Andrzej Tukiendorf

Warfarin treatment in patients with atrial fibrillation: Observing outcomes associated with varying levels of INR control

INTRODUCTION We aimed to determine the level of INR control associated with reduced stroke and mortality. MATERIAL AND METHODS The study used a retrospective cohort design using linked inpatient, haematology and mortality data from Cardiff and the Vale of Glamorgan, UK. Anonymised patients admitted with a diagnosis of non-valvular atrial fibrillation (NVAF) were defined as warfarin or non-warfarin treated by number of repeated International Normalised Ratio (INR) tests. Warfarin treated patients (>5 INR tests) categorised as at moderate or high risk of stroke (CHADS2 score > or = 2) with varying levels of INR control were compared to those who did not receive warfarin treatment using Cox proportional hazards models controlling for age, sex and CHADS2 score. Outcome measures were time to stroke and mortality. RESULTS 6,108 patients with NVAF were identified. 2,235 (36.6%) of these patients had five or more INR readings and of these 486 (21.7%) had CHADS2 score > or = 2. There was significant improvement in time to stroke event in those patients with INR control of greater than 70% of time in therapeutic range (2.0 to 3.0) compared with the non-warfarin treatment group. Overall survival was significantly improved for all warfarin treated groups with INR control of greater than 40% of time in range. CONCLUSIONS Patients with INR control of above 70% of time in range had a significantly reduced risk of stroke. Patient suitability for warfarin treatment should be continuously assessed based on their ability to maintain a consistently therapeutic INR.

Radiotherapy of Painful Vertebral Hemangiomas: The Single Center Retrospective Analysis of 137 Cases

PURPOSE An evaluation of dose-response relationship and an attempt to define predictive factors. METHODS AND MATERIALS A total of 137 cases of painful vertebral hemangioma irradiations (101 patients). Fraction dose (fd) varied from 2 to 15 Gy (123 fractionated and 14 radiosurgical treatments), and total dose (TD) from 8 to 30 Gy (111 cases irradiated with fd of 2 GY to TD of 24 Gy). We evaluated pain relief, changes in analgesic requirements, and reossification. RESULTS Means of pain relief 1, 6, 12, and 18 months after radiotherapy (defined as a decrease of primary pain level expressed in percent) were 60.5%, 65.4%, 68.3%, and 78.4%, respectively. Proportion of patients with no need for analgesics and patients using tramadol were 39%, 40%, 44%, 57%, and 20%, 17%, 22%, and 11% in these times. The proportion of patients experiencing complete/partial pain relief changed from 36/48% 1 month, to 64/22% 1.5 years after radiotherapy. No impact of radiotherapy on reossification was found. The positive impact of fd and TD increase for analgesics uptake reduction and pain relief was found. An increase of the fd by 1 Gy results in 27% chance of analgesics uptake reduction and 3.8% reduction of pain, whereas 14% analgesics uptake reduction and 2.2% of pain reduction in case of the TD. The predictive factors improving results were found: female gender, older age, better performance states (the chance of the lower analgesic treatment decreases over 2.5 times in comparison to the higher Zubrod degree), bigger Hb concentration, shorter symptoms duration and lower analgesics uptake before radiotherapy. CONCLUSIONS The obtained data support the efficacy of radiotherapy in improving pain secondary to vertebral hemangioma, with the degree of pain amelioration being related to increasing fd and TD. The positive predictive factors were defined: female gender, older age, better performance status, increased Hb concentration, shorter symptoms duration, and lower analgesics uptake before radiotherapy.

Prognostic value and clinical correlations of 18-fluorodeoxyglucose metabolism quantifiers in gastric cancer.

