BackgroundSystemic anticancer therapy (SAT) near the end of life is an indicator of potentially aggressive cancer care. Although patient-level prognostic factors have been studied, the role of treatment escalation within hospital-centered oncology models remains insufficiently understood. This study evaluated late-stage SAT and its determinants.MethodsA retrospective cohort of 118 patients with metastatic solid tumors who died between March 25, 2020, and April 30, 2025, was analyzed. Receipt of SAT within the last 30 and 14 days of life was assessed. Multivariable logistic regression identified factors independently associated with SAT in the final 30 days. Indicators of end-of-life care intensity were examined.ResultsSAT was administered to 42.4% of patients within the last 30 days of life and to 13.6% within the last 14 days. A new systemic treatment line was initiated within the final 2 months of life in 44.1% of patients. Recent treatment escalation was independently associated with therapy use in the last 30 days (adjusted OR 4.21, 95% CI, 1.89-9.38; P < .001), whereas age, performance status, and prior treatment burden were not significant predictors. Median survival from last treatment to death was 40 days. Overall, 73.7% of patients died in the hospital, and 50% in the intensive care unit (ICU).ConclusionsRecent treatment escalation was the main determinant of exposure to late-stage SAT. High hospitalization and ICU death rates suggest end-of-life care was delivered within a hospital-centered model. Earlier integration of palliative care and structured prognostic communication may better align treatment decisions with patient-centered goals.

Objectives:Breast cancer is highly heterogeneous, and certain histopathologic subtypes-particularly invasive lobular carcinoma-exhibit low glucose metabolism that limits 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) performance. Fibroblast activation protein inhibitor (FAPi) imaging with Gallium-68 (68Ga)-FAPi PET/CT has emerged as a promising alternative for such tumors. The aim of this study was to evaluate the efficacy of 68Ga-FAPi PET/CT in staging, restaging, and recurrence detection of breast cancer, with emphasis on subtypes for which 18F-FDG PET/CT has low sensitivity. Methods:Twenty-nine women with pathologically confirmed breast cancer (mean age 57.7±11.6 years) were prospectively enrolled. Histopathology (available in 24 patients) showed lobular carcinoma in 16, ductal carcinoma in 6, signet ring cell carcinoma in 1, and mucinous carcinoma in 1. All underwent both 68Ga-FAPi and 18F-FDG PET/CT within one week for staging or restaging. Maximum standardized uptake values (SUVmax) of primary tumors and metastases were recorded for both tracers and compared using paired t-tests. Results:In 7/29 patients (24.1%), neither 18F-FDG PET/CT nor 68Ga-FAPi PET/CT detected pathological findings. Disease stage increased in 13/29 (44.8%) after 68Ga-FAPi PET/CT, including 10 patients with no pathologic findings on 18F-FDG PET/CT; nine were upstaged to stage 4 and one to stage 3. Additionally, one patient progressed from stage 1 to 2, one from 2 to 3, and another from 3 to 4. Among patients with lobular carcinoma, 8/16 (50%) were upstaged with 68Ga-FAPi PET/CT. Detection of nodal and distant metastases in lobular carcinoma was higher with 68Ga-FAPi than 18F-FDG. 68Ga-FAPi PET/CT also demonstrated higher SUVmax in primary lesions and metastases (p<0.05). Conclusion:68Ga-FAPi PET/CT provides a significant advantage for staging and restaging breast cancer-especially lobular carcinoma and other low 18F-FDG-avid subtypes-supporting its potential role in clinical decision-making and treatment planning.

