Introduction: CDK 4/6 inhibitors are effectively utilized among patients with hormone-positive, HER-2-negative metastatic breast cancer. The dose reduction for these patients varies between 35% and 57% across multiple trials. We aim to clarify the characteristics of patients who had dosage reduction and the effect of this reduction on survival outcomes. Materials and Methods: The study was designed as a retrospective, multicenter study. Patients who received CDK 4/6 inhibitors in the first-line and subsequent treatment settings were grouped based on dose reductions. Progression-free survival was compared between these groups, and factors influencing dose reduction were analyzed. Results: Multivariate logistic regression study demonstrated that patients aged 65 and older, with a Charlson CI score of 2 or higher, having metastases in three or more sites, and classed as normal weight, had greater dosage reductions. Dose reduction had no impact on progression-free survival (PFS) (p = 0.114 for first-line treatment, p = 0.528 for second and subsequent-line treatment; p > 0.05). Conclusions: Regarding the absence of disparity in progression-free survival between patients with dose reduction and those without, dose reduction should not be avoided in certain patient groups to ensure therapy continuity and mitigate potential adverse effects.

Background: Osteosarcoma is a rare but aggressive bone malignancy. Despite advances in multimodal therapy, survival remains suboptimal, highlighting the need for prognostic markers to guide treatment. Methods: This study included 162 osteosarcoma patients who received neoadjuvant chemotherapy followed by surgery between January 2009 and March 2024. Patients received either double (cisplatin + doxorubicin) or triple (MAP or PEI) chemotherapy. Survival analyses were conducted using Kaplan–Meier curves, log-rank tests, and Cox proportional hazards models. Results: The median age was 20 years (IQR: 18–29), and 53.1% were male. Patients who received triple chemotherapy regimens demonstrated significantly longer overall survival (OS) compared to those on doublet regimens. High tumor necrosis rates (>90%) and negative surgical margins were strongly associated with improved OS, while metastatic disease at diagnosis, elevated alkaline phosphatase (ALP), and male gender were linked to poorer survival. Multivariate analysis identified adjuvant therapy, age under 18, high necrosis rate, negative margins, and normal ALP as significant OS predictors. Conclusions: Triple-agent chemotherapy, necrosis rate ≥90 and negative surgical margins are strongly associated with prolonged survival in osteosarcoma. The key prognostic indicators such as ALP levels, surgical margins and age at diagnosis should guide personalized treatment strategies to improve outcomes in curable patients.

Background and Objectives: Total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC) offers significant advantages in terms of pathologic response and long-term survival; however, it is still unclear which patients will benefit the most from this treatment. This study aims to investigate the role of metabolic parameters on pretreatment positron emission tomography–computed tomography (PET/CT) images in predicting treatment response after TNT. Materials and Methods: The research was conducted using a single-center, retrospective design. Patients treated with total neoadjuvant therapy are included if they have locally advanced rectal cancer (cT3/T4-N0 or cTany-N1/N2). The patient group was categorized into two groups: CR and non-CR. Clinicopathologic features, PET/CT parameters, CA19-9, and CEA values were compared between these two groups. Results: In total, 52 patients were included. The CR group had 21 patients, and the non-CR group had 31 patients. The analysis demonstrated that the CR group had significantly lower metabolic tumor volume (MTV) and total lesion glycolysis (TLG) than the non-CR group (p = 0.022 vs. p = 0.003, p < 0.05). Also, CA19-9 values were lower than the non-CR group, and this difference was statistically remarkable (p = 0.40, p < 0.05). Conclusions: MTV and TLG parameters in PET/CT for pretreatment staging and pretreatment blood CA 19-9 levels are prognostic factors for predicting treatment response, and they may play a crucial role in choosing treatment. Comprehensive research is warranted on this subject with a larger patient population.

