Radiation Induced Abscopal Effect in a Patient With Malignant Pleural Mesothelioma on Pembrolizumab

Our plain-English summary of Radiation Induced Abscopal Effect in a Patient With Malignant Pleural Mesothelioma on Pembrolizumab, by R. Rittberg, E. Chan, S. Yip, et al (Curēus, 2022).

The study

• Authors: R. Rittberg, E. Chan, S. Yip, D. Alex, C. Ho
• Journal: Curēus
• Published: 2022;14(2):e22159
• Type of article: Case report
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Abscopal effect is a rare phenomenon in which treatment benefit from radiotherapy (RT) is seen outside the target field due to activation of the immune system inducing an anti-tumor effect. This phenomenon has been reported in cancer patients receiving immune checkpoint inhibitors (ICI). Here we report a case of presumed abscopal effect in malignant mesothelioma. The patient received second-line single-agent pembrolizumab however had disease progression after four cycles leading to palliative RT (20 Gray) to the right mainstem bronchus. Follow-up radiographic imaging confirmed benefit and pembrolizumab was continued. Follow-up computed tomography (CT) five months after RT, showed marked radiographic improvement of all measurable diseases with improvement in right-sided aerated lung volume. Because of the original disease progression on pembrolizumab, with marked improvements within and outside the RT field after RT, treatment response was presumed due to the abscopal effect.

Copyright © 2022, Rittberg et al.

In plain English

This case report described a 68-year-old man with a history of asbestos exposure and epithelial malignant pleural mesothelioma. The article did not say how he was exposed. Chemotherapy with carboplatin and pemetrexed reduced tumor size, but the disease later progressed. He then started second-line pembrolizumab, an immunotherapy drug, and during the first four cycles there was concern the disease was still progressing. Because of worsening breathlessness and tumor pressing on the right main airway, the patient received palliative radiotherapy (20 Gray in five fractions), and pembrolizumab was continued. A CT scan five months after radiotherapy showed marked improvement, including areas well outside the radiation field. The estimated air-filled right lung rose from 15% to 90%, the airway compression resolved, and a chest wall mass shrank. After 13 cycles of pembrolizumab, his breathlessness worsened rapidly, with worsening fluid around the lung (pleural effusion) and lung infiltration, and he died 43 months after diagnosis. The authors presumed this was an abscopal effect, meaning a response to radiotherapy outside the treated area. They stated that a delayed response to pembrolizumab could not be entirely excluded.

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 (single patient)
• Who was studied: One 68-year-old male patient with a history of asbestos exposure, diagnosed by pleural biopsy with epithelial malignant pleural mesothelioma judged inoperable; place and dates of treatment not stated
• Exposure: A history of asbestos exposure, with no fiber type, job or dose described. The treatments described were carboplatin and pemetrexed chemotherapy, then second-line pembrolizumab 200 mg every 21 days, plus palliative radiotherapy of 20 Gray in five fractions.
• Main results:
  • First-line carboplatin and pemetrexed chemotherapy reduced tumor size before the disease later progressed
  • During the first four cycles of pembrolizumab there was concern about clinical and radiographic progression
  • Because of progressive breathlessness and compression of the right mainstem bronchus, the patient received palliative radiotherapy of 20 Gray in five fractions to the right mediastinal pleura
  • Radiotherapy began to improve the patient's breathlessness, so a planned switch to chemotherapy did not happen and pembrolizumab was continued
  • CT five months after radiotherapy showed marked improvement, including regions well outside the radiation field
  • Before radiotherapy, after 4 cycles of pembrolizumab, the approximated aerated right lung was 15%
  • Five months after radiotherapy, after 12 cycles of pembrolizumab, the approximated aerated right lung was 90%
  • Compression of the right mainstem bronchus resolved, and the lateral chest wall mass decreased
  • The lateral chest wall mass measured 23x80 mm on the CT five months after radiotherapy, compared with 75x146 mm before radiotherapy
  • Pembrolizumab was given for a total of 13 cycles
  • After pembrolizumab, the patient had rapidly worsening breathlessness with worsening pleural effusion and lung infiltration; pneumonitis was ruled out
  • The patient's clinical status deteriorated rapidly, and he died 43 months after the original diagnosis of unresectable malignant mesothelioma
• The authors' conclusion: The authors presented the response as a presumed abscopal effect from radiotherapy combined with immunotherapy. They described added immune activation with radiotherapy as a hypothetical way to improve treatment response. They said many questions remain unanswered, including the best radiotherapy dose, fractionation and timing with immunotherapy.
• Limitations the authors state:
  • The authors stated that a delayed response to pembrolizumab cannot be entirely excluded, although they considered it extremely unlikely after progression over four cycles

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Pembrolizumab (Keytruda), checkpoint inhibitors, Mesothelioma, Disease Progression, Palliative Care, Bronchus.

Related studies

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• Radiation-induced mesothelioma among long-term solid cancer survivors: a longitudinal analysis of SEER database — A. Farioli, M. Ottone, et al. (2016)
• Pravastatin reduces radiation-induced damage in normal tissues — H. Doi, S. Matsumoto, et al. (2017)

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