First-ever Abscopal Effect after Palliative Radiotherapy and Immuno-gene Therapy for Malignant Pleural Mesothelioma

Our plain-English summary of First-ever Abscopal Effect after Palliative Radiotherapy and Immuno-gene Therapy for Malignant Pleural Mesothelioma, by A.R. Barsky, K.A. Cengel, S.I. Katz, et al (Curēus, 2019).

The study

• Authors: A.R. Barsky, K.A. Cengel, S.I. Katz, D.H. Sterman, C.B. Simone
• Journal: Curēus
• Published: 2019;11(2):e4102
• Type of article: Case report
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a highly aggressive disease, with few, if any, curative interventions. While there is growing interest in using immunotherapy and immuno-gene therapy to treat MPM, very limited data currently exist for combining these modalities with radiotherapy. Preclinical data suggest that radiotherapy may be combined with immunotherapy to produce disease regression, with abscopal effects in mice with MPM. We report the first-ever case of abscopal effect in a patient with MPM, following radiotherapy and immuno-gene therapy. The patient was a 67-year-old male with prior asbestos exposure who presented with progressive dyspnea and thoracic pain. He underwent partial right pleurectomy, pleural biopsy, and talc pleurodesis, with pathology revealing epithelioid MPM. A subsequent chest computed tomography (CT) scan and fluoro-deoxyglucose positron-emission tomography (FDG-PET) CT scan showed extensive, right-sided, fluoro-deoxyglucose (FDG) avid mass-like pleural thickening encasing the right lung, with likely mediastinal extension, nodal metastases, and vascular compression. He enrolled in a clinical trial in which he received intrapleural interferon-alpha gene therapy but needed to discontinue therapy due to supraventricular tachycardia and superior vena cava syndrome induced from tumor burden. He was emergently treated with palliative radiotherapy to 30 Gy in 10 fractions. He was then started on pemetrexed and cisplatin chemotherapy. His subsequent chest CT scan two months after radiotherapy completion showed a dramatic treatment response within, as well as outside of, the irradiated field. After completion of radiotherapy, he did experience radiation esophagitis requiring nasogastric tube placement. Herein, we highlight the feasibility and efficacy of combining immuno-gene therapy with palliative radiotherapy to produce a substantial treatment response and an abscopal effect in a patient with unresectable MPM.

In plain English

This case report describes a 67-year-old man, a former smoker with occupational asbestos exposure, whose epithelioid malignant pleural mesothelioma was too advanced for surgery. He joined a clinical trial and received one infusion of interferon-alpha gene therapy into the chest cavity. The second infusion was held after he developed a fast heart rhythm. Cardiologists favored the tumor pressing on blood vessels as the cause, but the authors could not rule out a link to the infusion. He then received urgent palliative radiotherapy (30 Gy in 10 fractions), followed by pemetrexed and cisplatin chemotherapy. After three chemotherapy cycles, a representative chest mass measured 1.2 x 8.5 cm, down from 3.9 x 9.1 cm two months earlier. The authors described response both inside and outside the radiation field, larger than they expected. They suggested this was potentially an "abscopal" effect, meaning tumor shrinking away from the treated area. He developed severe radiation esophagitis that required tube feeding. His disease later progressed, and he died in hospice care. The authors concluded that combining immuno-gene therapy with radiotherapy was feasible and could produce an abscopal effect. The report describes this one patient only.

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 67-year-old man, a former smoker with prior occupational asbestos exposure and recurrent bronchitis, with epithelioid malignant pleural mesothelioma (clinical T4, not a surgical candidate); family history of mesothelioma in a maternal uncle
• Exposure: Prior occupational asbestos exposure (no fiber type, job or dose given). The treatments described were one intrapleural interferon-alpha gene therapy infusion, then palliative radiotherapy of 30 Gy in 10 fractions, then pemetrexed and cisplatin chemotherapy.
• Main results:
  • Pathology review of the earlier pleural biopsy was consistent with malignant epithelioid mesothelioma.
  • He received only the first gene therapy infusion. The second was held after supraventricular tachycardia that required adenosine.
  • Cardiology favored tumor burden with vascular compression as the most likely cause of his heart symptoms. Because of the timing, the authors said a relationship to the gene therapy could not be definitively excluded.
  • His shortness of breath improved rapidly during radiotherapy.
  • After three cycles of chemotherapy, a representative right paratracheal mass measured 1.2 x 8.5 cm, compared with 3.9 x 9.1 cm two months earlier.
  • After six chemotherapy cycles, CT showed continued improvement, with profound response in the treated side of the chest and no evidence of pericardial disease on the opposite side.
  • The authors judged the response to be greater than expected for the volume irradiated and the dose used, and suggested it was potentially an abscopal effect.
  • He developed severe radiation esophagitis and weight loss, which required hospitalization, nasogastric tube feeds and opioid pain relief.
  • His disease later progressed despite maintenance pemetrexed and then gemcitabine. He moved to hospice care and died three months later.
• The authors' conclusion: The authors concluded that immuno-gene therapy combined with radiotherapy in malignant pleural mesothelioma was feasible and capable of producing durable locoregional and distant disease control, as well as an abscopal effect.
• Limitations the authors state:
  • The patient did not receive the initially planned treatment regimen.
  • A link between the heart rhythm problem and the gene therapy infusion could not be definitively excluded.
  • The authors raised the possibility that the recent gene therapy made him more susceptible to the severe esophagitis.

Topics

Medical terms in this study, explained in our Lexicon: Palliative Care, Pleural Mesothelioma, Immunotherapy, Asbestos Exposure, Dyspnea, Pleural Biopsy, Talc Pleurodesis, Pathology.

Related studies

• Initial clinical experience treating patients with palliative radiotherapy for malignant pleural mesothelioma on the HalcyonTM linear accelerator — A.R. Barsky, M.M. Kim, et al. (2020)
• Re-evaluating the role of palliative radiotherapy in malignant pleural mesothelioma — P. Jenkins, R. Milliner, et al. (2011)
• High-dose palliative radiotherapy for malignant pleural mesothelioma — F. Foroudi, J.G. Smith, et al. (2017)
• Analysis of the effect of radiotherapy on malignant pleural mesothelioma when given on adjuvant or palliative basis — H.A. El Hossieny, F. Aboulkasem, et al. (2010)
• Malignant Pleural Mesothelioma in Patients Who Previously Received Radiotherapy for Their First Malignant Tumor — I. Sekine, Y. Yamamoto, et al. (2021)
• Lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma: an international, multi-centre, single-arm, phase II trial (SAKK 17/16) — Y. Metaxas, M. Früh, et al. (2020)

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