Germline BRCA1/2-mutated (gBRCAm) hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer (MBC) is a biologically distinct subset in which the efficacy of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors remains incompletely characterized. We evaluated real-world outcomes and prognostic factors in a multicenter retrospective Turkish cohort treated with a CDK4/6 inhibitor plus endocrine therapy (June 2020–September 2025). Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier and Cox methods. Among 121 patients, 30 (24.8%) had BRCA1, 88 (72.7%) had BRCA2, and three (2.5%) had dual mutations; 66.9% received first-line therapy, with ribociclib in 69.4% and palbociclib in 29.8%. Objective response rate was 69.4% and the clinical benefit rate was 82.6%. Median PFS was 17.0 months and OS 47.0 months. PFS was numerically longer in BRCA1 than in BRCA2 carriers (25.0 vs. 14.0 months), although the difference was not statistically significant in the pairwise comparison (HR 1.50, 95% CI 0.88–2.56; log-rank p = 0.135); the dual BRCA1/2 subgroup (n = 3) had the poorest outcomes and was assessed descriptively. OS did not differ significantly between BRCA1 and BRCA2 carriers (57.0 vs. 49.0 months; log-rank p = 0.520). PFS did not differ between ribociclib and palbociclib (p = 0.192); OS favored ribociclib at borderline significance (p = 0.050), but this was not confirmed in Cox regression. In multivariable analysis, ECOG ≥ 1 (HR 1.85; p = 0.010) and fulvestrant-based therapy (HR 1.74; p = 0.041) predicted shorter PFS; fulvestrant also predicted worse OS (HR 2.39; p = 0.008). CDK4/6 inhibitor-based therapy shows meaningful activity in gBRCAm HR+/HER2- MBC; the numerically poorer outcomes observed in BRCA2 carriers are hypothesis-generating and warrant validation in larger cohorts.

Amaç: Bu çalışmanın amacı, son dönem böbrek yetersizliği olan hastalarda asimetrik dimetilarjinin (ADMA) düzeyleri ile ateroskleroz gelişimi arasındaki ilişkinin incelenmesidir. Gereç ve Yöntemler: Prospektif, gözlemsel ve kohort bir araştırma olarak planlanan bu çalışmaya 31 hemodiyaliz (HD), 28 periton diyalizi (PD) tedavisi alan ve 25 prediyaliz hastası dâhil edilmiştir. Her üç grubun ADMA, karotis arter intima-media kalınlığı, interlökin-6 (IL-6), interselüler adezyon molekülü-1 ve vasküler adezyon molekülü-1 düzeyleri ölçüldü. Öncelikle henüz diyaliz tedavisi başlanmamış son dönem kronik böbrek hastalığı olan hasta grubu ile diyaliz tedavisi uygulanan hastalar ADMA düzeyleri ve ADMA ile ateroskleroz göstergeleri arasında ilişki açısından karşılaştırıldı. Sonra HD veya PD tedavisi gören hastalar da ADMA düzeyleri ve ateroskleroz göstergeleri açısından karşılaştırıldı. Bulgular: Renal replasman tedavisi almayan prediyaliz grubu hastalarına kıyasla renal replasman tedavisi alan hastalarda karotis arter intima-media kalınlığı (p=0,016) ve IL-6 (p=0,009) düzeylerinin anlamlı olarak daha yüksek olduğu saptandı. PD uygulanan hastaların ADMA düzeylerinin HD uygulanan hastalara göre 0,1 µmol/L düşük olduğu saptandı, ancak bu fark istatistiksel olarak anlamlı değildi (p>0,05). ADMA ile karotis arter intima-media kalınlığı (r=0,371; p=0,001) ve IL-6 düzeyleri (r=0,240; p=0,035) arasında pozitif yönlü korelasyon olduğu saptandı. Karotis intima media kalınlığı ile IL-6 (r=0,321; p=0,004) ve serum kreatinin (r=0,377; p=0,015) düzeyleri arasında pozitif yönlü korelasyon olduğu saptandı. Sonuç: Bu çalışmada, son dönem böbrek yetersizliği gelişmiş hastalarda ateroskleroz gelişiminde geleneksel ateroskleroz risk faktörlerinin yanı sıra artmış ADMA düzeyi ve inflamasyon artışı gibi yeni risk faktörlerinin etkili olduğu saptanmıştır.

