Musa Barış Aykan

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.

Background and Objectives: Comprehensive real-world data on dose-adjusted EPOCH-R (DA-EPOCH-R) incorporating molecular prognostic stratification remain limited. We evaluated the long-term efficacy, safety, and prognostic determinants of DA-EPOCH-R in a multicenter Turkish cohort. Materials and Methods: This retrospective study included 140 patients with aggressive B-cell lymphoma (diffuse large B-cell lymphoma [DLBCL], n = 81; primary mediastinal B-cell lymphoma [PMBL], n = 39; other, n = 20) treated with DA-EPOCH-R at five academic centers (2015–2020). Molecular profiling included immunohistochemistry (MYC, BCL-2, BCL-6) and fluorescence in situ hybridization (FISH). Survival was estimated by Kaplan–Meier analysis with Cox regression for prognostic factors. Results: At a median follow-up of 50.1 months, 5-year overall survival (OS) and event-free survival (EFS) rates were 71.3% and 66.3%, respectively (complete response rate: 68.6%). Molecular subtypes included double-expressor (DEL; n = 39), triple-expressor (TEL; n = 21), double-hit (DHL; n = 17), and triple-hit lymphoma (THL; n = 11). Five-year OS by IPI risk group ranged from 88.6% (low) to 49.4% (high) (p = 0.005). DEL status did not confer inferior OS (p = 0.738), whereas DHL and THL had markedly poor outcomes (p < 0.001). In multivariate analysis, IPI ≥ 3 (HR 2.54; p = 0.007) and MYC FISH rearrangement (HR 3.62; p < 0.001) independently predicted inferior OS. Grade 3–4 neutropenia occurred in 57.1%, with no grade 3–4 cardiotoxicity. Conclusions: DA-EPOCH-R provides favorable long-term outcomes in aggressive B-cell lymphomas. DEL status did not confer a survival disadvantage, an association that is hypothesis-generating and requires confirmation, as the present design cannot establish a causal mechanism. FISH-defined DHL/THL remain associated with dismal outcomes, warranting novel therapeutic strategies.

Background and Objectives: Perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) is the standard of care for resectable gastric and gastroesophageal junction adenocarcinoma; however, up to 50% of patients develop metastatic recurrence. These patients have prior exposure to platinum and taxane agents, and optimal first-line treatment in the metastatic setting remains undefined. This study aimed to characterize real-world treatment patterns and outcomes in patients progressing after perioperative FLOT, focusing on relapse timing and HER2 status. Materials and Methods: This retrospective, multicenter cohort study included 296 patients from 31 centers across Türkiye, stratified into early relapse (≤6 months, n = 114) and late relapse (>6 months, n = 182) groups. Survival analyses were performed using the Kaplan-Meier method and Cox proportional hazards regression. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Results: Median PFS and OS for the entire cohort were 6 and 9 months, respectively. Early relapsers had significantly shorter median PFS (4 vs. 6 months, p = 0.029) and OS (8 vs. 12 months, p = 0.047); however, early relapse timing did not retain independent prognostic significance on multivariable analysis. No significant difference in PFS or OS was observed between cytotoxic chemotherapy regimens in either relapse group. HER2 positivity was the only independent predictor of improved PFS on multivariable Cox analysis (HR 0.48, 95% CI 0.29–0.81; p = 0.006). In the late relapse group, trastuzumab-based chemotherapy achieved a median PFS of 14 months and OS of 18 months, significantly superior to all cytotoxic regimens (PFS p = 0.007; OS p = 0.029). Conclusions: In patients progressing after perioperative FLOT, cytotoxic chemotherapy regimen selection did not demonstrate a statistically significant survival difference in this retrospective cohort, regardless of relapse timing. HER2 positivity is the dominant predictive biomarker, and trastuzumab-based therapy suggests a potential survival benefit that warrants prospective validation. Comprehensive biomarker profiling at metastatic diagnosis and prospective trials designed for this post-FLOT population are needed to establish evidence-based treatment standards.

