Objective: Women aged ≥80 years with ovarian cancer (OC) are significantly underrepresented in clinical trials, and their optimal management remains poorly defined. This study aimed to evaluate clinicopathologic characteristics and survival outcomes in this understudied population. Material and Methods: This retrospective study included 43 women aged ≥80 years diagnosed with advanced OC between 2009 and 2024 at a tertiary care center. Clinical, pathological, and treatment data were collected. Kaplan-Meier and Cox regression analyses were used to evaluate time to progression (TTP) and overall survival (OS). Results: The mean age was 83.4±4.1 years (range: 80-101); 95.3% had at least one comorbidity, and 46.5% had polypharmacy. Despite advanced age, 86% of patients underwent cytoreductive surgery and 79.1% received chemotherapy. Optimal cytoreduction (≤1 cm) was achieved in 89.2% of surgically treated patients, with no gross residual disease (R0) obtained in 64.9%. During a median follow-up period of 21.4 months, 76.7% of patients died. The median TTP was 20.9 months [95% confidence interval (CI): 0.0-42.8], and the median OS was 27.1 months (95% CI: 14.9-39.2). The 2 years TTP and OS rates were 49.4%±9.3 and 56.2%±7.8, respectively. Notably, cytoreductive surgery was associated with improved OS (hazard ratio: 0.171; p=0.001). Conclusion: Cytoreductive surgery can achieve high rates of optimal and complete resection in carefully selected women aged ≥80 years with advanced OC when performed at experienced, high-volume centers. These findings indicate that advanced chronological age alone should not be considered a contraindication to surgical evaluation in fit octogenarians.
Objective: Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) is the most common subtype but shows limited sensitivity to neoadjuvant chemotherapy (NAC), and its clinical benefit remains controversial. This study evaluated clinicopathological characteristics, pathological response patterns, and survival outcomes in HR+/HER2- BC patients treated with NAC. Material and Methods: This retrospective cohort study included 186 women with stage II-III HR+/HER2- BC who received NAC followed by surgery between 2015 and 2024 at two tertiary centers. Pathological responses, event-free survival (EFS), and overall survival (OS) were analyzed. Logistic regression identified predictors of pathological complete response (pCR), and Cox models evaluated prognostic factors for survival. Results: After a median follow-up of 30.6 months, pCR was achieved in 13.4% of patients and 42.5% showed a partial pathological response, resulting in a total pathological response rate of 55.9%. Grade 3 tumors and estrogen receptor (ER) expression <90% independently predicted pCR. Five-year EFS and OS rates were 77% and 88%, respectively. High ER expression (≥90%) and any pathological response were strong independent predictors of improved EFS and OS, whereas pCR alone was not associated with survival. Conclusion: In HR+/HER2- BC treated with NAC, overall pathological response and ER expression provide greater prognostic value than pCR alone.
Objective: The hemoglobin, albumin, lymphocyte, and platelet (HALP) score has been extensively studied as a prognostic biomarker in various malignancies; however, its predictive value for pathological response to neoadjuvant chemotherapy remains unclear. This study aimed to evaluate the association between the pretreatment HALP score and tumor regression grade (TRG) in patients with locally advanced gastric cancer (LAGC). Material and Methods: This retrospective single-center study included 65 patients with histologically confirmed LAGC who received neoadjuvant fluorouracil, leucovorin, oxaliplatin, and docetaxel chemotherapy followed by curative-intent surgery. The HALP score was calculated using baseline laboratory parameters obtained prior to treatment initiation. Pathological response was assessed using the Mandard TRG system. Receiver operating characteristic (ROC) analysis was used to determine the optimal HALP cut-off value. Logistic regression analysis was performed to identify predictors of treatment response. Results: Among the 65 patients, 34 (52.3%) were classified as good responders and 31 (47.7%) as poor responders. The HALP score was significantly higher in good responders (46.3±25.1 vs. 30.8±20.0; p=0.006). ROC analysis demonstrated moderate discriminatory ability [area under the curve: 0.700; 95% confidence interval (CI): 0.570-0.830; p=0.006], with an optimal cut-off value of 38.6. Low HALP scores were significantly associated with poor response (p=0.001) and with more advanced pathological stages. In logistic regression analysis, HALP was the only significant predictor of treatment response (odds ratio: 0.16; 95% CI: 0.05-0.49; p=0.001). Conclusion: The pretreatment HALP score is significantly associated with pathological response to neoadjuvant chemotherapy in LAGC. As a simple and accessible biomarker, HALP may aid in pre-treatment risk stratification and treatment decision-making. Prospective validation is warranted.
