Geometric inaccuracy and co-registration errors for CT, DynaCT and MRI images used in robotic stereotactic radiosurgery treatment planning.

PURPOSE: To measure the combined errors due to geometric inaccuracy and image co-registration on secondary images (dynamic CT angiography (dCTA), 3D DynaCT angiography (DynaCTA), and magnetic resonance images (MRI)) that are routinely used to aid in target delineation and planning for stereotactic radiosurgery (SRS). METHODS: Three phantoms (one commercial and two in-house built) and two different analysis approaches (commercial and MATLAB based) were used to quantify the magnitude of geometric image distortion and co-registration errors for different imaging modalities within CyberKnife's MultiPlan treatment planning software. For each phantom, the combined errors were reported as a mean target registration error (TRE). The mean TRE's for different intramodality imaging parameters (e.g., mAs, kVp, and phantom set-ups) and for dCTA, DynaCTA, and MRI systems were measured. RESULTS: Only X-ray based imaging can be performed with the commercial phantom, and the mean TRE ± standard deviation values were large compared to the in-house analysis using MATLAB. With the 3D printed phantom, even drastic changes in treatment planning CT imaging protocols did not greatly influence the mean TRE (<0.5 mm for a 1 mm slice thickness CT). For all imaging modalities, the largest mean TRE was found on DynaCT, followed by T2-weighted MR images (albeit all <1 mm). CONCLUSIONS: The user may overestimate the mean TRE if the commercial phantom and MultiPlan were used solely. The 3D printed phantom design is a sensitive and suitable quality assurance tool for measuring 3D geometric inaccuracy and co-registration errors across all imaging modalities.

Selective and super-selective C-arm based cone beam CT angiography (CBCTA) with DynaCT for CyberKnife radiosurgery planning of intracranial arteriovenous malformations (AVMs).

BACKGROUND: Successful radiosurgery for intracranial arteriovenous malformations (AVMs) requires accurate delineation of the nidus in 3D. Exact targeting and precise equipment is needed to achieve obliteration of the nidus while minimizing toxicity to the surrounding brain. In some micro-AVMs and poorly visible AVMs we have used cone beam CT angiography (CBCTA) with selective and super-selective angiography where a micro-catheter is advanced into the feeding arteries- to assist with nidus definition for CyberKnife radiosurgery planning. METHODS: Four patients who had AVMs inadequately visualized with MRI, MRA, CT, CTA, and dynamic CT angiography (dCTA) were identified for selective angiography (2 had super-selective angiography) for CyberKnife radiosurgery. The mean age at the time of treatment was 45 years (range: 22 - 71 years). All patients had suffered prior hemorrhage and were deemed inoperable. Super-selective angiography was done under general anesthesia to minimize motion artefact and the risk of arterial dissection. Angiography was performed using the biplane angiographic suite (ArtisQ; Siemens). Cone beam reconstructions were performed using DynaCT software. For each scan, volumetric data was acquired over 20 seconds in a single rotation of the C-arm mounted flat-panel detector cone-beam CT system. The data set was imported into the CyberKnife TPS and co-registered with the treatment planning CT, T2 MRI and Toshiba dCTA. Delineation of the AVM nidus was performed by the multi-disciplinary AVM team. RESULTS: There were no adverse events related to the angiography or radiosurgery treatment. CBCTA data sets created using DynaCT were accurately co-registered with the treatment planning scans in the CyberKnife treatment planning system (Multiplan). For all 4 patients, feeding arteries, draining veins and nidi were clearly visualized and used to develop radiosurgery plans. Mean nidus size was 0.45cc (range: 0.07 - 1.00cc). CONCLUSIONS: For intracranial micro-AVMs and AVMs otherwise poorly visualized using DSA, MRA, CTA or dCTA, selective and super-selective CBCTA images (created using DynaCT) can be successfully imported into the CyberKnife TPS to assist in nidus delineation. Advancement of a micro-catheter into the feeding arteries to allow continuous contrast injection during volumetric scanning constitutes super-selective CBCTA. This technique provides superior visualization of micro-AVMs and should be utilized for radiosurgery planning of poorly visualized AVMs.