Background Breast cancer is a highly heterogeneous disease, with different histopathologic subtypes exhibiting distinct biological behaviour and metabolic characteristics. While [¹⁸F]-FDG PET/CT is widely used for staging and restaging, its effectiveness is limited in tumors with low glucose metabolism, such as lobular carcinoma. In recent years, fibroblast activation protein inhibitor (FAPi)-based imaging with [⁶⁸Ga]Ga-FAPI PET/CT has emerged as a promising alternative, offering improved lesion detection in tumors with low FDG avidity. This study aims to evaluate the potential efficacy of [⁶⁸Ga]Ga-FAPi PET/CT in staging and restaging breast cancer patients with FDG-negative or low FDG uptake lesions. Results Twenty nine female patients referred for staging, restaging or investigation of recurrence were performed [18F]-FDG PET/CT and [68Ga]Ga-FAPi PET/CT. The mean age was 57.7 ± 11.6 years. Histopathologic examination from previous surgeries/biopsies available for 24 patients revealed lobular carcinoma in 16 cases, ductal carcinoma in 6 cases, signet ring cell carcinoma in one patient and mucinous cell carcinoma in one patient. In seven patients (24.1%), neither the [18F]-FDG PET/CT nor the [68Ga]Ga-FAPi PET/CT revealed any findings indicating recurrence or metastasis. Disease stage increased in 44.8% (n = 13) of patients after [68Ga]Ga-FAPi PET/CT imaging, with 10 of them showing no pathologic findings on [18F]-FDG PET/CT; after [68Ga]Ga-FAPi PET/CT imaging, 9 patients progressed to stage 4 and 1 to stage 3. One patient progressed from stage 1 to stage 2, one progressed from stage 2 to 3 and other patient 3 to stage 4 according to AJCC 8th edition. Fifty percent (n = 8) of the lobular carcinomas were upstaged after [68Ga]Ga-FAPi PET/CT. The detection of lymph nodes and distant metastases in lobular carcinoma was higher with [68Ga]Ga-FAPi PET/CT than with [18F]-FDG PET/CT. Furthermore, [68Ga]Ga-FAPi PET/CT showed a higher SUVmax in primary tumor foci and metastases (p < 0.05). Conclusion [68Ga]Ga FAPi PET/CT has been shown to be superior for staging and restaging indications in breast cancer, especially for tumors such as lobular carcinoma with low FDG affinity. It is anticipated that [68Ga]Ga FAPi PET/CT will play an important role in future guidelines for primary diagnosis and staging in breast cancer patients, especially in patients with the lobular histopathologic subtype.

Objectives: This study aimed to evaluate the potential efficacy of 68Ga-fibroblast activation protein inhibitor (FAPi) positron emission tomography/ computed tomography (PET/CT) for detecting, staging, and restaging digestive system malignancies that are 18F-fluorodeoxyglucose (18F-FDG) Methods: We conducted a prospective analysis of 30 patients with pathologically confirmed primary tumors or metastases of the digestive system. Participants underwent 68Ga-FAPi PET/CT and 18F-FDG PET/CT imaging for staging or restaging purposes within the same week. The efficacy of 68Ga-FAPi PET/CT was assessed by comparing its ability to detect lesions and influence disease staging with that of 18F-FDG PET/CT. Results: 68Ga-FAPi PET/CT imaging was performed in 30 patients with 18F-FDG-negative or indeterminate lesions. Of the 30 patients, 23 had gastric cancer and 7 had colorectal cancer. Among all patients, histopathological diagnosis of signet ring cell carcinoma was present in 15 (50%) patients. Primary tumor or local recurrence was detected in 19 (63%) patients, lymph node metastasis in 8 (27%) patients, visceral metastasis in 4 (13%) patients, peritoneal metastasis in 14 (47%) patients, and bone metastasis in 3 (10%) patients on 68Ga-FAPi PET/CT images. All patients underwent histopathological confirmation on 68Ga-FAPi PET/CT images. The disease stage was upgraded in 20 patients (67%) after 68Ga-FAPi PET/CT imaging. Of the 20 patients, 12 had no evidence of recurrence or metastasis on 18F-FDG PET/CT. Conclusion: Based on our study, 68Ga-FAPi PET/CT alters the disease stage in the majority of gastrointestinal malignancies with negative or equivocal 18F-FDG PET/CT findings. 68Ga-FAPi PET/CT appears to be effective in both staging and restaging of gastrointestinal malignancies, such as signet-ring cell carcinomas of the stomach that frequently show low 18F-FDG -avidity.

