Assessment of clinical utility and predictive potential of pre-chemotherapy soluble urokinase plasminogen activator receptor: Observational single center study

Alteration of urokinase plasminogen activator receptor (uPAR) in neoplasms is a prerequisite for invasiveness and metastatic ability. In the present study, we aimed to evaluate the relationship of pre-chemotherapy soluble uPAR (suPAR) with the odds for metastasis, lack of disease control, and its predictive ability for progression-free survival (PFS). Baseline plasma suPAR levels were measured by ELISA in 89 patients with various cancers prior to initiation of systemic treatment. Patients were followed prospectively until metastatic progression or death. TCGA Pan-Cancer dataset was mined for available RNAseq expression data of the PLAUR gene in patients with breast, colon, and lung cancer, and therelevant genomic and clinical data were extracted for further analysis. Pre-chemotherapy suPAR levels were significantly associated with white blood cell counts and fibrinogen and were significantly elevated both in patients with metastatic disease and in patients with progression. Increasing suPAR was significantly associated with odds for progression in the prespecified multivariate analysis (odds ratio 2.47, 95% confidence interval 1.3 – 5.11). In univariate Cox regression, suPAR was predictive of shortened progression-free survival (PFS) (hazard ratio 1.065, 95% confidence interval 1.002 – 1.13; p = 0.041). There was a trend towards shortened PFS in patients with higher baseline suPAR levels (cutoff 8.1 ng/mL). In the TCGA lung cancer cohort, PLAUR mRNA expression was significantly associated with shortened PFS in both univariate and multivariate analyses. High PLAUR gene expression conferred significant survival disadvantage only in patients with colon and lung cancer. SuPAR may bear predictive potential for adverse outcomes in cancer, but its utility as a biomarker seems to be more pronounced in cancers with associated inflammatory state

Liquid Biopsy – Possibilities for Monitoring the Therapeutic Response in Non-Small Cell Lung Cancer

Lung cancer is the leading cause of death from malignancy worldwide. Its heterogeneity and tumour biology make treatment considerably more difficult. The introduction of target molecules heralded the beginning of the personalized medicine which tailors medical treatments to the molecular and genetic profile of a patient. Liquid biopsy is an innovative, non-invasive method which is used both for diagnostic purposes and for therapeutic monitoring. Liquid biopsy has the potential to help manage non-small cell lung cancer throughout all stages of this cancer: screening, detection of minimal residual disease to guide adjuvant treatment, early detection of relapse, systemic treatment initiation, monitoring of response to targeted or immune therapy, and the emergence of resistance to applied treatment. At present, the study of circulating tumour DNA is used in clinical practice, but circulating tumour cells, miRNAs, exosomes, and platelets formed in the tumour also show promising results

The role of 18F-FDG PET/CT and single isotope 99mTc-tetrofosmin scintigraphy combined with SPECT in diagnosis of multiple endocrine neoplasia type 1 syndrome

We present a case of a 47-year-old woman with type 1 multiple endocrine neoplasia, primary hyperparathyroidism, insulinoma, and nonfunctioning pituitary adenoma. In July 2017, the patient was referred to the Department of Nuclear Medicine of St George University Hospital in Plovdiv for a PET/CT scan because of persistent hypoglycemic episodes and high serum insulin levels. A whole-body PET/CT examination was performed 65 min after intravenous application of 188 MBq 18F-FDG on a hybrid PET/CT scanner (Biograph mCT 64, Siemens). We detected a low metabolically active lesion 10 mm in diameter (SUVmax - 2.00), located below the left thyroid lobe suspicious for parathyroid adenoma. In the remaining scanned areas there were no PET/CT data for other areas with increased glucose metabolism with malignant characteristics that could be associated with the underlying disease. For further characterisation of the lesion, two months later we performed a single-isotope dual-phase 99mTc-tetrofosmin scintigraphy combined with an early SPECT technique on a SPECT gamma camera (SYMBIA E DUAL). The examination visualized a zone of hyperfixation located dorsally to the caudal portion of the left thyroid lobe associated with a hyperfunctioning parathyroid adenoma. This case allowed us to compare two nuclear medicine modalities with different equipment and radiopharmaceuticals – PET/CT with 18F-FDG and single-isotope dual-phase 99mTc-tetrofosmin scintigraphy combined with an early SPECT in one and the same patient. Different factors can explain the acquired different diagnostic information

