Germline Co-deletion of CDKN2A and CDKN2B Genes in Pleomorphic Xanthoastrocytoma: Case Report.

BACKGROUND/AIM: Gliomas are highly heterogeneous malignancies originating from diverse cell types within the brain. Although their precise etiology is frequently unknown, risk factors, such as chemical exposure, radiation, and specific uncommon genetic disorders have been identified. Diagnosis typically entails imaging tests, such as magnetic resonance imaging and computed tomography, complemented by a biopsy for confirmation, which may be further validated through genetic testing. CASE REPORT: Next-generation sequencing technology revealed germline co-deletion deletion of cyclin-dependent kinase inhibitor 2 A and B genes (CDKN2A and CDKN2B) in a patient diagnosed with pleomorphic xanthoastrocytoma based on the tumor's molecular characteristics. Following this result, we performed focused genetic analysis with use of multiplex ligation-dependent probe amplification technology for the mother that revealed the same co-deletion. Moreover, due to the father's neuroendocrine pancreatic cancer, application of the NGS technology detected a pathogenic variant in the BRCA1-interacting helicase 1 (BRIP1) gene. Comprehensive multi-gene testing conducted within the familial context, marked by a varied spectrum of cancer type, revealed a constellation of genetic predispositions. CONCLUSION: This case study underscores the critical importance of molecular testing for tumor characterization and highlights the pivotal role of genetic testing in facilitating early intervention and screening for at-risk family members. Furthermore, the identification of germline co-deletions in cancer lays the foundation for the development of targeted therapeutic strategies aimed at restoring normal cellular regulation and improving patient management.

Paraneoplastic dermatomyositis and Stevens-Johnson syndrome related to immunotherapy.

Paraneoplastic syndromes such as dermatomyositis, often emerge as the initial clinical manifestation across various cancer types and are characterized by the development of B-cell responses targeting cancer-cell antigens that cross-react with normal skin and muscle cells. While these syndromes may alleviate following antineoplastic intervention, their response to immunotherapy remains elusive due to the exclusion of patients with autoimmune phenomena from clinical trials. In this report, we present the case of a female patient with advanced urothelial cancer presenting with dermatomyositis, who subsequently underwent treatment with anti-PD1 immunotherapy and experienced the onset of Stevens-Johnson syndrome. We discuss these two autoimmune entities and provide a comprehensive review of the existing literature to elucidate similar associations.

Dermatomyositis, an inflammatory disorder that causes a skin rash, might be the first sign that someone has cancer. But when scientists test new cancer treatments, they often don't include people with this skin problem. So, we do not know much about how safe or effective these treatments are for them. Here's a story about someone who had bladder cancer and dermatomyositis. They received a treatment called immunotherapy, but it caused a serious problem called Stevens-Johnson syndrome. We also found similar cases in medical papers.

Prevalence and risk factors of dry eye disease in patients treated with aromatase inhibitors for breast cancer.

CLINICAL RELEVANCE: Treatment with aromatase inhibitors (AIs) in patients with breast cancer can lead to dry eye disease (DED). BACKGROUND: The purpose of the study is to determine the prevalence and risk factors of DED in patients treated with AIs for breast cancer. METHODS: Participants in this cross-sectional study were patients with breast cancer treated with AIs. Demographic and clinical data, including age, sex, type of cancer, stage, grade, duration of treatment and adjuvant chemotherapy and/or radiotherapy were collected. All patients underwent a detailed ophthalmic examination, as well as Tear Break up Time (TBUT) and Schirmer test, while Ocular Surface Disease Index (OSDI) questionnaires were administered. Based on the clinical findings, a diagnosis of DED was made, and prevalence was calculated. Univariate analysis of the association of different variables with DED was performed. A logistic regression analysis was done to identify risk factors for DED among study population. RESULTS: A total of 102 participants were included in the study. The mean age of patients was 62.4 ± 10.8 years. A total of 77 out of 102 patients (75.5%) had ductal, 16 (15.7%) lobular and 9 (8.8%) other types of breast cancer. A total of 83 patients (81.4%) received chemotherapy and 70 patients (68.6%) received radiotherapy. The mean duration of treatment was 24.4 ± 18.9 months. The prevalence of DED in the study sample was 69.6%. Patients who received radiotherapy (OR = 3.31, 95%CI = 1.30-7.82, p = 0.01) or were under treatment with AIs for more than 24 months (OR = 3.53, 95%CI = 1.47-9.21, p = 0.002) were found to have an increased risk of DED. CONCLUSION: There was a high prevalence of DED among the study population. Radiotherapy and duration of treatment with AIs were independently associated with DED.

RETRO-TAS, a Retrospective Observational Study of Trifluridine/Tipiracil in Chemorefractory Metastatic Colorectal Cancer.

