Introduction: Brain metastases from solid tumours are the most common intracranial neoplasms and significantly impact patients' quality of life and overall survival (OS). Despite advances in oncological therapies, these patients have often been excluded from clinical trials, limiting our understanding of the efficacy of new treatments, such as immunotherapy, in this population. Investigating the tumour microenvironment (TME) of brain metastases is challenging, particularly in determining whether immunotherapy is effective for these lesions. The aim of this study is to investigate the host's immune response to primary tumours and concomitant brain metastases in the central nervous system from various malignancies. Material and methods: A retrospective study was conducted to examine tumour-infiltrating lymphocytes (TIL) and the expression of programmed cell death 1 and programmed death ligand 1 (PD-L1) in tissue samples from 72 patients with predominant solid tumours and synchronous or metachronous brain metastases. Correlations with different parameters were analysed to evaluate the prognosis of these patients. Results: All metastatic tumour samples exhibited decreased intraepithelial CD3 and CD8 levels compared to primary tumours, with variable FOXP3 levels and no consistent difference in PD-L 1 levels in tumour cells. Programmed death ligand 1 expression in immune cells was generally lower in metastatic lesions compared to primary tumours. The median OS from diagnosis (OS1) was 19.1 months (95% CI: 13.6-35.1), and the median OS from the diagnosis of brain metastases (OS2) was 11.35 months. Conclusions: The brain TME demonstrates varying levels of TIL and immune checkpoint expression, highlighting the need for further research to develop effective therapies for intracranial metastases.

In view of the shifting standard of care for non-small cell lung cancer (NSCLC), we aimed to capture the evolution of the epidemiological and systemic treatment (ST) landscape in Greece. This non-interventional, single-country, multicenter, retrospective study, collected high-level aggregate data for adult patients who were newly diagnosed with histologically/cytologically confirmed Stage I-IV NSCLC between 01-Jan-2016 and 31-Dec-2020 (index period) at leading oncology clinics across the country. Overall, 10,644 patients were newly diagnosed with NSCLC during the entire 5-year index period at the 18 participating sites (63.8

INTRODUCTION:Radiotherapy for breast cancer has a clear benefit for long-term survival and local control rate. However, it can negatively impact a patient's quality of life by affecting healthy surrounding normal tissues, including the heart and lungs. This study aimed to clarify the contribution of echocardiography with Global Longitudinal Strain (GLS) to early radiation-induced cardiotoxicity detection. METHODS:A prospective study was conducted on 25 early-stage left-sided breast cancer patients. All underwent 2D strain echocardiography before and one year after RT. Normality was assessed using the Shapiro-Wilk test and box plots. The Wilcoxon signed-rank test was conducted to compare GLS values. A statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) version 25. RESULTS:Mean Global Longitudinal Strain value before and one year after radiotherapy was -20.2% and -21.2%, respectively. In half of these cases, the values ranged from -19.65% to -22.70% before radiotherapy and between -18.8% and -22.25% after radiotherapy. The non-parametric Wilcoxon test indicated no statistically significant difference before and after radiotherapy (Ζ = 0.902, p = 0.367). DISCUSSION:Although no statistically significant reduction in GLS was observed one year post-radiotherapy, a decrease was noted in patients receiving higher cardiac doses, suggesting potential early subclinical myocardial changes. Strain echocardiography shows promise as a sensitive tool for the early detection of radiation-induced cardiotoxicity, warranting further research with larger cohorts and extended follow-up. CONCLUSION:While this small cohort study did not show significant GLS changes post-RT, it highlights the need for larger studies with longer follow-ups to confirm the role of strain imaging in identifying early cardiotoxicity in breast cancer patients.