Reducing errors in prostate tracking with an improved fiducial implantation protocol for CyberKnife based stereotactic body radiotherapy (SBRT).

PURPOSE: Ultra-hypofractionated radiotherapy with SBRT is an established technique for treating localized prostate cancer. CyberKnife based SBRT requires implantation of fiducial markers for soft tissue target tracking by the orthogonal KV X-ray imaging system. The spatial distribution of fiducial markers must allow accurate calculation of a 3D transformation that describes the position of the prostate within the reference frame of the planning CT scan. Accuray provides a fiducial implantation guideline for tracking soft tissue lesions. Despite using the guideline we experienced an unacceptably high rate of rotational tracking failure due to problems with fiducial placement. We adapted the Accuray guideline to prostate SBRT for improved fiducial placement and more reliable target tracking.Methods and materials: 54 patients with prostate adenocarcinoma were treated with ultra-hypofractionated radiotherapy on CyberKnife. Patients had platinum fiducial markers implanted transrectally under ultrasound guidance by a Radiologist. For the first 26 patients, fiducial markers were positioned following the Accuray fiducial placement guidelines for soft tissue lesions (cohort 1). The initial rotational tracking error rate was unacceptably high (23%). On review, inappropriate fiducial placement was identified as the cause of error (especially insufficient spacing between seeds). In October 2016 we developed a seed placement protocol specifically for implanting fiducial markers within the prostate and a second cohort of patients was treated thereafter (cohort 2, 28 patients). The stipulations of the original guideline are maintained while the modified protocol requires that 4 fiducial markers be implanted in the postero-lateral peripheral zone in a single coronal plane. RESULTS: In cohort 1, patients had a median age of 64 years (50 - 74), PSA of 6.6mcg/L (1.1 - 14.7), and prostate volume of 56 cc (22 - 125), while in cohort 2 they had a mean age of 65 years (53 - 75), PSA of 6.2 mcg/L (1 - 12) and prostate volume of 47 cc (21 - 106). The fiducial markers were easily visualized and there were no cases of urosepsis related to fiducial implantation. In 6 of 26 patients (23%) from cohort 1, only translational mapping without accurate spatial rotations could be calculated. After adopting the prostate specific fiducial implantation protocol, rotational tracking error was eliminated. Accurate 6 degree tracking (accounting for translations and rotations) was achieved in all 28 patients from cohort 2. Using an in-house computer script we analyzed the dose distributions resulting from rotational misalignments of -10, -5, -3, 3, 5, and 10 degrees along all three rotational axes (pitch, roll and yaw). Rotational misalignments result in decreased minimum dose to the PTV and increased maximum dose to OARs. CONCLUSION: Implementing a prostate specific fiducial placement protocol for SBRT significantly improved our ability to track prostate motion in 6 degrees 77% to 100% reliability. Failure to track rotations can potentially lead to underdosing and overdosing of portions of the prostate and OARs respectively.

Comparison of four techniques for spine stereotactic body radiotherapy: Dosimetric and efficiency analysis.

PURPOSE: The aim of this study is to compare the dosimetric differences between four techniques for spine stereotactic body radiotherapy (SBRT): CyberKnife (CK), volumetric modulated arc therapy (VMAT), and helical tomotherapy (HT) with dynamic jaws (HT-D) and fixed jaws (HT-F). MATERIALS/METHODS: Data from 10 patients were utilized. All patients were planned for 24 Gy in two fractions, with the primary objectives being: (a) restricting the maximum dose to the cord to ≤ 17 Gy and/or cauda equina to ≤ 20 Gy, and (b) to maximize the clinical target volume (CTV) to receive the prescribed dose. Treatment plans were generated by separate dosimetrists and then compared using velocity AI. Parameters of comparison include target volume coverage, conformity index (CI), gradient index (GI), homogeneity index (HI), treatment time (TT) per fraction, and monitor units (MU) per fraction. RESULTS: PTV D2 and D5 were significantly higher for CK compared to VMAT, HT-F, and HT-D (P < 0.001). The average volume of CTV receiving the prescription dose (CTV D95) was significantly less for VMAT compared to CK, HT-F and HT-D (P = 0.036). CI improved for CK (0.69), HT-F (0.66), and HT-D (0.67) compared to VMAT (0.52) (P = 0.013). CK (41.86) had the largest HI compared to VMAT (26.99), HT-F (20.69), and HT-D (21.17) (P < 0.001). GI was significantly less for CK (3.96) compared to VMAT (6.76) (P = 0.001). Likewise, CK (62.4 min, 14059 MU) had the longest treatment time and MU per fraction compared to VMAT (8.5 min, 9764 MU), HT-F (13 min, 10822 MU), and HT-D (13.5 min, 11418 MU) (P < 0.001). CONCLUSION: Both CK and HT plans achieved conformal target coverage while respecting cord tolerance. Dose heterogeneity was significantly larger in CK. VMAT required the least treatment time and MU output, but had the least steep GI, CI, and target coverage.

