bims-lifras 2023-09-10 papers

Issue of 2023‒09‒10
three papers selected by
Joanna Zawacka-Pankau, Karolinska Institutet

IJU Case Rep. 2023 Sep;6(5): 286-289

A case of sequential medical therapy for advanced ureteral cancer in Li-Fraumeni syndrome.

Minami Une, Ryo Fujiwara, Arisa Ueki, Ryosuke Oki, Tetsuya Urasaki, Kentaro Inamura, Shunji Takahashi, Junji Yonese, Takeshi Yuasa.

Introduction: Li-Fraumeni syndrome, an autosomal dominant cancer predisposition syndrome caused by a pathogenic variant of TP53, a tumor suppressor gene, leads to a high risk from early childhood of developing various types of cancers. Here, we report a case of advanced ureteral cancer in Li-Fraumeni syndrome.Case presentation: A 73 years-old female patient, who had been diagnosed genetically as Li-Fraumeni syndrome; suffered from chondrosarcoma in the left pelvic joint, bilateral breast cancer, endometrial cancer, gastric cancer, and colon cancer in her history. She was diagnosed as unresectable advanced urothelial cancer during continuous magnetic resonance imaging surveillance, underwent avelumab maintenance therapy after the combination of gemcitabine and cisplatin chemotherapy. The efficacies of gemcitabine and cisplatin chemotherapy and avelumab maintenance therapy were good.
Conclusion: We report an advanced urothelial cancer in a patient with Li-Fraumeni syndrome who demonstrated good efficacies to sequential medical therapy.

Keywords: Li–Fraumeni syndrome; TP53 pathogenic variant; advanced urothelial cancer; avelumab; immune checkpoint inhibitor

DOI: https://doi.org/10.1002/iju5.12607

Am J Hematol. 2023 Sep 04.

Characteristics and clinical outcomes of patients with myeloid malignancies and DDX41 variants.

DDX41 is the most frequently mutated gene in myeloid neoplasms associated with germline predisposition including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We analyzed 3795 patients with myeloid neoplasms and identified 151 (4%) with DDX41 variants and a diagnosis of AML (n = 96), MDS (n = 52), and chronic myelomonocytic leukemia (n = 3). The most frequent DDX41 variants were the somatic variant p.R525H, followed by the germline variants p.M1I and p.D140fs. Most neoplasms had a normal karyotype (59%) and the most frequent co-mutations were TP53 (16%) and ASXL1 (15%). 30% of patients had no concomitant mutations besides DDX41 mutation. Patients with myeloid malignancies and DDX41 variants responded well to therapy, with an overall response rate for patients with treatment naïve AML and MDS of 87% and 84%, respectively. The median overall survival (mOS) of patients with treatment-naïve AML or MDS was 49 and 71 months, respectively. Patients with AML treated with low-intensity regimens including venetoclax had an improved survival (2-year OS 91% vs. 60%, p = .02) and lower cumulative incidence of relapse compared to those treated without venetoclax (10% vs. 56%, p = .03). In the 33% of patients receiving hematopoietic stem cell transplantation, the 2-year OS was 80% and 85% for AML and MDS, respectively.

DOI: https://doi.org/10.1002/ajh.27070

Hered Cancer Clin Pract. 2023 Sep 08. 21(1): 17

Familial pancreatic cancer: a case study and review of the psychosocial effects of diagnoses on families.

Tracy Lowe, Jane DeLuca, Ludovico Abenavoli, Luigi Boccuto.

BACKGROUND: Familial pancreatic cancer touches families through a genetic susceptibility to developing this neoplasia. Genetic susceptibility is assessed via family history, genetic testing, or both. Individuals with two or more first-degree relatives or three or more relatives of any degree diagnosed with pancreatic cancer are considered at elevated risk. Following a diagnosis of familial pancreatic cancer, patients and families face uncertainty and anxiety about the future. Psychosocial effects of a pancreatic cancer diagnosis on families include fear, concerns about personal health, and how lifestyle may impact the risk of developing pancreatic cancer.CASE PRESENTATION: A 66-year-old male was diagnosed with pancreatic ductal adenocarcinoma stage IIB, T3, N1, M0. A genetic referral was made due to a history of multiple cases of pancreatic cancer within the patient's family. Genetic testing revealed the patient had a pathogenic variant in the ATM gene that is associated with an increased risk for pancreatic cancer development. The patient's one adult child was offered testing due to the autosomal dominant pattern of inheritance for this variant. The adult child was found to have the same pathogenic variant. She expressed fear for her future and her child's future health and longevity. Discussing a case study allows us to capture the multi-faceted relationship between the disease, the affected individuals, and their families. Examining the psychosocial stresses and concerns when there is a pancreatic cancer diagnosis in the family is essential to provide holistic care to patients and families.
CONCLUSIONS: The psychosocial effects of FPC may be overwhelming for patients and families. Healthcare providers can offer education, support, and referrals to appropriate services to help families cope through stages of evaluation, diagnosis, and treatment of FPC.

Keywords: Familial pancreatic cancer; Genetics; Psychosocial impact; Screening

DOI: https://doi.org/10.1186/s13053-023-00261-5