Interobserver agreement on definition of the target volume in stereotactic radiotherapy for pancreatic adenocarcinoma using different imaging modalities.

PURPOSE: The aim of this study was to evaluate interobserver agreement (IOA) on target volume definition for pancreatic cancer (PACA) within the Radiosurgery and Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (DEGRO) and to identify the influence of imaging modalities on the definition of the target volumes. METHODS: Two cases of locally advanced PACA and one local recurrence were selected from a large SBRT database. Delineation was based on either a planning 4D CT with or without (w/wo) IV contrast, w/wo PET/CT, and w/wo diagnostic MRI. Novel compared to other studies, a combination of four metrics was used to integrate several aspects of target volume segmentation: the Dice coefficient (DSC), the Hausdorff distance (HD), the probabilistic distance (PBD), and the volumetric similarity (VS). RESULTS: For all three GTVs, the median DSC was 0.75 (range 0.17-0.95), the median HD 15 (range 3.22-67.11) mm, the median PBD 0.33 (range 0.06-4.86), and the median VS was 0.88 (range 0.31-1). For ITVs and PTVs the results were similar. When comparing the imaging modalities for delineation, the best agreement for the GTV was achieved using PET/CT, and for the ITV and PTV using 4D PET/CT, in treatment position with abdominal compression. CONCLUSION: Overall, there was good GTV agreement (DSC). Combined metrics appeared to allow a more valid detection of interobserver variation. For SBRT, either 4D PET/CT or 3D PET/CT in treatment position with abdominal compression leads to better agreement and should be considered as a very useful imaging modality for the definition of treatment volumes in pancreatic SBRT. Contouring does not appear to be the weakest link in the treatment planning chain of SBRT for PACA.

Metal-containing landfills as a source of antibiotic tolerance.

To unveil the potential effect of metal presence to antibiotic tolerance proliferation, four sites of surface landfills containing tailings from metal processing in Slovakia (Hnústa, Hodrusa, Kosice) and Poland (Tarnowskie Góry) were investigated. Tolerance and multitolerance to selected metals (Cu, Ni, Pb, Fe, Zn, Cd) and antibiotics (ampicillin, tetracycline, chloramphenicol, and kanamycin) and interrelationships between them were evaluated. A low bacterial diversity (Shannon-Wiener index from 0.83 to 2.263) was detected in all sampling sites. Gram-positive bacteria, mostly belonging to the phylum Actinobacteria, dominated in three of the four sampling sites. The recorded percentages of tolerant bacterial isolates varied considerably for antibiotics and metals from 0 to 57% and 0.8 to 47%, respectively, among the sampling sites. Tolerances to chloramphenicol (45-57%) and kanamycin (32-45%) were found in three sites. Multitolerance to several metals and antibiotics in the range of 24 to 48% was recorded for three sites. A significant positive correlation (p < 0.05) for the co-occurrence of tolerance to each studied metal and at least one of the antibiotics was observed. Exposure time to the metal (landfill duration) was an important factor for the development of metal- as well as antibiotic-tolerant isolates. The results show that metal-contaminated sites represent a significant threat for human health not only for their toxic effects but also for their pressure to antibiotic tolerance spread in the environment.

Improving interinstitutional and intertechnology consistency of pulmonary SBRT by dose prescription to the mean internal target volume dose.

PURPOSE: Dose, fractionation, normalization and the dose profile inside the target volume vary substantially in pulmonary stereotactic body radiotherapy (SBRT) between different institutions and SBRT technologies. Published planning studies have shown large variations of the mean dose in planning target volume (PTV) and gross tumor volume (GTV) or internal target volume (ITV) when dose prescription is performed to the PTV covering isodose. This planning study investigated whether dose prescription to the mean dose of the ITV improves consistency in pulmonary SBRT dose distributions. MATERIALS AND METHODS: This was a multi-institutional planning study by the German Society of Radiation Oncology (DEGRO) working group Radiosurgery and Stereotactic Radiotherapy. CT images and structures of ITV, PTV and all relevant organs at risk (OAR) for two patients with early stage non-small cell lung cancer (NSCLC) were distributed to all participating institutions. Each institute created a treatment plan with the technique commonly used in the institute for lung SBRT. The specified dose fractionation was 3â€¯× 21.5 Gy normalized to the mean ITV dose. Additional dose objectives for target volumes and OAR were provided. RESULTS: In all, 52 plans from 25 institutions were included in this analysis: 8 robotic radiosurgery (RRS), 34 intensity-modulated (MOD), and 10 3D-conformal (3D) radiation therapy plans. The distribution of the mean dose in the PTV did not differ significantly between the two patients (median 56.9 Gy vs 56.6 Gy). There was only a small difference between the techniques, with RRS having the lowest mean PTV dose with a median of 55.9 Gy followed by MOD plans with 56.7 Gy and 3D plans with 57.4 Gy having the highest. For the different organs at risk no significant difference between the techniques could be found. CONCLUSIONS: This planning study pointed out that multiparameter dose prescription including normalization on the mean ITV dose in combination with detailed objectives for the PTV and ITV achieve consistent dose distributions for peripheral lung tumors in combination with an ITV concept between different delivery techniques and across institutions.