Utility of CT-cisternogram for radiosurgery in trigeminal neuralgia: A not-to-be forgotten technique.

Radiosurgery (RS) is a well-established ablative therapy for trigeminal neuralgia (TGN). Successful RS requires the delivery of an extremely high dose of radiation to a small cisternal portion of the nerve, which lies amidst critical structures. This study describes the utility of CT-cisternogram in RS targeting for TGN. We report on patients with TGN who required CT-cisternogram for target identification for CyberKnife (CK) RS at our institution between September 2010 and April 2015. CT-cisternogram is a well-tolerated procedure that adds useful information to RS planning. Illustrative cases with complex anatomy and MRI artifacts related to postoperative changes and Teflon implant are described. CT-cisternogram is a complementary imaging modality that is useful in some patients, for RS target delineation.

Dynamic CT angiography for cyberknife radiosurgery planning of intracranial arteriovenous malformations: a technical/feasibility report.

BACKGROUND: Successful radiosurgery for arteriovenous malformations (AVMs) requires accurate nidus delineation in the 3D treatment planning system (TPS). The catheter biplane digital subtraction angiogram (DSA) has traditionally been the gold standard for evaluation of the AVM nidus, but its 2D nature limits its value for contouring and it cannot be imported into the Cyberknife TPS. We describe a technique for acquisition and integration of 3D dynamic CT angiograms (dCTA) into the Cyberknife TPS for intracranial AVMs and review the feasibility of using this technique in the first patient cohort. PATIENTS AND METHODS: Dynamic continuous whole brain CT images were acquired in a Toshiba 320 volume CT scanner with data reconstruction every 0.5 sec. This multi-time-point acquisition enabled us to choose the CT data-set with the clearest nidus without significant enhancement of surrounding blood vessels. This was imported to the Cyberknife TPS and co-registered with planning CT and T2 MRI (2D DSA adjacent for reference). The feasibility of using dCTA was evaluated in the first thirteen patients with outcome evaluation from patient records. RESULTS: dCTA data was accurately co-registered in the Cyberknife TPS and appeared to assist in nidus contouring for all patients. Imaging modalities were complementary. 85% of patients had complete (6/13) or continuing partial nidus obliteration (5/13) at 37 months median follow-up. CONCLUSIONS: dCTA is a promising imaging technique that can be successfully imported into the Cyberknife TPS and appears to assist in radiosurgery nidus definition. Further study to validate its role is warranted.

Influencing effect of heat-treatment on radon emanation and exhalation characteristic of red mud.

The reuse of industrial by-products is important for members of numerous industrial sectors. However, though the benefits of reuse are evident from an economical point of view, some compounds in these materials can have a negative effect on users' health. In this study, the radon emanation and exhalation features of red mud were surveyed using heat-treatment (100-1200 °C). As a result of the 1200°C-treated samples, massic radon exhalation capacity reduced from 75 ± 10 mBq kg(-1) h(-1) to 7 ± 4 mBq kg(-1) h(-1), approximately 10% of the initial exhalation rate. To find an explanation for internal structural changes, the porosity features of the heat-treated samples were also investigated. It was found that the cumulative pore volume reduced significantly in less than 100 nm, which can explain the reduced massic exhalation capacity in the high temperature treated range mentioned above. SEM snapshots were taken of the surfaces of the samples as visual evidence for superficial morphological changes. It was found that the surface of the high temperature treated samples had changed, proving the decrement of open pores on the surface.

