STRN -ALK Rearranged Malignant Peritoneal Mesothelioma With Dramatic Response Following Ceritinib Treatment

Our plain-English summary of STRN -ALK Rearranged Malignant Peritoneal Mesothelioma With Dramatic Response Following Ceritinib Treatment, by J.H. Rüschoff, E. Gradhand, A. Kahraman, et al (JCO Precision Oncology, 2019).

The study

• Authors: J.H. Rüschoff, E. Gradhand, A. Kahraman, H. Rees, J.L. Ferguson, A. Curioni-Fontecedro, M. Zoche, H. Moch, B. Vrugt
• Journal: JCO Precision Oncology
• Published: 2019;3
• Type of article: Case report
• Cited by: 39 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

In plain English

This case report described a previously healthy 13-year-old girl with malignant epithelioid mesothelioma of the peritoneum (abdominal lining). She had four months of increasing abdominal size. Scans showed large-volume fluid in the abdomen (ascites), widespread tumor deposits and swelling of both kidneys (hydronephrosis). The article states she had no history of asbestos or radiation exposure. Genetic testing of the tumor found a fusion of two genes, STRN and ALK. Four cycles of cisplatin and pemetrexed chemotherapy produced no response, and surgery was judged unsuitable. She then received ceritinib, a drug that targets ALK, at 450 mg once a day, used off-label. Scans 6 and 12 weeks later showed significant tumor reduction, less ascites, and resolution of the hydronephrosis. Apart from a temporary rise in the liver enzyme ALT, no side effects were noted. The authors also reported, from their unpublished data, no ALK expression in tumor samples from 221 pleural mesothelioma patients. The authors advised ALK fusion screening in peritoneal mesothelioma, especially in young patients. They said larger groups must be studied to learn how well and how long such treatment works.

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 previously healthy 13-year-old girl with malignant peritoneal mesothelioma. The article does not state the country or the dates of care.
• Exposure: No asbestos exposure: the article states she had no history of asbestos or radiation exposure. The study concerns a genetic alteration (STRN-ALK fusion) and treatment with the ALK inhibitor ceritinib, not an asbestos exposure.
• Main results:
  • Peritoneal biopsies met the criteria for malignant epithelioid mesothelioma.
  • Genomic profiling of the tumor found an isolated STRN-ALK rearrangement. Mutational burden was low and microsatellites were stable. FISH showed a 5′ ALK deletion in 96% of the patient's tumor cells.
  • BAP-1, p16 and MTAP protein expression were retained in the tumor.
  • Initial chemotherapy with four cycles of cisplatin and pemetrexed gave no clinical or radiologic response.
  • The patient was then treated with off-label oral ceritinib 450 mg once per day.
  • Imaging after starting ceritinib showed a significant reduction in tumor bulk and in the volume of ascites, and the hydronephrosis resolved.
  • At 12 weeks after starting ceritinib there was a further reduction in the volume of peritoneal disease and ascites.
  • Apart from a transient, self-limiting rise in alanine aminotransferase (ALT), no adverse effects were noted.
  • In their own unpublished data, the authors found no ALK expression in a tissue microarray of tumor samples from 221 patients with pleural mesothelioma.
• The authors' conclusion: The authors concluded that, based on the success of ALK inhibition in this patient, ALK fusion screening by comprehensive genomic profiling is highly advised in peritoneal mesothelioma, especially in young patients.
• Limitations the authors state:
  • The authors stated that a larger cohort is needed to determine the efficacy and durability of ALK inhibition, and that such a trial is difficult because this subtype is rare.

Topics

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma.

Related studies

• Complete pathological response after ceritinib for anaplastic lymphoma kinase-rearranged epithelioid peritoneal mesothelioma — S. Sakata, H. Rees, et al. (2021)
• STRN-ALK rearranged pediatric malignant peritoneal mesothelioma - Functional testing of 527 cancer drugs in patient-derived cancer cells — A. Murumägi, D. Ungureanu, et al. (2021)
• Dramatic tumour response to pemetrexed single-agent in an elderly patient with malignant peritoneal mesothelioma: a case report — G. Fasola, F. Puglisi, et al. (2006)
• STRN-ALK Fusion in a Case of Malignant Peritoneal Mesothelioma: Mixed Response to Crizotinib, Mode of Resistance, and Brigatinib Sequential Therapy — V. Gerthofer, A. Scheiter, et al. (2021)
• A Novel Malignant Peritoneal Mesothelioma with STRN Exon 2 and ALK Exon 20: A Case Report and Literature Review — C. Miyagawa, H. Takaya, et al. (2021)
• Chromosome 3 and 12p rearranged in a well-differentiated peritoneal mesothelioma — H.J. Decker, F.P. Li, et al. (1990)

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