A woman with a pleural mesothelioma and an inherited ATM mutation-a case report

Our plain-English summary of A woman with a pleural mesothelioma and an inherited ATM mutation-a case report, by M. Seca, B.C.J. Cho, A. Tryon, et al (Annals of Translational Medicine, 2025).

The study

• Authors: M. Seca, B.C.J. Cho, A. Tryon, S.A. Narod
• Journal: Annals of Translational Medicine
• Published: 2025;13(1):8
• Type of article: Case report
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Pleural mesothelioma (PM) is a rare and aggressive malignancy primarily linked to asbestos exposure. Up to 80% of patients have a history of such exposure. Several studies have investigated the possibility of a genetic predisposition for a subgroup of PM patients, but the data remains inconsistent. The ataxia-telangiectasia mutated (ATM) gene, crucial for DNA repair, is implicated in cancer susceptibility, with heterozygous mutations increasing risks, notably in breast and pancreatic cancers.

Case Description: We present a case of a 42-year-old woman, with no asbestos exposure history, diagnosed with metastatic PM. Initial treatment with immunotherapy showed limited efficacy. Given the rarity in young females, she opted for genetic testing via "The Screen Project", revealing a pathogenic ATM mutation. Due to enhanced radiosensitivity in ATM mutation carriers, to reduce adverse events conventional palliative radiotherapy (RT) was chosen over stereotactic hypofractionated RT. A follow-up computed tomography (CT) scan after 4 weeks indicated disease burden reduction.

Conclusions: This case highlights the importance of genetic testing in atypical PM cases, guiding treatment decisions tailored to individual genetic profiles. Awareness of ATM mutations can optimize therapeutic strategies, particularly regarding RT choices, in managing this challenging malignancy. Integrating genetic insights into clinical practice holds promise for enhancing treatment outcomes and refining management strategies in PM and related conditions.

Copyright © 2025 AME Publishing Company. All rights reserved.

In plain English

This article is a case report about a single patient. In November 2023, a 42-year-old woman who did not smoke went to an emergency department with shortness of breath, cough, fever and chest pain. To her knowledge, she had never been exposed to asbestos, either at work or in the environment. Tests showed a diffuse biphasic pleural mesothelioma that had spread, so surgery was ruled out. She was given the immunotherapy drugs nivolumab and ipilimumab. A scan after 8 weeks showed a partial response, but she still had severe fatigue and breathlessness and needed oxygen. She chose to have genetic testing, which found a harmful change (a pathogenic mutation) in the ATM gene, a gene involved in repairing DNA. People with ATM mutations can be more sensitive to radiation. Her doctors therefore chose a conventional palliative radiotherapy course of 20 Gy in 5 daily fractions rather than a more hypofractionated course. Ten days later she developed esophagitis and fever, which were treated with dexamethasone. A scan after 4 weeks showed less disease. The authors concluded that finding genetic mutations in mesothelioma patients is crucial for personalizing treatment.

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 one patient, with a discussion of earlier published studies
• Who was studied: One 42-year-old woman with no smoking history and an unremarkable medical background, who presented in November 2023. She had one maternal and one paternal relative with postmenopausal breast cancer.
• Exposure: No asbestos exposure was reported. To her knowledge, she had never been exposed to asbestos, environmentally or occupationally. The genetic factor described was a pathogenic ATM gene mutation.
• Main results:
  • Thoracentesis and pleural biopsy led to a diagnosis of diffuse biphasic pleural mesothelioma. A PET scan showed metastasis and invasion of surrounding structures.
  • After 8 weeks of first-line immunotherapy (nivolumab and ipilimumab every 3 weeks), a CT scan showed a partial response. She continued to have severe fatigue and shortness of breath requiring oxygen therapy.
  • Genetic testing through "The Screen Project" (next-generation sequencing) found a pathogenic ATM gene mutation, c.2377-2A>G.
  • Because of the enhanced radiosensitivity of ATM mutation carriers, she received conventional palliative radiotherapy of 20 Gy in 5 daily fractions. More hypofractionated courses, such as 30 Gy in 5 daily fractions, had been considered.
  • Ten days after radiotherapy she had esophagitis graded G2 and fever graded G1.
  • The esophagitis and fever were managed with a 7-day course of dexamethasone 4 mg, with what the authors called an excellent response.
  • A CT scan 4 weeks after radiotherapy showed a reduction in disease burden.
• The authors' conclusion: The authors concluded that identifying genetic mutations in patients with pleural mesothelioma is crucial for personalizing treatment and improving outcomes, because it may affect response to conventional and novel therapies. They also recommended that all patients with pleural mesothelioma be tested for a wide panel of genetic mutations, including ATM.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Asbestos Exposure, Immunotherapy, Palliative Care.

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