AIM To investigate the correlations of pre-treatment positron emission tomography-computer tomography (PET-CT) metabolic quantifiers with clinical data of unstratified gastric cancer (GC) patients. METHODS Forty PET-CT scans utilising 18-fluorodeoxyglucose in patients who received no prior treatment were analysed. Analysis involved measurements of maximum and mean standardised uptake volumes (SUV), coefficient of variation (COV), metabolic tumour volumes and total lesion glycolysis of different thresholds above which the tumor volumes were identified. The threshold values were: SUV absolute value of 2.5, 30% of SUVmax, 40% of SUVmax, and liver uptake-based (marked 2.5, 30, 40 and liv, respectively). Clinical variables such as age, sex, clinical stage, performance index, weight loss, tumor histological type and grade, and CEA and CA19.9 levels were included in survival analysis. Patients received various treatment modalities appropriate to their disease stage and the outcome was defined by time to metastasis (TTM) and overall survival (OS). Clinical and metabolic parameters were evaluated by analysis of variance, receiver operating characteristics, univariate Kaplan-Meier, and multivariate Cox models. P < 0.05 was considered statistically significant. RESULTS Significant differences were observed between initially disseminated and non-disseminated patients in mean SUV (6.05 vs 4.13, P = 0.008), TLG2.5 (802 cm(3) vs 226 cm(3); P = 0.031), and TLG30 (436 cm(3) vs 247 cm(3), P = 0.018). Higher COV was associated with poor tumour differentiation (0.47 for G3 vs 0.28 for G1 and G2; P = 0.03). MTV2.5 was positively correlated to patient weight loss (< 5%, 5%-10% and > 10%: 40.4 cm(3) vs 123.6 cm(3) vs 181.8 cm(3), respectively, P = 0.003). In multivariate Cox analysis, TLG30 was prognostic for OS (HR = 1.001, 95%CI: 1.0009-1.0017; P = 0.047) for the whole group of patients. In the same model yet only including patients without initial disease dissemination TLG30 (HR = 1.009, 95%CI: 1.003-1.014; P = 0.004) and MTV2.5 (HR = 1.02, 95%CI: 1.002-1.036; P = 0.025) were prognostic for OS; for TTM TLG30 was the only significant prognostic variable (HR = 1.006, 95%CI: 1.001-1.012; P = 0.02). CONCLUSION PET-CT in GC may represent a valuable diagnostic and prognostic tool that requires further evaluation in highly standardised environments such as randomised clinical trials.

The results of treatment of prostate cancer bone metastases after CyberKnife radiosurgery.

BACKGROUND Bony metastases from prostate cancer are often associated with severe pain. Standard palliative radiotherapy does not provide full analgesic effect in most patients. CyberKnife radiosurgery allows for the precise treatment of small lesions, such as prostate cancer metastases, located in bones or near critical organs. object. Pilot study of the effectiveness of CyberKnife radiosurgery in the treatment of patients with bony oligometastases from prostate cancer. MATERIAL AND METHODS CyberKnife radiosurgery was used in 48 cases of prostate cancer bone metastases (32 patients). Patients were treated with fraction doses of 6 to 15 Gy, delivered in 1-3 fractions, to a total dose of 6 to 45 Gy. PSA before the treatment varied from 0.01 to 387 ng/ml (mean 28.67; median 3.12). Lesions were located in the spine (31), pelvis (8), ribs (5) and cranium (4). Statistical analysis was performed for 12-months of follow-up using hierarchical linear modeling. RESULTS PSA concentration decreased to 0.0-22.4 ng/ml (mean 5.8; median 4.4) during the first month of follow-up. Linear correlations were found between total dose delivered and PSA concentration and pain relief. At the end of the follow-up period, an analgesic effect was observed, with complete pain relief in 28 patients and partial in 16. CONCLUSION CyberKnife radiosurgery may be an effective method for the local treatment of patients with prostate cancer bone oligometastases, leading to a reduction of pain, reduced PSA concentration and a high rate of locoregional control.

