Whether clinicopathological features of de novo Luminal A metastatic breast cancer (MBC) have evolved across recent diagnostic periods remains unclear. In this retrospective, multicenter cohort study, we evaluated temporal changes in tumor biology and outcomes among 401 women diagnosed with de novo Luminal A MBC (ER/PR-positive, HER2-negative, Ki-67 ≤ 14%) between 2017 and 2025. Patients were stratified into four consecutive diagnostic periods spanning pre-pandemic, pandemic, and post-pandemic phases. A progressive increase in tumor proliferative activity was observed, with mean Ki-67 rising from 6.38% to 13.48% (p < 0.001), accompanied by declining ER/PR expression and increasing tumor size and histologic grade. Receiver operating characteristic analysis identified 9.5% as the optimal Ki-67 cutoff for overall survival (AUC = 0.785; p < 0.001). Both Ki-67 ≥ 9.5% and later diagnostic period independently predicted poorer survival in multivariable models (HR: 2.106 and 2.412; both p < 0.001). These findings suggest a temporal shift toward a more aggressive biological phenotype, underscoring the clinical relevance of monitoring proliferation indices even within the Luminal A subtype. While causality cannot be inferred, identification of a clinically actionable Ki-67 threshold may aid risk stratification and supports future research integrating molecular profiling to clarify mechanisms underlying temporal biological change.

Thymic carcinoma (TC) is a rare and aggressive malignancy with limited evidence guiding second-line treatment after prior systemic therapy. We evaluated real-world outcomes of second-line systemic therapy in a multicenter cohort. Adults with unresectable, recurrent, or metastatic TC who received second-line systemic therapy after prior systemic therapy between 2010 and 2023 were retrospectively analyzed. Treatments were categorized as multidrug chemotherapy, gemcitabine monotherapy, PD-1 inhibitor therapy, or targeted therapy (sunitinib). For the primary comparison of multidrug chemotherapy versus gemcitabine monotherapy, propensity scores based on age, sex, ECOG performance status, Masaoka–Koga stage IV, prior surgery, and calendar year were used to generate overlap weights. Weighted Cox models used robust standard errors clustered by treatment center. A sensitivity propensity-score model additionally included first-line carboplatin–paclitaxel exposure (yes/no). A total of 107 patients from 20 treatment centers were included. Median age was 53.2 years (IQR, 41.5–58.0), 78 (72.9

Purpose:The prognostic value of cetuximab-related electrolyte disturbances in metastatic colorectal cancer (CRC) remains unclear. The available reports on the prognostic effect of hypomagnesemia are controversial, while there are no comprehensive analyses regarding hypokalemia. This study aimed to evaluate the impact of hypomagnesemia and hypokalemia on treatment outcomes in patients with RAS/RAF wild-type metastatic CRC receiving first-line cetuximab-based therapy. Patients and Methods:We retrospectively analysed 305 patients treated across seven oncology centers between March 2013 and December 2024. Patients with baseline renal insufficiency or pre-existing electrolyte disturbance were excluded. Serum magnesium and potassium levels were assessed from the initiation of cetuximab until one month after its discontinuation. Results:There was one patient with missing magnesium levels and one patient with missing potassium levels. Three-hundred and four patients were available for the final analyses (n=304). Hypomagnesemia and hypokalemia occurred in 29.9% and 20.7% of the patients, respectively. Neither hypomagnesemia nor hypokalemia was significantly associated with progression-free survival (PFS) (11.9 vs 11.7 months for each; p=0.528 and p=0.327) or overall survival (OS) (25.3 vs 27.9 months; p=0.705 and 22.0 vs 28.8 months; p=0.824, respectively). Hypokalemia was correlated with a higher disease control rate (96.8% vs 87.1%, p= 0.028). In multivariate analyses, only metastatic burden (≥2 sites) independently associated with inferior outcomes for both PFS (HR 1.61, 95% CI 1.25-2.08, p< 0.001) and OS (HR 1.77, 95% CI 1.31-2.39, p< 0.001). Conclusion:Hypomagnesemia and hypokalemia did not significantly impact survival outcomes despite previous studies indicating otherwise. Moreover, hypokalemia was linked to improved disease control. These results provide incremental evidence regarding the clinical relevance of electrolyte disturbances, particularly hypokalemia, and highlight the need for prospective studies to clarify their prognostic and predictive significance.