PURPOSE: Early-onset gastrointestinal cancers are concerning entities globally, yet early-onset biliary tract cancers (EOBTCs) are understudied. Early-stage disease is crucial for young patients' survival. METHODS: TOG/GI-SAFRADJU (ClinicalTrials.gov identifier: NCT06975917 ) is a multicenter, hospital-based, registry initiative of the Turkish Oncology Group, including patients with resected BTCs. Early-onset was defined as a diagnosis at age <50 years. Characteristics and survival of EOBTC and non-EOBTC were compared. Among patients with EOBTC, prognostic factors for recurrence-free survival (RFS) and overall survival (OS) were analyzed. Risk scores were assigned on the basis of hazard ratios. RESULTS: Six hundred seventeen patients from 44 centers were included. 12.6% (n = 78) were EOBTC. R1 resection rate was significantly higher among EOBTC (37.1% v 25.7%, P = .038). Adjuvant treatments did not differ between EOBTC and non-EOBTC. Among patients who received adjuvant chemotherapy, RFS (13.9 months [95% CI, 11.4 to 22.1] v 15.9 months [95% CI, 13.6 to 18.9], P = .947) and OS (35.6 months [95% CI, 28.0 to 81.4] v 31.3 months [95% CI, 27.8 to 44.3], P = .670) were similar between EOBTC and non-EOBTC groups. Among patients with EOBTC, R1-resection and high CA19-9 levels were associated with shorter RFS, and gallbladder localization and high CA19-9 were associated with shorter OS in adjusted analyses. Using these factors, risk scores early-stage EOBTC RFS score (EOB-RS) for RFS and early-stage EOBTC OS score (EOB-OS) for OS were formed, each including three ranks. Both scores significantly ordered the prognosis of patients with EOBTC (EOB-RS, [0 points]: 22.7 months, [1 or 2]: 10.3 months, [3]: 5.7 months, P < .001, EOB-OS: [0]: 110.9 months, [1 or 2]: 29.6 months, [3]: 10.1 months, P < .001). CONCLUSION: Resected EOBTC patients showed survival comparable to older counterparts receiving surgery/adjuvant therapy. This study suggests a potential risk scoring system for early-stage EOBTC, pending validation.

PURPOSE: Primary bone sarcomas, including osteosarcoma, chondrosarcoma, and Ewing sarcoma, have poor prognoses, with 5-year overall survival (OS) rates of < 20%-30% in metastatic or recurrent disease. Although tyrosine kinase inhibitors (TKIs) targeting angiogenic and oncogenic pathways have shown efficacy in phase II trials, there is a lack of supporting real-world data. This study aimed to evaluate the efficacy and safety of TKI use in patients with advanced bone sarcomas in a real-world setting. MATERIALS AND METHODS: This multicenter, retrospective study included 72 patients with advanced or metastatic osteosarcoma, chondrosarcoma, or Ewing sarcoma who received at least one TKI (regorafenib, pazopanib, sorafenib, or cabozantinib) at multiple centers in Türkiye. Progression-free survival (PFS) and OS were estimated using the Kaplan-Meier method. Adverse events were recorded and graded according to standard criteria. RESULTS: The median age was 28.5 years (range, 17-72 years), and 62.5% (n = 45) of the patients were male. The most frequently used TKIs were regorafenib (n = 31, 43.1%) and pazopanib (n = 22, 30.6%); in the majority of patients (n = 68, 94.4%), TKIs were used as second-line or subsequent treatment. The median PFS for the entire cohort was 4.8 months (95% CI, 3.05 to 6.48), and the median OS was 9.9 months (95% CI, 6.48 to 13.25). In histologic subgroup analyses, the median PFS was 4.4 months for osteosarcoma, 4.8 months for chondrosarcoma, and 5.4 months for Ewing sarcoma. Adverse events were observed in 50% (n = 36) of patients, and 89.2% (n = 58) of these were grade 1-2. Dose reduction was required in 27.8% (n = 20) of patients, and permanent treatment discontinuation due to toxicity was necessary in 6.9% (n = 5) of patients. CONCLUSION: In this real-world cohort, although TKIs were associated with limited survival outcomes, they had an acceptable safety profile in patients with advanced bone sarcomas. These findings are consistent with the results of phase II studies and suggest that TKIs may be a treatment option for patients who have disease progression after standard therapies.

Background/Objectives: Despite improved survival with immune checkpoint inhibitors, the optimal treatment after anti-PD-1 progression in metastatic melanoma remains unclear. This study compared survival outcomes and treatment responses between chemotherapy (CT)- and immunotherapy (IO)-based therapies administered after nivolumab progression in patients with BRAF-negative metastatic melanoma. Methods: This multicenter retrospective study included patients with BRAF-negative metastatic melanoma who developed disease progression during nivolumab treatment. Post-progression systemic therapies were categorized as CT- or IO-based treatments. Treatment responses were assessed according to RECIST version 1.1 criteria. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier method, and prognostic factors were evaluated using Cox regression analyses. Results: A total of 141 patients were included. Following nivolumab progression, 107 (75.9%) received CT and 34 (24.1%) received IO. Based on best response to nivolumab, the objective response rate (ORR; CR + PR) was 55.1% in the CT group and 44.1% in the IO group. After post-nivolumab treatment, ORRs were 29.9% and 32.4% in the CT and IO groups, respectively, whereas complete response rates were higher with IO (21.2% vs. 3.0%). Median PFS was 4.17 months in the CT group and 3.9 months in the IO group (p = 0.403). Median OS was 7.83 and 8.17 months, respectively (p = 0.416). Elevated LDH level was identified as an independent adverse prognostic factor. Conclusions: In this multicenter real-world cohort, no statistically significant differences in survival were observed between patients receiving CT or IO after nivolumab progression. Given the retrospective, non-randomized study design, these findings should not be interpreted as evidence of comparative treatment efficacy. The higher CR rate observed with IO should be interpreted cautiously due to potential selection bias. Prospective studies are warranted to define the optimal treatment strategy after anti-PD-1 failure.