Objective: Anaplastic lymphoma kinase (ALK) and ROS proto-oncogene 1 (ROS1) rearrangements are unique, mutually exclusive mutations that drive non-small cell lung cancer. Concurrent immunohistochemical positivity for both markers is exceedingly rare and may lead to diagnostic and therapeutic uncertainty, particularly when molecular confirmation is lacking. Case Presentation: A 54-year-old woman presented with a solitary brain metastasis and underwent surgical resection, followed by whole-brain radiotherapy with a focal boost. Histopathology confirmed metastatic lung adenocarcinoma. Baseline staging with positron emission tomography-computed tomography (PET-CT) demonstrated a 20×19- mm hypermetabolic lingular lung nodule, mediastinal lymphadenopathy, and multiple sclerotic bone lesions. Immunohistochemistry of the tumor showed strong ALK (D5F3) and ROS1 (D4D6) expression, whereas deoxyribonucleic acid-based next-generation sequencing did not detect actionable rearrangements. Based on the immunophenotype, lorlatinib was initiated as first-line therapy. Serial PET-CT and brain magnetic resonance imaging demonstrated complete metabolic and radiologic remission of both intracranial and systemic disease, which has been sustained for nine months. Conclusion: This case illustrates a rare discordance between immunohistochemical and molecular findings. In this individual patient, treatment with lorlatinib coincided with sustained systemic and intracranial disease control. These observations should be interpreted cautiously, but may provide practical insights for similar complex clinical scenarios.
Objective: Accurate pretreatment risk assessment remains an important challenge for patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing lutetium- 177-labeled prostate-specific membrane antigen (Lu-177 PSMA) radioligand therapy, highlighting the need for reliable prognostic markers. Material and Methods: We retrospectively analyzed 52 consecutive patients with mCRPC who underwent Lu-177 PSMA radioligand therapy at a single tertiary referral center. Baseline demographic, laboratory, and imaging characteristics were recorded before treatment initiation. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and baseline factors associated with PFS were examined using Cox proportional hazards regression models. Results: After a median follow-up of 14.0 months, the median PFS and OS were 8.34 and 16.99 months, respectively. Disease progression occurred in 48 patients (92.3%), while 42 (80.8%) died during follow-up. Elevated baseline prostate-specific antigen (PSA) levels and the presence of visceral metastases were associated with significantly shorter PFS. In multivariable analysis, baseline PSA [adjusted hazard ratio (HR): 1.446; 95% confidence interval (CI): 1.204-1.738; p<0.001] and visceral metastasis (adjusted HR: 2.441; 95% CI: 1.049-5.682; p=0.038) remained independently associated with disease progression. Baseline maximum standardized uptake value (SUVmax) and mean SUV did not demonstrate significant prognostic value. Conclusion: Baseline PSA and visceral metastasis were independently associated with shorter PFS in patients with mCRPC treated with Lu-177 PSMA, whereas conventional semiquantitative PSMA positron emission tomography/computed tomography parameters were not. These findings suggest that routinely available baseline clinical characteristics may help identify patients at increased risk of early progression prior to radioligand therapy.
Objective: Biliary tract cancers (BTCs) are highly aggressive malignancies associated with poor clinical outcomes; metastatic disease is already present at diagnosis in many patients. We investigated whether baseline inflammation-based biomarkers could provide prognostic information in patients with de novo metastatic BTC. Material and Methods: This retrospective study included 70 patients with BTC who were treated with initial chemotherapy for de novo metastatic disease between January 2013 and December 2024. Clinical features and laboratory parameters at the time of metastatic diagnosis were obtained. Inflammation-based biomarkers, namely neutrophil-to-lymphocyte ratio, systemic immune-inflammation index, hemoglobin-albumin-lymphocyte-platelet (HALP) score, lactate dehydrogenase, and C-reactive protein (CRP), were evaluated. Overall survival (OS) was used as the primary outcome to evaluate the prognostic significance of baseline inflammation-based biomarkers. Results: The cohort was followed for a median of 10.8 months, during which the median progression-free survival was 6.6 months [95% confidence interval (CI): 5.1-8.1] and the median OS was 10.8 months (95% CI: 7.4-14.1). In multivariable analysis, elevated CRP [hazard ratio (HR): 9.187; p<0.001], Eastern Cooperative Oncology Group performance status (ECOG-PS) 2 (HR: 2.439; p=0.022), and low HALP score (HR: 3.091; p<0.001) were independently associated with worse OS. Stratification by HALP score demonstrated a significant difference in survival, with median OS of 18.6 months among patients with high HALP, compared with 5.9 months among those with low HALP. Conclusion: Poor ECOG-PS, elevated CRP, and low HALP score were independently related to worse survival in de novo metastatic BTC. These widely accessible and inexpensive parameters may provide a practical approach for identifying high-risk patients at baseline and improving prognostic stratification in routine clinical practice.
