Microsatellite Instability Is Insufficiently Used as a Biomarker for Lynch Syndrome Testing in Clinical Practice.

PURPOSE: The pan-cancer presence of microsatellite instability (MSI)-positive tumors demonstrates its clinical utility as an agnostic biomarker for identifying immunotherapy-eligible patients. Additionally, MSI is a hallmark of Lynch syndrome (LS), the most prevalent cancer susceptibility syndrome among patients with colorectal and endometrial cancer. Therefore, MSI-high results should inform germline genetic testing for cancer-predisposing genes. However, in clinical practice, such analysis is frequently disregarded. METHODS: A next-generation sequencing (NGS)-based technique was used for MSI analysis in 4,553 patients with various tumor types. Upon request, somatic BRAF gene analysis was conducted. In addition, hereditary testing of cancer-associated genes was performed in MSI-high cases using a capture-based NGS protocol. MLH1 promoter methylation analysis was conducted retrospectively in patients with colorectal and endometrial cancer to further investigate the origin of MSI at the tumor level. RESULTS: The MSI positivity rate for the entire cohort was 5.27%. Endometrial, gastric, colorectal, urinary tract, and prostate cancers showed the highest proportion of MSI-high cases (15.69%, 8.54%, 7.40%, 4.55%, and 3.19%, respectively). A minority of 45 patients (22.73%) among the MSI-high cases underwent germline testing to determine whether the mismatch repair pathway deficiency was inherited. 24.44% of those who performed the genetic test carried a pathogenic variant in an LS-associated gene. Three MSI-high individuals had non-LS gene alterations, including BRCA1, BRCA2, and CDKN2A pathogenic variants, indicating the presence of non-LS-associated gene alterations among MSI-high patients. CONCLUSION: Although MSI analysis is routinely performed in clinical practice, as many as 77% of MSI-high patients do not undergo LS genetic testing, despite international guidelines strongly recommending it. BRAF and MLH1 methylation analysis could shed light on the somatic origin of MSI in 42.50% of the MSI-high patients; however, MLH1 analysis is barely ever requested in clinical practice.

Impact of Hippocampal Avoidance - Prophylactic Cranial Irradiation in Small Cell Lung Cancer Patients.

BACKGROUND/AIM: Prophylactic cranial irradiation (PCI) is a well-established treatment of small cell lung cancer (SCLC) patients following response to initial chemoradiotherapy. The benefit of PCI does, however, come at the cost of cognitive decline. This has been attributed to radiation-induced toxicity at the hippocampus, a crucial anatomic area for cognition. Modern radiotherapy techniques allow dose reduction at the hippocampal region. In this review, the safety profile, effect on cognition, and changes on brain imaging modalities of hippocampal avoidance-PCI (HA-PCI) will be presented, aiming to identify a potential clinical rationale for SCLC patients. MATERIALS AND METHODS: A systematic review of the literature was performed in Pubmed, Cochrane library databases and ClinicalTrials.gov with no past date limitations until 07/01/2022. Principles as outlined in the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement were followed. RESULTS: Eight studies published from 2015 to 2021 were included. CONCLUSION: HA-PCI is safe, yet its effect on neurocognition and imaging remains unclear, as studies have shown contradictory results.

Primary Sarcoma of the Lung - Prognostic Value of Clinicopathological Characteristics of 26 Cases.

BACKGROUND/AIM: Primary sarcomas of the lung (PSL) represent a rare, largely unknown entity. We herein present a retrospective study of 26 patients diagnosed with PSL. PATIENTS AND METHODS: For a period of 10 years, the records of patients from 5 centers were gathered and analyzed. RESULTS: Median age at diagnosis was 61.96 years (range=31-75 years). Eight patients (33.33%) had mediastinal node invasion (MNI). From 17 patients (70.83%) with localized disease, 11 patients (64.70%) underwent surgery. Recurrence rate was 72.72%. Median disease-free interval was 15 months. The median overall survival (OS) of patients with metastatic disease was 4 months and 10 months for the whole population. Only surgery had an impact on survival. CONCLUSION: Prognosis of PSL is somber. The high proportion of patients with MNI at diagnosis may serve as an indication for surgical evaluation of mediastinum and raises the question whether patients with locoregional PSL should be treated with a more aggressive approach.