Adult gliomas vary significantly in terms of their genetics, epigenetics, phenotypes as well as clinical outcomes1. Optimal tumor classification that leads to more precise diagnoses, and which influences therapy selection is hence critically important. Targeted next-generation sequencing (NGS) is a highly reliable and efficient novel tool for the identification of biomarkers for the diagnosis of CNS tumors2. In this study, we aimed to determine the implications of integrating NGS findings with the traditional diagnostic data on clinical diagnostics and patient management. All patients who were diagnosed with glioma at our institution between 2019-2020 and whose tumor biopsy materials were analyzed by both traditional histomorphological and immunohistochemical diagnostic techniques as well as NGS were included in our study. Patients’ information was retrieved from the electronic medical record. Data analyzed included the histopathologic diagnosis, tumor grade, ki67, and the mutation status of TP53 and /or IDH, as well as other genes such as BRAF and HER2 for some patients. The overall concordance between NGS and the traditional diagnostic tools for IDH and TP53 mutations was also evaluated. Further, we derived the overall survival of patients using the Kaplan-Meier estimate. We identified 9 patients with grade 3-4 gliomas whose biopsy materials were analyzed by NGS as well as traditional diagnostic tools. Our patients were 33.3% females and had a median age of 43 years old at diagnosis. In terms of the identification of gene mutations by NGS in comparison to immunohistochemistry (IHC), it was found that the concordance for mutant identification was 77.8% (7/9) for IDH mutations and 55.6% (5/9) for TP53 mutations. NGS further led to a change in patient management in which evidence-based targeted therapy (dabrafenib plus trametinib) was used for one patient (11.1%) with BRAF V600E mutated astroblastoma. Integrating NGS with traditional diagnostic tools for the diagnosis of gliomas can have significant implications on patients. Such integrated diagnosis can lead to more precise diagnosis, enhanced identification of molecular markers, and offers the potential of using targeted therapies for patients.

Neuroendocrine tumors (NETs) of the breast represent 1% of breast carcinomas.Histopathological misinterpretation of breast NET is common.We present the case of a female patient who had a breast mass diagnosed as invasive ductal carcinoma initially by histopathological examination.Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) revealed 2 ametabolic hypodense liver lesions.Subsequently, the patient underwent fibroblast activation protein inhibitor (FAPI)-PET/CT, which did not reveal any FAP expression in the liver lesions, but increased FAP expression was observed in the soft tissue mass of the mesenteric root.Consequently, the pathology of the biopsy taken from the nodule in the right breast was revised, and a diagnosis of grade 2 NET was established.The benefit of FAPI-PET/CT on NETs has been previously investigated.Further prospective studies are required to establish the role of FAPI-PET/CT in NET management.

e14611 Background: Expression of programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC) has often been measured by the Tumor Proportion Score (TPS) (1). Recently, the Combined Positive Score (CPS), which evaluates PD-L1 expression in tumor and inflammatory cells and applies to other types of cancer including gastric and head and neck cancers, was found to be equally predictive of the response to immunotherapy in NSCLC (1). In this study, we aimed to conduct a single center retrospective analysis to evaluate the clinical use and impact of using TPS and CPS data in patients with metastatic NSCLC. Methods: Patients with NSCLC who had TPS and CPS scores and received PD-1/PD-L1 inhibitors between 2021-2022 as a monotherapy or in combination with chemotherapy were included. Patients’ data was retrieved from the electronic medical record data and analysis included histopathological data, lung cancer surgical history, presence of EGFR mutation, ALK mutation, Ki67, use of adjuvant chemotherapy, type of immunotherapy used, and development of immune checkpoint inhibitor- related toxicity and treatment as applicable. TPS and CPS positivity was defined as >1 % and >1 respectively. Statistical methods employed included descriptive approaches such as calculated means as well as the Kaplan-Meier estimate. Results: 40 patients with NSCLC were included. Patients’ age ranged from 19 to 82 years old with an average age of 64.3 years old. Most patients had adenocarcinoma (65 %) and were at stage IV (72.5 %). TPS positivity was identified in 29 patients (72.5 %) and CPS positivity was identified in 35 patients (87.5 %). Patients received immunotherapy mostly as first or second line of treatment (90 %). Immune checkpoint inhibitors received by patients were pembrolizumab (50 %), nivolumab (35 %), atezolizumab (12.5 %), and durvalumab (2.5 %). The median overall survival was 16, 12, and 17 months in the <1 %, 1-49 % and > 49 % TPS groups respectively (p= 0.354); while the median overall survival was 11, 16 and 17 months in the <1, 1-49, and > 49 CPS groups respectively (p= 0.417). It is critical to highlight that there were 7 patients (17.5 %) with TPS of zero who had CPS positivity (score range: 1-10). Most of these patients had adenocarcinoma (71.4 %), received pembrolizumab or atezolizumab (85.7 %) and had a median survival of 16 months. Conclusions: The Combined Positive Score (CPS) has proven to be an effective method in evaluating the level of expression of PD-L1 in NSCLC (1,2). Similar to TPS, CPS provides critical information that can be applied to guide the use of immunotherapy, and which can greatly impact patients with NSCLC. 1. De Marchi et al., 2021. 2. Ulas et al., 2023.