Objective: To evaluate the presence of residual preinvasive or invasive cervical disease after re-conization or hysterectomy in women with positive surgical margins following excisional treatment for high-grade squamous intraepithelial lesions (HSIL), and to identify pathological factors that may be related to residual disease. Material and Methods: This retrospective cohort included 48 women with positive ectocervical margins, endocervical margins, or endocervical curettage (ECC) margins after initial excisional procedures (cold-knife conization, loop electrosurgical excision procedure, or needle excision of the transformation zone). All patients underwent either re-conization or hysterectomy. Cone volume was calculated using the semi-ellipsoid formula (π/6 × anteroposterior × transverse × length). Categorical variables, including margin type, ECC results, human papillomavirus status, and excisional technique, were compared using the chi-square test or Fisher’s exact test. Results: Residual HSIL or carcinoma was identified in 45.9% of patients undergoing repeat excision, whereas 54.1% had only low-grade intraepithelial lesions or no preinvasive lesion. Ectocervical margin positivity showed limited predictive value for residual high-grade pathology. Endocervical margin positivity and ECC positivity demonstrated similar distributions, with residual HSIL or carcinoma present in approximately half of these patients. Residual pathology occurred following both cold-knife conization and electrosurgical excisional techniques. Residual disease occurred more frequently after cold-knife conization than after electrosurgical techniques; however, this difference was not statistically significant (p=0.051). Conclusion: Residual high-grade disease was detected in nearly half of the patients undergoing repeat surgery after a margin-positive conization. Although certain variables such as excisional technique and endocervical margin involvement showed numerical differences, none reached statistical significance. These findings suggest that no single clinical or pathological factor reliably predicts residual disease, and margin status alone may be insufficient to guide management decisions.
Objective: Malignant pleural mesothelioma (MPM) is a rare and aggressive form of cancer with limited treatment options and a grim prognosis. While platinum-based chemotherapy remains the primary treatment for inoperable or metastatic disease, the role of radiotherapy (RT) in current treatment approaches remains incompletely defined. This study aimed to assess the effect of RT after first-line systemic chemotherapy on survival outcomes in patients with metastatic or inoperable malignant mesothelioma. Material and Methods: We conducted a retrospective review of the medical records of 58 patients with unresectable or metastatic MPM who were treated from January 2022 through December 2024 at a tertiary oncology center. All patients received platinum-pemetrexed-based first-line chemotherapy followed by pemetrexed maintenance. Based on post-treatment management, patients were categorized into RT and non-RT groups. Kaplan-Meier analyses were conducted to assess progression-free survival (PFS) and overall survival (OS), and statistical significance was assessed using the log-rank test. Results: RT was administered to 41.4% of patients after initial chemotherapy. The RT group showed a significantly longer median PFS (14.1 months) compared with the non-RT group (9.7 months) [hazard ratio (HR): 0.34; 95% confidence interval (CI): 0.16-0.73; p<0.045]. Similarly, median OS was notably longer in the RT group (24.6 months vs. 14.5 months; HR: 0.55; 95% CI: 0.31-0.72; p<0.003). Moreover, a greater proportion of RT patients received second-line immunotherapy. No grade ≥3 RT-related toxicities were observed. Conclusion: RT after first-line chemotherapy may provide a survival advantage in certain patients with metastatic or inoperable mesothelioma, particularly when incorporated into sequential treatment plans that include immunotherapy. Further prospective studies are necessary to validate these results and improve patient selection.
