Emine Bihter Eniseler

Objective: To evaluate the prognostic value of the PET-derived SUVmax–lactate dehydrogenase–albumin–lymphocyte (SUV-LAL) index in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer treated with pertuzumab. Methods: This retrospective single-center study included patients with HER2-positive metastatic breast cancer treated with pertuzumab-containing regimens between January 2018 and October 2025. Baseline clinical, pathological, laboratory, and ¹⁸ F-fluorodeoxyglucose PET/computed tomography data were retrospectively collected. The SUV-LAL index was calculated as (primary tumor maximum standardized uptake value × lactate dehydrogenase)/(albumin × absolute lymphocyte count). Overall survival (OS) and progression-free survival (PFS) were evaluated using Cox proportional hazards regression analyses. Kaplan–Meier survival analysis, receiver operating characteristic (ROC) analysis, and time-dependent ROC analyses were performed to assess prognostic performance. Results: A total of 80 patients were included, of whom 36 (45.0%) died during follow-up. The SUV-LAL index remained an independent prognostic factor for OS in multivariate analysis [hazard ratio = 1.755, 95% confidence interval (CI) = 1.053–2.927; P = 0.031], together with the number of pertuzumab cycles (hazard ratio = 0.921, 95% CI = 0.872–0.972; P = 0.003). Patients with a high SUV-LAL index had significantly shorter OS and PFS than those with a low SUV-LAL index (log-rank P < 0.001 and P = 0.002, respectively). ROC analysis yielded an area under the curve (AUC) of 0.760. Compared with its individual components, the SUV-LAL index showed the strongest association with OS in univariate Cox regression analysis and achieved the highest 1-year time-dependent AUC (0.735), while maintaining acceptable prognostic performance at 3 years (AUC = 0.705). Conclusion: The PET-derived SUV-LAL index independently predicts OS in HER2-positive metastatic breast cancer treated with pertuzumab.

AIM: Although curative resection remains a cornerstone treatment for hepatocellular carcinoma (HCC), recurrence continues to limit durable disease control in a considerable proportion of patients. Improved postoperative risk assessment may facilitate more individualized surveillance and management strategies. Accordingly, we examined the prognostic performance of a dynamic alpha-fetoprotein–lactate dehydrogenase (AFP–LDH) Index in predicting recurrence after curative resection.METHODS: Patients who underwent curative resection for HCC between January 2020 and January 2025 were retrospectively analyzed. The AFP–LDH Index was calculated as log10 (postoperative AFP × LDH / preoperative AFP). Survival probabilities were estimated using the Kaplan–Meier method, and the relationship between clinical variables and outcomes was examined with Cox proportional hazards models. Receiver operating characteristic (ROC) analysis was used to identify the optimal cutoff value. Internal validation of the discriminative performance of the AFP–LDH Index was performed using bootstrap resampling (2000 repetitions), and optimism-corrected area under the curve (AUC) estimates with bootstrap-derived 95% confidence intervals were reported.RESULTS: A total of 50 patients were included, with a median follow-up duration of 27.9 months. Recurrence occurred in 26 patients (52.0%). The median RFS was 23 months (95% confidence interval [CI]: 14.5–31.5). ROC analysis identified an optimal AFP–LDH Index cutoff value of >1.67, demonstrating promising discriminative performance (AUC = 0.960). In multivariable analysis, the AFP–LDH Index remained an independent predictor of recurrence (hazard ratio [HR]: 27.24, 95% CI: 5.41–137.14, p < 0.001). ROC analysis demonstrated good discriminative performance for recurrence prediction (AUC = 0.960; 95% CI: 0.863–0.995; p < 0.001).CONCLUSIONS: The dynamic AFP–LDH Index was independently associated with recurrence risk after curative resection for HCC. This exploratory composite biomarker demonstrated promising prognostic performance; however, further multicenter validation is required before routine clinical application.

