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Background/Objectives: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are commonly used as first-line treatment for hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. However, the optimal timing of CDK4/6i initiation remains uncertain. This study compared overall survival (OS) between upfront first-line and deferred second-line CDK4/6i use in routine clinical practice. Methods: This retrospective, two-center cohort study included 403 patients with hormone receptor-positive, HER2-negative metastatic breast cancer who received a CDK4/6i between January 2019 and December 2024. Patients were categorized into upfront-use and deferred-use groups according to whether CDK4/6i treatment was initiated in the first or second metastatic treatment line. Overall survival was estimated using the Kaplan–Meier method. An exploratory analysis of progression-free survival (PFS) from CDK4/6i initiation was also performed. Cox proportional hazards regression, inverse probability of treatment weighting (IPTW), and a 12-month landmark analysis were performed. Results: Of 403 patients, 311 received upfront treatment and 92 received deferred treatment. At a median follow-up of 63.0 months, the deferred-use group had higher rates of visceral metastasis and endocrine-resistant disease. Median PFS from CDK4/6i initiation was longer in the upfront-use group than in the deferred-use group (27.0 vs. 14.0 months; log-rank p < 0.001). Median OS was 61.0 months in the upfront-use group and 76.0 months in the deferred-use group, without a statistically significant difference (log-rank p = 0.059). After adjustment for clinical factors and year of metastatic diagnosis, deferred use was not independently associated with OS (adjusted hazard ratio [HR] 1.167, 95% confidence interval [CI] 0.772–1.765, p = 0.463). Similar results were obtained in the IPTW analysis (HR 0.925, 95% CI 0.552–1.549; p = 0.766) and the 12-month landmark analysis. Conclusions: Deferred second-line CDK4/6i use was not independently associated with inferior overall survival compared with upfront use. These findings support an individualized, risk-adapted sequencing approach in carefully selected patients but do not establish equivalence or justify routine deferral.

Male breast cancer (MBC) is a rare disease, representing approximately 1% of all breast cancers worldwide

Aims: This study aimed to evaluate responses to first- and second-line treatments, survival outcomes, and potential factors affecting survival in patients with metastatic gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC). Methods: This retrospective study included 42 patients with metastatic GEP-NEC from three centers. First and second-line chemotherapy regimens were examined. The median progression-free survival (mPFS1 and mPFS2) for first and second-line treatments and overall survival (mOS) were evaluated. The effects of CRP levels, LDH levels, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) on survival were investigated as potential prognostic factors. Results: Median follow-up was 15 months (3-113). mPFS1 was 5 months (95% CI: 2.88-7.11) and mPFS2 was 2 months (95% CI: 1.67-2.32). The mOS was 15 months (95% CI: 10.90-19.09). Curative surgery patients had a 28-month mOS, and patients who could not undergo surgery had a mOS of 14 months (p=0.010). Patients with NLR

Aims: Prognostic factors and treatment modalities in chondrosarcoma (CS) remain poorly defined. This study aimed to present our institutional experience with CS patients. Methods: We retrospectively reviewed the medical records of 69 CS patients treated at our Cancer Institute between 2010 and 2023. Results: Median age at diagnosis was 47 years, with a slight male predominance (52%) and a median follow-up of 93 months. Grade 1 (34%) and grade 2 (34%) tumors were most common, predominantly affecting the lower extremities (40%) and pelvis (26%). At presentation, 63 patients had localized disease and 6 had metastases; metastases later developed in 13 additional patients, most frequently in the lungs. All 63 patients with localized disease underwent surgery, and 7 received adjuvant chemotherapy (CT). Recurrence developed in 26 patients, of whom 9 were treated with systemic therapy. Among 6 patients with stage IV disease, 5 underwent palliative surgery and received CT. The most commonly used regimens included doxorubicin based CT, pazopanib, sirolimus, and celecoxib. Among patients who developed metastasis during follow-up, 12/13 died. The median time from diagnosis to metastasis was 17.0 months (95% CI: 10.8–23.1), and median survival thereafter was 21.0 months (95% CI: 12.7–29.2). All six patients metastatic at presentation died, with a median progression-free survival of 7.0 months (95% CI: 2.1–11.8) and OS of 12.0 months (95% CI: 0.0–33.6). OS was 75%, 63%, and 57% at 5, 10, and 15 years, respectively. Female sex, low–intermediate grade, and stage I–II disease correlated with better OS in univariate analysis, but only stage at diagnosis remained significant in multivariate analysis (p=0.002). Conclusion: Our findings highlight that early tumor stage is the only independent predictor of overall survival, underscoring the critical importance of early diagnosis and timely intervention in CS.