Objective: Systemic inflammation, nutritional status, and metabolic reserve are recognized determinants of survival in metastatic gastric cancer patients. The serum albumin-to-creatinine ratio (ACR) combines nutritional and renal/metabolic information, but its prognostic value in gastric cancer remains unclear. We aimed to investigate the association between baseline ACR and survival outcomes in patients with de novo metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric cancer. Material and Method: This retrospective, single-center study included 112 adults with histologically confirmed de novo metastatic HER2-negative gastric cancer diagnosed between April 2011 and January 2024. Baseline serum albumin and creatinine levels obtained within 15 days prior to treatment initiation were used to calculate the ACR. Patients were categorized into low and high ACR groups according to the cohort median. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox proportional hazards models. Results: The median follow-up duration was 40.6 months. The median PFS for the entire cohort was 6.8 months, and the median OS was 13.7 months. Patients with high ACR had significantly longer PFS (7.2 vs. 6.0 months; p=0.005) and OS (16.9 vs. 10.2 months; p<0.001) than those with low ACR. In multivariable analysis, high ACR remained independently associated with improved PFS [hazard ratio (HR): 0.65; 95% confidence interval (CI): 0.44-0.97; p=0.034) and OS (HR: 0.38; 95% CI: 0.21-0.67; p<0.001)]. Eastern Cooperative Oncology Group performance status ≥1 was also independently associated with worse survival outcomes. Conclusion: Baseline serum ACR is an independent prognostic marker for both PFS and OS in patients with de novo metastatic HER2-negative gastric cancer. As a simple and routinely available laboratory parameter, ACR may contribute to risk stratification in advanced disease.
Objective: Metastatic rectal and rectosigmoid cancers remain associated with poor prognosis despite advances in systemic therapy. Although outcomes in metastatic colorectal cancer have improved overall, population-level survival trends specific to rectal cancer and their evolution across calendar time remain incompletely characterized. Material and Methods: This population-based retrospective cohort study used data from the surveillance, epidemiology, and end results program. Adults diagnosed with metastatic rectal or rectosigmoid adenocarcinoma between 2000 and 2022 were included and categorized into prespecified diagnosis eras (2000-2007, 2008-2017, and 2018-2022). Overall survival (OS) was estimated by the Kaplan-Meier method and evaluated with multivariable Cox proportional hazards models adjusted for demographic and treatment-related factors. Adjusted survival curves were generated using regression standardization, and restricted mean survival time (RMST) was calculated over 60 months. Effect modification by age was assessed using stratified analyses and testing for interaction; proportional hazards assumptions were formally evaluated. Results: A total of 33,277 patients with metastatic rectal or rectosigmoid cancer were included in the study. Median OS for the overall cohort was 16.2 months. Survival improved among patients diagnosed during 2008-2017 compared with those diagnosed during 2000-2007, with higher observed and adjusted survival estimates and longer RMST. In contrast, no statistically significant improvement in OS was observed in the most recent era (2018-2022). Older age was independently associated with worse OS, whereas receipt of chemotherapy and surgery to the primary tumor were associated with improved OS. Age-by-era interaction analyses did not demonstrate significant effect modification. Conclusion: In this large population-based analysis, OS among patients with metastatic rectal and rectosigmoid cancer improved during the mid-diagnosis era, but appeared to plateau in more recent years. These findings indicate that survival gains have not occurred uniformly over time and underscore the importance of interpreting population-level outcomes within specific calendar eras and disease subtypes.
Objective: The optimal management of early-stage breast cancer in elderly patients remains challenging due to age-related comorbidities, limited life expectancy, and underrepresentation in clinical trials. This study aimed to evaluate the impact of adjuvant treatment preferences on survival outcomes in women aged 65 years and older with early-stage, node-negative, hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Material and Methods: In this retrospective cohort study, 157 patients aged ≥65 years who underwent surgery between 2003 and 2022 were analyzed. Patients were categorized into two groups according to adjuvant treatment strategy: chemotherapy (CT) followed by hormonal therapy (HT), or HT alone. Clinicopathological characteristics, comorbidities, relapse-free survival (RFS), and overall survival (OS) were compared between groups. Survival outcomes were assessed using Kaplan-Meier analysis, and prognostic factors were evaluated using univariate and multivariate Cox proportional hazards regression models, including clinically relevant variables. Results: Of the 157 patients, 49 (31.2%) received CT followed by HT, and 108 (68.8%) received HT alone. Patients treated with HT alone were significantly older and had smaller tumors and earlier-stage disease. Despite these favorable tumor characteristics, OS was significantly lower in the HT group compared with the CT group (p=0.003). No significant difference in RFS was observed between the groups (p=0.782). In multivariate analysis of OS, age [hazard ratio (HR): 1.17; 95% CI: 1.08-1.26; p<0.001] and multicentricity (HR: 6.51; 95% CI: 2.16-19.64; p=0.001) were independently associated with worse survival, while the treatment group was not independently associated with survival after adjustment. In multivariate analysis of RFS, age (HR: 1.24; 95% CI: 1.10-1.39; p<0.001) and the Charlson comorbidity score (HR: 2.07; 95% CI: 1.04-4.14; p=0.038) were independently associated with recurrence. Conclusion: In elderly patients with early-stage hormone receptor-positive breast cancer, survival outcomes appear to be influenced more strongly by age and comorbidity burden than by treatment choice alone. While HT is frequently preferred, adjuvant CT may still be considered in carefully selected patients. A personalized, multidisciplinary approach is essential to optimize treatment decisions in this population.
