Mehmet Fatih Ozbay

Background: We developed clinical–laboratory models for early progression or death within 90 days (EPD90) during PD-1/PD-L1 blockade in advanced non-small cell lung cancer. EPD90 is a pragmatic early-risk endpoint, not a diagnosis of hyperprogressive disease. Methods: This retrospective single-centre cohort included patients treated between January 2018 and March 2026. The four-item baseline score, EPS-4, combined bone metastasis, lactate dehydrogenase (LDH), albumin and C-reactive protein. Among patients alive and progression-free at day 42, D1 added six-week changes in neutrophil-to-lymphocyte ratio (NLR), and D2 additionally included LDH changes. Internal validation used bootstrap resampling and repeated cross-validation. Results: Among 282 patients, 83 (29.4%) had EPD90. In the common baseline complete-case set (n = 252; 76 events), EPS-4 had an apparent area under the curve (AUC) of 0.729 (95% confidence interval [CI] 0.665–0.793). In 238 landmark-eligible complete cases (56 subsequent events), adding NLR change increased AUC from 0.718 to 0.801. Adding LDH yielded an AUC of 0.816, a modest, statistically non-significant increment (delta AUC 0.016; p = 0.094). Bootstrap-corrected calibration slopes were 0.980 for D1 and 0.957 for D2. Conclusions: NLR provided the principal dynamic contribution. D1 is emphasized as the main dynamic model; D2 remains an exploratory extension with uncertain incremental value. Unavailable laboratory collection dates and lack of external validation limit interpretation. The models and proposed thresholds require independent validation before clinical use.

Background: Tumour-growth kinetics required to diagnose hyperprogressive disease are often unavailable in routine care. We developed baseline and dynamic clinical–laboratory models for progression or death within 90 days (EPD90), a pragmatic endpoint for early clinical deterioration, and assessed whether six-week laboratory change improved risk estimation. Methods: This retrospective single-centre cohort included consecutive adults with advanced or unresectable non-small cell lung cancer treated with PD-1/PD-L1 blockade between January 2018 and March 2026. EPS-4 combined bone metastasis, lactate dehydrogenase (LDH) >240 U/L, albumin < 3.5 g/dL and C-reactive protein >10 mg/L. Day-42 landmark models added log2 ratios of neutrophil-to-lymphocyte ratio (NLR) and LDH. Performance was assessed with 2000 bootstrap resamples and repeated cross-validation. Results: Among 282 assessable patients, 83 (29.4%) had EPD90. In common complete cases (n = 252; 76 events), EPS-4 had an AUC of 0.729 (95% CI 0.665–0.793). Among 238 patients alive and progression-free at day 42 (56 subsequent events), AUC increased from 0.718 for EPS-4 alone to 0.801 after adding NLR change and 0.816 after adding LDH change. The final increment from LDH was modest (ΔAUC 0.016; P = 0.094). Conclusions: Baseline EPS-4 and early NLR change identified higher-risk patients, but the models remain development-stage and require independent prospective validation.

Aims: Male breast cancer (MBC) is a rare disease, and treatment approaches are largely extrapolated from female breast cancer. This study aims to evaluate clinicopathological features, immunohistochemistry-based surrogate subtypes, treatment approaches, and survival outcomes in MBC patients from Turkiye, where data on this rare disease remain limited. Methods: Forty-seven MBC patients diagnosed between 2005-2024 were retrospectively analyzed. Demographic characteristics, tumor features, immunohistochemistry-based surrogate subtypes, treatment modalities, and survival data were evaluated. Survival analyses were performed using the Kaplan-Meier method, and group comparisons were conducted using the log-rank test. Exploratory associations with overall survival (OS) were evaluated using univariate Cox regression analysis. Analyses used available cases without imputation. Surrogate subtypes were derived from ER, PR, HER2 and Ki-67; HR-positive/HER2negative tumours without Ki-67 were not assigned to luminal A-like or luminal B-like/HER2-negative categories. Results: The median age was 58.4 years (range 31–90), and the median follow-up was 54.9 months (range 2.8–197.3). Stage II was the most common presentation (59.5%), and stage III–IV disease was present in 28.6%. ER/PR/HER2 data were available for 44 patients. Complete five-category immunohistochemistry-based surrogate subtype classification was possible in 35 patients: luminal A-like 31.4% (11/35), luminal B-like/HER2-negative 42.9% (15/35), luminal B-like/HER2-positive 17.1% (6/35), HER2 positive/non-luminal 5.7% (2/35), and triple-negative 2.9% (1/35). Nine additional HR-positive/HER2-negative tumours could not be divided into the two HER2-negative luminal categories because Ki-67 was unavailable. ER positivity was 93.2%, PR positivity 86.4%, and HER2 positivity 18.2%. OS was evaluable in 46 patients; the median OS was 194.3 months and the median disease-free survival was 155.8 months. In exploratory univariate Cox analysis, older age (per 10-year increase: HR 1.76, 95% CI 1.03–2.98, p=0.037), grade 3 histology (HR 3.35, 95% CI 1.17–9.59, p=0.024) and a high Ki-67 index (≥20% vs