BackgroundOver 50% of newly diagnosed patients with breast cancer are aged ≥65 years. Due to age-related factors and the presence of comorbidities, these patients are particularly vulnerable to developing cardiac toxicity associated with cancer treatments, which may lead to suboptimal interventions and undertreatment, resulting in poorer health outcomes, quality of life (QoL) deterioration, and increased health care costs. Given the underrepresentation of older patients with breast cancer in clinical trials and the increasing recognition of the impact of psychosocial and behavioral factors on cardiovascular disease onset, broader and interdisciplinary studies are required to develop new and innovative best practices for this clinical population. ObjectiveUsing an innovative eHealth approach combining the CARDIOCARE (An Interdisciplinary Approach for the Management of the Elderly Multimorbid Patient with Breast Cancer Therapy Induced Cardiac Toxicity—grant agreement 945175) mobile app and technologically advanced wearable devices (ie, the Garmin Venu SQ watch and Polar H10 sensor), the CARDIOCARE prospective study pursues a twofold aim: (1) testing the effectiveness of the CARDIOCARE mobile app to monitor and assess the intrinsic capacity and QoL of older patients with breast cancer and evaluating the CARDIOCARE eHealth interventions’ effectiveness on these parameters and (2) developing a holistic, patient-centered risk prediction model specific for the detection of cardiotoxicity before it clinically emerges. MethodsThis prospective and multicentric study involves 6 clinical and 5 technical partners across Europe. In total, 750 older patients with breast cancer (aged ≥60 years) are assigned to either the standard practice or enhanced monitoring group, with only patients in the latter receiving access to eHealth psychological, behavioral, and functional interventions implemented on the CARDIOCARE eHealtHeart app. Patients will be recruited in 6 clinical centers and will undergo clinical procedures to collect multimodal data, including clinical data, cardiac imaging, biochemical and psychological biomarkers and omics, intrinsic capacity, and QoL indicators measured at baseline (T0) and every 3 months up to 12 months (T5). ResultsCARDIOCARE is a project funded by Horizon 2020, and enrollment started in May 2023. As of October 17, 2024, a total of 50% (375/750) of the target number of patients had been recruited. ConclusionsThe CARDIOCARE prospective study will contribute to developing new best practice guidelines for managing older patients with breast cancer and multimorbidity while preserving their intrinsic capacity and improving their QoL. Furthermore, the CARDIOCARE mobile app and the wearable devices will allow clinicians to identify trajectories across the cardiotoxicity disease continuum and thus intervene in a preventative way among patients at higher risk. Such a health care approach will also benefit the health care system, which currently spends almost 40% of its resources on patients aged >60 years, with long-term care and hospital admissions being the primary cost drivers. Trial RegistrationClinicalTrials.gov NCT06334445; https://clinicaltrials.gov/study/NCT06334445 International Registered Report Identifier (IRRID)DERR1-10.2196/63455

Cancer-associated thrombosis (CAT) has become increasingly important due to its prevalence and impact on patient outcomes. The risk of venous thromboembolism (VTE) is significantly increased during cancer progression and cancer therapy, highlighting the urgent need for effective anticoagulant strategies. There are several categories of anticoagulants, the most important being low molecular weight heparins (LMWHs) and direct oral anticoagulants (DOACs). Investigating drug-drug interactions (DDIs) of these anticoagulants with oncology drugs is crucial to ensure effective and safe treatment options for cancer patients. Using a comprehensive search strategy, the PubMed and Embase databases were used to identify studies reporting DDIs between anticoagulants and antineoplastic drugs through December 2023. Four studies met the inclusion criteria and included 299 patients, mostly women, with different comorbidities and treatment regimens for anti-thrombotic and anti-neoplastic therapy. Studies have reported varying degrees of severity of DDIs, ranging from no interaction to contraindicated interactions, which affect the efficacy and safety results of the treatment, such as bleeding and thrombotic events. Compared to DOACs, LMWHs does not interact with chemotherapy drugs. While LMWHs is preferred due to its predictable response and minimal toxicity, DOACs are a more appropriate option despite concerns regarding their interaction with oncological drugs. Understanding and managing DDIs between anticoagulant medications and oncology drugs is critical to optimising treatment outcomes for cancer patients. Further studies are needed to elucidate the clinical implications of these interactions and guide therapeutic decisions in this complex patient population.