Objective: Systemic inflammatory response contributes to tumor progression and may influence survival outcomes in breast cancer. Blood-based inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), have been proposed as prognostic biomarkers. This study evaluated the prognostic value of pretreatment NLR, PLR, and SII across molecular subtypes of breast cancer. Material and Methods: This retrospective cohort study included 190 patients with invasive breast cancer who were treated between February 2012 and April 2022. Pretreatment NLR, PLR, and SII were calculated from complete blood counts. Optimal cut-off values were determined using a 60 months landmark receiver operating characteristic analysis. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method, the log-rank test, and Cox regression. Subgroup analyses were performed according to molecular subtype. Results: After a median follow-up of 58.8 months, 30 deaths (15.8%) and 44 DFS events (23.2%) occurred. Optimal cut-offs were 1.78 for NLR, 138.08 for PLR, and 449.55 for SII. In the overall cohort, elevated NLR was associated with numerically worse OS (hazard ratio [HR]=2.05; p=0.096) and DFS (HR: 1.78; p=0.088), although these associations did not reach statistical significance. In the triple-negative breast cancer subgroup, high NLR was associated with poorer OS (log-rank p=0.019) and DFS (log-rank p=0.025); however, ridge-penalized Cox estimates were imprecise [OS: HR=1.52, 95% confidence interval (CI)=0.42-5.57; DFS: HR=1.75, 95% CI=0.50-6.11]. Multivariate analysis identified Ki-67 ≥20% and lymph node positivity as independent predictors of OS, while progesterone receptor positivity, Ki-67 ≥20%, and Stage III independently predicted DFS. Conclusion: NLR was not independently prognostic in the overall cohort. Its association with survival outcomes in triple-negative breast cancer is preliminary and hypothesis-generating and requires validation in larger independent cohorts.
Objective: CDK4/6 inhibitors are the standard of care for metastatic hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Markers for predicting prognosis and survival during follow-up of these patients are not yet available. Therefore, this study aimed to examine the effect of changes in prognostic nutritional index (PNI) and systemic immune-inflammation index (SII) on survival in patients treated with CDK4/6 inhibitors plus letrozole. Material and Methods: This was a retrospective study of 88 patients. Both PNI and SII values were calculated just before, at 3 months, and at 6 months. Changes at 0-3 months and 0-6 months were divided into two groups: increasing and decreasing. Changes in progression-free survival (PFS) between these two groups were analyzed. Results: PFS was 28.2 months [95% confidence interval (CI): 23.6-32.89] in the PNI-increasing group and 23.3 months (95% CI: 15.55-31.21) in the PNI-decreasing group at the 3rd month of treatment (p=0.048). At 6 months, PFS was 29.1 months (95% CI: 24.2-33.9) in the PNI increasing group and 23.2 months (95% CI: 15.9-30.6) in the PNI decreasing group. In the group with decreased SII at 3 months, PFS was almost 7 months longer than in the group with increased SII. At month 6, PFS was 27.7 months (95% CI: 23.4-32.1) in the SII-decreasing group and 14.8 months (95% CI: 10.5-19.1) in the SII-increasing group (p=0.017). In multivariate Cox regression analysis, only a reduction in SII between 0-6 months was a negative independent risk factor for PFS, hazard ratio 0.24 (95% CI: 0.06-0.87), p=0.031. Conclusion: A decrease in PNI during follow-up is associated with poor survival in metastatic HR-positive and HER2 negative patients receiving letrozole in combination with a CDK4/6 inhibitor, whereas a decrease in SII may be a prognostic indicator in these patients.