The role of 18F-FDG PET/CT and single isotope 99mTc-tetrofosmin scintigraphy combined with SPECT in diagnosis of multiple endocrine neoplasia type 1 syndrome

We present a case of a 47-year-old woman with type 1 multiple endocrine neoplasia, primary hyperparathyroidism, insulinoma, and nonfunctioning pituitary adenoma. In July 2017, the patient was referred to the Department of Nuclear Medicine of St George University Hospital in Plovdiv for a PET/CT scan because of persistent hypoglycemic episodes and high serum insulin levels. A whole-body PET/CT examination was performed 65 min after intravenous application of 188 MBq 18F-FDG on a hybrid PET/CT scanner (Biograph mCT 64, Siemens). We detected a low metabolically active lesion 10 mm in diameter (SUVmax - 2.00), located below the left thyroid lobe suspicious for parathyroid adenoma. In the remaining scanned areas there were no PET/CT data for other areas with increased glucose metabolism with malignant characteristics that could be associated with the underlying disease. For further characterisation of the lesion, two months later we performed a single-isotope dual-phase 99mTc-tetrofosmin scintigraphy combined with an early SPECT technique on a SPECT gamma camera (SYMBIA E DUAL). The examination visualized a zone of hyperfixation located dorsally to the caudal portion of the left thyroid lobe associated with a hyperfunctioning parathyroid adenoma. This case allowed us to compare two nuclear medicine modalities with different equipment and radiopharmaceuticals – PET/CT with 18F-FDG and single-isotope dual-phase 99mTc-tetrofosmin scintigraphy combined with an early SPECT in one and the same patient. Different factors can explain the acquired different diagnostic information

A single-center study of bone mineral density in adult patients with severe hemophilia A in correlation with markers of bone metabolism

Introduction: Osteopenia and osteoporosis are well-known hemophilia A comorbidities. The pathogenesis of bone turnover alteration resulting in reduced bone mass includes impaired osteoblastic differentiation and disinhibition of RANKL-induced osteoclastogenesis as a result of a low FVIII level. Aim: To evaluate the bone mineral density (BMD) in adult patients with severe hemophilia A and assess a possible correlation with the bone remodeling biomarkers OPG/RANKL, CTX-1, osteocalcin, and Vit D. Materials and methods: 28 male subjects with severe hemophilia A and 33 age-matched controls were recruited. The biomarkers were tested with the ELISA assay and BMD with DEXA of the lumbar spine (LS) and total hip (TH). Results: The patients had lower LS-BMD (−0.955±0.145 vs. 1.118±0.079, p=0.05) and TH-BMD (−0.840±0.147 vs. 0.951±0.075, p=0.05) than those of the controls. The TH T-scores were −1.41±0.91 vs. 0.4±0.49 (p=0.05) and the LS T-scores −1.16±1.046 vs. 0.14±0.72 (p=0.05). 66.6% of patients under 50 years had osteopenia and 8.3% had osteoporosis. Fifty percent of those over 50 years old had osteopenia and 20% had osteoporosis. We found significantly higher OPG levels (123.69±107.05 vs. 41.98±18.95, p=0.05) than that in controls and lower sRANKL levels (23.49±29.39 vs. 131.32±201.27, p=0.05) and sRANKL/OPG ratio (0.27±0.35 vs. 5.28±10.01, p=0.05) than those in controls. A positive correlation was found between sRANKL and the BMD T-score of lumbar spine (p=0.001) in the patient group. Conclusions: sRANKL level and ratio can be used as predictors of low BMD

Liquid biopsy: an innovative and reliable method for detecting not only somatic, but also germline mutations in patients with colorectal and non-small cell lung carcinoma

