Current Oncology

Despite the increasing popularity of upfront decompressive surgery, there are still patients with malignant spinal cord compression (MSCC) and expected longer-term survival receiving irradiation alone. In these patients, local progression-free survival (LPFS) may be improved with doses beyond the commonly applied regimen of 10 × 3.0 Gy. A prospective phase 2 trial (RAMSES-01) investigated the benefit of two regimens, 15 × 2.633 and 18 × 2.333 Gy, compared with a 10 × 3.0 Gy (historical control). Patients in the phase 2 cohort had significantly better local progression-free survival (LPFS) after 1 year. Since recurrent MSCC-related motor weakness is a serious situation, it must be avoided as long as possible. In this respect, it is important to know whether the superiority of 15 × 2.633 and 18 × 2.333 Gy found in the RAMSES-01 trial still exists after 2 or 3 years. This led to the current study. In the phase 2 group, 2- and 3-year LPFS rates were 93.1% and 93.1%, respectively, and survival rates were 54.2% and 36.1%, respectively. According to propensity-adjusted Cox regression analyses, radiotherapy regimens in the phase 2 cohort resulted in significantly better LPFS at 2 (p = 0.017) and 3 (p = 0.013) years. In contrast, survival was not significantly different (p = 0.251 and p = 0.288, respectively). Radiation myelopathy and pathologic vertebral fractures were not observed in any group. Given the limitations of this study, irradiation 15 × 2.633 or 18 × 2.333 Gy may be an alternative option for patients with MSCC and longer expected survival treated with irradiation alone.

KRAS-targeted therapy has opened new doors in the world of oncology, and many trials are underway for KRAS specific treatments for gastrointestinal (GI) malignancies. Outlining the current state of KRAS therapy and the remaining research gaps pertaining to these deadly cancers is crucial for the development of future therapeutics. In this review, we focus on the relationship between KRAS and GI malignancies. Current therapies are discussed with an in-depth exploration of the KRAS gene and how it connects to pancreatic, colorectal and other GI malignancies. Promising clinical trials and future therapies are highlighted while discussing the molecular biology behind them. Specifically, trials focusing on upcoming KRAS on and off inhibitors in development as well as variant focused inhibitors targeting the more common mutations G12D and G12V. We discuss exciting new pan/multi KRAS inhibitors that have been successful in pre-clinical trials. More unique therapeutic options include KRAS T cell therapies, vaccines, and combination strategies with immunotherapy. Furthermore, we address the difficulties with KRAS therapy, and the potential future directions needed to overcome them. An in-depth current literature review was done along with a review of the active clinical trials for KRAS-targeted therapeutics involving GI malignancies.

Juvenile nasopharyngeal angiofibroma (JNA), a rare vascular tumor in adolescent males, involves dysregulated angiogenesis and hormonal interplay. Key molecular drivers include HIF-1α, VEGF, bFGF, and β-catenin, promoting tumor growth via pathways like Wnt/β-catenin and Ras signaling. Androgens and estrogen modulate progression, though mechanisms remain debated. Targeted therapies reduce tumor proliferation and vascularity in preclinical studies, yet clinical translation is hindered by drug resistance and inconsistent biomarker expression. Hormonal and MMP-targeted approaches also show potential but require validation. This review consolidates JNA’s molecular landscape, emphasizing the need for personalized strategies, biomarker refinement, and combination therapies to improve therapeutic outcomes for this challenging tumor.