Feasibility, detectability and clinical experience with platinum fiducial seeds for MRI/CT fusion and real-time tumor tracking during CyberKnife® stereotactic ablative radiotherapy.

BACKGROUND AND PURPOSE: The purpose of this study is to review our experience with platinum fiducials in terms of feasibility of placement and detectability by both MRI and orthogonal x-ray images used in robotic SABR.Materials and Methods: 29 consecutive SABR patients (30 tumors) treated using fiducial tracking between January 2011 and February 2012 were reviewed. A total of 108 fiducials implanted in or around various tumor sites were identified. The pixel value contrast (PVC) of fiducials seen on MRI mages and treatment unit x-ray images of patients and phantoms were analysed. RESULTS: Migration rates were similar for PS versus GS and GC (6.2%). No difference was noted between the mean PVC in cirrhotic versus non-cirrhotic liver (60.4 vs. 47.9; p = 0.074). MRI sequences for tumors in the liver and other organs revealed a mean PVC for platinum superior to that of gold (p<0.001). No PVC difference was seen between gold and platinum on analysis of the treatment unit x-rays. CONCLUSION: Platinum seeds provide a superior detectability in comparison to gold seeds or coils on MRI images and are detected equally well by an image guidance system using orthogonal x-rays, making them a better choice for fiducial-based CT-MRI registration.

Autologous dendritic cell based adoptive immunotherapy of patients with colorectal cancer-A phase I-II study.

Dendritic cell-based active immunotherapies of cancer patients are aimed to provoke the proliferation and differentiation of tumor-specific CD4(+) and CD8(+) T-lymphocytes towards protective effector cells. Isolation and in vitro differentiation of circulating blood monocytes has been established a reasonable platform for adoptively transferred DC-based immunotherapies. In the present study the safety and tolerability of vaccination by autologous tumor cell lysates (oncolysate)- or carcinoembriogenic antigen (CEA)-loaded DCs in patients with colorectal cancer was investigated in a phase I-II trial. The study included 12 patients with histologically confirmed colorectal cancer (Dukes B2-C stages). Six of the patients received oncolysate-pulsed, whereas the other six received recombinant CEA-loaded autologous DCs. The potential of the tumor antigen-loaded DCs to provoke the patient's immune system was studied both in vivo and in vitro. The clinical outcome of the therapy evaluated after 7 years revealed that none of the six patients treated with oncolysate-loaded DCs showed relapse of colorectal cancer, whereas three out of the six patients treated with CEA-loaded DCs died because of tumor relapse. Immunization with both the oncolysate- and the CEA-loaded autologous DCs induced measurable immune responses, which could be detected in vivo by cutaneous reactions and in vitro by lymphocyte proliferation assay. Our results show that vaccination by autologous DCs loaded with autologous oncolysates containing various tumor antigens represents a well tolerated therapeutic modality in patients with colorectal cancer without any detectable adverse effects. Demonstration of the efficacy of such therapy needs further studies with increased number of patients.

CyberKnife for inoperable renal tumors: Canadian pioneering experience.

INTRODUCTION: Stereotactic ablative body radiotherapy (SABR) is currently under study regarding its clinical application in management of patients with kidney tumors. CyberKnife can accurately deliver ablative tumor radiation doses while preserving kidney function. We report Canada's first use of CyberKnife SABR system in treating primary kidney tumors. MATERIALS AND METHODS: Between January 2011 and February 2012, we treated three patients with renal tumors using CyberKnife SABR. Two patients had tumors in solitary kidney. The third patient had a recurrent tumor after two previous radiofrequency ablation treatments. Platinum seed fiducials were used for real time tumor tracking. Magnetic resonance imaging registration was used for tumor delineation in all cases. The patients were followed with regular renal scans and renal function tests. RESULTS: The mean age was 79 years. Mean tumor size was 21.3 cm3. A dose of 39 Gy in 3 fractions was delivered. The post treatment follow up times were 15 months, 13 months and 12 months. Local control was obtained in all three patients. No acute or chronic toxicity was reported. Kidney functions remained unaffected after treatment. CONCLUSION: CyberKnife is technically feasible for treatment of medically inoperable renal tumors or tumors in a solitary kidney.