BACKGROUND: Trifluridine/tipiracil (FTD/TPI) is an oral antimetabolite agent comprised of trifluridine, a thymidine-based nucleoside analogue that inhibits cell proliferation following its incorporation into DNA, and tipiracil that helps maintain the blood concentration of trifluridine by inhibiting the enzyme thymidine phosphorylase which inactivates trifluridine. It is approved as a third-line treatment option for patients with metastatic colorectal cancer (mCRC) and is administered at 35 mg/m2 two times daily from day 1 to 5 and from day 8 to 12 every 28 days. The aim of this investigator-initiated retrospective study (RETRO-TAS; NCT04965870) was to document real-world data on the clinical efficacy of FTD/TPI in patients with chemorefractory mCRC. METHODS: The clinical characteristics of patients with mCRC treated with FTD/TPI in 8 Cancer Centres were collected to assess physician's choice in the third or beyond line of treatment as well as the duration of treatment, dose modification, and toxicity. In addition, other important prognostic features related to mCRC such as molecular profile, performance status (PS), and primary site were analyzed. Statistical analysis for progression-free survival (PFS), overall survival (OS), 6-/8-month PFS rate and disease control rate (DCR) along with Cox regression model, Kaplan-Meier curves, and log-rank tests were carried out by using Stata/MP 16.0 for Windows. RESULTS: From October 2018 to October 2021, a total of 200 patients with mCRC and a median age of 67.0 (IQR 58.0, 75.0) years were treated with FTD/TPI. Τhe median follow-up time was 14 months (IQR 7, 23), 158 PDs and 106 deaths were reported at the time of this analysis. Of all the patients, 58% were males and 58% had mCRC at diagnosis. The molecular analysis identified mutations in KRAS (52%), NRAS (5%), HER2 (3.5%), BRAF (3.5%), and MSI (9%). Previous treatments included radical surgery in 51.5% and adjuvant chemotherapy in 39.5% of patients. FTD/TPI was administered in the third- (70.5%), fourth- (17.0%), or fifth-line (12.5%) treatment setting. Serious adverse events related to FTD/TPI included neutropenia (2%), anaemia (1%), thrombocytopenia (0.5%), diarrhoea (0.5%), nausea (0.5%), and fatigue (4%). A reduction of FTD/TPI dose, delay of next cycle initiation, and shorter duration were reported in 25%, 31%, and 14.5% of patients, respectively. Of all the patients 71.5% received FTD/TPI as monotherapy, 24.5% in combination with bevacizumab, and 4.0% with an anti-EGFR agent. The median FTD/TPI treatment duration was 119.5 days and 81% of patients discontinued treatment due to progressive disease. The DCR recorded by investigators' assessment was 45.5%. The median PFS was 4.8 and the median OS was 11.4 months. The 6- and the 8-month PFS rate was 41.4% and 31.5%, respectively. In the multivariate analysis, PS > 1 and presence of liver and lung metastasis were adversely associated with PFS and OS whereas mutational status and tumor sidedness were not. CONCLUSIONS: RETRO-TAS is a real-world observational study that confirms and adds on the findings of the pivotal RECOURSE Phase III study in relation to the efficacy of FTD/TPI in the third-line setting and in all subgroups of patients regardless of mutational status and sidedness.

The Impact of COVID-19 Pandemic on Surgical Treatment of Resectable Non-Small Cell Lung Cancer in Greece.

Background: The coronavirus disease (COVID-19) pandemic has posed an unprecedented challenge to health systems, and has significantly affected the healthcare of lung cancer patients. The aim of our study was to assess the impact of COVID-19 on early lung cancer patients' surgical treatment. Methods: All consecutive patients with early-stage non-small cell lung cancer eligible for surgical treatment stage I/II and resectable stage III, referred to our department during the first wave of COVID-19 between February to May 2020, were included and compared with those on the exact corresponding quarter in 2019, one year before the pandemic. Waiting time to surgical treatment, increase of tumor's size and increase on lung cancer stage were recorded and compared. All subjects were followed up for 12 months. Multiple linear and logistic regression models were applied to assess the differences in the management of the studied groups adjusting for potential confounders. Results: Sixty-one patients with early-stage lung cancer were included in the study; 28 (median age 67 years, SD: 7.1) during the pandemic and 33 (median age 67.1 years, SD: 7.5) one year earlier. A significantly longer period of waiting for treatment and an increase in tumor size were observed during the pandemic compared to before the pandemic [median time 47 days, interquartile rate (IQR): 23−100] vs. [median time 18 days, IQR: 11−23], p < 0.001. No significant differences were detected in the increase of the stage of lung cancer between the subgroups. Conclusion: The COVID-19 pandemic had a significant impact on surgical and oncological care, leading to significant delays on treatment and an increase in tumor size in early-stage lung cancer patients.