Radiation-induced injury of the exocrine pancreas after chemoradiotherapy for gastric cancer

BACKGROUND AND PURPOSE The pancreas is located almost entirely within the treatment area for radiotherapy of gastric cancer. The aim of this study was to analyze radiation-induced injury of the exocrine pancreas. MATERIAL AND METHODS The study included 127 gastric cancer patients, who underwent preoperative or postoperative chemoradiotherapy. A total dose of 45 Gy was given in 25 fractions. Concurrent chemotherapy was 5-fluorouracil-based. Lipase and α-amylase were assayed before, during and after treatment. RESULTS Lipase and α-amylase deficiencies were found in 48.2% and 19.7% of patients, respectively. In the univariant analysis, age and pretreatment α-amylase and lipase activities influenced on risk of injury of the exocrine pancreas (p<0.05). Younger patients (<65 years) had a lower risk of hypoamylasemia than older patients. The probability of insufficiency was lower than 0.2 for patients with pretreatment α-amylase and lipase activities above 50 U/L and 55 U/L, respectively. The multivariate analyses of the time to hypolipasemia showed that only pretreatment lipase activity was significant. CONCLUSIONS Gastric cancer patients have an increased risk of exocrine pancreatic insufficiency after chemoradiotherapy. Thus, the pancreas should be regarded as an OAR. Measuring lipase activity should be the standard for assessing radiation-induced pancreatic injury.

An evaluation of half-body irradiation in the treatment of widespread, painful metastatic bone disease.

Aims Evaluation of analgesic uptake, pain intensity, and quality-of-life changes after half-body irradiation of patients with bone metastases. Material and Methods Ninety-five patients (97 irradiations) were treated with single half-body irradiation fraction (3–8 Gy). Thirty-three patients had upper-half-body irradiation, 55 lower-half-body irradiation and 9 middle-half-body irradiation. The patients were examined on the day of irradiation, 2 and 4 weeks later, and then once a month. The intake of analgesics, pain level (from 0 to 10), and the quality of life (EORTC QLQ-C30) were evaluated. The fluctuations of pain levels and the particular scaling values of QLQ-C30 during a one-year period were analyzed (Kendall t correlation). Results Over the course of 5 months, the incidence of patients using strong opioids decreased from 43.8% to 33.3%, and the incidence of patients who did not need to resort to analgesics increased from 6.7% to 25%. The mean pain level decreased from 6.1 points (half-body irradiation) to 3.1 points 2 weeks later. An inverse correlation between pain level readings and time was statistically significant. An increase was observed in the values of the five functional scales as reflected on the EORTC QLQ-C30 questionnaire (four of which correlated significantly with the observation time). A similar situation prevailed with respect to global health status. A decrease was observed in most of the values on the symptoms scales; 6 saw a significant decrease, in correlation with the follow-up. Correlations were also found between pain intensity and functionality, and between symptoms scales readings and global health status. Conclusions Half-body irradiation of cancer patients suffering from painful multiple bone dissemination is an effective and simple treatment modality that affords significant quality-of-life improvement and pain relief, thus allowing for a reduction in the use of strong analgesics.

Thyroid Function after Postoperative Radiation Therapy in Patients with Breast Cancer

Objective: The aim of this study was to assess thyroid function in breast cancer patients exposed to therapeutic external beam radiation. The focus was on possible progressive changes and any relationships between the incidence of primary hypothyroidism, the time required to become hypothyroid, and factors such as chemotherapy, hormonotherapy and immunotherapy. Materials and Methods: Seventy females undergoing 3D conformal and IMRT radiation therapy for breast cancers were enrolled in a non-randomized prospective study. The patients was divided into two groups: those after mastectomy or breast conserving surgery (BCS) were irradiated to a scar of the chest wall/breast and the ipsilateral supraclavicular and the axillary areas (supraclavicular radiotherapy group - SC-RT group – 32 patients) and the control group receiving adjuvant chest wall/breast RT only (BCT group - 38 patients). The total doses were 50.0 to 70 Gy in 5 to 7 weeks. The median follow-up term was 24 months (range, 1–40 months). Thyroid function was evaluated by measuring thyroid stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3) levels. The minimum, maximum and mean thyroid gland doses for 20 Gy (V20) were calculated for all patients. Results: Statistically significant results were obtained for the SC-RT group. Two yearsa fter the end of RT the chance of an event was increased in 6% of the population (p=0.009) in the SC-RT group. In the BCT group no significance was noted. No statistically significant differences were found for V20, chemio-, immunotherapy and hormonotherapy or Ki67 values (p=0.12). No significant results were obtained for development of hypothyroidism and clinical factors (age, thyroid volume, treatment modalities). Conclusion: Radiotherapy is associated with a higher incidence of thyroid toxicity in breast cancer patients. Routine thyroid function monitoring should be recommended in such cases.