Post-operative management of primary glioblastoma multiforme in patients over 60 years of age.

BACKGROUND AND PURPOSE: Optimal treatment for elderly patients with glioblastoma multiforme is not well defined. We evaluated the efficacy of post-operative radiotherapy with or without concomitant and/or adjuvant temozolomide in patient, aged > or = 60 years to assess survival and identify prognostic factors of survival. METHODS: A retrospective analysis of overall survival and progression-free survival in patients with newly diagnosed glioblastoma multiforme aged > or = 60 years treated with post-operative radiotherapy with or without temozolomide chemotherapy was conducted at our institutions. Prognostic factors were determined by univariate and multivariate analyses. RESULTS: Of 75 study participants (54.7% male; median age at first diagnosis, 65.1 years), 29 (38.7%) underwent gross total resection, whereas others underwent partial resection or biopsy only. All but 1 patient received radiotherapy. Twenty patients received concomitant temozolomic e only. Adjuvant temozolomide (1-50 cycles) was administered in 42 patients; 16 received > or = 6 cycles. Median overall survival was 10.3 months. One- and 2-year overall survival rates were 42.6% and 6.7%, respectively. Median progression-free survival was 4.1 months. Radiochemotherapy was generally well tolerated. Median overall survival was 15.3 and 29.6 months for patients who received 6-12 cycles and >12 cycles of adjuvant temozolomide, respectively. There were no significant differences in overall survival between age groups (60-64, 65-69, and > or = 70 years). Adjuvant temozolomide, Karnofsky performance status > or = 70, and additional surgery after progression were significant prognostic factors of longer overall survival (p<0.05). CONCLUSIONS: Radiochemotherapy, including > or = 6 cycles of adjuvant temozolomide, was safe and prolonged survival of glioblastoma patients aged > or = 60 years. Aggressive therapy should not be withheld from patients aged > or = 60 years with good performance status because of age.

Malignancies associated with systemic sclerosis.

The outcome of systemic sclerosis (SSc) has become more favorable during the past years. Respiratory failure or renal crisis became less frequent, therefore more attention should be paid to long-term comorbidities, such as malignancies secondary to scleroderma. The incidence of malignant lymphoproliferative diseases, as well as that of solid tumors are higher in a number of rheumatic diseases including SSc. Some cytotoxic agents, primarily cyclophosphamide used in the treatment of SSc, as well as exposure to chemicals or smoking may further increase cancer risk. We also present malignancies in 218 scleroderma patients undergoing follow-up in our department were assessed for secondary malignancies. Although the number of SSc patients with tumor is relatively small, we compared our cohort to the Health for All Hungarian database and calculated standard incidence ratios (SIR). We identified 11 cases of malignancy in 10 SSc patients (4.6%). One patient had two types of tumor: breast cancer before the onset of SSc and later malignant lymphoma. Half of SSc patients with cancer belonged to the diffuse cutaneous (dcSSc) subtype. The mean age at onset of SSc was 54.6 years, while that at the diagnosis of malignancy was 61.5 years. The mean disease duration of scleroderma at the time of cancer diagnosis was 6.6 years. Five patients died, 4 due to the underlying malignancy. Among the five surviving patients, the mean survival time was 4.9 years. Altogether 3 patients had non-Hodgkin's lymphoma, 2 had bronchial cancer, 2 had breast cancer, one had leiomyosarcoma of the leg, one had esophageal cancer, one had cervix cancer and one had skin cancer. In comparison to the Health for All database, the overall SIR of all malignancies in SSc was 1.07 (CI: 0.82-1.38) varying between 5.8 and 52.4 in different tumor types. Only one cancer patient received cyclophosphamide therapy. In conclusion, secondary tumors including lung, skin and breast cancer, as well as lymphomas are more common in SSc than in the general population. The adequate treatment and follow-up of scleroderma patients may help us to lower the risk of malignancies secondary to SSc.