Background: Accurate prognostic stratification is essential for clinical decision-making in metastatic renal cell carcinoma (mRCC). Although the International Metastatic RCC Database Consortium (IMDC) model is widely used, its discriminatory capacity may be limited in specific clinical subpopulations. The Royal Marsden Hospital (RMH) score, based on serum albumin, lactate dehydrogenase, and the number of metastatic sites, has not been evaluated as a prognostic tool in patients with de novo mRCC receiving first-line tyrosine kinase inhibitor (TKI) therapy. Methods: We retrospectively analyzed the data of 149 patients with de novo metastatic renal cell carcinoma who received first-line TKI therapy (pazopanib, sunitinib, or cabozantinib) at two tertiary oncology centers in Turkey. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify independent prognostic factors. Results: The median OS and PFS were 23.1 months (95% CI: 19.4–26.8) and 9.4 months (95% CI: 7.0–11.8), respectively. The OS showed a stepwise decline across RMH risk groups, ranging from 40.7 months in patients with an RMH score of 0 to 8.6 months in those with an RMH score of 3. In the multivariate analysis, the RMH score (HR 1.29, 95% CI: 1.03–1.61; p = 0.026) and sarcomatoid differentiation (HR 2.01, 95% CI: 1.09–3.72; p = 0.025) were independently associated with worse OS. The IMDC score did not retain independent prognostic significance (p = 0.129). The RMH score was not significantly associated with PFS after multivariable adjustment, and the IMDC score was not significantly associated with PFS in univariate analysis and was therefore not entered into the multivariable PFS model. Conclusions: The RMH score independently predicted overall survival in patients with de novo mRCC receiving first-line TKI therapy, whereas the IMDC score did not retain independent prognostic significance in this cohort. Given its simplicity and reliance on objective parameters, the RMH score may provide complementary prognostic information in this patient population; however, external validation in independent cohorts is required before broader clinical implementation can be considered.

Background: Autologous stem cell transplantation (ASCT) is a standard treatment for relapsed or high-risk lymphoma. While disease-related factors are well-known, the impact of host-related factors like nutritional status remains less defined. We aimed to evaluate the prognostic value of the prognostic nutritional index (PNI) and other factors in lymphoma patients undergoing ASCT. Methods: We conducted a single-center retrospective cohort study including adult patients with Hodgkin and non-Hodgkin lymphoma who underwent ASCT between January 2015 and December 2023. Pre-transplant clinical, laboratory, and transplant-related variables were analyzed. The prognostic nutritional index (PNI) was calculated using serum albumin and absolute lymphocyte count and dichotomized according to the cohort median. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan–Meier and Cox regression analyses. We conducted a retrospective single-center cohort study including adult patients with Hodgkin and non-Hodgkin lymphoma who underwent ASCT between January 2015 and December 2023. Results: A total of 43 patients were included. Median age was 38 years, and 72.1% were male. Patients transplanted in complete remission (CR) had significantly longer PFS compared with those transplanted in partial remission (PR) (log-rank p = 0.022). Patients with higher pre-ASCT PNI demonstrated significantly improved PFS (median 45 vs. 7 months; log-rank p = 0.021). In multivariable Cox regression analysis, both higher PNI (HR 0.39; 95% CI 0.16–0.97; p = 0.043) and complete remission prior to ASCT (HR 0.41; 95% CI 0.17–0.98; p = 0.046) remained independently associated with improved PFS. Higher infused CD34⁺ (hematopoietic stem cell) dose was associated with shorter hospitalization but showed no statistically significant association with engraftment kinetics or survival. No variable was independently associated with OS, likely due to the limited number of death events. Conclusions: Pre-transplant prognostic nutritional index and disease response independently predict progression-free survival after ASCT in lymphoma. These findings highlight the complementary role of host-related and disease-related factors in transplant outcomes and suggest that PNI may serve as a practical tool for pre-transplant risk stratification and patient optimization. Given the small sample size and limited number of events, these findings should be interpreted with caution.

