnoea, dry cough, fever and bilateral pulmonary interstitial infiltrates. The incidence of taxane-induced pneumonitis is rare, and many patients respond to steroid therapy; however, fatal cases have been reported. Patients with NSCLC are routinely tested for the presence of tumour oncogenes to determine their candidacy for targeted therapies, such as TKI. EGFR-TKI can cause pneumonitis characterized by progressive dyspnoea and hypoxia. EGFR-TKIassociated ILD rarely presents as an AIP with rapidly progressive respiratory failure and high mortality rates. The most recent development in lung cancer therapy has been the discovery of immune checkpoint inhibitor (ICI). ICI pneumonitis has been increasingly recognized as a common complication of ICI therapy, with reported incidence as high as 19% in some clinical settings. Early-grade ICI pneumonitis may be asymptomatic; however, high-grade ICI pneumonitis can result in progressive dyspnoea, hypoxia and respiratory failure. ICI pneumonitis is unique in that only half of the patients will improve with steroid treatment, and mortality rates are high. As treatment of NSCLC evolves, providers must be able to recognize and respond to the development of drug-induced pulmonary toxicities.

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Section: Risk Factorsmentioning

confidence: 99%

Pulmonary toxicity of systemic lung cancer therapy

Long

Suresh

2020

Respirology

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“…Generally, the distribution of immune-related pneumonitis is not limited to a specific area of the lung. A study conducted by Voong et al provided an in-depth understanding of immunerelated pneumonitis and further compared with radiation-related pneumonitis in patients treated with prior thoracic radiation (13). It demonstrated that there were spatial distribution differences between the two types of pneumonitis with immunerelated pneumonitis mainly within lung volume that is outside the high radiation dose delivery.…”

Section: Discussionmentioning

confidence: 99%

Radiation Recall Pneumonitis Induced by Anti-PD-1 Blockade: A Case Report and Review of the Literature

et al. 2020

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Background: Radiation recall pneumonitis (RRP) is an unpredictable but relatively severe subclinical radiation damage which occurs in the previously irradiated fields of pulmonary tissue after administration of a systemic agent. Previous reports of RRP were mainly attributed to chemotherapy and molecular-target agents. RRP induced by immunotherapy has been rarely reported. Here we describe a case of a novel pattern of RRP induced by anti-PD-1 blockade Camrelizumab 2 years after radiotherapy, with some focus on further understanding of this phenomenon. Case Report: A 64-year-old man with non-small cell lung cancer (NSCLC) received two cycles of chemotherapy with cisplatin and pemetrexed first. Subsequently, he underwent concomitant chemoradiotherapy with cisplatin and pemetrexed to simultaneous integrated boost (SIB) radiotherapy. After 15 months, due to tumor progression and brain metastasis, he started with administration of anti-PD-1 blockade Camrelizumab (200 mg q2w) and stereotactic radiosurgery (SRS). The patient developed fever, dyspnea and cough after the eighth administration of Camrelizumab. Meanwhile, his chest CT revealed patchy consolidation and ground-glass opacities localized within the previously irradiated area. Subsequent treatment regimen was adjusted to 80 mg q12h prednisolone with discontinuation of Camrelizumab. Then the symptoms gradually eased and reexamination of CT showed significant improvement in RRP after 2 weeks. Conclusion: Our case report presents a novel pattern of RRP induced by anti-PD-1 blockade Camrelizumab 2 years after radiotherapy. This indicates that previous radiotherapy combined with subsequent anti-PD-1 blockade has a potential to cause overlapping damage to lung, suggesting that intensive attention might be needed for patients who are treated with anti-PD-1 blockade in conjunction with a prior history of thoracic radiation.

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“…Some evidence has shown that administration of immune checkpoint inhibitors (ICI) after radiotherapy of lung lesions may cause recall effects (37,38). Study showed that immune-related (IR) pneumonitis was more common in NSCLC patients treated with ICI who received curative-intent chest radiotherapy, but no radiotherapy parameter was significantly associated with IR pneumonitis (39). The PACIFIC study showed the safety of radiotherapy combined with ICI.…”

Section: Discussionmentioning

confidence: 99%

Anti-PD-1 Immunotherapy Combined With Stereotactic Body Radiation Therapy and GM-CSF as Salvage Therapy in a PD-L1-Negative Patient With Refractory Metastatic Esophageal Squamous Cell Carcinoma: A Case Report and Literature Review

2020

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Esophageal squamous cell carcinoma (ESCC) is a malignancy with poor prognosis, which is often diagnosed at a late stage. Effective treatment options are limited when patients fail standard systemic therapy. The application of PD-1 inhibitors have led to a paradigm shift in the treatment of ESCC, but its efficacy as monotherapy is limited. Previous studies have shown that the antitumor effects may be reinforced when a PD-1 inhibitor is combined with radiotherapy or GM-CSF. This study aimed to report a case of a patient about advanced unresectable ESCC negative expression of PD-L1, who experienced tumor progression after chemoradiotherapy and targeted therapy.A significant systemic effect was seen after PD-1 inhibitor combined with GM-CSF and stereotactic body radiotherapy (SBRT) for metastatic lesions, however, severe pneumonia occurred after the triple-combination therapy. This study also reviewed several reports about the efficacy and safety of combination therapy.

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Relationship Between Prior Radiotherapy and Checkpoint-Inhibitor Pneumonitis in Patients With Advanced Non–Small-Cell Lung Cancer

Cited by 84 publications

References 22 publications

Pulmonary toxicity of systemic lung cancer therapy

Pulmonary toxicity of systemic lung cancer therapy

Radiation Recall Pneumonitis Induced by Anti-PD-1 Blockade: A Case Report and Review of the Literature

Anti-PD-1 Immunotherapy Combined With Stereotactic Body Radiation Therapy and GM-CSF as Salvage Therapy in a PD-L1-Negative Patient With Refractory Metastatic Esophageal Squamous Cell Carcinoma: A Case Report and Literature Review

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