Background: Ampullary adenocarcinoma is a rare cancer for which there are no standard adjuvant treatment recommendations due to the lack of randomized clinical trials. The primary aim of this analysis is to investigate the efficacy of adjuvant FOLFIRINOX treatment in patients with resected ampullary adenocarcinoma. Materials and Methods: This multicenter retrospective cohort study was conducted at 15 institutions in Turkey between August 2007 and January 2024, involving 211 patients with resected, non-metastatic ampullary adenocarcinoma receiving adjuvant chemotherapy with various chemotherapy regimens with or without chemoradiation. Clinicopathological and treatment-related parameters were recorded. Disease-free survival (DFS) and overall survival (OS) were analyzed by using Kaplan–Meier estimates. Cox proportional hazards regression was used to identify covariates associated with OS. Results: The median follow-up time was 52 months, and 116 patients (55.2%) were alive at the time of the analysis. The median age was 61 years (32–82). mFOLFIRINOX was administered to 16.6% of the patients (n = 35). The 3-year DFS rate was 79.41% in the FOLFIRINOX-treated arm and 53.9% in the other treatment arm (p = 0.034 for mDFS). The median OS was non-reached in patients receiving mFOLFIRINOX treatment, while it was 51 months in patients receiving other treatments (p = 0.071). While no statistically significant results were reached, a trend toward statistically significant survival times was observed in the FOLFIRINOX arm. After adjustment for other prognostic parameters, mFOLFIRINOX remained an independent statistically significant parameter for better OS (HR; 95% CI: 3.24; 1.02–10.9; p = 0.046). Conclusions: FOLFIRINOX treatment has shown efficacy in the adjuvant treatment of ampullary cancer, independent of histological subtype. The findings should be validated in large prospective trials.

Background: Adenocarcinoma arising from the ampulla of Vater is an extremely rare neoplasm, and there are limited data regarding frontline therapy for metastatic disease. We investigated the outcomes of first-line treatment with FOLFIRINOX by comparing it with other treatments in patients with advanced ampullary adenocarcinoma. Methods: We included 123 patients with advanced ampullary adenocarcinoma who were treated with frontline FOLFIRINOX (n = 32), fluorouracil (FU)-based chemotherapy (n = 20), and gemcitabine-based chemotherapy (n = 65) between August 2007 and January 2024 in this retrospective study. The median progression-free survival (mPFS) and overall survival (mOS) according to treatment and clinicopathological features were calculated using the Kaplan–Meier method. Results: The median age of the patients was 62 years (range, 36–78), and 75,6% of the patients had an ECOG performance status of 0–1. The mOS were 13 months (95% CI, 10.6–14.4), 11 months (95% CI, 10.6–14.4), and 12 months (95% CI, 10.6–14.4), respectively [p = 0.865]. There were no significant differences in OS among the chemotherapeutic agents according to histological subtypes. However, FOLFIRINOX and FU-based treatments appeared more effective in the intestinal subtype, while gemcitabine-based therapies were less effective. In the pancreaticobiliary subtype, FU-based therapies yielded a shorter outcome compared to FOLFIRINOX and gemcitabine-based therapies. Grade 3 or 4 hematologic toxicities were higher in patients treated with FOLFIRINOX. Conclusions: In advanced ampullary adenocarcinoma, despite higher toxicity, frontline FOLFIRINOX showed a trend toward an OS benefit in the intestinal subtype while providing a similar outcome in the pancreaticobiliary subtype.

Background and Objectives: Although breast cancer is the most common type of cancer among women, bilateral breast cancer (BBC) remains exceedingly rare. BBC can present as either synchronous (SBBC) or metachronous (MBBC) disease. Data regarding the clinical characteristics of BBC are limited. In this study, we aimed to share our multicenter, retrospective experience on the clinicopathological and demographic features of SBBC and MBBC, their survival outcomes, and the factors influencing survival, in light of current knowledge. Material and Method: A total of 125 patients who were treated and followed between 2015 and 2024 across six different centers were included in the study. The patients were categorized into synchronous (SBBC) and metachronous (MBBC) groups. Their clinicopathological characteristics were analyzed, along with disease-free survival (DFS) and 5-year overall survival (OS) outcomes. Results: DFS was 5.7 years in the SBBC group and 5.6 years in the MBBC group (p = 0.95). The 5-year OS rate was 95.2% in the MBBC group and 80.7% in the SBBC group (p = 0.035). Hormone receptor negativity was identified as an independent risk factor for lower DFS in the overall patient cohort (HR: 0.55, 95% CI: 0.31–0.98, p = 0.04). Conclusion: Significant differences were found between the SBBC and MBBC groups in terms of hormone receptor status, presence of an invasive lobular carcinoma component, recurrence/metastasis status, and molecular subtype discordance between the two primary tumors. Although DFS did not significantly differ between the groups, the 5-year OS was significantly higher in the MBBC group. In multivariate regression analysis, hormone receptor negativity was identified as an independent risk factor for decreased DFS among all BBC patients. Our study is noteworthy for shedding light on the clinical features of BBC in the context of current knowledge and for its multicenter design.