Amaç: Neoadjuvan kemoterapi (NAKT) uygulanan evre II–III invaziv meme kanserinde HER2-low alt tiplerinin patolojik tam yanıt (pCR) ve sağkalım sonlanımları ile ilişkisini değerlendirmek ve progresyonun bağımsız belirleyicilerini incelemek.Gereç ve Yöntemler: Akdeniz Üniversitesi Tıp Fakültesi’nde 2016-2024 yılları arasında NAKT alıp küratif cerrahi uygulanan 227 ardışık hasta retrospektif olarak analiz edildi. Demografik ve klinikopatolojik özellikler ile ER, PR, Ki-67, HER2 durumu, lenfovasküler invazyon (LVI) ve perinöral invazyon kaydedildi. Patolojik tam yanıt ( pCR ) ve Miller-Payne skoru ile; radyolojik yanıt standart kriterlere göre değerlendirildi. Sağkalım Kaplan-Meier yöntemiyle analiz edildi, gruplar log-rank testi ile karşılaştırıldı. Progresyonun bağımsız belirleyicileri çok değişkenli Cox regresyon analizi ile araştırıldı. HER2-low kavramının HER2-negatif spektrumda yorumlanması gereği dikkate alınarak, HER2-pozitif olgular dışlandıktan sonra HER2-low ve HER2-0 arasında duyarlılık analizi yapıldı.Bulgular: Ortalama yaş 50,1 yıl idi. HER2-low oranı %32,2 (%95 GA: %26,4–%38,5) ve pCR oranı %40,5 (%95 GA: %34,4–%47,0) olarak saptandı. Medyan takip süresi 43,5 ayda 5 yıllık OS %96,1 ve 5 yıllık PFS %86,6 idi. Ana analizde HER2-low ve HER2-0 grupları arasında pCR, OS ve PFS açısından anlamlı fark izlenmedi (tüm p>0,05). Çok değişkenli analizde PR pozitifliği PFS için bağımsız koruyucu faktör (HR 0,31; %95 GA 0,12–0,83), LVI varlığı bağımsız risk faktörü (HR 4,02; %95 GA 1,15–13,96) ve pCR elde edilmesi bağımsız koruyucu faktör (HR 0,20; %95 GA 0,04–0,89) olarak belirlendi. Duyarlılık analizinde de HER2-low ile HER2-0 arasında anlamlı fark gözlenmedi.Sonuç: HER2-low fenotipi tek başına pCR ve sağkalım sonuçlarını belirgin biçimde ayrıştırmazken, PR durumu, LVI ve pCR progresyon riskini daha güçlü ve bağımsız biçimde öngörmektedir.

Background and Aims: During liver transplantation, hepatocellular carcinoma (HCC) recurrence remains a critical challenge for patient survival. Targeted therapies, such as sorafenib and regorafenib, have been utilized to manage relapsed HCC in this unique setting. This study aimed to assess the efficacy of Sorafenib and Regorafenib in patients with HCC who experienced recurrence after liver transplantation. We focused on survival outcomes, treatment responses, and the management of side effects in this patient group. Methods: We conducted a retrospective analysis of 73 patients who experienced HCC recurrence post-liver transplantation between 2012 and 2022 across 11 oncology centers in Turkey. Patients were categorized according to Child–Pugh classification and treated with sorafenib as first-line therapy and Regorafenib in case of progression. Survival rates were analyzed using the Kaplan–Meier method, and risk factors were evaluated using Cox regression analysis. Results: Of the 73 patients included in the study, 62 were male (84.9%), and 11 were female (15.1%), with a mean age of 61.5 ± 10.9 years. All patients received sorafenib as first-line treatment. Among patients who experienced progression with sorafenib or discontinued treatment due to toxicity, 45.2% (n = 33) continued treatment with regorafenib. The median progression-free survival (PFS1) time with sorafenib was 5.6 months, and the one-year survival rate was 24.3%. The median progression-free survival (PFS2) time with regorafenib, which was administered as second-line treatment, was also calculated as 5.9 months. Overall survival (OS) duration was determined as 35.9 months. The most common side effects associated with both drugs included fatigue, hand and foot syndrome, and hypertension. Significantly better survival outcomes were shown in the Child–Pugh A group compared to other patients. Conclusions: These results suggest that Sorafenib and Regorafenib treatments offer a survival advantage in patients with relapsed HCC post-transplantation. However, individualized treatment strategies and close follow-up are crucial for optimizing outcomes. Further studies are needed to refine therapeutic protocols and enhance the care of this specific patient group.