AbstractLiquid biopsy is a non-invasive method of detecting cancer-related mutations from circulating cell-free DNA (cfDNA) and has emerged as a promising alternative to traditional tissue biopsies. However, its utility has so far been limited to the detection of somatic mutations in cancer cells. Our study examined germline mutations that are associated with pharmacogenetics in 19 patients diagnosed with colorectal cancer and 12 patients with non-small cell lung carcinoma, utilizing the highly advanced and non-invasive technique of liquid biopsy, followed by subsequent next-generation sequencing for comprehensive analysis. Despite the relatively modest sample size of patients under consideration, our results indicated a noteworthy correlation between the presence of adverse effects and the identified germline mutations. We have identified the following mutations with significant implications for pharmacogenetics: MTHFR c.1286A > C, MTHFR c.665C > T, DPYD c.2194G > A, DPYD c.85C > T, XPC c.2815C > A, UMPS c.638G > C, SLC22A2 c.808T > G, EGFR c.1562G > A, ABCB1 2677 T > G, GSTP1 c.313A > G, ERCC2 c.2251A > C, and SLC19A1 c.80A > G. In addition, we observed various adverse drug reactions in our patient cohort, encompassing myelosuppression, hepatotoxicity, neurotoxicity and gastrointestinal toxicity. Liquid biopsy has the potential to revolutionize cancer diagnosis and treatment by detecting both somatic and germline mutations. The preliminary results of studies on germline mutations are promising, but further research is needed to address the remaining challenges and to establish the utility of liquid biopsy as a reliable diagnostic tool for germline mutations

Clinical characteristics, disease evolution and survival in patients with chronic myeloid leukemia, BCR-ABL1 (+) and T315I mutation.

Introduction: The T315I mutation in patients with chronic myeloid leukemia (CML) has been associated with therapeutic resistance and an unfavourable prognosis.Aim: To study the frequency of T315I mutation in patients with CML, BCR-ABL (+), their clinical characteristics, disease evolution, and median survival.Patients and methods: We studied 75 patients with CML and BCR-ABL1 (+). T315I mutation was detected by digital droplet PCR and BCR-ABL1 was analyzed by RT-PCR. A comparative analysis was performed by sex, age, disease phase, risk group, treatment, molecular response (MR), and median survival in T315I (+) and T315I (−) patients.Results: T315I mutation was detected in 11 patients (14.7%). No significant difference was found in the phase, risk group, and first-line therapy. A significantly higher proportion of T315I (+) did not achieve MR >3.5 log: 8 (72.7%) vs. 22 (34.4%) (p=0.023). The lowest mean BCR-ABL1 levels were significantly higher in the CML T315I (+) group compared to the CML T315I (−) group: 12.1±6.0 vs. 3.77±1.28 (p=0.009). The median survival of T315I (+) patients was significantly shorter: 73 months vs. 175 months (p<0.0001, CI 95%).Conclusions: Our data confirm the world experience on the frequency of T315I mutation, including the unfavourable evolution, resistance to TKI treatment and short survival. ddPCR is a highly sensitive method for early detection of genetic mutations which gives the chance for effective treatment

Analysis of the pharmacotherapeutic effectiveness of the tyrosine kinase inhibitors therapy in patients with Chronic Myeloid Leukemia in a single hematology center in Plovdiv, Bulgaria

Aim. The aim of this study is to evaluate treatment retrospectively, response to the therapy and outcomes in patients with chronic myeloid leukemia (CML) and to what extent the European recommendations of LeukemiaNET (ELN) are followed at the Hematology Clinic, University Hospital “St. Georgi”, MU Plovdiv. Methods. All patients with Ph+, BCR-ABL1+ CML who were treated and observed between 01.01.2018 and 12.31.2022 at the clinic were included in the study and were analyzed retrospectively. Results. One hundred and eighty-eight patients with a mean age of 61.26 (21–91) years were analyzed. 151 (80.3%) were in chronic phase (CP), 27 (14.4%) in accelerating one and 10 (5.3%) in blast crisis. The actual overall survival rate was 79.26%, while for CP it is very high – 86.75%, and the mortality rate is 20.74%. All patients received some form of tyrosine kinase inhibitors therapy (TKIs-therapy). The first line TKI was imatinib in 120 patients (64%), and 68 (36%) received a second-generation TKI. Treatment response was monitored with TKIs by RT-qPCR. Conclusion. CML patients treated in the hematology clinic receive standard care in accordance with ELN and BMSH recommendations. Overall survival (OS) in routine care is comparable to published data from international studies. Molecular monitoring provides a good basis for disease control in CP. There are unmet needs in the treatment of patients in advanced stages

Autoimmune Phenomena in Patients with Solid Tumors

Introduction: Autoimmune disorders have been documented in solid tumors and malignant hematological disorders. They are very common and well studied in lymphomas which are associated with immune imbalance. They are less common in solid tumors and are categorized as paraneoplastic syndromes with unclear pathogenesis