Ludovic Fournel1,2, Pascaline Boudou-Rouquette3,4, Mathilde Prieto5, Remi Hervochon6, Claude Guinet6, Jennifer Arrondeau3,4, Jérôme Alexandre3,4, Diane Damotte3,7, Marie Wislez3,8, Frédéric Batteux3,9, Philippe Icard5,10, François Goldwasser3,4, Marco Alifano5,3. 1. Thoracic Surgery Department, Cochin Hospital, AP-HP.Center-University of Paris, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France. ludovic.fournel@aphp.fr. 2. Immunomodulatory Therapies Multidisciplinary Study Group (CERTIM), Cochin Hospital, AP-HP.Center-University of Paris, Paris, France. ludovic.fournel@aphp.fr. 3. Immunomodulatory Therapies Multidisciplinary Study Group (CERTIM), Cochin Hospital, AP-HP.Center-University of Paris, Paris, France. 4. Oncology Department, Cochin Hospital, AP-HP.Center-University of Paris, Paris, France. 5. Thoracic Surgery Department, Cochin Hospital, AP-HP.Center-University of Paris, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France. 6. Radiology Department, Cochin Hospital, AP-HP.Center-University of Paris, Paris, France. 7. Pathology Department, Cochin Hospital, AP-HP.Center-University of Paris, Paris, France. 8. Respiratory Medicine and Thoracic Oncology Department, Cochin Hospital, AP-HP.Center-University of Paris, Paris, France. 9. Biology and Immunology Department, AP-HP.Center, University of Paris, Paris, France. 10. INSERM U-119, UNICAEN, University of Caen-Normandy, Caen, France.
Abstract
PURPOSE: The widespread use of Nivolumab results in an increasing number of side effects and adverse events. Herein, we evaluated the impact of Nivolumab on crude and normalized pulmonary artery diameter (PAD). METHODS: We analyzed clinical, morphometric, pathological and radiological data of lung cancer patients treated by Nivolumab in an 18-month period. Blinded radiological evaluation was performed, by three observers measuring axial PAD and Aorta diameter (AoD) in secondarily matched pre- and post-Nivolumab CT-scans. Correlation between ΔPAD and clinicopathological data was investigated. RESULTS: 59 patients receiving Nivolumab for treatment of advanced lung carcinoma were identified. Pre-and post-Nivolumab comparison of CT-scan measures revealed that mean PAD was 26.3 ± 2.8 mm versus 28.0 ± 3.0 mm (p < 0.001), and mean PAD/AoD ratio was 0.82 ± 0.09 versus 0.87 ± 0.11 (p < 0.001), respectively. Median ΔPAD was 0.05 [0.01-0.122] was significantly higher in hypometabolic patients exhibiting low Rest Energy Expenditure (p = 0.03). Patients exhibiting ΔPAD > 1% had significantly lower serum albumin level (p = 0.03), and higher nutritional risk (p = 0.02), compared to others. Unlike Nivolumab therapy, there was no increase of PAD after chemotherapy in the same cohort of patients with available scans (n = 45, 25.9 ± 2.9 mm pre-chemotherapy versus 25.7 ± 2.4 mm post-chemotherapy, p = 0.51). Anti-PD-1 treatment was associated with immune-related adverse events in 11 (18.6%) cases including 2 cases of life-threatening acute pulmonary hypertension, both exhibiting post-treatment PAD/AoD ratio > 1. CONCLUSION: Nivolumab is associated to PAD enlargement, a potential marker of pulmonary hypertension, sometimes leading to lethal adverse events. Careful CT-scan and echocardiographic evaluation of PAD should be part of the therapeutic work-up of patients receiving Nivolumab, especially those suffering cancer-associated malnutrition.
PURPOSE: The widespread use of Nivolumab results in an increasing number of side effects and adverse events. Herein, we evaluated the impact of Nivolumab on crude and normalized pulmonary artery diameter (PAD). METHODS: We analyzed clinical, morphometric, pathological and radiological data of lung cancerpatients treated by Nivolumab in an 18-month period. Blinded radiological evaluation was performed, by three observers measuring axial PAD and Aorta diameter (AoD) in secondarily matched pre- and post-Nivolumab CT-scans. Correlation between ΔPAD and clinicopathological data was investigated. RESULTS: 59 patients receiving Nivolumab for treatment of advanced lung carcinoma were identified. Pre-and post-Nivolumab comparison of CT-scan measures revealed that mean PAD was 26.3 ± 2.8 mm versus 28.0 ± 3.0 mm (p < 0.001), and mean PAD/AoD ratio was 0.82 ± 0.09 versus 0.87 ± 0.11 (p < 0.001), respectively. Median ΔPAD was 0.05 [0.01-0.122] was significantly higher in hypometabolic patients exhibiting low Rest Energy Expenditure (p = 0.03). Patients exhibiting ΔPAD > 1% had significantly lower serum albumin level (p = 0.03), and higher nutritional risk (p = 0.02), compared to others. Unlike Nivolumab therapy, there was no increase of PAD after chemotherapy in the same cohort of patients with available scans (n = 45, 25.9 ± 2.9 mm pre-chemotherapy versus 25.7 ± 2.4 mm post-chemotherapy, p = 0.51). Anti-PD-1 treatment was associated with immune-related adverse events in 11 (18.6%) cases including 2 cases of life-threatening acute pulmonary hypertension, both exhibiting post-treatment PAD/AoD ratio > 1. CONCLUSION:Nivolumab is associated to PAD enlargement, a potential marker of pulmonary hypertension, sometimes leading to lethal adverse events. Careful CT-scan and echocardiographic evaluation of PAD should be part of the therapeutic work-up of patients receiving Nivolumab, especially those suffering cancer-associated malnutrition.
Authors: Ruben Mylvaganam; Ryan Avery; Isaac Goldberg; Courtney Makowski; Ravi Kalhan; Victoria Villaflor; Michael J Cuttica Journal: Pulm Circ Date: 2021-02-09 Impact factor: 3.017