Background: The combination of Lutetium-177 (Lu-177) PSMA-617 radioligand therapy (RLT) with androgen receptor pathway inhibitors (ARPIs) has shown promise in metastatic castration-resistant prostate cancer (mCRPC). However, real-world data on the efficacy and safety of this combination are limited. This study aimed to evaluate the impact of combination therapy with Lu-177 PSMA-617 RLT and ARPIs on progression-free survival (PFS) and overall survival (OS) in patients with mCRPC. Methods: In this retrospective study, 104 mCRPC patients receiving Lu-177 PSMA-617 RLT at our institution between December 2017 and January 2024 were divided into the following two groups those receiving Lu-177 PSMA-617 RLT plus ARPI (n = 34) and those receiving Lu-177 PSMA-617 RLT alone (n = 70). Patients received 150 to 200 millicuries Lu-177 PSMA-617 RLT in each cycle. PFS and zOS were assessed using Kaplan–Meier analysis and Cox proportional hazard models. Results: The combination therapy significantly prolonged median PFS compared to Lu-177 PSMA-617 RLT alone (11 vs. 5.6 months; HR, 0.47; 95% CI, 0.28–0.79; p < 0.01). A trend towards improved OS was also observed in the combination group (20.3 vs. 15.9 months; HR, 0.58; 95% CI, 0.33–1.02; p = 0.06). Age was a significant predictor of OS (21.2 vs. 12.4 months for younger vs. older patients; p < 0.01), while Gleason score and visceral involvement did not significantly impact PFS. The safety profile indicated that adverse effects were generally comparable between the two groups, with no statistically significant differences in the incidence of anemia, neutropenia, thrombocytopenia, nephrotoxicity, or hepatotoxicity. Conclusions: This study provides evidence that combining Lu-177 PSMA-617 RLT with ARPIs may significantly improve PFS in mCRPC patients. The potential OS benefit warrants further investigation in larger prospective trials. Age should be considered when making treatment decisions for mCRPC patients.

