The prognostic significance of body composition parameters in patients with HR + /HER2 − metastatic breast cancer treated with CDK4/6 inhibitors remains poorly defined. The cachexia index (CXI), a composite marker integrating skeletal muscle mass, nutritional status, and systemic inflammation, may provide additional prognostic information in this setting. This study aimed to evaluate the prognostic value of body composition parameters, with a particular focus on CXI, in this patient population. This retrospective single-center study included 84 patients with HR + /HER2 − metastatic breast cancer receiving CDK4/6 inhibitor therapy. Body composition parameters were assessed using baseline imaging at the L3 vertebral level. Sarcopenia was defined as skeletal muscle index (SMI) < 38.5 cm2/m2. CXI was calculated as [skeletal muscle index × serum albumin]/neutrophil-to-lymphocyte ratio. Prognostic factors were evaluated using univariate and multivariate Cox regression analyses. At a median follow-up of 42.0 months, median PFS and OS were 40.8 and 49.6 months, respectively. The median SMI was 32.1 cm2/m2 (IQR 25.2–39.9). Sarcopenia was present in 50 patients (64.3

Triple-positive breast cancer (TPBC), characterized by concurrent ER, PR, and HER2 positivity, poses unique therapeutic challenges due to ER–HER2 crosstalk. The optimal adjuvant endocrine therapy in TPBC patients receiving anti-HER2 regimens remains poorly defined. This multicenter retrospective cohort study included 1044 early-stage TPBC patients (stage II–III) treated with neoadjuvant chemotherapy and HER2-targeted therapy between 2007 and 2024. Disease-free survival (DFS) was analyzed using Kaplan–Meier estimates and Cox regression models, with separate multivariate analyses for premenopausal (n = 474) and postmenopausal (n = 570) patients. At a median follow-up of 52 months, the 5-year DFS was 88.2

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 Germline BRCA1/2-mutated (gBRCAm) hormone receptor-positive/HER2-negative (HR+/HER2−) metastatic breast cancer (MBC) represents a biologically distinct subset in which the efficacy of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors remains incompletely characterized. Given the interplay between DNA damage repair deficiency and cell-cycle regulation, BRCA-associated tumors may demonstrate differential therapeutic sensitivity. We evaluated real-world outcomes, safety, and prognostic factors in a multicenter cohort. Methods This multicenter retrospective cohort study included patients with pathogenic germline BRCA1 and/or BRCA2 mutations treated with a CDK4/6 inhibitor plus endocrine therapy for HR+/HER2 − MBC (June 2020–September 2025) at participating centers in Turkey. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier methods and compared by log-rank testing. Cox proportional hazards models were used for univariable and multivariable analyses. Results Among 121 patients, 30 (24.8%) had BRCA1, 88 (72.7%) BRCA2, and 3 (2.5%) dual BRCA1 + BRCA2 mutations; 66.9% received CDK4/6 inhibitors as first-line therapy. Ribociclib was used in 69.4% and palbociclib in 29.8%. Objective response rate was 69.4% and clinical benefit rate 82.6%. Median PFS was 17.0 months and median OS was 47.0 months. PFS differed significantly by BRCA subtype (25.0 months for BRCA1, 14.0 months for BRCA2, and 6.0 months for BRCA1 + 2; log-rank p = 0.013). Median OS also differed (57.0, 49.0, and 11.0 months, respectively; log-rank p = 0.016). PFS did not differ between ribociclib and palbociclib (p = 0.192); OS favored ribociclib at a borderline level (p = 0.050), not confirmed in Cox regression. In multivariable analysis, ECOG ≥ 1 (HR 1.846; p = 0.010) and fulvestrant-based therapy (HR 1.735; p = 0.041) predicted shorter PFS; fulvestrant predicted worse OS (HR 2.389; p = 0.008). Dose reductions occurred in 16.5% and discontinuation in 2.5%. Conclusions CDK4/6 inhibitor–based therapy demonstrates clinically meaningful activity in gBRCAm HR+/HER2 − MBC; however, survival outcomes differ by BRCA subtype, suggesting underlying biological heterogeneity. These findings support further investigation of BRCA subtype–specific tumor biology and its implications for therapeutic sequencing in this molecularly defined population.