Time management in radiation oncology: evaluation of time, attendance of medical staff, and resources during radiotherapy for prostate cancer: the DEGRO-QUIRO trial.

PURPOSE: In order to evaluate resource requirements, the German Society of Radiation Oncology (DEGRO) recorded the times needed for core procedures in the radio-oncological treatment of various cancer types within the scope of its QUIRO trial. The present study investigated the personnel and infrastructural resources required in radiotherapy of prostate cancer. METHODS: The investigation was carried out in the setting of definitive radiotherapy of prostate cancer patients between July and October 2008 at two radiotherapy centers, both with well-trained staff and modern technical facilities at their disposal. Personnel attendance times and room occupancy times required for core procedures (modules) were each measured prospectively by two independently trained observers using time measurements differentiated on the basis of professional group (physician, physicist, and technician), 3D conformal (3D-cRT), and intensity-modulated radiotherapy (IMRT). RESULTS: Total time requirements of 983 min for 3D-cRT and 1485 min for step-and-shoot IMRT were measured for the technician (in terms of professional group) in all modules recorded and over the entire course of radiotherapy for prostate cancer (72-76 Gy). Times needed for the medical specialist/physician were 255 min (3D-cRT) and 271 min (IMRT), times of the physicist were 181 min (3D-cRT) and 213 min (IMRT). The difference in time was significant, although variations in time spans occurred primarily as a result of various problems during patient treatment. CONCLUSION: This investigation has permitted, for the first time, a realistic estimation of average personnel and infrastructural requirements for core procedures in quality-assured definitive radiotherapy of prostate cancer. The increased time needed for IMRT applies to the step-and-shoot procedure with verification measurements for each irradiation planning.

Phylogeny and biogeography of Hydra (Cnidaria: Hydridae) using mitochondrial and nuclear DNA sequences.

The polyp hydra is ubiquitous in freshwater and is highly variable, with many species names assigned to different strains. Types of hydra do fall into four morphologically recognizable groups but many of the species determinations are confusing. To assess the diversity of hydra we collected 101 strains from six continents and built a phylogeny using three genetic markers. Each of the four well-defined groups of species represents a clade in our phylogeny. The green hydra group diverged first, followed by the braueri group and finally the sister groups vulgaris and oligactis. Each of eight species easily definable by morphological criteria represents a distinct clade in our phylogeny. Hydra of two clades, the green and the vulgaris hydra, are found on all continents (except Antarctica) and many islands, whereas hydra of the other two groups (braueri and oligactis) are restricted to the Northern Hemisphere. Our best estimate of the time of origin of hydra is about 60 Ma, long after the breakage of Pangea into northern and southern landmasses. Hydra appear to have diversified in the Northern Hemisphere, and their current diversity is greatest here. Two species were then able to disperse to the Southern Hemisphere, perhaps due to their thermal tolerance.

High skeletal muscle adenylate cyclase in malignant hyperthermia.

Malignant hyperthermia occurs in humans with several congenital myopathies, usually in response to general anesthesia. Commonly, individuals who develop this syndrome lack symptoms of muscle disease, and their muscle lacks specific pathological changes. A biochemical marker for this myopathy has not previously been available; we found activity of adenylate cyclase and content of cyclic AMP to be abnormally high in skeletal muscle. Secondary modification of protein phosphorylation could explain observed abnormalities of phosphorylase activation and sarcoplasmic reticulum function.

Antepartum percutaneous renal biopsy.

