Evaluation of helical tomotherapy in the treatment of high-grade gliomas near critical structures.

BACKGROUND: Our purpose was to investigate the role of helical tomotherapy using a simultaneous integrated boost technique for the treatment of high-grade gliomas near intracranial critical structures. METHODS AND MATERIALS: Of 27 patients treated with helical tomotherapy, 11 were eligible. Only patients whose tumors were within 0.5 cm of the optic chiasm, the optic nerve or the brainstem were included. The therapeutic approach was a simultaneous integrated boost, prescribing 66 and 60 Gy to the PTV1 and PTV2, respectively, in 30 fractions. All patients received concomitant temozolomide at a dose of 75 mg/m2 daily during radiation therapy. RESULTS: Of the 11 patients considered, 3 patients (27%) died after 4 months from the completion of the combined treatment. Three patients (27%) presented local progression, and the median time to disease progression was 6 months (range, 1-12). Five patients (45%), at the time of this evaluation, did not have signs or symptoms of recurrence or progression of the disease. Acute toxicity, evaluated during radiochemotherapy, was minimal, with all patients experiencing RTOG grade 0 and grade 1 toxicity. CONCLUSIONS: . Helical tomotherapy proved to be an effective and safe treatment modality, with an improvement of accuracy in delivery of high-dose radiotherapy despite the presence of nearby critical structures.

Early clinical experience with volumetric modulated arc therapy in head and neck cancer patients.

BACKGROUND: To report about early clinical experience in radiation treatment of head and neck cancer of different sites and histology by volumetric modulated arcs with the RapidArc technology. METHODS: During 2009, 45 patients were treated at Istituto Clinico Humanitas with RapidArc (28 males and 17 females, median age 65 years). Of these, 78% received concomitant chemotherapy. Thirty-six patients were treated as exclusive curative intent (group A), three as postoperative curative intent (group B) and six with sinonasal tumours (group C). Dose prescription was at Planning Target Volumes (PTV) with simultaneous integrated boost: 54.45 Gy and 69.96 Gy in 33 fractions (group A); 54.45 Gy and 66 Gy in 33 fractions (group B) and 55 Gy in 25 fractions (group C). RESULTS: Concerning planning optimization strategies and constraints, as per PTV coverage, for all groups, D98% > 95% and V95% > 99%. As regards organs at risk, all planning objectives were respected, and this was correlated with observed acute toxicity rates. Only 28% of patients experienced G3 mucositis, 14% G3 dermitis 44% had G2 dysphagia. Nobody required feeding tubes to be placed during treatment. Acute toxicity is also related to chemotherapy. Two patients interrupted the course of radiotherapy because of a quick worsening of general clinical condition. CONCLUSIONS: These preliminary results stated that volumetric modulated arc therapy in locally advanced head and neck cancers is feasible and effective, with acceptable toxicities.

Quality assurance program for whole blood prothrombin time-international normalized ratio point-of-care monitors used for patient self-testing to control oral anticoagulation.

Whole blood coagulation monitors are increasingly used for patient self-testing to control oral anticoagulation, but there are no comprehensive quality assurance (QA) programs to check their performance. We report on the experience with one of such programs applied in a field study where patients on prothrombin time (PT)-international normalized ratio (INR) self-testing were asked to bring their monitors to the anticoagulation clinic for checking. PT-INR testing was performed three times over 3 months with 14 patient's monitors and test strips on three recalcified QA plasmas by an experienced laboratory operator. Each patient was also asked to perform PT-INR self-testing (his/her own capillary blood) which was then compared to the laboratory PT-INR (plasma). Overall, the comparison between the observed and the consensus PT-INR on QA plasmas was acceptable with the majority of measurements lying within +/-15% or 20% of the consensus values. The comparison between the PT-INR self-testing and the laboratory method was also acceptable: overall, there was no statistical significant difference between the mean PT-INR values and the majority of paired measurements were less than 15% or 20% apart. In conclusion, our results show that the proposed QA scheme is feasible and may be implemented on a larger scale. Monitors should be recalled periodically to the clinic where they have been prescribed to the patient. During each visit, the clinic may check the monitors and patient self-testing performance as described. Such comprehensive QA system would make monitoring of oral anticoagulant treatment by self-testing safer and more effective.

Standardization of the endogenous thrombin potential measurement: how to minimize the effect of residual platelets in stored plasma.

Platelet contamination in stored plasma may affect coagulation assays, including the endogenous thrombin potential (ETP), which has been proposed for the investigation of hyper- and hypo-coagulability. The current recommendation of filtering plasma before freezing cannot be always met. This study provides evidence that filtering frozen plasma after thawing, prior to testing, may help to eliminate the unwanted effect of residual platelets on the ETP. This may have important implications in future studies, as the ETP could be determined with plasma that have been collected without precautions relating to platelet contamination, as is the case for plasmas collected in epidemiological studies.

Thrombin generation assessed as endogenous thrombin potential in patients with hyper- or hypo-coagulability.