Trastuzumab deruxtecan (T-DXd) has demonstrated significant efficacy in metastatic breast cancer (mBC) with varying HER2 expression. Statins have been shown to increase HER2 membrane localization and stability, potentially enhancing responses to HER2-targeted therapies. We investigated whether statins enhance T-DXd activity through a translational approach combining a preclinical HER2-negative model and a real-world HER2-positive mBC cohort. In the preclinical arm, 60 female Wistar albino rats were induced with mammary tumors using N-methyl-N-nitrosourea (MNU). Animals were randomized into five groups: Control, MNU-only, MNU + T-DXd, MNU+statin, and MNU + T-DXd+statin. In the clinical arm, 109 patients with HER2-positive mBC who received T-DXd were retrospectively analyzed. The combination of T-DXd and statin significantly reduced tumor volume compared to either monotherapy (p < 0.0001) in a preclinical rat model. HER2 protein levels were found to be elevated in the statin and combination groups, as demonstrated by both IHC and Western blot analyses. In a real-world cohort of 109 heavily pretreated patients with HER2-positive mBC receiving T-DXd, concomitant statin use was associated with significantly improved median progression-free survival (mPFS) and median overall survival (mOS). Our findings revealed that statin use significantly enhanced the efficacy of T-DXd in both a preclinical HER2-negative rat model and patients with HER2-positive mBC. Prospective clinical trials are warranted to validate these observations.

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.

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.

Despite numerous studies on second-line therapies in metastatic pancreatic cancer, there is no randomized study evaluating the efficacy of gemcitabine plus nab-paclitaxel as a second-line treatment. This study aims to examine the efficacy of gemcitabine plus nab-paclitaxel in second-line therapy. In this retrospective study, a total of 218 patients from 23 centers were included. The primary endpoint was progression-free survival (PFS), secondary endpoints included overall survival (OS), treatment efficacy based on ECOG performance status (PS), and tumor marker (CEA, CA 19 - 9) levels. In the second-line treatment with gemcitabine plus nab-paclitaxel, the median PFS was 5.1 months (95% CI, 5.6 to 7.1), and the median OS was 8.6 months (95% CI, 7.3 to 10.0). Median PFS was 6.6 months in patients with normal CEA levels compared to 4.4 months in patients with high CEA levels (P = 0.01). Median PFS was 6 months in patients with ECOG PS 0-1 compared to 3.8 months in patients with PS 2 (P < 0.01). This study demonstrates the contribution of gemcitabine plus nab-paclitaxel in both OS and PFS in second-line treatment of metastatic pancreatic cancer. It was found to be a good option especially for young patients with good ECOG PS.

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: 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.

2087 Background: Adult medulloblastoma (MB) is rare, and there is no standard salvage approach for relapsed or refractory cases. High-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) has shown potential, but evidence in adults remains limited. This study evaluated the response rate, survival and toxicity after HDC with ICE regimen followed by ASCT in MB, with further focusing on post-ASCT response and pretransplant intracranial residual disease (ICRD). Methods: We retrospectively analyzed adult patients with relapsed/refractory MB who underwent HDC with the ICE regimen followed by ASCT. Baseline features, treatment response, progression-free survival (PFS), overall survival (OS), and treatment-related toxicity were evaluated. Subgroup analyses focused on post-ASCT response and pretransplant intracranial residual disease (ICRD). Results: The study included 23 patients (median age: 24 years; male: 52%, with 43% classic subtype and 61% pretransplant ICRD). The overall and complete response (CR) rates to HDC was 73.9% and 48%, respectively. The median PFS was 12.8 months, and OS was 45.1 months, with 2-year PFS and OS rates of 31% and 63%, respectively. Patients achieving CR after ASCT had significantly longer OS (NR vs 16.4 months; HR, 0.15; 95% CI, 0.03–0.72; P=.02), corresponding to an 85% reduction in mortality risk compared with non-CR patients. OS was markedly shorter in patients with pretransplant intracranial residual disease compared with those without (22.5 vs. 74.0 months; HR, 7.08; 95% CI, 1.3–36.3; p = 0.008).The large cell/anaplastic subtype remained the poorest prognostic group despite ICE induction. Toxicity was dominated by universal grade 4 myelosuppression and febrile neutropenia, but no transplantation-related mortality occurred. Conclusions: This study showed that HDC with ICE followed by ASCT is feasible in adults with relapsed/refractory MB, with encouraging survival and manageable toxicity. Pretransplant ICRD clearance and achievement of CR were major prognostic determinants, while non-CR patients remained at high risk, highlighting the need for treatment intensification in this subgroup.