Correlations between clinicopathological parameters and molecular signatures of primary tumors for patients with stage T3n0 colorectal adenocarcinomas: a single center retrospective study on 100 cases.

BACKGROUND/AIMS: To examine the clinical and protein expression characteristics of tumor tissues for prediction of prognosis in colorectal cancer (CRC). METHODOLOGY: We retrospectively analyzed the clinicopathological data of patients with stage T3N0 CRC, operated between 1997-2003 and the surgical materials for the relation between disease prognosis and p53, p21, p16, ß-catenin, E-cadherin, EGFR, hMLH1, hMSH2 and TS protein expressions. RESULTS: A significantly shorter 3-year disease free survival was observed in patients under the age of 50. The worst 5-year overall survival (OS) observed for patients over 70. Tumor localization and number of processed lymph nodes significantly affected prognosis. The EGFR, hMSH2 and TS expressions and the 5-fluorouracyl treatment were not found to be of prognostic value; p53 and p21 positivity had significantly worse survival. When ß-catenin membrane expression disappeared on tumor cells, the 5-year OS rate decreased and time to metastasis shortened significantly. Membrane ß-catenin expression, processed lymph nodes number and age were detected as independent prognostic markers. CONCLUSIONS: These results suggest that the evaluation of a clinicopathological profile, based on age, tumor localization, number of examined lymph nodes, p53, p21 and E-cadherin ß-catenin expression appears to be useful in identifying high risk patients.

Investigation of ß-catenin and E-cadherin expression in Dukes B2 stage colorectal cancer with tissue microarray method. Is it a marker of metastatic potential in rectal cancer?

ß-catenin and E cadherin are both membrane-associated proteins which are essential regulators and providers of cellular adhesion. In the metastatic cascade of malignant tumours, detachment of tumour cells from each other is a very important step. It has been shown in several tumour types, that reduced expression of these proteins is important. The aim of our study was to clarify the expression profile of these proteins, and correlate the findings with the metastasizing potential of early stage colon and rectal cancers. Formalin fixed and paraffin embedded samples from 79 Dukes B2 stage colorectal cancer were examined using a tissue microarray approach. The expression of ß-catenin and E-cadherin proteins was determined immunohistochemically. Our findings indicated that there is a tendency for metastatic spread in cases when membranous expression of ß-catenin is lost (p = 0.062). Similarly metastases in negative cases developed more rapidly, than in positive ones (p = 0.05). Survival rate was worse in the negative cases. The risk of metastasis in rectal cancer was significantly higher in the ß-catenin membranously negative than positive groups (p = 0.024) and in case of ß-catenin nuclear expression the risk was also higher (p = 0.047). Reduced E-cadherin expression also correlated with development of metastatic disease, but this association was statistically not significant. The immunohistochemical analysis of 79 cases shows that in Dukes B2 stage colorectal tumours clarification of ß-catenin and E-cadherin expression patterns is reliable for predicting the metastatic potential of early stage rectal cancer and hence the method may have relevant implications in the therapeutic management of these cancers.

[The emotions of oncologists]. / Az onkológusok érzelmei.

Emotions are parts of organizational reality to an ever increasing extent. Importantly, they are not just tools in the hand of healthcare workers to achieve better physician / healthcare professional-to-patient interactions but intrinsic processes and characteristics with psychic, cognitive and somatic actions. For a thorough investigation of the issue, a PANAS-X questionnaire was used to examine the emotions of 187 physicians and other healthcare professionals, all engaged in oncology, in 2009. The research succeeded in exploring the overall emotional state oncology professionals had assumed in relation with their job as well as enabled the authors of this study to draw the respondents' emotional map and assess their fundamental emotional attitudes. Furthermore, the authors managed to identify groups of respondents that had felt more intense positive, and/or less intense negative emotions that are socially accepted than others. They included those of senior experienced oncologists, males, individuals with families, childless individuals, ward workers, and skilled professionals. According to the findings, the range of emotions an oncologist experiences / feels intently during his everyday work is dependent upon a great number of factors.