Simple Summary This study investigates the real-world efficacy and safety of combining pembrolizumab, a novel immunotherapy agent, with chemotherapy in early-stage triple-negative breast cancer treatment. We specifically aimed to validate clinical trial results in routine practice. A total of 108 Turkish patients receiving neoadjuvant therapy were examined. The combined regimen demonstrated high efficacy, with 64% of patients achieving pathological complete response, and exhibited generally favorable safety profiles with predominantly mild adverse events. These findings support the use of this combination as a standard treatment for this aggressive breast cancer subtype. However, the results underscore the need for further research to identify optimal patient selection criteria, which can inform oncologists' decision-making and potentially enhance outcomes for patients with triple-negative breast cancer.Abstract Background/Objectives: Following the results of the phase 3 KEYNOTE-522 trial, the U.S. Food and Drug Administration approved pembrolizumab, a humanized IgG4 kappa monoclonal antibody, in combination with neoadjuvant chemotherapy as a new standard of care for high-risk early-stage triple-negative breast cancer (TNBC). This retrospective, multicenter study in T & uuml;rkiye assessed the real-world efficacy and safety of neoadjuvant pembrolizumab combined with chemotherapy in early-stage TNBC. Methods: The study included 108 patients treated between 2021 and 2023 across 14 oncology centers. Three distinct neoadjuvant regimens incorporating pembrolizumab were administered at the discretion of the treating physicians. The primary outcomes were the pathological complete response (pCR) rate after neoadjuvant therapy and the 2-year event-free survival (EFS) and overall survival (OS) rates. Results: The observed pCR rate was 63.9%, closely mirroring the 64.8% reported in the KEYNOTE-522 trial. At the two-year mark, the EFS rate was 87.2% and the OS rate was 92.3%. Multivariable analysis identified pCR as the sole independent predictor of both EFS and OS. The safety profile was consistent with previous clinical trial data, with most adverse events being of grade 1-2 in severity. Conclusions: These findings provide valuable real-world confirmation of the efficacy and safety of neoadjuvant pembrolizumab-chemotherapy in early-stage TNBC, complementing evidence from randomized trials.

Background Diffuse leptomeningeal glioneuronal tumors (DL-GNT) are rare glioneuronal neoplasms with oligodendroglioma-like cells. These tumors can present as a dominant intracranial mass or as a solitary spinal cord mass without leptomeningeal involvement. In this study, we aimed to determine the magnetic resonance imaging and histopathological features, treatment modalities, and clinical outcomes of the parenchymal forms of DL-GNTs. Methods This is a retrospective three-center case series study of 5 patients with a confirmed parenchymal form of DLGTs, out of which 4 patients were adults. Brain and spinal cord MR imaging were performed in all patients at either 1.5 or 3T. The patients' age ranged from 5 years to 50 years with a mean age of 27.6 years at presentation. Results Four of the tumors were located in the frontal lobe, and one in the tectum. They were usually solid-cystic enhancing tumors as the other mixed neuronal-glial tumors. All of the tumors had an extension to the superficial surface of a cerebral hemisphere. One had systemic bone metastases. The clinical signs and symptoms of the parenchymal form varied based on the location of the mass, in contrast to the leptomeningeal form associated with hydrocephalus. In one case, the tumor's initial grade was defined as intermediate. The initial histopathology of the two cases was low-grade and no up-grade occurred in the follow-up period. In two cases, although the tumors were low grade initially, they progressed to an anaplastic form in the follow-up period. Conclusion The parenchymal form of DL-GNTs is common in adults. Extension to the superficial surface of a cerebral hemisphere is a distinctive imaging feature. Systemic osseous metastasis may occur. Due to the presence of common histopathological features, including the biphasic composition of glial and neuronal cell elements and oligodendroglioma-like cells, a proposed classification approach might be more beneficial for the histopathological and imaging description, and management of the glioneuronal tumors with oligodendroglioma-like features.