Triple-negative breast cancer (TNBC) shows substantial heterogeneity in response to neoadjuvant therapy (NAT). Simple, reproducible biomarkers that help identify patients more likely to achieve pathologic complete response (pCR) are needed. This multicenter retrospective cohort included 137 patients with TNBC treated with anthracycline–taxane–based NAT between 2015 and 2023, with or without carboplatin. The Ki67 proliferation index and pan-immune-inflammation value (PIV = neutrophil × monocyte × platelet / lymphocyte) were evaluated for their association with pCR Receiver operating characteristic (ROC) analyses identified optimal cut-offs (Ki67: 27.5

Background: Neuroendocrine prostate cancer (NEPC) is a rare and aggressive malignancy with limited prognostic tools. The Lung Immune Prognostic Index (LIPI), derived from dNLR and lactate dehydrogenase, has demonstrated prognostic value in small-cell lung cancer but has not been evaluated in NEPC. This study assessed the prognostic role of LIPI in NEPC. Methods: This multicenter retrospective study included 34 patients with NEPC (21 secondary, 13 de novo) from four centers in Turkey. Laboratory data were collected at NEPC diagnosis (T3), initial prostate cancer diagnosis (T1), and castration-resistant prostate cancer diagnosis (T2). LIPI was scored using original fixed cut-offs. Survival analyses included Kaplan–Meier, Cox regression, and ROC methods. Results: At NEPC diagnosis, 18 patients (52.9%) had Good LIPI and 16 (47.1%) Intermediate + Poor LIPI. Intermediate + Poor LIPI was associated with significantly shorter overall survival (median 4 vs. 15 months; log-rank p = 0.001; HR 3.83, 95% CI 1.65–8.90). In multivariable analysis, albumin was an independent predictor (HR 0.37, p = 0.015), while LIPI showed a trend (HR 2.35, p = 0.091). LIPI demonstrated the highest discriminatory ability for 6-month overall survival (AUC 0.763, p = 0.009). LIPI at earlier disease stages did not predict time to transformation or castration resistance. Among secondary NEPC patients, worsening LIPI trajectory was associated with shorter survival (median 4 vs. 10 months; log-rank p = 0.031). Conclusions: LIPI at NEPC diagnosis was associated with overall survival and demonstrated the highest discriminatory ability among the inflammatory indices assessed. As a routine blood-based score, LIPI may support risk stratification at NEPC diagnosis. Prospective validation is warranted.

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.

Objectives: In patients receiving immune checkpoint inhibitors (ICIs), baseline nutritional status is frequently recorded, but what happens during treatment may be at least as informative. We examined whether the 3-month change in Mini Nutritional Assessment (ΔMNA)–Short Form (SF) is associated with survival, and how this relates to baseline systemic inflammation measured by modified Glasgow Prognostic Score (mGPS). Methods: We retrospectively screened institutional records and included 54 adults with advanced/metastatic solid tumors treated with ICIs who had MNA-SF documented at treatment start and again at approximately 3 months. ΔMNA was defined as MNA-SF (~3 months) minus baseline MNA-SF (higher values indicate improvement) and was categorized for Kaplan–Meier analyses as worsened (≤ −1), stable (= 0), or improved (≥ +1). Baseline mGPS was derived using CRP >5 mg/L and albumin <35 g/L. Overall survival (OS) and progression-free survival (PFS) were measured from ICI initiation. Cox regression assessed ΔMNA as a continuous variable, with prespecified adjustment for baseline mGPS, age, and sex.Results: Median follow-up was 317 days (IQR 170.5–457.3). Death occurred in 16/54 patients and a PFS event in 27/54. Median OS was 706 days (1-year OS 71.3%; 2-year OS 49.4%), and median PFS was 337 days (1-year PFS 48.5%; 2-year PFS 15.1%). Nutritional categories shifted toward better status at 3 months (baseline normal/risk/malnutrition 29/23/2 vs 35/17/2 at follow-up). In univariable Cox models, higher ΔMNA was associated with longer survival (PFS: HR 0.72, 95% CI 0.56–0.94; P=0.016; OS: HR 0.56, 95% CI 0.38–0.82; P=0.003). In prespecified multivariable models, baseline mGPS was independently associated with OS (HR 1.86, 95% CI 1.00–3.45; P=0.048). After adjustment, the association between ΔMNA and outcomes remained in the protective direction but did not meet conventional statistical significance (OS: HR 0.67, 95% CI 0.42–1.06; P=0.086; PFS: HR 0.72, 95% CI 0.56–1.05; P=0.094). In an exploratory lung cancer subgroup (n=36), ΔMNA was associated with improved PFS (HR 0.62; P=0.008) and OS (HR 0.59; P=0.018). These subgroup findings should be interpreted as hypothesis-generating.Conclusions: Baseline mGPS captured inflammatory risk at ICI start, while ΔMNA captured what happened to nutritional status over the first 3 months. In this cohort, nutritional improvement showed a consistent protective direction for OS and PFS even after accounting for baseline inflammation, and mGPS retained an independent association with OS. These findings support prospective studies that reassess nutrition during immunotherapy rather than relying on a single baseline measurement.