Background: Abemaciclib has been approved in combination with endocrine therapy in adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, early breast cancer (BC) at high risk of recurrence and locally advanced or metastatic BC. We aimed to assess real-world toxicity and efficacy data of patients with BC who received treatment with abemaciclib. Methods: This was a prospective collection of clinicopathological, toxicity and outcome data from patients with early- or advanced- stage HR-positive/HER2-negative BC who received treatment with abemaciclib in combination with endocrine therapy. Treatment combinations of abemaciclib with any endocrine therapy were accepted. Patients needed to have received at least two months of treatment with abemaciclib. The primary end point was toxicity rate in all patients of the study, both with early and advanced BC. Results: From June/2021 to May/2024, 227 women received abemaciclib/endocrine combination therapy; median age was 56 years, and 152 (70.4%) patients were postmenopausal. Hormonal therapies given in combination with abemaciclib in advanced BC were fulvestrant (0.7%), aromatase inhibitors (88.6%) and tamoxifen (10.7%). Abemaciclib was administered as adjuvant treatment in 157 (69.1%) patients. At the time of the data cutoff (May 2024), 4 (2.5%) patients had completed the 2-year treatment period, and 133 (84.7%) patients remained in the 2-year treatment period. The most common adverse events (AEs) were diarrhea (46.5%), fatigue (18.5%), ALT/AST increase (7.0%) and arthralgia (6.4%). Grade 3 diarrhea was reported in 8 (5.1%) patients; no Grade 4 diarrhea was observed. Diarrhea was observed at a median of 6 days from treatment initiation (range 1 to 270 days). No thrombotic event was reported. AEs led to dose modification and treatment discontinuation in 42 (26.8%) and 8 (5.1%) patients, respectively. There was no difference in modification/discontinuation rates between older patients (>65 years) and the remaining patients. Patients who received abemacilib as adjuvant treatment had similar toxicity rates with patients with advanced BC. The median 1-year and 2-year disease-free survival rate for patients who received adjuvant treatment with abemaciclib was 100% and 98.7%, respectively. Almost half (47.1%, 33/70) of the patients were diagnosed with de novo metastatic disease. In patients with advanced cancer (70, 30.8%), a median of one site of metastasis was reported at diagnosis of advanced disease (most commonly bones, 54,3%). With a median follow up of 11.8 months, 14 patients had disease progression; median progression-free survival (PFS) was not reached yet and 12-month PFS rate was 79.3%. Conclusions: This study provides prospectively collected real-world data on abemaciclib in combination with endocrine treatment, confirming the safety and efficacy in an unselected patient population. These results are consistent with the registration trials and no new safety concerns were reported.Clinical trial registration: ClinicalTrials.gov NCT04985058 Citation Format: Elena Fountzilas, Panagiota Economopoulou, Katerina Dadouli, Ioannis Binas, Anastasia Vernadou, Evangelia Moirogiorgou, Eleftherios Vorrias, Adamantia Nikolaidi, Sofia Karageorgopoulou, Anna Koumarianou, Ioannis Boukovinas, Davide Mauri, Stefania Kokkali, Athina Christopoulou, Anastasios Vagionas, Avraam Assi, Achilleas Nikolakopoulos, Zacharenia Saridaki, Nikolaos Spathas, Paris Kosmidis, George Fountzilas, Amanda Psyrri. Real-world study of Abemaciclib in Patients with Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer: a Multi-Institutional Prospective Study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-10-02.