Background and Objectives: Bone metastases in patients can cause significant quality-of-life declines due to skeletal-related events (SREs). SRE is defined as the occurrence of radiotherapy for bone pain, pathologic fracture, bone surgery, spinal cord compression, or hypercalcemia. Bone-modifying agents (BMAs), such as denosumab and zoledronic acid, are crucial in reducing the frequency and severity of SREs. The inhibition of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors has emerged as the standard treatment for hormone receptor-positive metastatic breast cancer, demonstrating significant improvements in survival outcomes. This study aims to compare the effectiveness of denosumab and zoledronic acid in preventing SRE in patients receiving CDK4/6 inhibitors with endocrine therapy. Materials and Methods: This retrospective study included 328 patients diagnosed with bone metastatic breast cancer receiving first-line CDK4/6 inhibitor therapy (palbociclib or ribociclib). Patients were assigned to receive either subcutaneous denosumab or intravenous zoledronic acid every 4 weeks. Time to the first skeletal-related event post bone-modifying agent initiation, SRE incidence, and the safety data were evaluated. The data were analyzed using independent samples t-tests, chi-square tests, and Kaplan–Meier methods for time-to-event data. Results: In the denosumab group, the median time to the first skeletal-related event was significantly longer than in the zoledronic acid group (44.55 months and 29.16 months, respectively). Denosumab treatment was associated with a statistically significant reduction in the risk of developing the first SRE after bone-modifying agent initiation compared to zoledronic acid (HR: 0.56, p = 0.001). Additionally, ECOG PS and the number of metastatic bone sites were identified as independent prognostic factors for time to the first SRE. The safety profile was consistent with previous studies reported in the literature. Conclusions: Our study demonstrated that when used with CDK4/6 inhibitors, denosumab is associated with a delay in SREs and a lower SRE incidence than zoledronic acid in patients with bone metastases. These findings support the efficacy of denosumab in preventing SREs and suggest that CDK4/6 inhibitors may have distinct effects on the bone microenvironment, particularly when combined with denosumab.

This study aimed to compare the efficacy of CDK4/6 inhibitors plus endocrine therapy in two groups of patients with HR-positive/HER2-negative metastatic breast cancer: those with symptomatic, high tumor burden disease and those with asymptomatic disease. This retrospective study included 193 patients who received either ribociclib or palbociclib in combination with first-line ET. Patients were divided into symptomatic and asymptomatic groups and compared regarding baseline characteristics and progression-free survivals (PFS). Symptomatic patients had a significantly shorter mPFS than asymptomatic patients (22.7 months vs. 35.0 months, p = 0.009). Among symptomatic patients, those treated with ribociclib had a longer mPFS than those treated with palbociclib (28.26 months vs. 17.18 months, p = 0.021). Multivariate analysis identified the symptomatic disease and liver metastasis as independent predictors of shorter mPFS (HR; 1.835, 95% CI; 1.146-2.939 and HR; 2.433, 95% CI; 1.329-4.454, respectively). Our analysis revealed that although symptomatic individuals who underwent CDK4/6 inhibitor plus ET experienced a significant reduction in mPFS durations compared to asymptomatic patients, the 22-month mPFS indicated that CDK4/6 inhibitor plus ET is an effective treatment option.

Background/Objectives: Dose reductions in CDK4/6 inhibitors, such as ribociclib and palbociclib, are often necessary due to treatment-related toxicities in patients with advanced breast cancer. This study aims to evaluate the impact of the timing of dose reductions on progression-free survival (PFS) and overall survival (OS) in a real-world cohort. Methods: This single-center, retrospective study included patients treated with ribociclib or palbociclib between 2019 and 2023 at a cancer center in Turkey. Dose reductions due to drug-related toxicities were recorded, and survival outcomes were analyzed. Patients were categorized based on the timing of dose reductions: within the first 3 months (early) and after 3 months (late). Results: Among 392 patients (mean age 57.13 years), 16.8% had dose reductions within 3 months, 21.7% had late dose reductions, and 61.5% had no dose reductions. The mPFS was 14.26 months for early dose reductions, 33.12 months for late dose reductions, and 20.6 months for no dose reductions (p < 0.001). The mOS was 37.12 months for early dose reductions, not reached for late dose reductions, and 57.76 months for no dose reductions (p < 0.001). Hematological toxicity, primarily neutropenia, was the most common cause of dose reductions. The ECOG performance status, line of therapy, and CDK4/6 inhibitor type were also significant predictors of PFS and OS. Conclusions: Early dose reductions in CDK4/6 inhibitors negatively affect PFS and OS, highlighting the importance of maintaining treatment intensity in the first 3 months. However, late dose reductions do not negatively affect progression-free survival (PFS) or overall survival (OS), with late dose reductions associated with better outcomes. Prospective studies in larger patient populations will further clarify our knowledge on this subject.