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/OBJECTIVES:Malignant melanoma remains a highly aggressive malignancy with substantial mortality despite advances in systemic therapy. Identifying simple and reproducible prognostic biomarkers is essential for improving risk stratification. Inflammation- and nutrition-based indices-including the Systemic Immune-Inflammation Index (SII), Systemic Inflammatory Response Index (SIRI), dynamic SIRI, and the Controlling Nutritional Status (CONUT) score-have shown prognostic value in various cancers. This study assessed the prognostic significance of these indices in patients with locally advanced or metastatic melanoma using real-world data. METHODS:A retrospective cohort of 138 patients treated between 2010 and 2023 was analyzed. Baseline demographic, clinical, nutritional, and inflammatory parameters were collected. Optimal cut-off values for SII, SIRI, 6-month SIRI, and dynamic SIRI were determined using receiver operating characteristic analysis. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, and independent predictors were identified with multivariate Cox regression. RESULTS:Elevated baseline SII and SIRI were significantly associated with shorter overall survival. Both 6-month SIRI and dynamic SIRI demonstrated strong prognostic value, emphasizing the importance of longitudinal inflammatory changes. In multivariate analysis, response to first-line therapy emerged as the only independent predictor of disease progression. Patients with a CONUT score ≥ 3 showed significantly shorter OS and PFS in univariate analyses, underscoring the prognostic relevance of nutritional status. CONCLUSIONS:SII, SIRI, 6-month SIRI, dynamic SIRI, and CONUT are practical, accessible, and reproducible biomarkers with meaningful prognostic value in advanced melanoma. Incorporating these indices into routine clinical assessment may enhance risk stratification and support more personalized treatment decision-making.

Background and Objectives: Nasopharyngeal carcinoma (NPC) is a distinct type of head and neck cancer with unique epidemiological and pathological characteristics. Inflammatory and nutritional markers have been increasingly recognized as prognostic indicators in cancer. In this study, we aim to evaluate the significance of the prognostic nutritional index (PNI) and C-reactive protein/albumin ratio (CRP/Alb) in the prognosis of patients with locally advanced nasopharyngeal carcinoma (NPC). Materials and Methods: We retrospectively analyzed a total of 78 patients diagnosed with locally advanced NPC who received chemoradiotherapy (CCRT) with or without induction or adjuvant chemotherapy between January 2010 and April 2024. Patient characteristics, treatment modalities, inflammatory and nutritional markers, overall survival (OS), and progression-free survival (PFS) were assessed. Kaplan–Meier survival analysis and Cox regression models were used to evaluate the prognostic impact of PNI and CRP/Alb. Results: A lower PNI (≤52.90) and lower CRP/Alb ratio (≤0.14) were significantly associated with higher mortality risk (p = 0.043 and 0.023, respectively). Tumor size (≥32.85 mm) was also found to be a significant prognostic factor (p = 0.041). Patients receiving CCRT alone or with adjuvant chemotherapy had a better OS and PFS compared to those who received induction chemotherapy plus CCRT (p = 0.028 and 0.002, respectively). Multivariate Cox regression analysis indicated that CCRT + AC (HR: 0.17, p = 0.029) and CCRT (HR: 0.25, p = 0.049) significantly reduced the risk of death. Conclusions: PNI and CRP/Alb ratio are independent prognostic markers in locally advanced NPC, providing valuable insights into patient stratification and treatment optimization. These findings support their integration into routine clinical practice for risk assessment. Future large-scale, multicenter studies are warranted to confirm these findings.

