Ferhat Ekinci

Background/Objectives: Despite the established benefits of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, survival outcomes remain heterogeneous among patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer. We developed the Metabolic–Muscle Reserve Index (MMRI), integrating tumor metabolic activity, biochemical status, and skeletal muscle quantity, and investigated its relationship with progression-free survival (PFS) and overall survival (OS). Methods: We conducted a retrospective study involving 168 patients with HR+/HER2− metastatic breast cancer who were treated with CDK4/6 inhibitors. MMRI incorporated baseline PET/CT-derived maximum standardized uptake value (SUVmax), serum lactate dehydrogenase (LDH), albumin, and CT-derived psoas volume index (PVI). Receiver operating characteristic (ROC) analysis identified an exploratory MMRI cut-off. We examined survival using Kaplan–Meier analysis and Cox regression. Results: ROC analysis identified an MMRI cut-off of 10.68 for mortality discrimination, with an AUC of 0.642 (95% CI: 0.563–0.716). Patients with MMRI > 10.68 had shorter median PFS (14.1 vs. 28.1 months; p < 0.001) and OS (29.7 months vs. not reached; p < 0.001) than those with MMRI ≤ 10.68. In multivariable Cox analysis, higher MMRI was associated with shorter PFS (HR: 1.857, 95% CI: 1.329–2.596; p = 0.0003) and OS (HR: 1.974, 95% CI: 1.368–2.846; p = 0.0003). Conclusions: Patients with higher MMRI values experienced shorter PFS and OS during CDK4/6 inhibitor treatment for HR+/HER2− metastatic breast cancer. Given its modest discriminative performance, these findings remain exploratory and require prospective external validation before clinical application.

Basal cell carcinoma (BCC) is the most common skin malignancy. For locally advanced or metastatic cases not amenable to surgery or radiotherapy, Hedgehog pathway inhibitors represent an effective treatment option. A 50-year-old female, previously treated with surgery, radiotherapy, and chemotherapy, presented with recurrent BCC invading the mastoid bone and dura. The tumor was deemed unresectable, and neoadjuvant carboplatin-docetaxel showed minimal benefit. Vismodegib 150 mg daily was initiated, resulting in significant clinical and radiological regression. Sustained disease control has been achieved for five years without major toxicity. This case highlights the durable efficacy of vismodegib in aggressive, locally advanced BCC and supports its use as a valuable therapeutic strategy when conventional modalities are not feasible.

Background and Purpose: The Lung Immune Prognostic Index (LIPI), based on derived neutrophil-to-lymphocyte ratio (dNLR) and Lactate Dehydrogenase (LDH), is a recognized biomarker in various malignancies. However, its incremental value over the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score in metastatic renal cell carcinoma (mRCC) remains debated. This study evaluated the prognostic role of LIPI in mRCC and its association with clinicopathological features.Methods: We retrospectively analyzed 304 mRCC patients treated between 2010 and 2023 at two oncology centers. Patients were stratified into good, intermediate, and poor LIPI groups. Survival outcomes were assessed using Kaplan–Meier and Cox regression. The prognostic performance of LIPI was compared and combined with the IMDC model using the Akaike Information Criterion (AIC).Results: Of 304 patients, 35.2% were good, 44.1% intermediate, and 17.8% poor LIPI risk. Poor LIPI was significantly associated with liver metastasis (p=0.009) and poor IMDC risk (p=0.001). Median overall survival was 45, 30, and 14 months for good, intermediate, and poor groups, respectively (p

Background: CDK4/6 inhibitors with endocrine therapy are standard first-line treatment for hormone receptor-positive, HER2-negative metastatic breast cancer, yet simple pretreatment prognostic markers are lacking. The LDH-to-albumin ratio (LAR) and the Glasgow Prognostic Score (GPS) both incorporate serum albumin and are each reported as prognostic, but have not been compared within a single cohort, and LAR has not been examined during CDK4/6 inhibitor therapy. This study evaluated both indices in this setting. Methods: Consecutive patients (n = 139) receiving palbociclib or ribociclib plus endocrine therapy (2020–2025) were analysed retrospectively. LAR was modelled continuously on the logarithmic scale, with hazard ratios per doubling; an external cut-off (46.27) served for Kaplan–Meier illustration only. GPS was calculated in its original form. As both contain albumin, each entered a separate multivariable Cox model with identical covariates. Endpoints were overall survival (OS) and progression-free survival (PFS). Results: Over a median follow-up of 50.0 months, 72 deaths and 110 progression events occurred. LAR was independently associated with OS (adjusted HR 2.87 per doubling, 95% CI 1.78–4.62, p < 0.001) and PFS (2.21, 1.45–3.35, p < 0.001). GPS was independently associated with OS (1.72, 1.05–2.82, p = 0.032) but not PFS (1.32, 0.88–1.98, p = 0.187). LAR-based models had lower Akaike information criterion values (ΔAIC 12.3 and 10.9), but concordance did not differ significantly between the indices (ΔC ≈ 0.04, p > 0.20). Conclusions: Baseline LAR, an inexpensive routine index, was associated with both endpoints, whereas GPS was associated with overall survival alone. Discrimination was modest for both indices (C-index ≤ 0.61) and did not differ significantly between them. External validation is required.