Cardiovascular toxicity constitutes a major adverse effect associated with cancer therapies. The optimal moment to evaluate and implement strategies for the prevention of cardiovascular toxicity in cancer patients is at the point of cancer diagnosis, preceding the commencement of oncological interventions. This study presents a machine learning pipeline for discovering pre-treatment prognostic biomarkers of asymptomatic cancer-therapy related cardiac dysfunction (CTRCD), using a dataset of 485 female patients diagnosed with breast cancer at the age of 55 or older. We examine a comprehensive set of clinical, biochemical, cardiac imaging markers and integrate them into a feature selection approach based on recursive feature elimination with cross-validation. The results identified a panel of significant features which exhibits an area under the ROC curve (ROC-AUC) equal to 0.75±0.07, including left ventricular ejection fraction, trastuzumab loading dose, body surface area, platelet count, left ventricular posterior wall diameter, white blood cell count, body mass index and interventricular septal diameter in ≥90% of the resampling iterations.Clinical Relevance— Early identification of high-risk patients for CTRCD enables proactive interventions, including the initiation of cardioprotective medications, adjustment of cancer treatments, and enhanced cardiac surveillance. Identifying biomarkers indicative of early cardiac injury allows clinicians to customize strategies aimed at preserving cardiac function and enhancing long-term outcomes for breast cancer patients.

Metastatic colorectal cancer (mCRC) remains a significant challenge in contemporary oncology, with treatment sequencing playing a pivotal role in reported patient outcomes. Although currently available therapeutic options have led to improved median overall survival rates, the prognosis for patients with stage IV disease still remains dismal. This article provides a comprehensive review of the current landscape of treatment sequencing strategies in mCRC, focusing on the rationale behind various approaches and the evolving evidence supporting their efficacy. We consider the roles of chemotherapy, targeted therapy, and immunotherapy agents, as well as emerging trends in personalized medicine and sequential therapy regimens. The concept of a "continuum of care" has emerged as a fundamental principle, aiming to provide all available therapies through an individualized approach to maximize clinical benefit. By elucidating the underlying complexities of treatment sequencing in mCRC, this review aims to guide clinicians in optimizing therapeutic strategies and improving patient care.

Lynch syndrome is an autosomal dominant genetic disorder associated with early-onset colorectal cancer (CRC), endometrial cancer and other malignancies. This condition is defined by deficient DNA mismatch repair and high microsatellite instability (dMMR/MSI-high), exhibiting a substantial response to immunotherapy. However, microsatellite-stable (MSS) tumours may infrequently occur in individuals with Lynch syndrome. Our aim was to evaluate the efficacy of immunotherapy in patients with Lynch Syndrome and dMMR/MSS colorectal cancer. A systematic review of the literature in medical databases, major related conferences and relevant oncology journals was conducted to identify the available evidence. Medical records from the Medical and Clinical Oncology Department of the University Hospital of Ioannina were also reviewed. Four cases of MSS colorectal cancer associated with Lynch syndrome and MSH6 germline mutation were identified. Three of these four patients were treated with immune checkpoint inhibitors. Two patients with metastatic disease experienced disease progression, but one patient who received neoadjuvant immunotherapy achieved a partial response. All four patients were diagnosed with colorectal cancer in ages younger than 52 (16–51 years old). MSS CRC tumours in patients with Lynch syndrome is an infrequent phenomenon and under-represented in the literature. The limited efficacy of immune checkpoint inhibitors is highlighted in this rare subset of patients.

Background Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. The presence of the KRAS G12C mutation in patients with CRC is associated with poor responses to standard therapies and worse outcomes. This study systematically reviewed and analyzed the existing evidence on the efficacy of KRAS G12C inhibitors. Methods PubMed, Scopus, and ISI Web of Knowledge were searched, along with conference proceedings, posters, and major oncology journals. Eligibility criteria included clinical trials involving adult patients with KRAS G12C-mutant CRC. Data on treatment outcomes, study design, and patient demographics were extracted and analyzed using a random-effects model, with heterogeneity assessed via I2 statistics. Results Seventeen trials, comprising 663 patients with KRAS G12C-mutant metastatic CRC, were included. Monotherapy with KRAS G12C inhibitors demonstrated an objective response rate of 23%, while combination therapies with agents such as cetuximab and panitumumab showed a higher response rate of 43%. Stable disease rates were also higher in monotherapy (62%) compared to combination therapy (44%). The highest disease control rates were observed with combination therapies (96%). The overall progressive disease rate was lower with combination therapies (1%) than with monotherapies (10%). Conclusions The results indicate that KRAS G12C inhibitors, particularly in combination with other agents, show promising efficacy in treating metastatic CRC. High heterogeneity across studies suggests variability due to small sample sizes and early-phase trial designs. While preliminary data are promising, further large-scale phase III trials are essential to establish these inhibitors as a standard treatment for KRAS G12C-mutant CRC.