Background: Sorafenib remains an important treatment option for patients with radioiodine-refractory differentiated thyroid cancer (RAI-R DTC). This study evaluated real-world outcomes and prognostic factors in patients treated with sorafenib. Materials and Methods: This retrospective multicenter study included 176 patients with RAI-R DTC treated with sorafenib between 2000 and 2024 across sixteen centers. Clinical, pathological and treatment-related variables, including metastatic sites, radiotherapy, dose reduction, inflammatory markers (neutrophil-to-lymphocyte ratio [NLR] and platelet-to-lymphocyte ratio [PLR]) and pretreatment thyroglobulin (Tg), were analyzed. Progression-free survival (PFS) was evaluated using Kaplan-Meier analysis. Prognostic factors were assessed using univariate and multivariate Cox regression analyses. Results: The median follow-up duration was 24 months and the median PFS was 21 months (95% CI: 15.5-26.5). Partial response was observed in 82 patients (46.6%), stable disease in 55 (31.3%) and progressive disease in 35 (19.9%). Patients who underwent dose reduction had longer PFS than those without dose reduction (42 vs. 19 months, p = 0.030), and absence of dose reduction remained independently associated with progression risk. Patients who received radiotherapy had shorter PFS than those who did not receive radiotherapy (16 vs. 37 months, p = 0.002), and radiotherapy-related variables remained independent predictors of progression. Patients with PLR values >138.2 had shorter PFS than those with PLR values ≤ 138.2 (19 vs. 34 months, p = 0.047), although this association was not maintained in Cox regression analysis. Similarly, associations between NLR and Tg values and PFS did not reach statistical significance (p = 0.112 and p = 0.072, respectively). Hand-foot syndrome was the most common toxicity, occurring in 59 patients (33.5%), while Grade 3 hand-foot syndrome was observed in 7 patients (4.0%). Conclusions: Sorafenib provided meaningful disease control with a median PFS of 21 months in this real-world cohort. Dose reduction was associated with longer PFS, whereas radiotherapy requirement appeared to reflect a higher-risk subgroup. Toxicities were generally manageable.

BACKGROUND: Triple-negative breast cancer (TNBC) shows substantial heterogeneity in response to neoadjuvant therapy (NAT). Simple, reproducible biomarkers that help identify patients more likely to achieve pathologic complete response (pCR) are needed. METHODS: This multicenter retrospective cohort included 137 patients with TNBC treated with anthracycline–taxane–based NAT between 2015 and 2023, with or without carboplatin. The Ki67 proliferation index and pan-immune-inflammation value (PIV = neutrophil × monocyte × platelet / lymphocyte) were evaluated for their association with pCR Receiver operating characteristic (ROC) analyses identified optimal cut-offs (Ki67: 27.5%; PIV: 292). Patients were categorized into four Ki67–PIV subgroups. Multivariable logistic regression was used to examine associations with pCR, and a nomogram was developed incorporating tumor size, clinical nodal status, chemotherapy regimen, and Ki67–PIV subgroup. Discrimination, calibration, and internal validation were assessed using ROC AUC, calibration plots, and bootstrap resampling (B = 1000). RESULTS: The overall pCR rate was 41% (56/137). pCR rates differed across Ki67–PIV subgroups (p < 0.001), with the High Ki67–Low PIV subgroup showing the highest pCR proportion (84%; 31/37) and the lowest proportions observed in Low Ki67–High PIV (12%; 4/34) and Low Ki67–Low PIV (11%; 1/9) subgroups. In multivariable analysis, the High Ki67–Low PIV phenotype was independently associated with pCR (OR 1.88, 95% CI 1.34–2.97; p < 0.001), and carboplatin-containing NAT was also independently associated with higher pCR likelihood (OR 1.75, 95% CI 1.12–2.64; p < 0.001). The nomogram demonstrated strong discrimination (AUC = 0.86), with a bootstrap-corrected AUC of 0.84 and good calibration. CONCLUSION: In this retrospective multicenter cohort, integrating Ki67 and PIV enabled biomarker-defined stratification of pCR after NAT in TNBC. A nomogram incorporating clinical variables, regimen, and the Ki67–PIV phenotype may provide a pragmatic approach for risk stratification, although external validation is required before broader clinical application.

