Interstitial lung abnormalities in treatment-naïve advanced non-small-cell lung cancer patients are associated with shorter survival

Nishino, Mizuki; Cardarella, Stephanie; Dahlberg, Suzanne E.; Araki, Toshimitsu; Lydon, Christine; Jackman, David M.; Rabin, Michael S.; Hatabu, Hiroto; Johnson, Bruce E.

doi:10.1016/j.ejrad.2015.01.021

Cited by 61 publications

(88 citation statements)

References 27 publications

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“…It is believed that CT scans may present an overestimation of the comorbidity rate of ILD. The ILD comorbidity rate in our study was 12%, which is comparable to the previously reported incidence of radiographic interstitial abnormality in patients with NSCLC . Considering the higher incidence of comorbidity with ILD in the Japanese population, the incidence of preexisting ILD was reasonable in this study .…”

Section: Discussionsupporting

confidence: 84%

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Efficacy and safety of nivolumab in non‐small cell lung cancer with preexisting interstitial lung disease

et al. 2018

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BackgroundThe risk of developing lung cancer is high in patients with interstitial lung disease (ILD), as few treatment options are available. Immune checkpoint inhibitors (ICI) are used for the treatment of non‐small cell lung cancer (NSCLC) in clinical practice; however, in patients with preexisting ILD, the risk of ICI‐related pneumonitis is unknown. We evaluated the efficacy and lung toxicity of nivolumab in patients with NSCLC and ILD.MethodsWe retrospectively reviewed the medical records of 216 NSCLC patients who had received nivolumab therapy. The existence of ILD in these patients was determined by lung computed tomography findings; 26 patients had ILD. We evaluated the efficacy of nivolumab by measuring the response rate (RR), progression‐free survival (PFS) duration, and lung toxicity by incidence, severity, and outcome of nivolumab‐related ILD.ResultsThe RR and median PFS of the ILD and non‐ILD groups were 27% versus 13% (P = 0.078) and 2.7 (95% confidence interval [CI], 1.7–5.3) versus 2.9 months (95% CI 2.1–3.4; P = 0.919), respectively. The incidences of total and severe nivolumab‐related pneumonitis were significantly higher in the ILD group than in the non‐ILD group (31% vs. 12%, P = 0.014 and 19% vs. 5%, P = 0.022, respectively). No death from nivolumab‐related pneumonitis occurred. Over 50% of the patients in both groups with nivolumab‐related pneumonitis showed improvement over time.ConclusionRelative to the non‐ILD group, nivolumab‐related pneumonitis was observed more frequently in the ILD group; however, most cases were manageable.

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Section: Discussionsupporting

confidence: 84%

“…Patients with interstitial lung disease (ILD) have a twofold higher risk of developing lung cancer than smokers without ILD or chronic obstructive pulmonary disease (COPD) . Lung cancer patients with ILD have few treatment options because surgery, radiotherapy, and chemotherapy elevate the risk of exacerbation of ILD …”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of nivolumab in non‐small cell lung cancer with preexisting interstitial lung disease

et al. 2018

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“…The precise role of bronchoscopy and bronchoalveolar lavage (BAL) in the management of PD-1 pneumonitis is currently unclear, but BAL may help identify an underlying pulmonary infection. Without biopsy, both patients in the present series lack histologic assessments of pneumonitis, which is often the case with patients who have known advanced malignancy receiving systemic therapy (12, 16). A COP pattern of pneumonitis in the present cases was characterized by the radiographic appearance of the lung abnormalities of pneumonitis, based on the assessment of extent, distribution, and specific CT findings, as described previously (11, 12).…”