Background/Objectives: The prevalence of breast cancer (BC) is significant globally. The malignancy itself and the related treatments have a considerable impact on patients’ overall well-being. The adoption of e-health solutions for patients is increasing rapidly worldwide, since these innovative tools hold significant potential to positively impact the mental health and quality of life (QoL) of BC patients. However, their overall impact is still being explored, and further understanding and analysis are required. This review paper aims to present, quantify, and summarize the cumulative available randomized evidence on the state of the art of supportive interventions delivered via e-health applications for patients’ mental health and QoL before, during, and after BC treatment. Methods: A systematic review was conducted following the PRISMA guidelines in the Scopus and PubMed databases on 7 November 2024 to identify studies that utilized internet-based interventions in BC patients. The inclusion criteria were as follows: adult men and women (aged > 18 years) diagnosed with breast cancer (BC) who received patient-directed e-health interventions, compared to standard care or control interventions. The studies had to focus on outcomes such as quality of life (QoL), anxiety, depression, and distress, and be limited to randomized controlled trials (RCTs). The PRISMA-P guidelines were followed. Risk of bias was assessed using the Cochrane risk-of-bias (RoB) tool for randomized controlled trials. Results: A total of 27 randomized studies, involving 2898 patients, were included in this systematic review. The e-health interventions significantly affected patients’ anxiety (SMD = −0.80; 95% CI: −1.33 to −0.27; p < 0.01; and I2 = 94%), depression (SMD = −0.74; 95% CI: −1.40 to −0.09; p = 0.026; and I2 = 95%) and QoL (SMD = 0.65; 95% CI: 0.27 to 1.04; p < 0.01; and I2 = 90%) but had no significant effect on distress (SMD = −0.78; 95% CI: −1.93 to 0.37; p = 0.184; and I2 = 95%). Conclusions: This study showed that e-health interventions can improve QoL, reduce anxiety, and decrease depression in adult BC patients. However, no noticeable impact on reducing distress levels was observed. Additionally, given the diversity of interventions, these results should be interpreted with caution. To determine the optimum duration, validate different intervention approaches, and address methodological gaps in previous studies, more extensive clinical studies are needed.

Colorectal cancer (CRC) is the fourth most common cancer worldwide and a leading cause of cancer-related mortality. Despite improvements in cancer prevention, early diagnosis, and therapeutic options, metastatic CRC (mCRC) remains a major challenge, with a significantly lower 5-year survival rate compared to localized CRC. The heterogeneity of CRC, both localized and metastatic, necessitates a thorough molecular characterization to guide treatment strategies. A significant aspect of CRC progression involves the tumor microenvironment, particularly tumor-associated macrophages (TAMs), which are abundant and exhibit high plasticity. Tumor-associated macrophages, especially those polarized into the M2 phenotype, support various aspects of tumor progression, including angiogenesis, metastasis, and immune evasion. The PD-1/PD-L1 immune checkpoint axis, overexpres-sed in M2 TAMs, contributes to immune suppression, facilitating tumor growth. While some studies suggest that TAMs may have a positive role in CRC prognosis, others associate TAM infiltration with poor outcomes, particularly in metastatic disease. The relationship between TAMs and the PD-1/PD-L1 axis in CRC is still not fully understood, though emerging data highlight their potential to shape the immune resistance environment. Further research is needed to clarify the role of TAMs and the PD-1/PD-L1 network in CRC progression and to develop more effective immunotherapies targeting these pathways. This review systematically explores the current literature on TAMs and their interaction with the PD-1/PD-L1 axis in CRC, emphasizing the need for continued investigation to improve patient outcomes.