BACKGROUND/OBJECTIVES:Whether inflammatory and nutritional parameters shift meaningfully in the first months of systemic treatment - and whether these shifts predict outcomes - has not been adequately addressed. We set out to track these changes from treatment initiation to month 3 in adults with newly diagnosed solid tumors, with progression-free and overall survival as primary endpoints. METHODS:This was a single-center prospective study running from August 2023 through August 2024. Patients aged ≥ 18 with histologically proven solid tumors who were about to start systemic anticancer therapy were consecutively enrolled; 100 completed both assessment points. At each visit - baseline and month 3 - we recorded anthropometric data, performed BIA for body composition, administered the MNA-SF, measured handgrip strength and gait speed, and collected fasting blood samples for biochemical analysis. Wilcoxon signed-rank test, Spearman correlation, ROC curves, and logistic regression were the main analytical tools. RESULTS:No sarcopenia was detected at baseline. By month 3, only one patient (1%) had developed it. Body fat percentage dropped significantly (P = 0.019); SMI and muscle mass stayed stable. MNA scores were essentially unchanged. Third-month CRP was the only independent predictor of both progression and survival (cut-off 4.74 mg/L; AUC 0.672; P = 0.008). CRP ≥ 4.74 mg/L conferred a 3.63-fold higher progression risk on multivariate analysis (OR 3.63; 95% CI 1.34-9.85; P = 0.011). Albumin correlated with SMI at month 3 (r = 0.214; P = 0.033). CONCLUSIONS:Sarcopenia was uncommon this early in the disease course. Inflammation, however, was not. Third-month CRP predicted outcomes independently - even in patients whose nutritional scores and muscle indices remained intact. This dissociation suggests inflammatory activation precedes measurable compositional decline. The positive correlation between albumin and SMI supports albumin's role as both a nutritional and functional marker. Routine CRP and albumin checks during early treatment may prove useful for identifying patients who need closer follow-up.

Background and Objectives: Reliable pretreatment biomarkers to guide treatment selection in HER2-positive metastatic breast cancer (mBC) remain an unmet need. Systemic inflammatory indices derived from routine blood tests have emerged as accessible prognostic markers. This study evaluated the prognostic value of inflammation-based indices in patients with HER2-positive mBC treated with trastuzumab emtansine (T-DM1). Materials and Methods: In this retrospective single-center cohort study, 50 patients with HER2-positive mBC treated with T-DM1 in the second-line setting were analyzed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. ROC analysis assessed the prognostic performance of the CRP/albumin ratio (CAO), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Variables associated with PFS were further evaluated using multivariable Cox regression. Results: The median follow-up was 46 months. Median OS from initial diagnosis and median PFS from T-DM1 initiation were 96 and 7 months, respectively. Metastatic pattern (p = 0.010), CNS involvement at T-DM1 initiation (p = 0.025), liver metastasis (p = 0.041), and best radiologic response (p < 0.001) were associated with PFS. ROC analysis showed modest discrimination (CAO AUC 0.694, NLR 0.658, PLR 0.646, and SII 0.653). In multivariable analysis, best radiologic response to T-DM1 was strongly associated with progression risk and appeared to reflect treatment sensitivity rather than acting as a pretreatment predictor. Conclusions: T-DM1 provided meaningful disease control in this real-world cohort. Treatment response was the main determinant of progression, while baseline inflammatory markers offered modest complementary prognostic value. These findings may aid patient selection for T-DM1, particularly in settings with limited access to trastuzumab deruxtecan.