Objective: High-grade gliomas (HGGs), particularly glioblastoma, remain among the most aggressive primary central nervous system malignancies. Despite standard treatment consisting of maximal safe resection followed by radiotherapy with concurrent and adjuvant temozolomide, disease recurrence is nearly inevitable. Therapeutic options after progression remain limited, and the optimal management of recurrent HGGs continues to be debated. This study aimed to evaluate the real-world efficacy of second-line irinotecan plus bevacizumab in patients with recurrent HGGs. Material and Methods: This retrospective single-center study included patients with recurrent HGGs treated at University of Health Sciences Türkiye, Başakşehir Çam and Sakura City Hospital between January 2020 and December 2024. Demographic, clinical, pathological, treatment, and survival data were collected from institutional medical records. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Objective response rates (ORRs) were assessed according to radiological evaluations documented in routine clinical practice. Results: A total of 55 patients were included. The median age was 50 years, and 76% of patients had glioblastoma. Following first-line chemoradiotherapy, 48 patients received adjuvant temozolomide, with a median PFS of 5.0 months. Fifty patients subsequently received second-line irinotecan plus bevacizumab, achieving an ORR of 46%. The median PFS associated with irinotecan plus bevacizumab was 8.8 months. At the final analysis, the median OS for the entire cohort was 23.4 months. Conclusion: Second-line irinotecan plus bevacizumab demonstrated meaningful clinical activity in recurrent HGGs, yielding encouraging response rates and disease control in a real-world setting. These findings support the continued use of bevacizumab-based strategies for selected patients with recurrent disease.
Objective: The optimal selection of second-line biological therapy remains unclear in patients with RAS wild-type metastatic colorectal cancer (mCRC) who develop disease progression following first-line anti-vascular endothelial growth factor (VEGF)-based treatment. This study aimed to compare the efficacy and safety outcomes of continuation of second-line anti-VEGF therapy versus switching to anti-epidermal growth factor receptor (EGFR) therapy. Material and Methods: This retrospective single-center study included 38 patients with RAS wild-type mCRC who were treated between January 2015 and December 2025. All patients received bevacizumab-based chemotherapy in the first-line setting and subsequently developed disease progression. Patients were divided into two groups according to the second-line biological therapy administered concomitantly with chemotherapy: anti-VEGF continuation (n=20) and anti-EGFR switch (cetuximab/panitumumab; n=18). The primary endpoints were second-line progression-free survival (PFS2) and overall survival (OS). Results: Median PFS2 was 7.1 months in the anti-VEGF group and 10.0 months in the anti-EGFR group (p=0.404). Median OS were 28.2 months and 25.5 months, respectively (p=0.752). No significant differences were observed between the groups in survival outcomes. Left-sided colon tumors were more frequent in the anti-EGFR group, whereas right-sided colon tumors were more frequent in the anti-VEGF group. Skin rash was significantly more common with anti-EGFR therapy (22.2%; p=0.041), while other toxicities were manageable. Conclusion: In patients with RAS wild-type mCRC progressing after first-line anti-VEGF therapy, second-line anti-VEGF continuation and anti-EGFR switch strategies demonstrated comparable survival outcomes. Treatment selection should be individualized based on tumor sidedness, prior treatment response, toxicity profile, and patient characteristics.
Objective: The prognostic and predictive significance of kirsten rat sarcoma viral oncogene homologue (KRAS) mutations in metastatic non-small cell lung cancer remains controversial, particularly in the immunotherapy era. Most previous studies compared KRAS-mutant tumors with heterogeneous KRAS wild-type populations that included other oncogenic driver alterations. This study aimed to evaluate the clinical impact of isolated KRAS mutations in patients with metastatic lung adenocarcinoma receiving first-line systemic therapy. Material and Methods: This retrospective single-center study included patients with metastatic lung adenocarcinoma who underwent next-generation sequencing (NGS) between January 2023 and December 2025. Patients were categorized into two groups: those with isolated KRAS-mutant tumors and those with pan-wild tumors without any detectable oncogenic alterations on NGS. Patients with co-occurring oncogenic alterations were excluded. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox regression analysis. Results: A total of 75 patients were included, comprising 28 with isolated KRAS mutations and 47 without detectable oncogenic alterations. Programmed death-ligand 1 expression ≥50% was significantly more frequent in the KRAS-mutant group (p=0.001). However, KRAS mutation status was not significantly associated with PFS or OS in either univariate or multivariate analyses. Median PFS was 10.77 months in the KRAS-mutant group and 7.84 months in the pan-wild group (p=0.597), while median OS was 18.97 months in the KRAS-mutant group and 18.27 months in the pan-wild group (p=0.926). Similarly, no significant differences in survival were observed between the immunotherapy-containing and chemotherapy-alone subgroups. Conclusion: Isolated KRAS mutations were not associated with significantly different survival outcomes compared with tumors lacking detectable oncogenic alterations. These findings suggest that KRAS mutation status alone may have limited prognostic value in metastatic lung adenocarcinoma.