To the Editor, I am writing in response to the recently published study titled "Sodium levels and immunotherapy efficacy in mRCC patients with bone metastases: sub analysis of Meet-Uro 15 study" (1). This work provides valuable insights into the prognostic significance of natremia in pretreated renal cell carcinoma (RCC) patients with bone metastases (BMs) receiving immunotherapy. However, I would like to address some concerns and suggestions for further analysis that could enhance the robustness of the findings.Metastatic renal cell carcinoma (mRCC) is a challenging disease with a poor prognosis, particularly for patients with bone metastases. The effectiveness of immunotherapy in these patients has been limited, with response rates ranging between 20% and 40%. (2) Identifying factors that may impact immunotherapy efficacy is crucial for improving outcomes in this patient population.In addition to RCC, prognostic scoring systems have been widely used in other cancer types during the era of immunotherapy. For instance, in non-small cell lung cancer (NSCLC), the Lung Immune Prognostic Index (LIPI) has been developed, which combines the neutrophil-to-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) levels to predict outcomes in patients treated with immune checkpoint inhibitors. The use of LIPI has demonstrated that integrating inflammatory markers can significantly improve prognostic accuracy in patients receiving immunotherapy. This approach is similar to the proposed method for RCC patients, where serum sodium levels are incorporated. When looking at other cancer types, particularly NSCLC, it is evident that multivariable prognostic scoring systems provide valuable insights into patient outcomes and could potentially serve as a model forRecent studies have suggested that hyponatremia, or low sodium levels, may be associated with worse prognosis in cancer patients, including those with metastatic renal cell carcinoma (mRCC) (4).Hyponatremia has been linked to increased inflammation, immune dysregulation, and altered tumor microenvironment, all of which could potentially influence the response to immunotherapy. (5) In particular, this study extends the findings of the previous work by Rebuzzi et al. (6), which evaluated metastatic renal cell carcinoma patients treated with nivolumab. In their study, Rebuzzi and colleagues developed a novel prognostic score focused on inflammatory indices and clinical factors. This current analysis further contributes to the literature by specifically evaluating patients with bone metastases, providing a more targeted assessment of their treatment responses.The decision to focus exclusively on patients with bone metastases in this study is understandable, given the poor prognosis associated with BMs. However, a comprehensive analysis of hyponatremia across the entire cohort of RCC patients in the Meet-URO 15 study could provide more generalizable findings. By first analyzing hyponatremia's prognostic value in the full patient population, the study could then offer a more targeted analysis within subgroups, such as those with BMs. This approach would clarify whether hyponatremia is a universal prognostic factor in RCC or if its significance is confined to specific patient subgroups (6).By building on these findings, the current study has the potential to explore whether hyponatremia is an independent prognostic factor across the entire RCC cohort or whether its impact is modulated by specific conditions such as bone metastases. Furthermore, by integrating renal function into the analysis, as Attalla et al.suggested, it would be possible to assess whether the combined effect of hyponatremia and renal impairment contributes more significantly to poor outcomes. This could allow for a more nuanced understanding of the role sodium levels play in RCC prognosis, leading to more personalized and effective treatment strategies for patients based on their broader clinical profile. (7) Consideration of Renal Function and Serum Creatinine Levels RCC patients frequently experience impaired renal function due to the nature of their disease and the treatments they undergo, such as nephrectomy and nephrotoxic medications. Since reduced renal function can contribute to hyponatremia, it is surprising that serum creatinine levels, an important indicator of renal function, were not considered in the analysis (8,9). Ignoring this variable could confound the results, as hyponatremia might be more a reflection of impaired renal function rather than an independent prognostic factor. I suggest that future analyses should adjust for serum creatinine levels to more accurately isolate the impact of natremia on survival outcomes.It is well known that the IMDC (International Metastatic RCC Database Consortium) score was developed and validated in the context of tyrosine kinase inhibitor (TKI) therapy, and its applicability to patients undergoing immunotherapy has been questioned. Recent publications have increasingly highlighted the importance of serum sodium levels in predicting outcomes for patients receiving immunotherapies (10,11,12). In light of these findings, it may be worth considering the development of a new risk scoring system that incorporates both serum sodium and creatinine levels. Such a scoring system could provide a more accurate prognosis for RCC patients undergoing immunotherapy, potentially guiding treatment decisions and improving patient outcomes.While the study makes a significant contribution to our understanding of prognostic factors in RCC patients with bone metastases, addressing the above concerns would further strengthen the findings. Specifically, incorporating renal function parameters and expanding the analysis to the full patient cohort would provide a more comprehensive assessment of hyponatremia's role in RCC prognosis.Additionally, limitations of the IMDC scoring system stem from its focus on a limited set of parameters that may not fully...