Background: Non-small cell lung cancer (NSCLC) is the most prevalent form of malignancy and the leading cause of cancer-related fatalities. In clinical practice, metastatic sites are identified on a case-by-case basis. ALK rearrangements are detected in 3-5% of NSCLC cases and are known to have a tendency (tropism) to metastasize to the brain. Methods: Data from 81 ALK-positive and 91 ALK-negative metastatic NSCLC patients were retrospectively analyzed. Systemic markers, including HALP score, NLR, PLR, LMR, and LDH, were calculated from blood tests at the time of metastasis. Optimal cut-off values were determined using ROC analysis. Survival outcomes and prognostic factors were assessed using Kaplan-Meier and Cox regression analyses. Results: ALK-positive patients were significantly associated with female gender (p = 0.002), non-smoking status (p = 0.001), adenocarcinoma histology (p = 0.001), and a higher incidence of brain metastases (p = 0.001). In univariate analysis, age, time to metastasis, liver metastasis, and NLR were prognostic for survival. Crucially, multivariate analysis identified liver metastasis as an independent predictor of poor prognosis (HR = 1.618; 95% CI: 1.050-2.494; p = 0.029), indicating a 61.8% increased risk of death or progression. While inflammation markers (NLR, HALP, PLR, LMR) did not predict metastasis to specific sites, elevated LDH levels were significantly associated with liver metastasis (p = 0.007). Conclusion: ALK-positive NSCLC demonstrates a marked CNS tropism; however, liver metastasis remains a more critical adverse prognostic factor than brain metastasis in real-world settings. While routine inflammation markers showed limited utility in predicting site-specific metastasis, LDH levels correlated significantly with liver involvement. Aggressive management strategies are warranted for ALK-positive patients presenting with liver metastases.

Aim: Reliable prognostic biomarkers are needed to improve risk stratification in patients with advanced pancreatic adenocarcinoma. We developed and validated a simple composite risk score that integrates clinical, laboratory, and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) derived parameters to predict survival. Methods: This retrospective single-center study included 50 patients with advanced pancreatic adenocarcinoma who underwent a baseline 18F-FDG PET/CT before systemic treatment. Receiver operating characteristic (ROC) analysis was used to determine cut-off values for total lesion glycolysis (TLG), metabolic tumor volume (MTV), and serum carbohydrate antigen 19-9 (CA19-9). A composite risk score (0-4) was created by assigning one point each for liver metastasis, MTV above the cut-off, TLG above the cut-off, and CA19-9 >1000 U/mL. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Results: The median OS and PFS were 13.73 and 7.23 months, respectively. ROC analysis identified cut-off values of 15.55 cm3 for MTV, 93.88 for TLG, and 1000 U/mL for CA19-9. Twenty-three patients (46.0%) were classified as low risk (score 0-1) and 27 (54.0%) as high-risk (score ≥2). High-risk patients had significantly shorter OS (10.35 vs. 14.62 months, p=0.018) and PFS (6.01 vs. 7.29 months, p=0.048) than low-risk patients. One-year OS rates were 41.7% and 81.0%, respectively. Conclusions: The proposed composite risk score was associated with distinct survival outcomes in patients with advanced pancreatic adenocarcinoma. By integrating routinely available clinical, laboratory, and PET/CT-derived variables, this pragmatic model may assist baseline prognostic stratification. These findings require validation in larger prospective multicenter cohorts before clinical implementation.

Given the lack of an effective systemic therapy for recurrent glioblastoma, this study aims to compare response rates, progression-free survival, overall survival, and toxicity profiles of bevacizumab in combination with temozolomide (TMZ) versus irinotecan. We retrospectively analyzed patients with recurrent glioblastoma from seventeen oncology centers in Türkiye who received bevacizumab combined with either TMZ or irinotecan after progression. Outcomes included response rates, progression-free survival (PFS), overall survival (OS), and adverse events assessed by CTCAE v4.0. Among 210 patients with recurrent glioblastoma, the median PFS was 7.9 months overall (5.2 months with TMZ–bevacizumab and 8.2 months with irinotecan–bevacizumab), and the median OS was 10.6 months overall (11.3 and 10.3 months, respectively). Six-month PFS and OS rates were 60