INTRODUCTION/OBJECTIVE:Significant advancements have been achieved with the use of targeted molecular therapies for the treatment of Soft Tissue Sarcomas (STS). However, data remain scarce about the potential benefits and toxicity of this therapeutic option. In this narrative review, we aim to better clarify the potential wound healing complications in STS patients undergoing neoadjuvant (NA) radiotherapy (RT) combined with targeted therapies. METHODS:We used the PubMed database to retrieve journal articles, and the inclusion criteria were all studies that illustrated the potential RT toxicity, combined with targeted therapies, in the NA setting of STS patients. RESULTS:Our search resulted in seven studies that fulfilled the inclusion criteria. Delayed wound complication rates were observed similarly to RT alone, while one study reported intolerable toxicity without referring specifically to wound complications. CONCLUSION:The combination of RT with targeted therapies in STS seems to be effective and well tolerated. Due to the lack of studies with a high level of evidence, further research is required to enhance the existing knowledge for its potential value in this field.

Background: Inflammatory bowel diseases (IBDs) have been associated with a higher risk of colorectal cancer (CRC) development and chronic colonic inflammation seems to have a critical role in the pathogenesis of CRC in patients suffering from IBD. In respect to that, surveillance colonoscopy at regular intervals is recommended in patients with colitis. Objective: This review aims to explore the chemopreventive potential of a range of agents, including mesalazine, thiopurines, anti-TNF agents, statins, ursodeoxycholic acid, aspirin, folic acid, and nutraceuticals. Results: These agents target inflammation, oxidative stress, and oncogenic pathways, thereby offering the potential to reduce the risk of CRC in patients with IBD. Anti-TNF agents, such as infliximab and adalimumab, not only reduce colonic inflammation, but also play a protective role against CRC by lessening the carcinogenic effects associated with prolonged inflammatory processes. Furthermore, mesalazine and thiopurines have demonstrated established efficacy, while newer biologics, including interleukin inhibitors, show promising advancements. Although nutraceuticals and dietary interventions require further clinical validation, they offer additional possibilities for non-pharmacological prevention. Conclusion: Despite progress, knowledge gaps persist regarding the long-term safety, optimal dosing, and combined use of these agents. A significant reduction in the incidence of CRC in patients with IBD could be achieved by advancing chemoprevention and personalizing strategies.

Background/Objectives: This study aimed to assess real-world toxicity and efficacy data of patients with early and advanced breast cancer (BC) who received treatment with abemaciclib. Methods: This was a prospective/retrospective multi-institutional collection of clinicopathological, toxicity, and outcome data from patients with early or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative BC who received treatment with abemaciclib in combination with endocrine therapy in departments of oncology in Greece. Treatment combinations of abemaciclib with any endocrine therapy were accepted. The primary end point was toxicity rate in all patients of the study. Results: From June/2021 to May/2024, 245 women received abemaciclib/endocrine combination therapy; the median age was 57 years. Of these, 169 (69%) received abemaciclib as adjuvant therapy for early-stage disease, while 76 (31%) were treated for advanced BC. At the time of the data cutoff, 133 (84.7%) patients remained in the 2-year treatment period. The most common adverse event (AE) was diarrhea (51%), primarily Grade ≤ 2. Dose modifications due to AEs were required in 19.2% of cases, while treatment discontinuation occurred in 5.1%. There was no difference in dose modification/discontinuation rates between older patients (>65 years) and the remaining patients. For early-stage BC patients, the 2-year DFS and OS rates were 90.8% and 100%, respectively. In patients with advanced cancer (70, 30.8%), 1-year PFS and OS rates were 78% and 96.3%, respectively. Conclusions: This study confirms the safety and effectiveness of abemaciclib in alignment with registrational trials offering valuable insights into toxicity management and clinical outcomes in routine practice without identifying new safety concerns. Clinical Trial Registration: ClinicalTrials.gov NCT04985058