OBJECTIVE: To assess the value and adverse effects of an ultrasound-guided renal biopsy technique in women with normal and pathologic pregnancies. METHOD: Biopsy samples were taken from 36 women with hypertensive disease (28 with pre-eclampsia) and 18 healthy pregnant women using a thin needle and an ultrasound-guided biopsy device. RESULTS: Glomerular endotheliosis, a structural change typical of pre-eclampsia, was found in all hypertensive women, but it was more pronounced in the 28 pre-eclamptic women than in the 8 women with nonproteinuric hypertension. A similar change, however, was seen in 11 of the 18 controls. One serious adverse event occurred, retroperitoneal hematoma, in the woman with the most severe pre-eclampsia. CONCLUSION: Glomerular endotheliosis is not to be considered pathognomonic for pre-eclampsia. Few complications followed renal biopsy in this study, but complications arose in the sickest patient. It is probably not advisable to perform antepartum renal biopsies in pregnant women with a rapidly deteriorating renal function and swollen kidneys. In these women, the biopsy does not facilitate diagnosis and is hazardous.

The effect of membrane preparation and cellular maturation on human erythrocyte adenylate cyclase.

We found that adenylate cyclase activity of human erythrocytes is potentially labile during isolation of their plasmalemma. Addition of 1 mM EGTA to solution used to remove hemoglobin from lysed cells protected activity. Human erythrocyte adenylate cyclase is minimally activated by catecholamines, in the absence or presence of exogenous guanyl nucleotide, but substantially by 5'-guanylyl imidodiphosphate or sodium fluoride and concentration-dependently by Mg2+ or Mn2+. Basal catalytic activity is an age-dependent component of the human erythrocyte; 5'-guanylyl imidodiphosphate- or fluoride-activated activities decline with cellular maturation proportionally to the decrease in basal activity.

Duchenne carriers: lactate dehydrogenase isoenzyme 5 in serum and muscle.

Only two (5.5%) of 36 possible of known carriers of the gene in Duchenne dystrophy showed increased lactate dehydrogenase isoenzyme 5 (LDH-5) (L/M) in serum, while creatine kinase (CK) was increased in ten (27.8%). LDH-5 and CK did not increase simultaneously; in all five known carriers CK activity was abnormal but LDH-5 was normal. In muscle biopsy, LDH-5 was reduced in patients with Duchenne dystrophy (25.6 +/- 11.5% of total, mean +/- SD; control 59.9 +/- 10.3%; p less than 0.01) and in two of nine possible carriers, but as a group the carriers did not differ from controls: (49.9 +/- 12.1%; p less than 0.05).

Active transport of carnitine into skeletal muscle.

Skeletal muscle carnitine concentration exceeds plasma carnitine concentration. To determine whether this concentration gradient is maintained by active transport we studied rat soleus and extensor digitorum longus muscles. Observations consistent with the existence of an active transport mechanism were that the soleus accumulated carnitine linearly for 3 hours of incubation to exceed a distribution ratio of 1; the temperature coefficient for carnitine accumulation between 33 degrees C and 43 degrees C was 2.0; anaerobic incubation reduced carnitine accumulation by 30 percent; and the rate of carnitine accumulation was saturated at high substrate concentrations and competitively inhibited by gamma-butyrobetaine. The Km for carnitine of the carnitine transport mechanism of the soleus muscle was 0.259 mM and of the extensor digitorum longus muscle, 0.585 mM. The greater affinity of the soleus transport mechanism may explain the difference in carnitine transport by red and white muscle in intact animals. A defect in active transport of carnitine may be involved in the pathogenesis of some human myopathies characterized by excessive lipid storage and in diphtheritic cardiomyopathy.

Neuroleptic malignant syndrome caused by dopamine-depleting drugs in a patient with Huntington disease.

Prior reports of neuroleptic malignant syndrome (NMS) concerned patients with psychiatric disorders, usually schizophrenia, who were taking dopamine receptor blocking agents. We report the syndrome in a patient with Huntington disease who was treated with dopamine-depleting agents. He had a negative evaluation for malignant hyperthermia (MH), and we suggest that NMS differs from MH. The occurrence of NMS caused by dopamine-depleting agents suggests that anticholinergic properties of phenotiazines are not the only cause. Central dopaminergic systems probably participate in thermoregulation, and dopamine depletion probably plays a pathogenetic role in this syndrome.

Chronic GM2 gangliosidosis masquerading as atypical Friedreich ataxia: clinical, morphologic, and biochemical studies of nine cases.