Background andAims: During liver transplantation, hepatocellular carcinoma (HCC) recurrence remains a critical challenge for patient survival. Targeted therapies, such as Sorafenib and Regorafenib, have been utilized to manage relapsed HCC in this unique setting. This study aimed to assess the efficacy of Sorafenib and Regorafenib in patients with HCC who experienced recurrence after liver transplantation. We focused on survival outcomes, treatment responses, and the management of side effects in this patient group. Methods: We conducted a retrospective analysis of 73 patients who experienced HCC recurrence post-liver transplantation between 2012 and 2022, across 11oncology centers in Turkey. Patients were categorised according to Child-Pugh classification and treated with Sorafenib as first-line therapy and Regorafenib in case of progression. Survival rates were analysed by Kaplan-Meier method and risk factors were evaluated by Cox regression analysis. Results: Of the 73 patients included in the study, 62 were male (84,9%) and 11 were female (15,1%) with a mean age of 61,5 ± 10,9 years. All patients received sorafenib as first-line treatment. Among patients who experienced progression with sorafenib or discontinued treatment due to toxicity, 45,2% (n=33) continued treatment with regorafenib. The median progression-free survival (PFS1) time with Sorafenib was 5,6 months and the one-year survival rate was 24,3%. The median progression-free survival (PFS2) time with Regorafenib, which was administered as second-line treatment, was also calculated as 5,9 months. Overall survival (OS) duration was determined as 35,9 months. The most common side effects associated with both drugs included fatigue, hand-foot syndrome and hypertension. Significantly better survival outcomes were shown in the Child-Pugh A group compared to other patients. Conclusion: These results suggest that Sorafenib and Regorafenib treatments offer a survival advantage in patients with relapsed HCC post-transplantation. However, individualized treatment strategies and close follow-up are crucial for optimizing outcomes. Further studies are needed to refine therapeutic protocols and enhance the care of this specific patient group.

Lung cancer is the leading cause of cancer-related death globally and is often diagnosed at an advanced stage. Nivolumab represents a significant advancement for treating advanced non-small cell lung cancer (NSCLC). However, the absence of reliable biomarkers predicting treatment response hinders personalized therapy. Eosinophils play a notable role in cancer biology, particularly when treated with immune checkpoint inhibitors. Eosinophils can infiltrate tumor tissues, directly interacting with tumor cells or modifying the tumor microenvironment. This study aims to assess the potential of PD-L1 expression and peripheral blood eosinophil count in predicting treatment response and patient survival. This retrospective cohort study was conducted in three major cancer centers in Turkey, including 174 advanced NSCLC patients who had progressed after chemotherapy between July 2019 and November 2023. Demographic and clinical data, PD-L1 levels, and eosinophil counts were analyzed using SPSS 27.0. Survival analyses were performed with Kaplan-Meier and Cox regression models. Increased peripheral blood eosinophil count was positively associated with response to Nivolumab treatment and overall survival. Among treatment responders, 54.1% had eosinophil levels between 100-499 cells/mm³ before treatment, increasing to 70.8% post-treatment. In patients with high PD-L1 positivity (>50%), eosinophil levels averaged 266.0 cells/mm³, with improved survival outcomes (mean survival: 24.06 months, median: 20.0 months). Non-responders had a mean survival of 19.05 months and a median survival of 15.2 months. Peripheral eosinophil count appears to be a potential biomarker for predicting response to Nivolumab treatment and survival in NSCLC patients. Combined evaluation of eosinophil count and PD-L1 expression may enhance personalized treatment strategies. Further validation in prospective, randomized studies is necessary.

Objective: Pazopanib is a multi-kinase inhibitor used in metastatic renal cell carcinoma or sarcomas (mRCC or mSTS). We aimed to investigate the relationship between pazopanib and macrocytosis and evaluate the clinical significant of this effect in mRCC or mSTS. Methods: Patients diagnosed with mRCC and mSTS and have been treated with pazopanib were included. Drug-induced macrocytosis was defined as MCV >100 fL during any mount of treatment. ΔMCV was defined as difference between MCV during pazopanib treatment and baseline MCV. Data was collected retrospectively. Results: 50 patients were included the study. During the pazopanib treatment, significant increase in MCV levels was observed and the mean MCV at the 0, 1, 3, 6, and 9 months were found as 86.7±7.6 fL, 87.8 ± 7.5, 92.4 ± 8.9, 94.8 ± 11.1 and 99.0 ± 10.7 fL, retrospectively (p