Neoadjuvant chemoradiotherapy (nCRT) is the standard treatment for locally advanced rectal adenocarcinoma, yet therapeutic response varies widely and reliable biomarkers are lacking. This study evaluated the immunohistochemical expression of Beclin-1, LC3A, HIF-1α, Bcl-2, and eIF2α in pretreatment biopsies and explored their association with tumor regression grade (TRG) and survival. A retrospective analysis was performed on 53 patients with rectal adenocarcinoma who underwent neoadjuvant therapy and surgical resection between 2010 and 2025. Immunohistochemical expression of 5 markers was evaluated semiquantitatively and correlated with TRG (both Modified Mandard and AJCC systems) and survival outcomes. Among the evaluated markers, only Beclin-1 expression correlated significantly with poorer histopathologic response in both TRG systems (Modified Mandard: ρ =0.35, P =0.010; AJCC: ρ =0.34, P =0.012). ROC analysis confirmed its discriminatory ability (AUC=0.80), identifying high Beclin-1 as a marker of reduced nCRT sensitivity. Lymphovascular invasion (LVI) and perineural invasion (PNI) were also associated with poor response ( P =0.002 each). In multivariate analysis, PNI showed borderline significance for nonresponse (OR=4.09, P =0.050). During follow-up, overall survival was adversely affected by LVI, PNI, higher T and N stage, and metastasis ( P P =0.026), while no marker correlated with disease-free survival. Beclin-1 overexpression may indicate therapy resistance through autophagy-related mechanisms, whereas eIF2α acts as a stress-response marker influencing survival. High Beclin-1 expression may serve as a predictive biomarker of poor nCRT response in rectal adenocarcinoma, while eIF2α shows prognostic significance for overall survival.

Choroidal metastases represent a rare manifestation of metastatic breast cancer, occurring in approximately 2–7% of cases, and typically indicate advanced systemic disease with poor prognosis.We report a 49-year-old premenopausal woman with hormone receptor–positive, HER2-negative metastatic breast carcinoma involving the pleura and bones. She presented with progressive dyspnea, back pain, and blurred vision in the right eye. Imaging revealed a large malignant pleural effusion, extensive osteolytic lesions, and a left breast mass with axillary lymphadenopathy. Ophthalmologic evaluation confirmed a right choroidal metastasis.Given her worsening respiratory function and recurrent pleural effusion despite drainage, the clinical picture was consistent with an impending visceral crisis. Systemic treatment with ovarian suppression, letrozole, ribociclib, and denosumab was promptly initiated.Follow-up revealed marked systemic improvement and complete resolution of visual symptoms. This case underscores the importance of rapid ophthalmologic assessment in patients with breast cancer with visual complaints. It highlights that timely systemic therapy may induce regression of choroidal lesions and prevent progression to overt visceral crisis.

Background: Cetuximab-based therapies continue to play an important role in the management of recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) despite the increasing use of immunotherapy. However, data regarding treatment outcomes and prognostic factors remain limited. This study aimed to evaluate treatment outcomes and prognostic factors associated with survival in patients with R/M HNSCC treated with cetuximab-based regimens. Methods: This retrospective single-center cohort study included patients with recurrent/metastatic HNSCC who received cetuximab-based systemic therapy at the Department of Medical Oncology, Manisa Celal Bayar University Faculty of Medicine, between May 2012 and September 2025. Demographic, clinical, laboratory, and PET/CT data were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared using the log-rank test. Prognostic factors associated with survival were evaluated using univariable and multivariable Cox proportional hazards regression analyses. Results: A total of 57 patients were included in the study. The median age was 65 years, and 91.2% of patients were male. Most patients had ECOG performance status 0–1 (94.7%) and stage IV disease (71.9%). The larynx was the most common primary tumor site (50.9%), while distant lymph node metastasis (63.2%) and lung metastasis (61.4%) were the predominant metastatic sites. Median PFS and OS were 4.6 months and 13.8 months, respectively. Kaplan–Meier analysis demonstrated that patients with a body mass index (BMI) > 25 had longer OS, whereas chronic kidney disease (CKD), primary tumor localization, and best response to first-line treatment were significantly associated with survival. In multivariable Cox regression analysis, chronic kidney disease (CKD) (HR: 5.15, p = 0.004), oral cavity primary tumor localization (HR: 2.55, p = 0.013), progressive disease as the best response to first-line treatment (HR: 4.44, p < 0.001) and the absence of grade 1–2 cetuximab-related dermatologic toxicity (HR: 3.20, p = 0.027) remained independent adverse prognostic factors. BMI was not independently associated with survival in multivariable analysis. Conclusions: Cetuximab-based therapy demonstrated clinically meaningful activity in patients with R/M HNSCC. Comorbidities, primary tumor localization, the absence of grade 1–2 cetuximab-related dermatologic toxicity and treatment response appear to substantially influence survival outcomes. Larger prospective studies are warranted to validate these findings.

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.