Objective: The exact role of nivolumab in the perioperative systemic treatment of locally advanced-gastric/gastroesophageal junction (LA-G/GEJ) adenocarcinoma remains unclear. This study aimed to evaluate the real-world effectiveness and safety of perioperative nivolumab in patients with LA-G/GEJ adenocarcinoma. Material and Methods: Clinical and pathological data were retrospectively collected for previously untreated patients with human epidermal growth factor receptor 2-negative, clinical stage T2-4bN0-3M0 (stage II-III) G/GEJ adenocarcinoma, either microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) or microsatellite stable (MSS)/proficient MMR (pMMR) with a programmed death-ligand 1 (PD-L1) combined positive score (CPS) of ≥5, who received perioperative nivolumab in combination with chemotherapy or ipilimumab between January 2021 and April 2025. Kaplan-Meier survival analysis was used to estimate disease-free survival (DFS) and overall survival (OS). Results: Fifteen eligible patients were identified among 134 with stage II-III G/GEJ adenocarcinoma. Seven patients (46.7%) were classified as MSI-H/dMMR, and 11 patients (73.3%) had a PD-L1 CPS of ≥5. The median numbers of immunotherapy and chemotherapy cycles prior to surgery were 6 (range, 3-8) and 8 (range, 1-8), respectively. Objective response and disease control rates were 60% and 100%, respectively. All patients underwent surgical resection, and the R0 resection rate was 93.3%. Pathological complete response and major pathological response rates were both 71.4% in the MSI-H/dMMR subgroup, compared to 25% and 37.5%, respectively, in MSS/pMMR patients with a PD-L1 CPS ≥5. During follow-up [median 17.0 months (95% confidence interval: 13.0-20.9)], four patients experienced tumor recurrence, and three died. All cases of disease recurrence and death occurred in the MSS/pMMR subgroup, with 18 months DFS and OS rates of 35.7% and 47.6%, respectively. Conclusion: For the treatment of LA-G/GEJ adenocarcinoma, perioperative nivolumab combined with total neoadjuvant chemotherapy might be effective for both MSI-H/dMMR patients and MSS/pMMR patients with a PD-L1 CPS of ≥5, and have an acceptable safety profile.
Objective: The prognostic role of stromal tumor-infiltrating lymphocytes (sTIL) is well recognized in triple-negative and human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC), but their meaning in hormone receptor-positive, HER2-negative tumors is still debated. In luminal BC, lymphocytic infiltration may reflect biologically aggressive disease rather than an effective antitumor response. We investigated clinicopathological factors associated with high sTIL and examined their relationships with disease-free survival (DFS) in an early-stage luminal BC cohort treated in routine clinical practice. Material and Methods: This retrospective single-center study included 120 patients with early-stage estrogen receptor-positive, HER2-negative BC who were treated surgically between 2017 and 2021. Hematoxylin and eosin-stained slides were used to evaluate sTIL in accordance with International TILs Working Group recommendations. A 10% cut-off was used to define low-sTIL and high-sTIL categories. The relationship between sTIL category and clinicopathological variables was tested in univariable analyses and then explored using multivariable logistic regression. DFS was analyzed using the Kaplan-Meier method and groups were compared with the log-rank test. Results: Twenty-three patients (19.2%) were classified as having high sTIL. In univariable analysis, high sTIL status was associated with grade 3 tumors, lymphovascular invasion, and Ki-67 ≥20%. In the adjusted model, Ki-67 >20% remained the only independent factor associated with high sTIL (odds ratio: 8.68; 95% confidence interval: 1.07-70.45; p=0.043). During a median follow-up of 56.5 months, DFS did not differ significantly between patients with low and high sTIL (p=0.37); however, the high-sTIL group showed a numerically longer DFS. Conclusion: In this real-world cohort of early-stage luminal BC, high sTIL density was most strongly associated with proliferative activity, but not with a statistically significant DFS benefit. These results suggest that immune infiltration in luminal tumors, when assessed by conventional pathology, may be interpreted primarily as a feature of aggressive tumor biology rather than a consistent marker of effective antitumor immunity.