BACKGROUND AND OBJECTIVES: The endogenous thrombin potential (ETP) represents the balance between pro- and anti-coagulant forces operating in plasma and can be used to investigate hyper- and hypo-coagulability. As a preliminary step to larger clinical studies we investigated the effect on ETP of phospholipids, tissue factor (TF) and residual platelets in frozen plasma. DESIGN AND METHODS: We investigated platelet-poor and platelet-rich plasmas from healthy subjects, patients on oral anticoagulants (OA), or with hemophilia and women on oral contraceptives (OC), chosen as examples of the normal, hypo- and hyper-coagulable states in which ETP has been reported to be impaired. RESULTS: Phospholipids had only a slight effect on ETP in all conditions except in women on OC, in whom the best diagnostic efficacy was observed at 0.5 microM. TF had only a slight effect in all conditions except hemophilia, in which an ETP impairment was observed only at low (1 pM) concentration. Residual platelets had considerable effects on ETP in frozen plasmas, but this was abrogated by filtration before freezing. ETP in platelet-rich plasma at 150x103/mm3 was similar to that obtained in filtered-plasma with 1.5 microM phospholipids in healthy subjects, patients on OA and patients with severe hemophilia, but not in those with mild- or moderate-hemophilia, where the ETP was higher in platelet-rich plasma. INTERPRETATION AND CONCLUSIONS: The results suggest that the method can be used for investigations on the clinical value of ETP. Platelet-rich and platelet-poor plasma are suitable testing materials. The latter should be filtered before freezing to minimize the effect of residual platelets.

International sensitivity index calibration of the near-patient testing prothrombin time monitor, ProTime.

Near-patient testing devices (monitors) capable of measuring prothrombin time on an unmeasured drop of blood would be suitable alternatives to centralized laboratory monitoring of patients receiving oral anticoagulants. The essential prerequisite for the use of these monitors is their conformity to the international sensitivity index (ISI) calibration model recommended by the World Health Organization. We report on the ISI calibration of the ProTime monitor (International Technidyne, Edison, NJ) designed and approved for patient self-testing. According to our results, this monitor can be calibrated by adopting the model already used for other monitors. The apparent ISI was close to unity. Overall, the international normalized ratio values displayed by the monitor agreed with those measured with the international reference preparation for thromboplastin. Confirmation of these results in a large multicenter study is warranted.

Laboratory diagnosis of lupus anticoagulants--effect of residual platelets in plasma, assessed by Staclot LA and silica clotting time.

Residual platelets in plasma are considered detrimental after freezing-thawing, as phospholipids released from ruptured platelets may quench lupus anticoagulants (LA). We aimed at assessing the effect of residual platelets after freezing-thawing plasmas tested with two procedures for LA. Blood from 52 patients suspected of having LA were centrifuged at 2,500 g. Plasmas were subdivided into 2 aliquots. One was filtered to remove residual platelets and both were frozen and stored at -70 degrees C. Silica clotting time (SCT) at low and high phospholipid concentrations and Staclot LA with and without Hexagonal phospholipids were performed on thawed plasmas. Plasmas were considered LA-positive when both SCT and Staclot LA performed on filtered plasmas were diagnostic for LA. Forty-two of 52 plasmas fulfilled the diagnostic criteria and were retained for subsequent analysis. SCT on non-filtered plasmas was diagnostic for LA in 42 of 42 plasmas. Though the median (range) percentage correction recorded after phospholipids addition for filtered plasmas, i.e., 67% (36%-83%) was reduced to 54% (25%-81%) for non-filtered plasmas (p <0.001), it was still above the cut-off (i.e., 20.9%). Staclot LA on non-filtered plasmas was diagnostic for LA in 42 of 42 plasmas. Though the median (range) clotting time difference recorded after phospholipid addition for filtered plasmas, i.e., 40.8 (10-103.5) s was reduced to 31.7 (2.8-88.8) s for non-filtered plasmas (p <0.001), it was still above the cut-off (i. e., 1.7 s). In conclusion, residual platelets do not affect the diagnostic efficacy of SCT and Staclot LA. However, the fact that the percentage correction for SCT and the clotting time difference for Staclot LA are reduced by residual platelets, suggests that weak LA may be lost upon freezing-thawing non-filtered plasmas.

How to evaluate the influence of blood collection systems on the international sensitivity index. Protocol applied to two new evacuated tubes and eight coagulometer/thromboplastin combinations.

Previous reports indicate that the international sensitivity index (ISI) of coagulometer/thromboplastin combinations (measuring systems) may be influenced by blood collection systems. We applied a new protocol to assess the extent with which two new blood collection systems (evaluation tubes) influence the ISI of eight widely used measuring systems. The evaluation tubes were made of plastic and had draw volumes of 1.8 and 2.7 ml; citrate concentration was 0.109 M. Well-established collection tubes (from the same manufacturer)-which were made of siliconized glass with draw volume and citrate concentration of 4.5 ml and 0.105 M, respectively-served as control. Plasmas from 20 healthy subjects and 60 patients on oral anticoagulants, collected with the evaluation and control tubes, were tested for prothrombin time (PT) with the eight measuring systems. Plasmas collected with the control tubes were also tested with an international standard for thromboplastin. Results were used to calculate the ISIs of the measuring systems. These were then used to calculate the differences of the crossover international normalized ratio (INR) (i.e., the INR obtained with PT ratios of plasmas collected into the evaluation tubes and the ISI determined with plasmas collected into the control tubes). Overall, the differences were small but measurable, especially for the 2.7-ml draw evaluation tubes and with some of the measuring systems (mean difference,