Nutritional status has been associated with prognosis in several cancers. We investigated whether baseline prognostic nutritional index (PNI) and geriatric nutritional risk index (GNRI) as well as their variations during treatment predicted response and survival in extensive-stage small cell lung cancer (ES-SCLC) patients treated with atezolizumab plus chemotherapy. In this multicenter study, records of ES-SCLC patients who received first-line atezolizumab plus platinum-etoposide combination were reviewed retrospectively. Baseline PNI <45 and GNRI <98 were accepted as low. They were reassessed on day 1 of the third cycle to calculate changes from the baseline (ΔPNI and ΔGNRI). Regression models were used to determine predictive factors for response, progression-free and overall survival (PFS and OS). The study included 145 patients. High baseline PNI was independently associated with objective response (odds ratio=2.50, P=0.02). In patients with a low baseline PNI, median PFS was significantly shorter (6.1 vs. 8.7 mo, P=0.04) and it significantly predicted PFS (hazard ratio=1.52, P=0.03). Median OS was significantly shorter in patients with ΔPNI ≤-10% (11.1 vs. 14.9 mo, P=0.01), which independently predicted OS (hazard ratio=2.10, P=0.001). Baseline GNRI and ΔGNRI were not associated with efficacy. However, in patients 65 years of age or older, median PFS was significantly shorter in cases with a low baseline GNRI (7.1 vs. 10.7 mo, P=0.04). PNI and its variations as convenient and cost-effective markers can help predict response and prognosis in ES-SCLC patients receiving first-line atezolizumab plus chemotherapy. GNRI might emerge as an additional prognostic tool in patients 65 years of age or older.

Background/Objectives: We aimed to evaluate the real-world outcomes of first-line osimertinib in patients with advanced EGFR-mutant non-small cell lung cancer, together with the progression patterns, including the management and outcomes of oligoprogressive disease in the real-world setting. Methods: Patients who received first-line osimertinib at 33 oncology centers across Türkiye were retrospectively analyzed. Results: The median (IQR) age of 143 patients was 59.4 (50.9-68.9), 62.9% were female, and 68.5% were non-smokers. The most frequently identified EGFR mutations were exon 19 deletion (64.3%) and exon 21 L858R (28.7%). The median progression-free survival (PFS) was 17.6 months (95% CI 14.6-20.6). Exon 19 deletion subgroup had significantly longer median PFS than exon 21 L858R subgroup (22.0 vs. 11.7 months; HR = 0.40 [95% CI 0.25-0.64]; p < 0.001). Of the patients who experienced disease progression, 51.2% had oligoprogression. Among these, 81.8% received local ablative treatments (LATs) while continuing osimertinib. The median time to osimertinib discontinuation was significantly longer in patients treated with LATs than in those who continued osimertinib without LATs (8.5 vs. 3.0 months; p = 0.001). In the overall cohort, 12- and 24-month overall survival (OS) rates were 93.0% and 82.5%, respectively. The median OS was significantly longer in patients with oligoprogression compared to those with systemic progressive disease (57.7 vs. 36.5 months; p = 0.007). Any-grade and grade ≥ 3 osimertinib-related adverse events occurred in 55.2% and 6.3% of patients, respectively. Conclusions: This study supports the real-world effectiveness and tolerability of first-line osimertinib. Oligoprogression was associated with longer OS compared with systemic progression, and the integration of LATs in carefully selected patients with oligoprogression may be associated with prolonged osimertinib treatment duration and favorable post-progression outcomes.

This multicenter retrospective study evaluated the impact of type 2 diabetes mellitus (DM) on clinical outcomes and immune-related adverse events (irAEs) in 450 patients with metastatic non-small cell lung cancer (NSCLC) treated with second-line nivolumab at 17 centers between 2016 and 2024. Among these patients, 118 (26.2%) had DM. Baseline demographic and clinical characteristics, including age, sex, smoking status, ECOG performance status, histology, and PD-L1 expression, were similar between patients with and without DM. Nivolumab demonstrated similar antitumor activity in both groups, with no significant differences in median progression-free survival (PFS), overall survival (OS), or objective response rates. However, the incidence of Grade 3-4 irAEs was significantly higher in patients with DM. HbA1c levels were not associated with survival outcomes in univariate analyses, and metformin or insulin use did not affect PFS or OS among patients with DM. These findings indicate that DM does not compromise immunotherapy efficacy but is associated with a higher risk of severe toxicity. Clinicians should consider metabolic status and closely monitor patients with DM receiving immunotherapy. Further prospective studies are needed to clarify underlying mechanisms and optimize treatment strategies for this population.