bims-myxlip 2024-05-05 papers

Issue of 2024–05–05
three papers selected by
Laura Mannarino, Humanitas Research

Anticancer Res. 2024 May;44(5): 2125-2132

Predicting Trabectedin Efficacy in Soft Tissue Sarcoma: Inflammatory Biomarker Analysis.

BACKGROUND/AIM: Trabectedin is used as a treatment for advanced-stage soft tissue sarcomas (STSs), particularly liposarcoma and leiomyosarcoma. Aside from its direct effect on tumor cells, trabectedin can affect the immune system in the tumor microenvironment. This study aimed to evaluate whether inflammatory biomarkers predict trabectedin efficacy in STSs.
PATIENTS AND METHODS: We retrospectively reviewed the clinical features and outcomes of patients with STS treated with trabectedin at our institution between 2016 and 2020. The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation response index (SIRI=neutrophil × monocyte/lymphocyte) were calculated based on the blood samples obtained prior to trabectedin treatment initiation. Analyses of overall survival (OS) and progression-free survival (PFS) were performed according to various factors.
RESULTS: Of the 101 patients identified, 54 had L-sarcoma (leiomyosarcoma: 30; liposarcoma: 24), and 47 had other types of STSs. Elevated SIRI, NLR, PLR, LMR, and C-reactive protein (CRP) were associated with worse PFS (p<0.001, p=0.008, p=0.027, p=0.013, and p<0.001, respectively) according to the results of the univariate analysis. Multivariate analysis showed that elevated SIRI, other histology, and CRP were associated with poor PFS (p=0.007, p=0.008, and p=0.029, respectively). In addition, the multivariate analysis of OS showed that SIRI was an independent prognostic factor (hazard ratio=2.16, p=0.006).
CONCLUSION: Pretreatment SIRI can be considered a biomarker for the prognostic prediction of patients with STS treated with trabectedin.

Keywords: Predictive factor; soft tissue sarcoma; systemic inflammation response index; trabectedin

DOI: https://doi.org/10.21873/anticanres.17018

J Mol Histol. 2024 May 02.

An overview on liposarcoma subtypes: Genetic alterations and recent advances in therapeutic strategies.

Anju M S, Chandramohan K, Rexeena V Bhargavan, Thara Somanathan, Lakshmi Subhadradevi.

Liposarcoma (LPS) is a rare malignancy of adipocytic differentiation. According to World Health Organization classification, LPS comprises of four principle subtypes Atypical lipomatous tumor/Well-differentiated liposarcoma (ATL/WDLPS), Dedifferentiated liposarcoma (WDLPS), Myxoid liposarcoma (MLPS), and Pleomorphic liposarcoma (PLPS). Each subtype can develop at any location and shows distinct clinical behavior and treatment sensitivity. ATL/ WDLPS subtype has a higher incidence rate, low recurrence, and is insensitive to radiation and chemotherapy. DDLPS is the focal progression of WDLPS, which is aggressive and highly metastasizing. MLPS is sensitive to radiation and chemotherapy, with a higher recurrence rate and metastasis. PLPS subtype is highly metastasizing, has a poor prognosis, and exhibiting higher recurrence rate. Initial histological analysis provides information for the characterization of LPS subtypes', further molecular and genetic analysis provides certain subtype specifications, such as gene amplifications and gene fusions. Such molecular genetic alterations will be useful as therapeutic targets in various cancers, including the LPS subtypes. A wide range of novel therapeutic agents based on genetic alterations that aim to target LPS subtypes specifically are under investigation. This review summarizes the LPS subtype classification, their molecular genetic characteristics, and the implications of genetic alterations in therapeutics.

Keywords: Liposarcoma; Molecular genetics; Subtypes; Therapeutics

DOI: https://doi.org/10.1007/s10735-024-10195-4

Int J Gynecol Cancer. 2024 Apr 30. pii: ijgc-2023-005170. [Epub ahead of print]

Pegylated liposomal doxorubicin combined with trabectedin as a treatment option in uterine sarcomas: a single-institution retrospective analysis.

Magdalena Steinlechner, Laura Strobel, Katharina Leitner, Teresa L Pan, Barin Feroz, Christian Marth, Alain G Zeimet.

OBJECTIVE: The use of conventional doxorubicin in combination with trabectedin leads to a considerable prolongation of progression-free survival in the treatment of uterine sarcomas but is associated with dose-limiting toxicities. Significant progression-free survival improvement was recently obtained through treatment prolongation with trabectedin single agent. We hypothesize that the therapeutic index of pegylated liposomal doxorubicin combined with trabectedin could be superior to the combination with conventional doxorubicin due to a more favorable toxicity profile.
METHODS: In this retrospective cohort study, the clinical outcome was analyzed in patients with advanced or recurrent uterine sarcomas with measurable disease treated with pegylated liposomal doxorubicin 30 mg/m2 plus trabectedin 1.5 mg/m2 given every 3 weeks between January 2011 and April 2023 at the University Hospital in Innsbruck. Response evaluation was done every three cycles. Toxicity was evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria on 107 administered cycles.
RESULTS: A total of 21 patients were included in the study. In 67% (n=14) of patients, pegylated liposomal doxorubicin plus trabectedin was given as first-line treatment. One patient (5%) achieved a complete response and four (19%) a partial response, resulting in an objective response rate of 24%. Four other patients (19%) had stable disease. The median duration of the response was 14 months (range 3-74). Progression was recorded in 12 patients (57%). Median progression-free survival was 6 months (95% CI 1 to 11 months), while median overall survival was 26 months (95% CI 9 to 43 months). A median of 6 (range 1-11) cycles per patient were administered. Regarding grade ≥3 toxicity, neutropenia was recorded in 29%, thrombocytopenia in 14%, and febrile neutropenia in 19% of patients. Hematologic toxicity was the most frequent reason for dose delays (n=16) and dose reductions (n=5).
CONCLUSION: Our study found an overall clinical benefit for the combination of pegylated liposomal doxorubicin plus trabectedin in metastatic uterine sarcomas of 43% and appears to exhibit a favorable toxicity profile which allows prolonged administration of this regimen.

Keywords: Gynecology; Sarcoma

DOI: https://doi.org/10.1136/ijgc-2023-005170