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

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 Optimal sequencing of trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) in HER2 positive metastatic breast cancer (mBC) remains uncertain, and real-world evidence on the impact of prior T-DM1 exposure on subsequent T-DXd outcomes is limited. Methods We conducted a multicenter, retrospective cohort study across 21 oncology centers in Türkiye including consecutive adults with HER2 positive mBC who received at least one cycle of T-DXd between 2020 and 2025. Patients were classified as T-DM1 pretreated or T-DM1 naive at T-DXd initiation. The primary endpoint was progression free survival (PFS); secondary endpoints included objective response rate (ORR), duration of response (DOR), and overall survival (OS). To address confounding by indication, we applied stabilized inverse probability of treatment weighting (IPTW) based on prespecified clinical covariates and assessed covariate balance using standardized mean differences. Results Among 218 patients treated with T-DXd, 137 (62.8%) had received prior T-DM1 and 81 (37.2%) were T-DM1 naive. The ORR was 71.9%, including 15.2% complete and 56.7% partial responses. Median DOR in the overall cohort was 20.96 months (95% CI, 15.71–26.22). In the IPTW-weighted analysis, prior T-DM1 exposure was associated with significantly shorter PFS: 12.1 months (95% CI, 10.3–20.5) versus 26.0 months (95% CI, 18.9 - not reached) in T-DM1 naive patients (IPTW-weighted log-rank p=0.006). Prior T-DM1 remained independently associated with higher progression risk (HR 1.99, 95% CI 1.09 - 3.62; p=0.02). Median OS was 18.9 months (95% CI, 17.2–not reached) in T-DM1 pretreated patients and not reached in T-DM1 naive patients; the IPTW-weighted OS hazard ratio did not reach statistical significance (HR 1.80, 95% CI 0.86–3.79; p=0.12). Conclusions Trastuzumab deruxtecan demonstrated substantial real-world activity after prior T-DM1 exposure, but PFS was significantly shorter compared with T-DM1 naive patients, even after rigorous adjustment for measured confounding. These findings highlight the clinical relevance of antibody drug conjugate sequencing and support prospective studies to define the optimal positioning of T-DXd in HER2 positive mBC treatment algorithms.

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.

5028 Background: The prognostic significance of a teratoma component in relapsed or refractory germ cell tumors (GCT) treated with high-dose chemotherapy followed by autologous stem cell transplantation (HDCT-ASCT) remains unclear. While teratoma has been extensively studied in earlier treatment lines, data specifically addressing its impact in the transplant setting are limited. Identification of factors influencing outcomes after HDCT is critical for patient selection and treatment optimization. Methods: This single-center retrospective study included 132 GCT patients who underwent autologous stem cell–supported HDCT. Primary tumor specimens were re-evaluated by an experienced pathologist for the presence of a teratoma component. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared between teratoma-positive and teratoma-negative groups. Univariate Cox regression and predefined subgroup analyses were performed to identify factors associated with survival outcomes. Results: Baseline pathological data were available for 132 patients; 59 (44.7%) had a teratoma component and 73 (55.3%) did not. Baseline clinicopathological characteristics, including age, primary tumor site, stage, IGCCCG risk group, metastatic pattern, biomarker status, and response to first-line therapy, were comparable between groups. After a median follow-up of 55.6 months, median PFS was 6.8 months (95% CI, 4.1–9.6). Median PFS was significantly shorter in teratoma-positive patients compared with teratoma-negative patients (5.6 vs 10.0 months; log-rank p = 0.011). The 2-year PFS rates were 34% and 50%, respectively. Teratoma presence was associated with inferior PFS in univariate analysis (HR 1.77, 95% CI 1.13–2.77; p = 0.013). Median OS was not reached overall; median OS was 68.9 months in teratoma-positive patients and not reached in teratoma-negative patients, with no significant difference between groups (p = 0.986). The 2-year OS rates were similar (64% vs 67%). Subgroup analyses showed numerically poorer OS with teratoma across most strata, without statistical significance. Conclusions: In relapsed or refractory GCT patients undergoing HDCT, the presence of a teratoma component was associated with inferior disease control but not with a statistically significant OS disadvantage, possibly due to limited follow-up. Teratoma status may help identify patients requiring more intensive transplant strategies and early post-transplant treatment optimization. Prospective studies with longer follow-up are warranted.

