Establishment and validation of nomogram for predicting immuno checkpoint inhibitor related pneumonia

Abstract

Objective Cancer is one of the main causes of death worldwide. Although immunotherapy brings hope for cancer treatment, it is also accompanied by immune checkpoint inhibitor-related adverse events (irAEs). Immune checkpoint inhibitor pneumonia (CIP) is a potentially fatal adverse event, but there is still a lack of effective markers and prediction models to identify patients at increased risk of CIP. Methods A total of 369 cancer patients treated between 2017 and 2022 with immune checkpoint inhibitors at Shengjing Hospital of China Medical University and Liaoning People's Hospital were recruited for this study. Independent variables were selected by differences and binary logistic regression analysis, and a risk assessment nomogram was constructed for CIP risk. The accuracy and discriminative abilities of the nomogram were evaluated by calibration plots, receiver operating characteristic curves (ROCs) and decision curve analyses (DCAs). Results Binary logistic regression analysis showed that smoking history, acute phase proteins [interleukin (IL-6) and C-reactive protein (CRP)], CD8 + T lymphocyte count and serum alveolar protein [surface protein-A (SP-A) and Krebs Von den Lungen-6 (KL-6)] were significantly associated with CIP risk. A nomogram consisting of these variables was established and validated by different analyses. Conclusions We developed an effective risk nomogram for CIP prediction in immune-checkpoint inhibitor administrated cancer patients, which will further assist early detection of immunotherapy-related adverse events.

Nintedanib in an elderly non-small-cell lung cancer patient with severe steroid-refractory checkpoint inhibitor-related pneumonitis: A case report and literature review

“…An increased proportion of activated autoimmune indicators, CD3+ T cells/HLA-DR + T cells, was associated with the severity grading of CIP ( 39 ). Malignant NSCLC tumor cells may have more cross-antigens than normal lung tissues, as they are incubated in the same pulmonary environment ( 76 ). Tumor antigens, autoantigens, and neoantigens released from cytotoxic T-lymphocyte-mediated cell lysis induced persistent amplification of immune responses through “epitope spreading” ( 77 ).…”

“…Laboratory plasma and BALF examinations of patients with NSCLC-CIP showed an increasing spectrum of common inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-17A, IL-35, C-reactive protein, and procalcitonin ( 72 , 76 , 80 , 81 ). The levels of surfactant protein-A, surfactant protein-D, and Krebs von den Lungen-6 (KL-6) produced by type II alveolar epithelial cells, which reflect alveolar epithelial cell injury, were also increased ( 75 , 76 , 82 , 83 ). These biomarkers usually would decrease to normal levels when the initial respiratory symptoms are relieved.…”

Nintedanib en un paciente anciano con cáncer de pulmón no-microcítico y neumonitis grave, refractaria a esteroides, inducida por inhibidores de puntos de control: Reporte de un caso y revisión de la literatura

“…Una mayor proporción de indicadores autoinmunes activados, células T CD3+/HLA-DR + células T, se asoció con el grado de gravedad de la CIP [39]. Las células tumorales malignas del CPNM pueden tener más antígenos cruzados que los tejidos pulmonares normales, porque se incuban en el mismo entorno pulmonar [76]. Los antígenos tumorales, los autoantígenos y los neoantígenos liberados por la lisis celular mediada por linfocitos T citotóxicos indujeron una amplificación persistente de las respuestas inmunitarias a través de la «propagación de epítopos» [77].…”

“…El examen de laboratorio del plasma y el LBA de los pacientes con CPNM-CIP mostró un espectro creciente de citocinas inflamatorias comunes, como la interleucina (IL)-1β, IL-6, IL-17A, IL-35, proteína C reactiva y procalcitonina [72, 76, 80, 81]. También aumentaron los niveles de proteína surfactante A, proteína surfactante D y Krebs von den Lungen-6 (KL-6) producidos por las células epiteliales alveolares de tipo II, lo que refleja la lesión de las células epiteliales alveolares [75, 76, 82, 83]. Estos biomarcadores suelen disminuir hasta niveles normales cuando se alivian los síntomas respiratorios iniciales.…”

Immune checkpoint inhibitor-related pneumonitis: research advances in prediction and management

“…Multiple retrospective clinical studies reveal the correlation between smoking and the development of CIP. Smoking history is an independent influence and the most influential prognostic factor in CIP ( 40 , 41 ). Studies also showed that clinical outcomes of CIP worsen more frequently in patients with a history of smoking ( 7 ).…”