Comparison of Pathvysion and Poseidon HER2 FISH assays in measuring HER2 amplification in breast cancer: a validation study.

AIMS: The current study was done as a validation study prior to setting up a clinical HER2 testing service using the new commercial Poseidon HER2 fluorescence in situ hybridisation (FISH) assay. However, it was felt that the experience of the authors of this study may be of interest to other laboratories when considering setting up a HER2 diagnostic facility. METHODS: 122 patients who had been diagnosed with invasive breast cancer were selected. Immunolabelling with HercepTest, PathVysion and Poseidon FISH assays were carried out using tissue microarray blocks. RESULTS: Concordance correlation coefficients showed near perfect agreement in average HER2 and centromere specific signal counts per cell and in the HER2/CEP17 ratios between the PathVysion and the Poseidon FISH assays. In addition, the kappa measure showed perfect agreement (kappa 0.9441, p<0.0001), and if only 2+ cases were considered there was substantial agreement (kappa 0.7671, p=0.0006), between the two assays. The sensitivity and the specificity of the Poseidon FISH kit were calculated to be 95.2% and 100%, respectively, whereas the positive predictive value (PPV) and negative predictive value (NPV) were 100% and 99%, respectively. With regard to the ability to presume HER2 polysomy, the Poseidon FISH kit had a sensitivity of 93.3% and a specificity of 99.1%, with PPV and NPV of 93.3% and 99.1%, respectively, as assessed with PathVysion classification as the reference. CONCLUSIONS: Statistical analysis confirmed that the two FISH assays are comparable in terms of detection of HER2 gene amplification. Proceeding from these findings, the genetic diagnoses obtained with the Poseidon kit can be considered to be as valuable as the results from the Food and Drug Administration approved PathVysion assay, and its utilisation in routine HER2 diagnostics is proposed.

Analysis of EGFR gene amplification, protein over-expression and tyrosine kinase domain mutation in recurrent glioblastoma.

Gefitinib and erlotinib are both selective EGFR tyrosine kinase inhibitors (EGFR-TKIs) that have produced responses in a small subgroup of lung cancer patients. The strongest evidence for a role of EGFR in the biology of glioblastoma stems from clinical trials in which 15-20% of recurrent glioblastoma patients experienced significant tumour regression in response to these small-molecule EGFR kinase inhibitors. We examined the protein-kinase domain of the EGFR gene, EGFR protein expression and EGFR gene amplification in 20 cases of recurrent GBMs. EGFR protein over-expression was found in 65% of cases. EGFR protein over-expression was associated with EGFR gene amplification in 35% of cases, and with high polysomy in 15% of cases. No mutations were found in the TK domain of the EGFR gene. Our results confirm that mutations in the kinase domain are absent in recurrent GBM, and this might be a preponderant factor in the lack of major clinical responses of TKIs in GBM, recent studies have suggested that responsiveness to EGFR kinase inhibitors was strongly associated with coexpression of EGFRvIII and PTEN. Further prospective validation of EGFRvIII and PTEN as predictors of the clinical response to EGFR kinase inhibitors in recurrent GBM is strongly anticipated.

[Prophylaxis of chemotherapy-induced vomiting and nausea]. / A kemoterápia okozta hányás csillapítása.

Chemotherapy-induced vomiting and nausea is the most common adverse event of anticancer therapy. In different guide-lines (MASCC, NCCN, ESMO and ASCO) antiemetic prophylaxis is directed toward the emetogenic potential of the chemotherapy and the type of vomiting and nausea. Chemotherapeutic agents are classified into four emetic risk groups: high, moderate, low, and minimal. Steroids, dexamethasone, metoclopramide, cannabinoids, benzodiazepines, 5-HT3 receptor antagonists (ondansetron, granisetron, tropisetron) and a new group of antiemetics, the neurokinin1 receptor antagonists are used to prevent anticipatory, acute and delayed vomiting and nausea. This paper examines evidence-based recommendations for optimal use of antiemetics.

