bims-myxlip 2021-01-31 papers

Issue of 2021–01–31
three papers selected by
Laura Mannarino, Mario Negri Institute

Dtsch Med Wochenschr. 2021 Feb;146(3): 157-161

[Treatment of soft tissue sarcomas including GIST - Update 2021].

Soft tissue sarcomas are rare tumors that represent a major challenge due to varying clinical presentations and often interdisciplinary treatment concepts. Gold standard for the treatment of localized resectable soft tissue sarcomas is complete surgical removal. So far, multimodality treatment does not represent a clininal standard. However, several newer analyses and studies suggest that a subgroup of patients seems to derive an overall survival benefit from perioperative chemotherapy. In metastatic soft tissue sarcoma systemic therapy is the treatment of choice. Most active drugs are the anthracyclines and ifosfamide. Combination chemotherapy has improved both response rate and progression-free survival at the costs of increased toxicity in comparison to single agent therapy but without impact on overall survival in first-line therapy. In pretreated patients, treatment options consist of trabectedin, pazopanib, gemcitabine plus docetaxel or DTIC, and eribulin. Recent data have shown that histiotype-specific treatment options including targeted therapy represent a major improvement for several sarcoma subtypes.In GIST, imatinib is the gold standard for patients with advanced or metastatic disease. In imatinib refractory or intolerant patients, sunitinib in an individualized treatment schedule is recommended. Regorafenib has been approved for third-line therapy. Recently, avapritinib has been approved for treatment of patients with the so far resistant D842V mutation in the PDGFRA exon 18. Ripretinib has shown very promising activity in forth and further lines of therapy and is already approved in the US. The use of adjuvant imatinib therapy in patients with completely resected localized GIST with a high risk of recurrence has significantly improved overall survival with a treatment duration of 3 years. These results have now been confirmed with a 10 years follow-up analysis.

DOI: https://doi.org/10.1055/a-1170-7731

Oncol Lett. 2021 Mar;21(3): 212

Immunological status of peripheral blood is associated with prognosis in patients with bone and soft-tissue sarcoma.

Youngji Kim, Eisuke Kobayashi, Yoshiyuki Suehara, Ayumu Ito, Daisuke Kubota, Yoshikazu Tanzawa, Makoto Endo, Fumihiko Nakatani, Tetsuya Nakatsura, Akira Kawai, Kazuo Kaneko, Shigehisa Kitano.

Immune-checkpoint inhibitors have shown promising antitumor effects against certain types of cancer. However, specific immune-checkpoint inhibitors for patients with sarcoma have yet to be identified, whereas the immunological status of peripheral blood in patients with bone sarcoma and soft-tissue sarcoma (STS) remains unknown. In addition, it is unclear whether the immunological status from the peripheral blood could be used as a prognostic indicator. Therefore, the present study aimed to clarify the immunological status of peripheral blood samples derived from patients with bone sarcoma and STS. Immune monitoring was performed using the peripheral blood samples of 61 patients with no metastasis of high-grade sarcoma. A total of 25 patients with metastatic sarcoma were used for comparison. A total of 41 immune cell subsets were analyzed using multicolor-flow cytometry. The patients that did not have metastasis demonstrated higher quantities of monocytic myeloid-derived suppressor cells (M-MDSCs) and T cell immunoglobulin and mucin domain-3 (Tim-3)+ CD8+ T cells, which were significantly associated with poor disease-free survival (DFS) time, while higher quantities of NKG2D+ CD8+ T cells were significantly associated with improved DFS time. Multivariate Cox regression analysis demonstrated that the number of Tim-3+ CD8+ T cells was associated with lower DFS time. A significant association was also found between the number of M-MDSCs and progression-free survival (PFS) time in patients with metastasis. The results suggested the occurrence of immune surveillance, which indicated that the host immune reaction against cancer existed in patients with bone sarcoma and STS. Notably, a high number of M-MDSCs was associated with both DFS and PFS time, suggesting a strong prognostic value. The data suggested that the immune status of peripheral blood was associated with the prognosis in patients with sarcoma, as previously reported in patients with other cancer types. In summary, the results may assist with the development of novel strategies for sarcoma treatment, based on the use of biomarkers or immunotherapy.

Keywords: T cell immunoglobulin and mucin domain 3; bone and soft-tissue sarcoma; immunological status; myeloid-derived suppressor cells; natural killer group 2 member D

DOI: https://doi.org/10.3892/ol.2021.12473

Front Oncol. 2020 ;10 599816

Identification of Iron Metabolism-Related Gene Signatures for Predicting the Prognosis of Patients With Sarcomas.

Jianyi Li, Chuan Hu, Yukun Du, Xiaojie Tang, Cheng Shao, Tongshuai Xu, Zheng Zhao, Huiqiang Hu, Yingyi Sheng, Jianwei Guo, Yongming Xi.

Iron is one of the essential trace elements in the human body. An increasing amount of evidence indicates that the imbalance of iron metabolism is related to the occurrence and development of cancer. Here, we obtained the gene expression and clinical data of sarcoma patients from TCGA and the GEO database. The prognostic value of iron metabolism-related genes (IMRGs) in patients with sarcoma and the relationship between these genes and the immune microenvironment were studied by comprehensive bioinformatics analyses. Two signatures based on IMRGs were generated for the overall survival (OS) and disease-free survival (DFS) of sarcoma patients. At 3, 5, and 7 years, the areas under the curve (AUCs) of the OS signature were 0.708, 0.713, and 0.688, respectively. The AUCs of the DFS signature at 3, 5, and 7 years were 0.717, 0.689, and 0.702, respectively. Kaplan-Meier survival analysis indicated that the prognosis of high-risk patients was worse than that of low-risk patients. In addition, immunological analysis showed that there were different patterns of immune cell infiltration among patients in different clusters. Finally, we constructed two nomograms that can be used to predict the OS and DFS of sarcoma patients. The C-index was 0.766 (95% CI: 0.697-0.835) and 0.763 (95% CI: 0.706-0.820) for the OS and DFS nomograms, respectively. Both the ROC curves and the calibration plots showed that the two nomograms have good predictive performance. In summary, we constructed two IMRG-based prognostic models that can effectively predict the OS and DFS of sarcoma patients.

Keywords: The Cancer Genome Atlas (TCGA); iron metabolism-related genes; nomogram; prognostic signature; sarcoma

DOI: https://doi.org/10.3389/fonc.2020.599816