Background: Immune checkpoint inhibitors (ICIs) are associated with rare but life-threatening immune-related adverse events. Myocarditis–myositis–myasthenia gravis (MMM) overlap is among the most severe neuromuscular–cardiac toxicity patterns, but population-scale data on disproportionality, reported death outcomes, and time-to-onset (TTO) remain limited. Methods: We conducted a retrospective pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS) from 2015Q1 to 2025Q4. Strict MMM overlap was defined at the report level by co-reporting of the Preferred Terms “myocarditis,” “myositis,” and “myasthenia gravis”. ICI exposure was restricted to selected PD-1, PD-L1, and CTLA-4 inhibitors recorded as primary or secondary suspect drugs (PS/SS), with a prespecified sensitivity analysis restricted to PS reports only. Disproportionality was assessed primarily using reporting odds ratios (RORs) with Haldane–Anscombe correction for sparse cells; the Information Component (IC) and IC025 were calculated as complementary Bayesian metrics. Drug-level TTO was estimated by linking therapy start dates and event dates within eligible reports. Results: Among 15,187,311 deduplicated FAERS reports, 151 met the strict MMM overlap definition, including 131 ICI-exposed reports. ICI exposure showed a strong disproportionality signal for strict MMM overlap (ROR 397.29, 95% CI 249.44–632.76; IC 5.50, IC025 5.24). Reported death outcomes were observed in 49/131 (37.4%) ICI-exposed MMM overlap reports, including 31/80 (38.8%) in PD-1 reports, 5/16 (31.3%) in PD-L1 reports, and 13/35 (37.1%) in combination ICI reports. Drug-level TTO was available for 53 ICI-exposed reports, with a median of 25 days (IQR 18–38); restricting to TTO ≤365 days yielded a similar median of 24 days (IQR 18–37), supporting a predominantly early-onset pattern. Sensitivity analyses restricted to PS were directionally consistent. Conclusion: In FAERS, ICI-associated strict MMM overlap showed a strong disproportionality signal and predominantly early reported onset; reported death outcomes were also observed in a substantial proportion of ICI-exposed overlap reports. These findings support heightened clinical vigilance for cardio-neuromuscular overlap toxicity, particularly during the first months after ICI initiation.

Background: Mucosal malignant melanoma (MMM) is a rare and aggressive malignancy with a dismal prognosis. While the Systemic Immune-Inflammation Index (SII) has emerged as a prognostic marker in various solid tumors, its specific value in MMM remains undefined. This study investigated the association between pretreatment SII and overall survival (OS) in patients with MMM. Methods: We retrospectively analyzed 106 adults with histologically confirmed MMM treated at six oncology centers in Turkey between 2005 and 2025. The baseline SII was calculated as platelet × neutrophil/lymphocyte counts obtained before definitive treatment. A receiver operating characteristic (ROC) analysis identified an optimal SII cutoff of 776 for overall survival (OS), defining low (<776) and high (≥776) SII groups. Results: Gastrointestinal and head and neck mucosa were the most frequent primary sites, and one-third of patients presented with metastatic disease. The median OS for the entire cohort was 23.3 months. Patients with a high versus low SII had a shorter OS (16.2 vs. 35.2 months; HR 2.71, 95% CI 1.67–4.40; p < 0.001). In multivariable analysis, a high SII (HR 1.88, 95% CI 1.12–3.14; p = 0.016), gastrointestinal primary site (HR 1.99, 95% CI 1.23–3.23; p = 0.005), and metastatic disease at diagnosis (HR 4.01, 95% CI 2.32–6.94; p < 0.001) independently predicted a worse OS. Conclusions: The SII is a novel, independent prognostic biomarker in MMM. Elevated pretreatment SII correlates with aggressive clinicopathologic features and inferior survival. As a readily accessible and cost-effective marker, SII may facilitate improved risk stratification in routine clinical practice for MMM patients.

Background and Objectives: Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy with a poor prognosis. Identifying reliable prognostic factors is crucial for risk stratification and optimizing treatment strategies. This study aimed to evaluate the impact of clinicopathologic factors and systemic inflammatory markers on survival outcomes in patients with MPM. Materials and Methods: This retrospective, multicenter study included 217 patients diagnosed with MPM between January 2009 and March 2024. Data on age, gender, histology, disease stage, treatment modalities, and inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein/albumin ratio (CAR) were collected. Survival outcomes were analyzed using Kaplan–Meier methods, and prognostic factors were evaluated using Cox regression analysis. Results: CAR was identified as an independent prognostic factor for both overall survival (OS) and progression-free survival (PFS). Patients with CAR < 0.98 had significantly longer OS (87.0 months vs. 14.0 months, p < 0.001) and PFS (17.61 months vs. 8.96 months, p = 0.010). While NLR was significant in univariate analysis (OS: 25.0 months for NLR < 2.58 vs. 21.0 months for NLR ≥ 2.58, p = 0.040), it did not retain significance in the multivariate model (p = 0.180). Epithelioid histology and early-stage disease were strongly associated with improved survival outcomes (OS: 32.0 vs. 11.0 months for epithelioid vs. non-epithelioid histology, p < 0.001; 32.0 vs. 12.0 months for early-stage vs. metastatic disease, p < 0.001). Conclusions: CAR is a strong independent prognostic factor in MPM, reflecting systemic inflammation and nutritional status. Epithelioid histology and early-stage disease are associated with significantly longer survival, underscoring the critical role of early detection in improving patient outcomes.