Tumor-associated antigens in systemic sclerosis and systemic lupus erythematosus: associations with organ manifestations, immunolaboratory markers and disease activity indices.

BACKGROUND: Some tumor-associated antigens (TAAs) are expressed on inflammatory cells. We previously detected increased production of CA15-3, CA19-9 and CA125 in rheumatoid arthritis (RA). The production of some TAAs may also be increased in patients with systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and other connective tissue diseases. Some of these TAAs contain sialylated carbohydrate motifs and they are involved in tumor-associated cell adhesion and metastasis. OBJECTIVES: We assessed levels of TAAs in the sera of SSc, SLE patients, patients with infectious diseases and healthy subjects. Serum TAA levels were correlated with each other, as well as with disease activity markers and organ involvement. METHODS: TAAs including CEA, CA15-3, CA72-4, CA125 and CA19-9 were assessed by immunoassay in the sera of 92 patients with SSc, 40 patients with SLE, 50 age- and sex-matched healthy controls, as well as with 40 patients with current bacterial or viral infections. Normal upper limits for these TAAs were 3.4 mg/l, 25 kU/l, 6.9 kU/l, 35 kU/l and 34 kU/l, respectively. RESULTS: There were significantly more SSc patients showing abnormally high levels of CA19-9 (8.8% vs 2.0%), CA125 (11.0% vs 6.0%) and CA15-3 (28.4% vs 14.0%) in comparison to controls (p < 0.05). In SLE, significantly more patients had elevated levels of CEA (32.5% vs 20.0%), CA19-9 (7.5% vs 2.0%), CA125 (15.0% vs 6.0%) and CA72-4 (15.0% vs 8.0%) than did controls (p < 0.05). The mean absolute serum levels of CEA (6.6+/-1.7 vs 1.8+/-1.4 mg/l) and CA15-3 (22.9 +/- 1.8 vs 18.6 +/- 2.2 kU/l) were also significantly higher in SSc compared to controls (p < 0.05). We found numerous correlations between the serum levels of different TAAs within the SSc and SLE population. Among SSc patients, serum CEA (R = 0.290; p = 0.005), CA15-3 (R = 0.260; p = 0.020) and CA19-9 (R = 0.257; p = 0.013) correlated with renal involvement. Serum CA15-3 also correlated with joint involvement (R = 0.329; p = 0.003), ANA positivity (R = 0.288; p = 0.010) and CRP levels (R = 0.407; p < 0.001). Within the SLE population, serum CA72-4 correlated with central nervous involvement (R = 0.624; p = 0.004) and CA125 correlated with the SLEDAI composite activity index (R = 0.666; p = 0.002). Patients with infections exerted serum TAA patterns similar to healthy controls. CONCLUSION: The concentration of some TAAs may be elevated in the sera of patients with SSc or SLE in comparison to healthy subjects. Pathogenically, most of these TAAs contain carbohydrate motifs and thus they may be involved in inflammation-associated adhesive events. Furthermore, the production of some TAAs may correlate with organ involvement or disease activity in scleroderma or lupus.

[Study of career motivators affecting the emotional labour of health care professionals in oncology]. / Az onkológiai szakdolgozók érzelmi munkájának vizsgálata a pályaválasztási motivációk tükrében.

In the course of their everyday work health care professionals (HCPs) often have to change their true feelings. The literature labels this performance as emotional labor. This article is presenting data on the characteristics of HCPs' most endangered by the negative consequences of emotional labor. Our simple choice question survey was conducted at Debrecen University Medical Healthcare Center with the help of 50 oncology HCPs volunteers. Nearly 90% of the HCPs examined change their true feelings in the course of work. It is very difficult to classify those threatened by the negative upshot of this emotional labor. Due to our research we found appalling differences of work motivation that were tightly interconnected with the respondents' emotional labor and their perceived role/emotional expectations. We succeeded in establishing three clusters and defining each cluster's characteristics. Figures suggest that only somewhat more than the half of the HCPs is authentic professional helper, and 45% of them does not or only slightly perceive the patients' demands concerning their work. Therefore, it is important that the work environment does not only assist the work of HCPs by professional means, but along emotional dimensions as well.