Objective: Enhancer of zeste homologue 2 (EZH2) serves as the enzymatic component of polycomb repressive complex 2, while SMARCB1/INI-1 is an essential subunit of the SWI/SNF chromatin remodeling complex; both function as epigenetic regulators with proposed roles in hepatocarcinogenesis. This study aimed to evaluate the expression of EZH2 and INI-1 by immunohistochemistry (IHC) in hepatocellular carcinoma (HCC) and to determine their association with clinicopathological features and survival outcomes. Material and Methods: We retrospectively studied 103 patients with histologically proven HCC who were treated at a single center between 2011 and 2019. EZH2 and INI-1 were evaluated by IHC in archival, paraffin-embedded specimens, with a case considered positive when at least 1% of tumor nuclei showed distinct staining. Relationships with clinicopathological variables were tested using the chi-square test or Fisher’s exact test, and overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier estimation and Cox proportional hazards modeling. Results: EZH2 positivity occurred in 45 patients (43.7%), whereas INI-1 loss occurred in 11 (10.7%). Over a median follow-up of 42.0 months, 71 deaths and 86 progression events were observed. EZH2-positive cases exhibited significantly shorter median OS (8.0 vs. 27.0 months; p=0.007) and PFS (5.0 vs. 9.0 months; p=0.012). In univariate Cox regression analysis, EZH2 positivity was a significant risk factor for both mortality [hazard ratio (HR): 1.88; 95% confidence interval (CI): 1.17-3.02; p=0.009] and disease progression (HR: 1.69; 95% CI: 1.10-2.60; p=0.018). However, EZH2 did not retain independent prognostic significance in multivariate analysis adjusted for Barcelona Clinic Liver Cancer (BCLC) stage for either OS (HR: 1.55; 95% CI: 0.95-2.53; p=0.078) or PFS (HR: 1.39; 95% CI: 0.89-2.17; p=0.146). INI-1 loss showed a trend toward longer PFS (22.0 vs. 6.0 months; p=0.051) and OS (30.0 vs. 15.0 months; p=0.097), but these differences did not reach statistical significance. Conclusion: EZH2 positivity is associated with inferior survival in HCC; however, this association does not remain independent of BCLC stage, indicating a stage-dependent rather than independent prognostic effect. INI-1 loss showed only borderline exploratory associations with survival that require validation in larger series. Together, these observations support the biological relevance of epigenetic regulators in HCC.
Objective: In this study, we aimed to evaluate the potential protective effects of black mulberry (Morus nigra, MN) extract, known for its antioxidant properties, against gastrointestinal mucositis induced by high-dose methotrexate (MTX) treatment, assessed using histological and biochemical parameters. Material and Methods: Male Wistar albino rats (200-250 g) were randomly assigned to four groups of 14 animals each: • Group 1 received 30 mg/kg MTX intraperitoneally on day 1 to induce intestinal damage. • Group 2 received 30 mg/kg MTX intraperitoneally on day 1, followed by 500 mg/kg of MN extract administered by gavage. One subgroup received MN for 4 days; the other subgroup received MN for 6 days. • Group 3 received intragastric saline only (0.001 mL/kg-2.5 mL/kg). • Group 4 received 500 mg/kg MN extract by oral gavage for 4 or 6 days, depending on the subgroup. The animals were sacrificed on either day 4 or day 6. Blood samples were analyzed for total oxidant status (TOS) and total antioxidant status (TAS). Tissue samples from the duodenum, jejunum, and ileum were examined for levels of Ki-67, myeloperoxidase (MPO), malon dialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin- 1 beta (IL-1β), TOS, and TAS. Results: In the group treated with both MTX and MN extract, levels of MDA, MPO, IL-1β, and TNF-α were significantly lower than those in the MTX-only group. Ki-67 levels were higher in intestinal tissues, indicating enhanced epithelial regeneration. Conclusion: Our findings suggest that MN extract protects against MTX-induced mucosal damage and promotes intestinal epithelial healing. These promising results highlight the potential of MN as a supportive treatment in preventing MTX-related toxicity; however, further large-scale and clinical studies are needed to confirm its efficacy.