Section: Discussionmentioning

confidence: 91%

Anti–PD-1 Inhibitor–Related Pneumonitis in Non–Small Cell Lung Cancer

Nishino

Chambers

Chong

et al. 2016

Cancer Immunology Research

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The recent approval of two PD-1 inhibitors for the treatment of non–small cell lung cancer (NSCLC) has rapidly led to the widespread use of these agents in oncology practices. Pneumonitis has been recognized as a potentially life-threatening adverse event among NSCLC patients treated with PD-1 inhibitors; however, the detailed clinical and radiographic manifestations of this entity remain to be described. We report two cases of anti–PD-1 pneumonitis in advanced NSCLC patients treated with nivolumab after its FDA approval. Both cases presented with ground-glass and reticular opacities and consolidations in a peripheral distribution on CT, demonstrating a radiographic pattern of cryptogenic organizing pneumonia (COP). Consolidations were extensive and rapidly developed within 8 weeks of therapy in both cases. Both patients were treated with corticosteroids with subsequent improvement of respiratory symptoms and radiographic findings. One patient experienced recurrent pneumonitis after completing corticosteroid taper, or a “pneumonitis flare”, in the absence of nivolumab retreatment, with subsequent improvement upon corticosteroid re-administration. With the increasing use of immune checkpoint inhibitors in a growing number of tumor types, awareness of the radiographic and clinical manifestations of PD-1 inhibitor–related pneumonitis will be critical for the prompt diagnosis and management of this potentially serious adverse event.

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“…Patients with scores 4 or 5 were considered to be positive for pneumonitis 2, 3 . Radiologists were instructed to disregard the findings indicative of tumoral involvement of the lung 2, 19 . Discrepancies between two readers were resolved by a consensus review of the original two readers (M.N., H.H.)…”

Section: Methodsmentioning

confidence: 99%

Drug-related pneumonitis during mammalian target of rapamycin inhibitor therapy in patients with neuroendocrine tumors: a radiographic pattern-based approach

Nishino

Brais

Brooks

et al. 2016

European Journal of Cancer

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Purpose Investigate the incidence of drug-related pneumonitis during mTOR inhibitor therapy in patients with neuroendocrine tumors (NET), and characterize radiographic patterns of pneumonitis. Methods Sixty-six patients (39 males, 27 females, age: 22-79 years) with advanced NET treated with mTOR inhibitor, everolimus, were retrospectively studied. Chest CT scans during therapy were reviewed for abnormalities suspicious for drug-related pneumonitis by an independent review of two radiologists. Extent, distributions, and specific findings were evaluated in cases positive for pneumonitis. Radiographic patterns of pneumonitis were classified using ATS/ERS classification of interstitial pneumonia. Results Drug-related pneumonitis was radiographically detected in 14 patients (21%). Time from the initiation of therapy to pneumonitis was within 6 months of therapy in 10 patients (71%), while it ranged from 1.0 to 27.7 months. Pneumonitis was more common in patients who had never smoked (p=0.03). Lower lungs were more extensively involved than upper and middle lungs. Peripheral and lower distribution was most common (n=8), followed by peripheral and multifocal distribution (n=3). Ground glass and reticular opacities were present in all cases, with consolidation in 8 cases. The radiographic pattern of pneumonitis was classified as cryptogenic organizing pneumonia (COP) pattern in 8, non-specific interstitial pneumonia (NSIP) pattern in 5, and hypersensitivity pneumonitis (HP) pattern in one patient. Conclusion Drug-related pneumonitis was noted in 21% of the advanced NET patients treated with everolimus. Radiographic pattern of pneumonitis was most commonly COP pattern, followed by NSIP pattern.

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Interstitial lung abnormalities in treatment-naïve advanced non-small-cell lung cancer patients are associated with shorter survival

Cited by 61 publications

References 27 publications

Efficacy and safety of nivolumab in non‐small cell lung cancer with preexisting interstitial lung disease

Efficacy and safety of nivolumab in non‐small cell lung cancer with preexisting interstitial lung disease

Anti–PD-1 Inhibitor–Related Pneumonitis in Non–Small Cell Lung Cancer

Drug-related pneumonitis during mammalian target of rapamycin inhibitor therapy in patients with neuroendocrine tumors: a radiographic pattern-based approach

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