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

Background and Objectives: This study aimed to evaluate the effects of 24 h versus 46 h continuous 5-fluorouracil (5-FU) infusion durations on pathological response, progression-free survival (PFS), and overall survival (OS) in patients with gastric and gastroesophageal junction adenocarcinoma receiving a perioperative FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) regimen. Materials and Methods: A total of 300 patients who received a perioperative FLOT regimen were retrospectively analyzed. The patients were divided into two groups as those receiving 24 h and 46 h continuous 5-FU infusion. Clinicopathological characteristics were compared. Survival analyses were evaluated using the Kaplan–Meier method. Factors affecting pathological response were analyzed by logistic regression, and factors affecting survival were examined by Cox regression analysis. Results: Pathological response rates were found to be significantly higher in patients receiving 46 h 5-FU infusion (multivariate analysis: OR = 2.884; 95% CI: 1.619–5.138; p < 0.001). The probability of pathological response was found to be significantly lower in patients with baseline cT4 and advanced nodal stage. Median OS times were 41.23 months and 33.73 months in the 24 h and 46 h groups, respectively, with no significant difference detected between the groups (p = 0.371). In contrast, median PFS time was significantly longer in the 24 h group (38.47 months vs. 18.00 months; p < 0.001). However, in multivariate analysis, 5-FU infusion duration could not be demonstrated as an independent prognostic factor for PFS. Moderately and poorly differentiated tumors and an increased number of positive lymph nodes were found to be independent risk factors for progression. Conclusions: Although 46 h 5-FU infusion in the perioperative FLOT regimen was associated with a higher pathological response rate, this advantage was not reflected in survival outcomes. It is considered that the observed difference in PFS may stem from the clinicopathological heterogeneity between the groups. Prospective randomized studies are needed to determine the optimal 5-FU infusion duration.

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

Background and Objectives: Although perioperative FLOT improves outcomes in locally advanced gastric cancer, postoperative recurrence remains frequent. This study evaluated the prognostic value of a PET-derived SUVmax/albumin ratio integrating tumor metabolism and nutritional status in patients treated with neoadjuvant FLOT. Materials and Methods: This retrospective single-center study included patients with gastric adenocarcinoma treated with neoadjuvant FLOT followed by curative gastrectomy between January 2017 and May 2025, using data obtained from existing medical records after ethical approval. Pre-treatment SUVmax from ¹⁸F-FDG PET/CT and serum albumin were recorded to calculate the SUVmax/albumin ratio. Progression-free survival (PFS) was the primary endpoint. Prognostic factors were analyzed using Cox regression, and discriminatory performance was assessed using receiver operating characteristic (ROC) analysis. Results: A total of 104 patients were included. During a median follow-up of 28 months (IQR, 16–46 months), 46 patients (44.2%) developed recurrence. Patients with recurrence had significantly lower serum albumin levels and higher PET SUVmax values and PET SUVmax/albumin ratios (all p < 0.001). In multivariable analysis, the PET SUVmax/albumin ratio remained significantly associated with PFS (HR 1.71; 95% CI 1.33–2.21; p < 0.001). ROC analysis demonstrated moderate discriminatory performance (AUC 0.733; 95% CI 0.638–0.815), while additional time-dependent ROC analyses yielded AUC values of 0.732 (95% CI 0.611–0.836) at 1 year and 0.829 (95% CI 0.694–0.947) at 3 years. Exploratory comparative analyses demonstrated that both PET SUVmax and serum albumin retained statistical significance when evaluated simultaneously in the same multivariable model. Conclusions: The pre-treatment PET SUVmax/albumin ratio was significantly associated with PFS in patients with gastric cancer treated with neoadjuvant FLOT and may represent an exploratory composite prognostic biomarker requiring further prospective validation.

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

Ejmi Eurasian Journal of Medical Investigation

Paratesticular Well-differentiated Liposarcoma: A Case Report - Journal of Oncological Sciences

This study aimed to evaluate the predictive role of the CA 15-3 × neutrophil-to-lymphocyte ratio (NLR) score in estimating pathologic complete response (pCR) in patients with invasive breast cancer who underwent neoadjuvant chemotherapy (NACT). A total of 330 patients treated with NACT between January 2015 and March 2025 were retrospectively analyzed. The CA 15-3 × neutrophil-to-lymphocyte ratio (NLR) score was calculated by multiplying pre-treatment serum CA 15-3 levels with the NLR. pCR was defined as the absence of invasive carcinoma in both the breast and axillary lymph nodes after surgery. Logistic regression analyses were performed to identify independent predictors of pCR, and receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal cutoff value for the composite score. The median age of the study population was 48 years. Pathologic complete response was achieved in 42.4% of patients. The median CA 15-3 × NLR score was significantly lower in the pCR group compared to the non-pCR group (21 vs. 24; p = 0.033). ROC analysis revealed an optimal cutoff value of ≤ 32.7 (AUC = 0.568), with 81.05% sensitivity and 33.9% specificity. In multivariate logistic regression analysis, CA 15-3 × NLR ≤ 32.7 remained an independent predictor of pCR (OR 1.931; 95% CI 1.086-3.433; p = 0.025), along with N stage 2 and the absence of perineural invasion. The CA 15-3 × NLR score demonstrates modest prognostic potential in predicting treatment response in breast cancer patients receiving neoadjuvant chemotherapy. While promising, these findings should be interpreted cautiously, and further validation is needed before clinical implementation.