Background/Aims:The treatment of hepatocellular carcinoma (HCC), which accounts for 90% of all liver cancers, is highly varied. The use of second-line treatments following progression on first-line atezolizumab and bevacizumab (Atez/Bev) for advanced HCC remains controversial. The aim of this study was to analyze the real-world clinical results of second-line treatments in progression after Atez/Bev and to determine the factors affecting prognosis. Materials and Methods:Fifty-eight patients treated with second-line sorafenib, regorafenib, and cabozantinib for progression after first-line Atez/Bev for advanced/metastatic HCC from 20 centers in Türkiye between October 2020 and June 2024 were retrospectively analyzed. Responses were evaluated by Response criteria, specifically Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria. Median overall survival (OS) and progression-free survival (PFS) were computed with the Kaplan-Meier method. The Cox regression model was utilized to analyze multivariate analyses. Results:About 82.8% of the patients were male and the median age of the whole group was 62 (range, 18-78) years. All patients progressed after first-line Atez/Bev and were given second-line treatment. The most commonly used second-line treatment option was sorafenib (70.7%), followed by regorafenib (12.1%) and cabozantinib (10.3%). Both median PFS (4.1 months) and median OS (7.8 months) were longer in patients treated with sorafenib compared to other treatments. In univariate analyses, Child-Pugh score B, high alpha-fetoprotein (AFP) levels (>200 ng/mL), extrahepatic spread, and Prognostic Nutritional Index (PNI) < 47.6 substantially raised the risk of overall mortality. Multivariate analysis showed that extrahepatic spread (HR (Hazard ratio): 0.41, P = .012), PNI level (HR: 0.24, P = .005), and AFP level (HR:1.97, P = .049) were independent predictors of OS. Conclusion:Although second-line therapies after Atez/Bev show different degrees of efficacy, survival rates are consistent with the literature. Extrahepatic spread, AFP level, and PNI level are the main prognostic factors. In light of this information, personalized treatment strategies may improve outcomes for this challenging patient group.

Background: Despite progress in treatment, many metastatic renal cell carcinoma (mRCC) patients still experience progression after first-line tyrosine kinase inhibitor (TKI), necessitating effective second-line options. While guidelines endorse combination therapies, accessibility limitations often restrict therapy to TKI monotherapy. Objectives: Existing decision-making relies on limited evidence, lacking direct comparisons between the leading second-line options (cabozantinib and nivolumab) which surpass everolimus in advanced mRCC. To address this gap, this study compares the efficacy of TKI versus nivolumab in second line while investigating factors influencing outcomes. Design: This was a retrospective cohort study. Methods: Turkish Oncology Group Kidney Cancer Consortium includes more than 1000 mRCC patients from 13 centers in Türkiye. It has the largest national data. We extracted 214 patients treated with a TKI in the first line and nivolumab or TKI in the second line. Results: The median overall survival (OS) and time to treatment failure (TTF) were similar in the TKI-TKI and TKI-immune checkpoint inhibitor (ICI; 41.1 and 44.8 months, p = 0.446 for OS; 27.4 and 29.8 months, p = 0.857 for TTF). The presence of previous nephrectomy for TTF made a significant difference in univariable and multivariable analysis. Bone metastases negatively affected TTF in both univariable and multivariable analyses. In the neutrophil-to-lymphocyte ratio (NLR)-high group, OS and TTF were longer in patients treated with TKI-ICI than in the TKI-TKI. In multivariable analysis, NLR was an independent prognostic factor for OS and TTF to select ICI in the second-line. Conclusion: Our analysis revealed no significant difference in OS between patients receiving ICIs or TKIs as second-line therapy. In the subgroup of patients with elevated NLR, ICI therapy was found to cause no improvement in OS. This finding suggests the potential utility of NLR as a biomarker to guide targeted selection of ICI therapy among patients progressing after first-line TKIs. Furthermore, our study identified other noteworthy prognostic factors influencing outcomes, including the presence of bone or liver metastases, Eastern Cooperative Oncology Group performance status, and International Metastatic Renal Cell Carcinoma Database Consortium risk score.