This study aims to evaluate the effectiveness and real-world applicability of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC), focusing on pathological complete response (pCR) and disease-free survival (DFS) across different chemotherapy regimens. In this multicenter retrospective study, patients treated between January 2019 and January 2023, 437 patients with locally advanced rectal cancer who underwent total neoadjuvant therapy followed by surgery were analyzed. Standard fluoropyrimidine-based chemotherapy regimens (CAPOX, FOLFOX, or FOLFIRINOX) were used according to institutional practice, and long-course chemoradiotherapy constituted the predominant radiotherapy approach. Patients were grouped based on chemotherapy sequencing as induction, consolidation, or sandwich regimens. Outcomes were evaluated using multivariable logistic regression for pathological complete response and Kaplan–Meier analysis with Cox proportional-hazards modeling for disease-free survival. The median follow-up duration was 66 months. The overall pCR rate was 26.3% (n = 115). pCR rates did not differ significantly between induction, sandwich, and consolidation chemotherapy regimens. A longer interval (> 8 weeks) between radiotherapy and surgery was associated with a higher likelihood of achieving pCR. In contrast, cT4 disease and baseline CEA levels > 3 ng/mL were associated with lower pCR rates.The estimated 3-year disease-free survival (DFS) rate was 83.8%. Recurrence rates within 3 years were numerically higher in patients receiving induction and sandwich regimens compared with consolidation chemotherapy, although these differences did not reach statistical significance. In multivariable analysis, poor tumor regression grade, ypT4 stage, ypN + disease, and post-TNT CEA ≥ 3 ng/mL were independently associated with an increased risk of recurrence. TNT is effective and feasible in real-world settings, achieving pCR and DFS outcomes comparable to clinical trials. No statistically significant differences were observed in pCR or recurrence rates between induction, consolidation, and sandwich chemotherapy regimens. Prospective phase III trials are needed to compare DFS and OS outcomes across these treatment strategies. The online version contains supplementary material available at 10.1007/s12672-026-04842-3.

Background: Trastuzumab deruxtecan (T-DXd) has transformed the treatment landscape of human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (mBC), with significant improvements in survival reported in clinical trials. However, limited data exist regarding its performance in real-world settings, particularly in lower-middle-income countries (LMICs). Objectives: To evaluate the real-world effectiveness and safety of T-DXd in patients with HER2+ mBC in Türkiye. Design: A multicenter retrospective cohort study. Methods: This multicenter, retrospective cohort study, conducted by the Turkish Oncology Group, evaluated the real-world outcomes and tolerability of T-DXd in patients with HER2+ mBC across 27 oncology centers in Türkiye. The primary endpoints were real-world progression-free survival (rwPFS) and overall survival (rwOS). Secondary endpoints included response rate, safety (with adverse events (AEs) graded according to CTCAE v5.0), and evaluation of the first post-T-DXd treatments. Results: A total of 269 patients were included. The median age was 49 years (interquartile range: 42–59), and the median follow-up was 12.9 months. The median rwPFS was 17.9 months (95% confidence interval: 13.3–22.5), and the median rwOS was 35.7 months (95% confidence interval: 27.8–43.6). The objective response rate was 71.4%, and the disease control rate was 95.2%. Patients receiving T-DXd in the second line experienced significantly longer rwPFS compared with those treated in later lines ( p < 0.001). Treatment-related AEs of any grade occurred in 68.4% of patients. Interstitial lung disease was reported in 21 patients (7.8%), with 4 cases being grade ⩾3. Conclusion: In this large national real-world cohort from an LMIC, T-DXd demonstrated robust antitumor activity and a manageable safety profile in patients with HER2+ mBC. These findings are consistent with prior clinical trial data and support the applicability of T-DXd in broader clinical settings.

Background/Objectives : Accurate prognostic assessment remains crucial in metastatic renal cell carcinoma (mRCC), especially as treatment options have expanded beyond vascular endothelial growth factor (VEGF)-targeted therapies to include immune checkpoint inhibitors (ICIs) and ICI–TKI combinations. The widely used IMDC classification shows important limitations in the modern therapeutic era, highlighting the need for complementary prognostic tools. In this context, the Meet-URO and CANLPH scores—incorporating clinical, inflammatory, and nutritional markers—have emerged as promising alternatives. To evaluate and compare the prognostic performance of the Meet-URO and CANLPH scoring systems in a real-world mRCC cohort predominantly treated with first-line tyrosine kinase inhibitor (TKI) monotherapy due to limited access to ICI-based combinations. Methods: This retrospective single-center study included 112 patients with mRCC. The Meet-URO score was calculated for all patients, while the CANLPH score was assessed in 56 patients with complete laboratory data. CAR, NLR, and PHR were computed using baseline pre-treatment measurements. Overall survival (OS) and progression-free survival (PFS), the latter defined exclusively for first-line therapy, were estimated using the Kaplan–Meier method. Correlations between inflammatory markers and survival outcomes were analyzed using Spearman’s rho. Results: Meet-URO demonstrated clear prognostic stratification across all five categories, with the most favorable outcomes in score group 2 and progressively poorer OS and PFS in higher-risk groups. CANLPH also showed meaningful survival discrimination, with the highest inflammatory group (score 3) exhibiting markedly reduced OS and PFS. CAR was the strongest individual predictor of survival, while NLR and PHR showed weaker associations. Conclusions: Both Meet-URO and CANLPH provide strong, complementary prognostic information in mRCC, even in a cohort largely treated with TKI monotherapy. Their integration into routine risk assessment may enhance clinical decision-making, particularly in resource-limited settings.

