Association of BAFF and BAFF-R polymorphisms with sarcoidosis in a Greek patient cohort.

Introduction: Sarcoidosis is a disease that results from a combination of environmental and genetic factors. Its genetic basis however, is yet to be clarified. The purpose of this study is to determine whether single nucleotide polymorphisms (SNPs) of the B-cell activating factor (BAFF) and its receptor (BAFF-R) are associated with sarcoidosis. Material and methods: Blood samples from one hundred and seventy-three sarcoidosis patients and one hundred and sixty-four controls were collected. All samples were genotyped for BAFF rs2893321, rs1041569 and rs9514828, and for BAFF-R rs61756766. Results: Out of the three BAFF polymorphisms, none genotype had any significant association with sarcoidosis, although the T allele in rs1041569 and rs9514828 was overrepresented in sarcoidosis patients. A marginally significant association with sarcoidosis was found in the case of the CT genotype and T allele of BAFF-R rs61756766. Haplotype analysis of the BAFF polymorphisms was also performed, revealing an overrepresentation of the ATT, GTA and GTT haplotypes in the group of patients with cardiac involvement. Conclusions: Taken together, the results of this study suggest a possible relationship between BAFF SNPs, rs1041569 and rs9514828, and BAFF-R SNP rs61756766 with sarcoidosis susceptibility and their potential as biomarkers for the disease.

Trifluridine/Tipiracil in Metastatic Colorectal Cancer: A UK Multicenter Real-world Analysis on Efficacy, Safety, Predictive and Prognostic Factors.

BACKGROUND: The orally administered combination trifluridine/tipiracil has been approved as third line treatment in mCRC, demonstrating survival benefit and acceptable toxicity profile in the phase III RECOURSE study. PATIENT AND METHODS: We performed a multicenter retrospective real-world analysis of patients with mCRC receiving trifluridine/tipiracil between 2016 and 2019 in eight cancer centers across the United Kingdom. RESULTS: A total of 236 patients were included with median age of 69 years. All patients had received at least 2 lines of fluoropyrimidine-based chemotherapy doublet with oxaliplatin or irinotecan. About 10% of patients had ECOG ≥ 2. Median duration of trifluridine/tipiracil treatment was 3 months with an ORR of 2.1% and disease control rate of 21.6%. Median OS was 7.6 and median PFS 3.3 months. A dose reduction was required in 27% of patients, while 7.6% discontinued treatment due to toxicity. The most common grade 3 toxicities were neutropenia (34%), fatigue (10%), anemia (9%) and febrile neutropenia (5%). Baseline NLR <5 and CEA <200 had favorable prognostic (HR: 0.52 and 0.39, P≤ .001) and predictive value (OR: 4.1 and 6.7, P< .05). Development of grade 3 neutropenia predicted treatment response (OR: 0.32, P< .001). Following treatment with trifluridine/tipiracil 41% were referred for phase I trial or rechallenged with chemotherapy. CONCLUSION: Trifluridine/tipiracil is well tolerated in refractory mCRC patients with comparable efficacy and toxicity profile to that of the phase III RECOURSE. Pretreatment NLR and CEA could serve as potential markers for patient selection, while treatment-induced grade 3 neutropenia predicted response. Prospective validation is needed.

Adjuvant radiotherapy in oesophageal cancer with positive circumferential resection margins-recurrence and survival outcomes.

BACKGROUND: The role of adjuvant radiotherapy in patients with microscopically positive circumferential resection margins (CRM), R1 specimen, in oesophageal resections for cancer with curative intent remains unclear. However, R1 specimens are associated with poorer survival outcomes. The aim was to assess the benefit of adjuvant radiotherapy on recurrence and survival in these patients. METHODS: Patients were identified in a single centre between July 2000 and December 2016. Patient demographics, tumour characteristics and survival outcomes were assimilated and compared between those who received adjuvant therapy and those who did not. RESULTS: Sixty-eight patients were included in the study; 57 (83.8%) male and 11 (16.2%) female with a median age of 67 years. The adjuvant radiotherapy regimen used was 40-50 Gy in 25 fractions over 5 weeks. Median follow-up was 13 months (interquartile range, 6-27 months). Twenty-five (36.8%) patients received adjuvant radiotherapy. There was no statistically significant correlation between administration of adjuvant radiotherapy and local recurrence (P=0.148), distant metastases (P=0.605), overall disease progression (P=0.561), progression-free survival (P=0.663) and overall survival (P=0.538). CONCLUSIONS: This study detects no benefit to oncological outcomes with the use of adjuvant radiotherapy in patients with microscopically positive CRM. Larger randomized studies are needed to further confirm these results.

Cardiac complications after radical radiotherapy.

Improvements in cancer therapy have led to increasing numbers of cancer survivors, and the long-term complications of these treatments are now becoming apparent. This article presents the current knowledge of adverse cardiovascular effects of radiotherapy to the chest. Medline literature searches relating to the cardiac complications of radiotherapy and subsequent prognosis were conducted. Potential adverse effects of mediastinal irradiation are numerous and can include coronary artery disease, pericarditis, cardiomyopathy, and valvular disease. Damage seems to be related to radiation dose, volume of irradiated heart, age at exposure, technique of chest irradiation, and patient-specific factors. The advent of technology and the newer sophisticated techniques in treatment planning and delivery are expected to decrease the incidence of cardiovascular diseases after radiation of the mediastinal structures. In any case, patients subjected to irradiation of the mediastinal structures require close multidisciplinary clinical monitoring.

Ionizing radiation affects epidermal growth factor receptor signalling and metalloproteinase secretion in glioma cells.

BACKGROUND: The effect of different doses of X(-)rays on apoptosis, proliferation, epidermal growth factor receptor (EGFR) and matrix metalloproteinase (MMP-2) expression was investigated in a human glioblastoma cell line. MATERIALS AND METHODS: The cell line LN18 was irradiated at room temperature with doses ranging from 0.5 to 15 Gy using 6 MV X(-)rays. Apoptosis was assessed using the annexin V binding assay, proliferation by the methyl tetrazolium (MTT) assay and MMP-2 secretion with zymography. The levels of phosphorylated (pEGFR) were estimated using a commercially available ELISA kit. RESULTS: Cell proliferation decreased in a dose-dependent manner, while apoptosis was increased after radiation. Doses below 2 Gy did not affect proliferation or apoptosis. MMP-2 levels were increased 48 h after radiation in a dose-dependent manner. In contrast, EGFR signaling was significantly activated 15 min after radiation in a dose-dependent manner. CONCLUSION: Ionizing radiation activates EGFR signalling and enhances MMP-2 secretion, suggesting that the molecular pathways involved may contribute to the invasiveness and malignant behaviour of glioma cells and help to explain the response of gliomas to ionizing radiation.