Proton Beam Therapy and Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma

Our plain-English summary of Proton Beam Therapy and Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma, by M.G. McCusker, K.A. Scilla, C.B. Simone, et al (Journal of Thoracic Oncology, 2019).

The study

• Authors: M.G. McCusker, K.A. Scilla, C.B. Simone, A. Sachdeva, K.D. Miller, A.P. Burke, C. Rolfo
• Journal: Journal of Thoracic Oncology
• Published: 2019;14(9):e185-e187
• Type of article: Case report
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

The authors described a patient with malignant pleural mesothelioma (MPM) who developed life-threatening toxicities after proton beam therapy was followed by an immune checkpoint inhibitor. The patient was a 69-year-old woman who had never smoked, with unresectable stage IV biphasic MPM. She received carboplatin and pemetrexed. After cycle three, imaging showed persistent bulky pleural disease and new right lung progression. Chemotherapy was stopped, and pencil beam scanning proton therapy was given to the entire pleura, to a total dose of 54 Gy to bulky disease sites. She tolerated it well, with near total pain control and grade 2 nausea and esophagitis that resolved. Three months later there was a strong right hemithorax response, but new metastatic foci had appeared in the right triceps and left pelvis. Thirty weeks after proton therapy her disease progressed, and nivolumab 240 mg was started on compassionate use. Two weeks after the first dose she had shortness of breath, grade 3 hypotension, tachycardia and hypoxia. Tests found a large pericardial effusion with grade 4 cardiac tamponade and grade 3 pneumonitis limited to the right lung. Pericardiocentesis removed 240 mL of fluid without malignant cells, and a biopsy showed alveolar injury. Corticosteroids led to rapid symptom resolution. The authors hypothesized that proton therapy caused immune "priming" and a later "recall" reaction. They concluded that the combination, particularly with very large treatment volumes, may worsen immune-related adverse events and needs further study.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This case report described one patient: a 69-year-old woman who had never smoked, with unresectable stage IV biphasic malignant pleural mesothelioma. Her disease progressed after three cycles of carboplatin and pemetrexed chemotherapy. She then received pencil beam scanning proton beam therapy to the entire pleura. Its side effects were limited to grade 2 nausea and grade 2 esophagitis, which resolved within 2 weeks. About 7 months later her disease progressed, and she received a single dose of the immune checkpoint inhibitor nivolumab (240 mg) on compassionate use. Two weeks later she had grade 3 pneumonitis limited to the right lung and a large pericardial effusion with grade 4 cardiac tamponade. Fluid drained from around the heart showed no malignant cells. With corticosteroid treatment her symptoms resolved rapidly. The authors hypothesized that proton therapy 'primed' the immune system and that nivolumab then triggered a severe immune response. They concluded that combining the two treatments, particularly over very large treatment areas, may have the potential to worsen immune-related side effects. The report did not discuss asbestos exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case report of a single patient
• Who was studied: One 69-year-old woman who had never smoked, with unresectable stage IV biphasic subtype malignant pleural mesothelioma; treated at the University of Maryland (place and dates not otherwise stated)
• Exposure: The article does not describe asbestos exposure. The exposures studied were treatments. The first was pencil beam scanning proton beam therapy to the whole pleura, at 45.0 Gy with boosts to a total dose of 54 Gy to bulky disease. This was followed months later by a single 240 mg intravenous dose of nivolumab, given after earlier carboplatin and pemetrexed chemotherapy.
• Main results:
  • After three cycles of carboplatin and pemetrexed, imaging showed persistent bulky pleural disease and new right lung disease progression.
  • The patient tolerated proton beam therapy well, with near total pain control. Side effects were limited to grade 2 nausea and grade 2 esophagitis, both resolving within 2 weeks.
  • Three months after proton therapy, imaging showed a strong response in the right chest, with residual disease only in the major fissure of the right lung. It also showed new metastatic foci in the right triceps and left pelvis.
  • Two weeks after one dose of nivolumab, the patient had grade 3 pneumonitis limited to the right lung and a large circumferential pericardial effusion with grade 4 cardiac tamponade.
  • Fluid removed from around the heart (240 mL) showed reactive mesothelial cells and no malignant cells. A lung biopsy showed alveolar injury.
  • The patient received methylprednisolone for 12 days and then a 3-month corticosteroid taper, and her symptoms resolved rapidly.
  • The authors hypothesized that proton therapy caused an immune 'priming' and later 'recall' phenomenon, which nivolumab then triggered.
• The authors' conclusion: The authors concluded that immune checkpoint inhibitors and proton beam therapy, used in combination and particularly over very large treatment volumes, may have the potential to worsen immune-related adverse events. They called for future studies.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Proton Therapy, checkpoint inhibitors, Pleural Mesothelioma, Unresectable, Biphasic Mesothelioma, Carboplatin, Pemetrexed (Alimta), Chemotherapy.

Related studies

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• Proton therapy for thoracic malignancies: a review of oncologic outcomes — N.V. Patel, N.Y. Yu, et al. (2021)
• Immune checkpoint inhibitors in non-small cell lung cancer (NSCLC): Approaches on special subgroups and unresolved burning questions — J. Remon, N. Vilariño, et al. (2018)
• Biomarkers for immune checkpoint inhibitors — L.A. Lievense, J.P. Hegmans, et al. (2014)
• Biomarkers for immune checkpoint inhibitors--authors' reply — L. Calabrò, M. Maio (2014)

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