Melanoma awareness and prevalence of dermoscopic examination among internet users: a cross-sectional survey

Introduction Melanoma presents the greater threat to health the later the disease is detected and treated, although treatment results can be improved by the widespread use of dermoscopy. However, scarce data are available concerning the awareness of dermoscopy and the frequency of its performance in the non-patient population. Aim To assess the awareness of melanoma detection by dermoscopic examination among the audience of a scientific website. Material and methods Respondents were invited to participate in an online cross-sectional survey. They were asked to complete an online questionnaire designed by the authors. The preliminary analysis of 5,154 collected forms and the exclusion of incomplete forms yielded 4,919 fully completed questionnaires; the resulting database was analyzed statistically using logistic regression with the R software program (95% CI). Results Less than two-fifths (39.2%) of respondents reported ever having sought the advice of a medical professional (dermatologist or other specialist), and 25.4% of the respondents had undergone dermoscopy at least once in their life. Furthermore, approximately one-tenth of respondents (10.7%) were not aware of this detection tool. The study respondents gained knowledge about dermoscopic examination from television and magazines. The performance of dermoscopy was more increasingly associated with inhabitants of larger locales, the use of higher-SPF sunscreens, and greater awareness of the relationship between the risk of melanoma and sunburn. Conclusions Awareness of melanoma and sun care varied within the analyzed population. A subset of individuals at high risk of melanoma was identified. This group included those who engaged in risky sun exposure behaviors and who had never been examined by dermoscopy.

Influence of interfraction motion on margins for radiotherapy of gastric cancer

OBJECTIVE The aim of this study was to evaluate interfraction uncertainties using kilovoltage (kV) radiographs for patients with gastric cancer during chemoradiotherapy and to calculate the planning target volume (PTV) margins. METHODS 1284 measurements of set-up errors were analysed for treated patients. The measurements of craniocaudal (axis y), laterolateral (axis x) and anteroposterior (axis z) shifts in kV radiographs were performed. Interfraction clinical target volume (CTV)-PTV margins for all directions were calculated using the van Herk formula. RESULTS The main shift for the y-axis was 0.7 mm [standard deviation (SD), ±7.6], for the x-axis was 0.4 mm (SD, ±3.7) and for the z-axis was 0.6 mm (SD, ±3.5). The CTV-PTV margin in the x, y and z directions was 8.3, 15.5 and 8.0 mm, respectively. We observed that the interfractional motion for patients increased approximately 0.0034 cm along the x direction with each subsequent fraction, whereas a 0.0058-cm reduction in length along the y-axis was observed. No time effects for the z direction were noticed. CONCLUSION According to our experience, a PTV margin of 9 mm along the x-axis, 16 mm along the y-axis and 8 mm along the z direction should be considered in the absence of image-guided radiotherapy. ADVANCES IN KNOWLEDGE This knowledge concerning PTV set-up margins could be particularly useful for centres without a kV on-board imaging system.

Analysis of haemostasis biomarkers in patients with advanced stage lung cancer during hypofractionated radiotherapy treatment

Objective To investigate the relationship between changes in inflammatory and coagulatory biomarkers before and after short palliative radiotherapy in patients with advanced stage lung cancer. Methods This prospective observational single-centre study enrolled patients with histologically- or cytologically-confirmed lung cancer who were eligible for palliative radiotherapy. Inflammatory and coagulatory biomarkers including complete blood count, D-dimer and fibrinogen levels were evaluated before and after short hypofractionated radiotherapy. Results Seventy-two patients with advanced stage lung carcinoma were enrolled in this study. Metastases were associated with an increase in white blood cells, neutrophils and mean platelet volume. Increased volume of the primary tumour had a borderline level of correlation with white blood cell and neutrophil counts. After radiotherapy, white blood cells, neutrophils, haemoglobin and lymphocyte counts were decreased. After radiotherapy, the change in fibrinogen and mean platelet volume were borderline significant. Conclusion The levels of inflammatory and coagulatory biomarkers can be used to monitor treatment.