Background: Accurate prognostic assessment remains crucial in metastatic renal cell carcinoma (mRCC), especially as treatment options have expanded beyond vascular endothelial growth factor (VEGF)–targeted therapies to include immune checkpoint inhibitors (ICIs) and ICI–TKI combinations. The widely used IMDC classification shows important limitations in the modern therapeutic era, highlighting the need for complementary prognostic tools. In this context, the Meet-URO and CANLPH scores—incorporating clinical, inflammatory, and nutritional markers have emerged as promising alternatives. Objective: To evaluate and compare the prognostic performance of the Meet-URO and CANLPH scoring systems in a real-world mRCC cohort predominantly treated with first-line tyrosine kinase inhibitor (TKI) monotherapy due to limited access to ICI-based combinations. Methods: This retrospective single-center study included 112 patients with mRCC. The Meet-URO score was calculated for all patients, while the CANLPH score was assessed in 56 patients with complete laboratory data. CAR, NLR, and PHR were computed using baseline pre-treatment measurements. Overall survival (OS) and progression-free survival (PFS) the latter defined exclusively for first-line therapy—were estimated using the Kaplan–Meier method. Correlations between inflammatory markers and survival outcomes were analyzed using Spearman’s rho. Results: Meet-URO demonstrated clear prognostic stratification across all five categories, with the most favorable outcomes in score group 2 and progressively poorer OS and PFS in higher-risk groups. CANLPH also showed meaningful survival discrimination, with the highest inflammatory group (score 3) exhibiting markedly reduced OS and PFS. CAR was the strongest individual predictor of survival, while NLR and PHR showed weaker associations. Conclusion: Both Meet-URO and CANLPH provide strong, complementary prognostic information in mRCC, even in a cohort largely treated with TKI monotherapy. Their integration into routine risk assessment may enhance clinical decision-making, particularly in resource-limited settings.

Background: Ewing sarcoma (ES) is a highly aggressive malignant tumor that predominantly affects children and young adults. Despite advances in multimodal therapy, relapse and refractory disease remain the leading causes of treatment failure. High-dose chemotherapy followed by autologous stem cell transplantation (HDCT-ASCT) has been proposed as a consolidation strategy for high-risk or relapsed ES; however, its clinical value remains controversial. Methods: We retrospectively analyzed 46 consecutive patients with locally advanced or metastatic ES who underwent HDCT-ASCT after at least one prior systemic therapy line. Clinical, pathological, and transplant-related variables were evaluated for associations with overall survival (OS), post-transplant OS (OS-2), and progression-free survival (PFS). Survival was estimated using the Kaplan–Meier method, and prognostic factors were assessed by Cox proportional hazards modeling. Results: The median age at diagnosis was 23 years (range: 14–55). Median OS from diagnosis was 42 months, while post-transplant OS-2 and PFS were 8 and 5 months, respectively. Younger patients (≤23 years) had significantly longer OS (50 vs. 34 months; p = 0.027). Liver metastasis predicted inferior OS (HR = 5.411; p = 0.006), whereas lung metastasis was associated with shorter OS-2 (HR = 2.672; p = 0.025) and PFS (HR = 6.037; p = 0.016). Treatment-related mortality was low (2.1%), though hematologic toxicity was universal. Overall, HDCT-ASCT provided transient disease control, with modest benefit confined to younger, chemosensitive, and medically fit patients. Conclusions: In this real-world cohort, HDCT-ASCT was feasible and safe but offered limited survival advantage in heavily pretreated Ewing sarcoma. Prognosis was primarily influenced by age and metastatic distribution, particularly hepatic and pulmonary involvement. These findings support a risk-adapted, biology-driven approach reserving HDCT-ASCT for selected patients and highlight the need for post-transplant maintenance strategies integrating targeted or immunotherapeutic modalities.