Pelvic osteosarcoma has a poor prognosis compared to osteosarcomas in other locations, and the reasons for this remain unknown. Surgical resection of pelvic osteosarcoma is technically demanding and often results in dysfunction and complications. In this study, we investigated the reasons underlying the poor prognosis of pelvic osteosarcoma by comparing it to femoral osteosarcoma using data from the Bone Tumor Registry in Japan. We used propensity score analysis to determine whether surgical resection of pelvic osteosarcoma improved its prognosis. We demonstrated that pelvic osteosarcoma had a poor prognosis because it occurred more often in the elderly, often had larger tumor size, and had metastasis at presentation more often in comparison to femoral osteosarcoma. These three factors were also associated with the non-surgical treatment of pelvic osteosarcoma, which also led to a poor outcome. The overall survival rate was only comparable in pelvic osteosarcoma and femoral osteosarcoma in cases treated with surgical resection. Propensity score analysis revealed that surgical treatment improved the prognosis of pelvic osteosarcoma. As such, we propose that surgical resection should be considered based on tumor stage and patient age in order to improve the prognosis of pelvic osteosarcoma.

Synovial sarcoma (SS), a rare subtype of soft-tissue sarcoma distinguished by expression of the fusion gene SS18-SSX, predominantly affects the extremities of young patients. Existing anticancer drugs have limited efficacy against this malignancy, necessitating the development of innovative therapeutic approaches. Given the established role of SS18-SSX in epigenetic regulation, we focused on bromodomain and extra-terminal domain protein (BET) inhibitors and epigenetic agents. Our investigation of the BET inhibitor ABBV-075 revealed its pronounced antitumor effects, inducing G1-phase cell-cycle arrest and apoptosis, in four SS cell lines. Notably, BET inhibitors exhibited regulatory control over crucial cell-cycle regulators, such as MYC, p21, CDK4, and CDK6. Additionally, RNA sequencing findings across the four cell lines revealed the significance of fluctuating BCL2 family protein expression during apoptotic induction. Notably, variations in the expression ratio of the anti-apoptotic factor BCLxL and the pro-apoptotic factor BIM may underlie susceptibility to ABBV-075. Additionally, knockdown of SS18-SSX, which upregulates BCL2, reduced the sensitivity to ABBV-075. These findings suggest the potential utility of BET inhibitors targeting the SS18-SSX-regulated intrinsic apoptotic pathway as a promising therapeutic strategy for SS.

Background: Bone metastasis is associated with a poor prognosis. Bone-modifying agents (BMA) are commonly used for the prevention or treatment of skeletal-related events (SRE) in patients with bone metastasis; however, whether or not treatment with BMA improves survival remains unclear. In this study, we investigated whether BMA was involved in post-bone metastasis survival. Methods: A total of 539 cancer patients were retrospectively analyzed to identify significant independent factors in post-bone metastasis survival. Results: Among the overall population, patients with the following cancers had a median survival longer than 24 months: thyroid, 97.2 months; breast, 51.5 months; prostate, 47.2 months; and kidney, 38.8 months. In contrast, median post-bone metastasis survival was significantly shorter in gastrointestinal (GI) (6.5 months), head and neck (6.3 months), and urinary tract (3.4 months) cancers. In non-small cell lung cancer (NSCLC), the log-rank test demonstrated that the epidermal growth factor receptor (EGFR) mutation was a significant factor for post-bone metastasis survival: EGFR mutation (−) n = 67, median post-bone metastasis survival 11.5 months (95% CI: 6.0–15.2); EGFR mutation (+) n = 39, median post-bone metastasis survival 28.8 months (95% CI: 18.1–35.7) (p < 0.05). Intriguingly, treatment with BMA was a significant positive prognostic factor: BMA (−) n = 203, median post-bone metastasis survival 7.8 months (95% CI: 5.8–12.5); BMA (+) n = 336, median post-bone metastasis survival 21.9 months (95% CI: 16.1–26.4) (p < 0.001). Moreover, the Cox proportional hazards model showed that this was particularly evident in cancer types with poor prognosis such as GI cancer (hazard ratio [HR]: 0.62, 95% CI: 0.40–0.95; p < 0.05) and NSCLC without the epidermal growth factor receptor (EGFR) mutation (HR: 0.56, 95% CI: 0.34–0.91; p < 0.05). Conclusions: Treatment with BMA is recommended not only for the prevention and/or treatment of SRE, but also may have a positive impact on post-bone metastasis survival, particularly in cancers with typically poor post-bone metastasis survival such as GI cancer and NSCLC without the EGFR mutation.

Background: Trabectedin binds covalently to the DNA minor groove and causes DNA to bend toward the main groove, then trabectedin regulates the transcription of the involved genes in cell proliferation or acts on the mononuclear phagocyte system in tumors, which contributes to its antitumor effects. Several clinical trials confirmed the efficacy of trabectedin for patients with advanced soft tissue sarcoma (STS) although clinically useful biomarkers remained unidentified. This study aimed to identify prognostic factors of trabectedin treatment, especially focusing on the systemic inflammatory, immune response, and nutritional status. Methods: This study included 44 patients with advanced STS treated with trabectedin from January 2018 to August 2022. We evaluated the associations of clinical factors that influence the efficacy of trabectedin treatment with progression-free survival (PFS) and overall survival (OS), focusing on systemic inflammatory, immune response, and nutritional status represented by the absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic inflammation response index (SIRI), prognostic nutrition index (PNI), and C-reactive protein (CRP) using the Kaplan–Meier method and the log–rank test. Results: ALC, LMR, PNI, NLR, PLR, and SIRI demonstrated no association with PFS. Patients with CRP of ≥0.3 had a significantly shorter PFS than those with CRP of <0.3 (median PFS: 863 vs. 105 days, P = 0.045). PNI of ≥44 (median: 757 days vs. 232 days, P = 0.021) and CRP of <0.3 (median: 877 days vs. 297 days, P = 0.043) were significantly good prognostic factors in terms of OS. Conclusions: The study results indicate pretreatment PNI and CRP levels as prognostic factors for trabectedin treatment in advanced STS.