For patients with advanced-stage metastatic castration-resistant prostate cancer (mCRPC) who do not respond to [177Lu]Lu-PSMA therapy, there are limited treatment options. Clinical results obtained with [225Ac]Ac-PSMA are promising. We retrospectively analyzed the outcomes of patients treated with [225Ac]Ac-PSMA between December 2018 and October 2022. Methods: We evaluated the treatment results of 23 patients (mean age, 70.3 ± 8.8 y) with mCRPC who were refractory to treatment with [177Lu]Lu-PSMA (2-9 cycles). The safety profile was assessed according to Common Technology Criteria for Adverse Events version 5.0. Treatment efficacy was assessed using prostate-specific membrane antigen PET progression criteria and prostate-specific antigen (PSA) response according to Prostate Cancer Working Group 2 criteria after the first cycle of [225Ac]Ac-PSMA treatment. Results: All patients received androgen-deprivation therapy, whereas 22 (96%) and 19 (83%) patients received chemotherapy and second-generation antiandrogen therapy, respectively. One patient received 4 cycles, 2 received 3 cycles, 8 received 2 cycles, and 12 received 1 cycle of [225Ac]Ac-PSMA. The median interval between cycles was 13 wk (range, 8-28 wk). [225Ac]Ac-PSMA was administered with a mean activity of 7.6 MBq (range, 6.2-10.0 MBq) in each cycle. Patients were at an advanced stage of disease, and tumor burden was very high. Although the best PSA response was observed in 5 patients (26%) after [225Ac]Ac-PSMA treatment, there was at least some level of decline in PSA observed in 11 patients (58%; n = 19). Treatment response was assessed in patients who underwent [68Ga]Ga-PSMA PET/CT imaging. After the first cycle of treatment (n = 18), 50% of patients (n = 9) showed disease progression according to prostate-specific membrane antigen PET progression criteria, and the disease control rate was calculated to be 50%. Median progression-free survival was 3.1 mo, and median overall survival was 7.7 mo. Grade 3 hematologic toxicity occurred in 1 patient, and grade 3 nephrotoxicity was observed in another patient. Parotid SUVmax decreased by 33%, although all patients complained of dry mouth before treatment. Conclusion: We observed that [225Ac]Ac-PSMA therapy was safe and showed potential even in cases with advanced-stage mCRPC in which all other treatment options were completed.

Objective: While several inflammatory markers are known to increase in familial Mediterranean fever (FMF) disease cases, the need remains for diagnostic tests specific for FMF that monitor inflammatory activity. We aimed to investigate resistin and calprotectin levels during both attack and attack-free periods of FMF disease and evaluate their use as novel biomarkers of inflammation in patients with FMF. Materials and Methods: This cross-sectional study included 68 male patients diagnosed with FMF and 20 healthy individuals as controls. Blood samples were obtained from the patients in attack-free periods (at least 15 days after the last attack) and attack periods (in the first 24 hours). Serum resistin and plasma calprotectin levels was measured by ELISA method. Results: Resistin and calprotectin levels were significantly higher in patients during both attack (p =0.001, p <0.001) and attack-free periods (p =0.017, p =0.01) compared to the control group. Logistic regression analysis indicated that resistin levels were predictive for the diagnosis of FMF disease (OR: 1.21; 95% CI: 1.04–1.42; p =0.016). Resistin and calprotectin levels significantly correlated with C-reactive protein, erythrocyte sedimentation rate, fibrinogen, and white blood cells (0.301≤ r ≤ 0.505, p <0.05). Conclusion: Resistin and calprotectin levels were significantly higher in patients than controls, and resistin was predictive for monitoring inflammatory activity in patients with FMF.

Background: Isolated pituitary gland metastasis is an extremely rare event in renal cell carcinoma. We present a unique case of isolated pituitary metastasis of renal cell carcinoma and a systematic review of literature on it. Case report: In this case, an abdominal ultrasound in an asymptomatic 51-year-old female patient showed a mass in her left kidney. Radical nephrectomy was performed and the tumor was diagnosed as a stage 1 clear cell carcinoma. Throughout the 3 months of the follow-up period, the patient started complaining of visual disturbances and headaches. A pituitary mass was found on brain magnetic resonance imaging and was suspected to be a macroadenoma. Surgical resection of the tumor was performed and the final pathological diagnosis was made as a pituitary metastasis of the renal cell carcinoma. After surgery, radiotherapy with sunitinib, a receptor tyrosine inhibitor, was performed. Conclusion: The clinical symptoms are usually related to the mass effect of the tumor and anterior pituitary involvement. Most of the cases mimic pituitary macroadenoma on MRI. The most preferred treatment combination is surgery and radiotherapy. We recommend adding sunitinib to this combination. This illustrative case and those found in a systematic review of the literature highlight the importance of histopathologic diagnosis and appropriate management since isolated pituitary metastasis is challenging to preoperative diagnosis.