Interrogating the interplay of angiogenesis and immunity in metastatic colorectal cancer.

Colon cancer is the third most common malignancy and the fifth most frequent cause of death from neoplastic disease worldwide. At the time of diagnosis, more than 20% of patients already have metastatic disease. In the last 20 years, the natural course of the disease has changed due to major changes in the management of metastatic disease such as the advent of novel surgical and local therapy approaches as well as the introduction of novel chemotherapy drugs and targeted agents such as anti-epidermal growth factor receptor, anti-BRAF and antiangiogenics. Angiogenesis is a complex biological process of new vessel formation from existing ones and is an integral component of tumor progression supporting cancer cells to grow, proliferate and metastasize. Many molecules are involved in this proangiogenic process, such as vascular endothelial growth factor and its receptors on endothelial cells. A well-standardized methodology that is applied to assess angiogenesis in the tumor microenvironment is microvascular density by using immunohistochemistry with antibodies against endothelial CD31, CD34 and CD105 antigens. Even smaller molecules, such as the microRNAs, which are small non-coding RNAs, are being studied for their usefulness as surrogate biomarkers of angiogenesis and prognosis. In this review, we will discuss recent advances regarding the investigation of angiogenesis, the crosstalk between elements of the immune microenvironment and angiogenesis and how a disorganized tumor vessel network affects the trafficking of CD8+ T cells in the tumor bed. Furthermore, we will present recent data from clinical trials that combine antiangiogenic therapies with immune checkpoint inhibitors in colorectal cancer.

Effects of an 8-Week Stress Management Program in Women with Breast Cancer: A Randomized Controlled Trial.

Stress management programs have demonstrated benefits for patients with breast cancer, but their adoption in clinical practice is limited mainly due to the absence of necessary resources. The aim of this study was to investigate the effects of an 8-week stress management program, carried out by one psychologist, in women treated for breast cancer. In this randomized controlled trial, patients were allocated to two groups (control and intervention groups) that received standard care; women in the intervention group also participated in an 8-week stress management program. Intervention included stress- and diet-related psychoeducation, diaphragmatic breathing, guided imagery, progressive muscle relaxation, and cognitive reconstruction. Anthropometric and psychological measurements were carried out in both groups, pre- and post-intervention, using a battery of questionnaires. A total of 53 patients participated in the study, of whom 27 in the intervention group. Analysis revealed statistically significant differences between the two groups post-intervention in body mass index (P = 0.040) and quality of life, including global health status (P = 0.019), emotional functioning (P = 0.024), cognitive functioning (P = 0.041), and diarrhea (P = 0.012). There was a statistically significant effect of the type of surgery (partial or total mastectomy) to role functioning (P = 0.030), with major benefits identified in the subgroup of patients that had undergone mastectomy with immediate reconstruction. This stress management program, carried out by a single health professional, significantly improved some psychosomatic health parameters of patients with breast cancer. Short interventional programs can be successfully implemented with minimal resources to deliver quality care in these women.

Survival Outcomes Following Combination of First-Line Platinum-Based Chemotherapy with S-1 in Patients with Advanced Gastric Cancer.

The efficacy of S-1 combined with a platinum agent in the first-line setting and in patients with advanced gastric adenocarcinoma has been previously demonstrated in randomized clinical trials. However, real-world data regarding S-1 efficacy in European patients remains limited. In the present study, we reviewed the data of a European cohort of patients with advanced gastric cancer treated with first-line therapy consisting of S-1 in combination with a platinum agent. Forty-eight patients (29 with locally advanced/inoperable and 19 with metastatic disease) were treated with S-1 plus oxaliplatin (33 patients) or S1 plus cisplatin (15 patients). The Cox regression analysis, adjusted with propensity score, indicated that the use of cisplatin as compared to oxaliplatin was associated with increased risk of death (HR 9.634, p = 0.000). Four SAEs (serious adverse events) GIII were recorded (1 fatigue, 1 neutropenia, 1 anemia, 1 diarrhea) in 3 patients. S-1 combination with a platinum agent in the first-line setting in European patients with advanced gastric cancer results to similar survival outcomes and toxicity with previously reported data from Asian populations. S-1 combination with oxaliplatin seems to be associated with superior efficacy as compared to cisplatin.

Pericardial Synovial Sarcoma: Case Report, Literature Review and Pooled Analysis.