Background: The role of high-dose chemotherapy followed by autologous stem-cell transplantation (HDCT–ASCT) in advanced Ewing sarcoma remains uncertain, with mixed prospective data and heterogeneous retrospective findings. Materials and Methods: We performed a single-center, retrospective cohort study of consecutive patients with histologically confirmed ES who received HDCT–ASCT after ≥1 prior systemic therapy line (N=46). Conditioning was ICE. Prespecified endpoints were overall survival (OS; diagnosis→death), post-transplant overall survival OS-2 (ASCT→death), and progression-free survival PFS (ASCT→progression/death). Survival was estimated by Kaplan–Meier and compared by log-rank. Prognostic factors (age at diagnosis, primary tumor site, metastatic organ involvement) were evaluated using Cox models. Results: Median age at diagnosis was 23.5 years (14–55); 69.6% were male and 21.7% had metastatic disease at presentation. Median OS was 42.0 months, median PFS and OS-2 after HDCT–ASCT were 5.0 months and 8.0 months, respectively. Younger age (≤23 years) was associated with longer OS (50.0 vs 34.0 months; p=0.027). Primary tumor site was not independently associated with PFS, OS-2, or OS. Metastatic site showed endpoint-specific effects: liver metastasis independently predicted worse OS (HR 5.411; p=0.006), while lung metastasis was associated with shorter PFS (HR 6.037; p=0.016) and OS-2 (HR 2.672; p=0.025). Post-transplant best responses were CR 8.7%, PR 17.4%, SD 15.2%, and PD 58.7%. Grade 3–4 hematologic toxicities were universal (febrile neutropenia, neutropenia, thrombocytopenia 100%; anemia 86.9%); common non-hematologic events included nausea/vomiting (82.6%), diarrhea (78.2%), and mucositis/stomatitis (65.2%). Treatment-related mortality was 2.1% (1/46). Conclusions: In this young-adult–predominant cohort, HDCT–ASCT achieved limited disease control with substantial but manageable toxicity. Prognosis was driven more by age and metastatic organ involvement than by primary site, with liver metastasis portending inferior OS and lung metastasis adversely affecting PFS/OS-2. These data support risk-adapted patient selection and exploration of post-transplant maintenance strategies in future prospective studies.

Background: Salvage treatment options have not been validated in relapsed or refractory germ cell tumors. Moreover, the study populations including these patients have different heterogeneities. This study aimed to evaluate the efficacy and safety of three cycles of TIP sequential high-dose chemotherapy in patients with testicular non-seminomatous germ cell tumors who relapsed or had a refractory course after first-line platinum-based chemotherapy. Methods: Data of 141 patients who underwent three cycles of TIP followed by HDCT due to relapsed/refractory gonadal NSGCTs after first-line cisplatin-based chemotherapy (BEP/EP) at Gulhane School of Medicine Hospital Medical Oncology Department between January 2017 and May 2024 were evaluated retrospectively. Patients underwent a treatment regimen consisting of two phases. Initially, they received three cycles of induction therapy using a combination known as TIP, which includes paclitaxel, ifosfomide, and cisplatin. Following this, they were given a single cycle of high-dose chemotherapy. Demographic and clinicopathological features of patients and treatment-related complications and survival outcomes were recorded. Results: Median follow-up for all patients was 35.2 (95% CI, 29.45 to 41.07) months. Complete Response (CR) or marker negative Partial Response (PR) after HDCT was achieved in 84 (59.6%) patients. Median time for PFS not reached (NR) (95% CI, NR) in the entire group. The 2-year PFS rate was 51.8%. Median time for OS not reached (95% CI, NR) and the 2-year OS rate was 72.3%. The most common myelotoxicity observed after HDCT until engraftment was grade 4 neutropenia (100%) and grade 4 thrombocytopenia (96.5%). Transplantation-related mortality occurred in 7.1% of patients. Variables that remained statistically significant in multivariable analysis and were associated with poor prognosis for overall survival were platinum refractory disease and AFP and/or beta HCG elevation. Conclusions: Significant survival can be achieved after three cycles of TIP consecutive HDCT, while treatment-related mortality was found to be low.