BACKGROUND: Pericardial synovial sarcomas (PSS) are very rare tumors, with dismal prognosis and limited data. We describe the clinical features and identify prognostic factors of primary PSS. CASE REPORT: We describe the case of a 56-year-old male patient with PSS managed by the multidisciplinary team of thoracic oncology. The therapeutic plan comprised surgery, chemotherapy, stereotactic radiosurgery and targeted therapy, with excellent results. MATERIALS AND METHODS: Data from 37 cases reported in English during the past 20 years were gathered and analyzed. PSS was found to occur at a mean age of 36±17.082 (range=13-67) years. Survival analysis was performed on 20 cases with follow-up of at least 6 months. CONCLUSION: Only complete resection of the tumor seems to be an independent prognostic factor. To our knowledge, this is the first report on the safety and effectivity of pazopanib in PSS and may provide guidance for similar cases in the future.

Paraneoplastic digital ischemia in clear-cell renal-cell carcinoma: Report of a case and review of the literature.

Digital ischemia has been rarely associated, as a paraneoplastic syndrome, with renal cancer. Since it can severely compromise the patients' quality of life, early recognition is important, in order to optimally address it with currently available treatment options, such as tyrosine inhibitors. Digital ischemia may occur in the general population and it can be the result of other non-cancerous diseases; accordingly, a thorough and aggressive work-up is mandatory, together with appropriate therapeutic steps such as tyrosine kinase inhibitors, vasodilators, and antiaggregants. Herein, we report a 78-year-old male patient with a history of clear-cell renal-cell cancer, who presented in the emergency department with critical ischemia in the upper limbs.

Role of stress, age and adjuvant therapy in the cognitive function of patients with breast cancer.

According to data largely obtained from retrospective studies, it has been postulated that chemotherapy exerts an aggravating effect on the cognitive function of patients with breast cancer. Potential individual factors related to the effects of chemotherapy on cognitive function have been indicated, such as age-related cognitive dysfunction and stress. Elderly patients differ from non-elderly patients as regards higher cognitive related comorbidities, such as dementia, as well as regarding lower stress levels, indicating that 'chemobrain' may differentially affect these two age groups. The aim of this review was to discuss the effects of stress and chemotherapy on cognitive dysfunction and identify any potential age-related differences in patients with breast cancer treated with adjuvant chemotherapy. For this purpose, a systematic review of the literature was carried out on the PubMed, Scopus and Web of Science databases. The inclusion criteria were original articles published in peer-reviewed journals, elderly and non-elderly patients with breast cancer, reporting on stress and at least one cognitive parameter pre- and/or post-treatment. Eight studies met the preset criteria and were further analyzed. In total, the data of 1,253 women were included, of whom 800 patients with breast cancer were treated with surgery only, systemic treatment only, or both. Although all the studies included a non-elderly breast cancer patient subpopulation, only two of the studies included patients over 65 years of age. All studies indicated a statistically significant association of stress with various domains of cognitive dysfunction in patients, as shown by either self-completed questionnaires, neuropsychological testing or both. An age over 60 years was linked to fewer cognitive difficulties mediated by lower levels of stress. Thus, the evidence supports the association of stress with cognitive deficits in patients with breast cancer, regardless of the type of cancer-related treatment. Therefore, stress should be appropriately addressed. However, further research is required to investigate the association of stress with cognitive function in elderly patients with breast cancer.

Ten-year survival outcomes of patients with potentially resectable gastric cancer: impact of clinicopathologic and treatment-related risk factors.

BACKGROUND: Despite therapeutic advancements, gastric cancer (GC) remains a leading cause of death worldwide. METHODS: This retrospective cohort study statistically analyzed the clinicopathologic characteristics, treatments and outcomes of patients with potentially resectable GC managed at our institution between 2006 and 2010. The STROBE checklist was applied. RESULTS: Preoperative assessment of 164 GC patients (male: female ratio 1.87, median age 65 years) assigned 132 (80.5%) to total (56; 42.4%) or subtotal (76; 57.6%) gastrectomy. Resection margins were microscopically tumor-free (R0) in 100 (75.8%), microscopically infiltrated (R1) in 25 (18.9%) and macroscopically infiltrated (R2) in 7 (5.3%) patients. Nodal plane dissection was D0 in 34 (25.8%), D1 in 62 (47.0%) and D2 in 36 (27.3%) patients. Early GC was diagnosed in 19 patients (14.4%). Fluorouracil-based chemotherapy was administered in 69.7% and chemoradiation in 18.2% of patients. The 5- and 10-year survival rates of patients with R0 resection were 74% and 65.4%, respectively. The 2-year survival rates for R1 and R2 resection were 28.9% and 0% respectively. The 5- and 10-year survival rates according to nodal plane dissection were 55.6% and 41.4% for D2, and 53.2% and 49.7% for D1, respectively. On multivariate analysis, T4, N3 and R1/R2 remained independent negative prognostic factors for overall survival. Microscopic or macroscopic infiltration of surgical margins was the worst adverse prognostic factor for survival. CONCLUSION: These results are equivalent to those from centers of excellence and indicate the urgent need for improvements in the field, particularly in the development of predictive models to guide personalized therapy.