A progressive spinocerebellar degenerative disorder was characterized in nine patients, aged 11 to 37 years, from four unrelated Ashkenazi Jewish families; affected individuals had markedly deficient beta-hexosaminidase A activity. Symptoms included early onset of cerebellar signs (tremor, incoordination, and dysarthia) and, with maturity, the development of upper and lower motor neuron disorders, marked dysarthia, and ataxia. Three older patients, aged 26, 32, and 37 years, had dementia or recurrent psychotic episodes. Membrane-bound lamellar cytoplasmic inclusions, consistent with lysosomal ganglioside accumulation, were observed in rectal ganglia. The activity of beta-hexosaminidase A was markedly deficient in all sources analyzed. Parents had activities consistent with heterozygosity, confirming autosomal-recessive transmission of the beta-hexosaminidase A-deficient gene and the adult variant disorder. Residual beta-hexosaminidase A activity, partially purified by anion-exchange chromatography from cultured skin fibroblasts of the affected individuals, was heat-labile and co-electrophoresed with normal beta-hexosaminidase A. These findings suggest that these patients were allelic for a new beta-hexosaminidase A mutation and may represent a genetic compound of this allele and the allele causing Tay-Sachs disease.

Locoregional recurrence of breast cancer following mastectomy: always a fatal event? Results of univariate and multivariate analysis.

PURPOSE: The outcome of patients with local-regional breast cancer recurrence after mastectomy often is described as fatal. However, certain subgroups with favorable prognoses are thought to exist. To determine these favorable subgroups, we analyzed prognostic factors for their influence on postrecurrence survival by univariate and multivariate analysis. METHODS AND MATERIALS: Between 1979 and 1992, 145 patients with their first isolated locoregional recurrence of breast cancer following modified radical mastectomy without evidence of distant metastases were treated at the Department of Radiation Oncology of the University of Wurzburg. Thirty-nine percent of patients (n = 67) had had postmastectomy radiotherapy, representing 7% of patients who had received routine postmastectomy irradiation at our institution. Systemic adjuvant hormonal therapy had been applied in 24% and systemic chemotherapy in 19% of patients. Several combinations were used. Treatment of recurrences consisted of surgical tumor excision in 74%, megavoltage irradiation in 83%, additional hormonal therapy in 41%, and chemotherapy in 12% of patients, employing different combinations. Local control in the recurrent site was achieved in 86%. Median follow-up for patients alive at the time of analysis was 8.9 years after recurrence. We tested different prognostic factors, including prior treatment and treatment of recurrence, for their influence on postrecurrence survival, using univariate and multivariate analysis. RESULTS: Eighty-two of the 145 patients (57%) developed distant metastases within the follow-up period. Metastases-free rate was 42% at 2 years and 36% at 10 years following recurrence. With development of distant metastases, the survival rate deteriorated. Recurrences appeared within the first 2 years from primary surgery in 56% of patients, and in 89% within 5 years. Overall, 2-year and 5-year survival rates following local-regional recurrence were 67% and 42%, respectively. Univariate analysis revealed statistically significant worsening of survival rates for pT3 + 4 primary tumors, primary axillary lymph node involvement, tumor grading 3 + 4, lymphatic vessel invasion, blood vessel invasion, tumor necrosis, negative estrogen (ER) and progesterone (PR) hormonal receptor status, postmastectomy chemotherapy and hormonal therapy, short time to recurrence (< 1 year), combined recurrences and supraclavicular site of recurrence, non-scar recurrence, size of the largest recurrent nodule > 5 cm, multiple recurrent nodules, no surgical excision of recurrence, small target volume of irradiation, chemotherapy for recurrence, and no local control within the recurrence site. The 2-year and 5-year survival rates ranged from 68% to 94%, and from 33% to 65%, respectively, in the favorable subgroups compared to 2-year and 5-year survival rates ranging from 20% to 59% and 0% to 35%, respectively, in the unfavorable subgroups. Multivariate analysis showed that site of recurrence and number of recurrent nodules have the strongest influence on postrecurrence survival, but time to recurrence, age at time of recurrence, local control in recurrent site as well as primary pT and axillary status, and the presence of tumor necrosis in the primary tumor specimen showed additional independent influences on survival. Thus, we identified a highly favorable subgroup of patients with a single chest wall or axillary recurrent nodule (in a patient aged > 50 years), a disease-free interval of > or = 1 year, pT1-2N0 primary tumor, and without tumor necrosis, and whose recurrence is locally controlled. This group (12 patients) had 5- and 10-year survival rates of 100% and 69%, respectively. CONCLUSION: We conclude that locoregional recurrence of breast cancer following mastectomy is not always a sign of systemic disease. Our data support previous findings, that subgroups with favorable prognosis exist and they still have a chance for cure, demanding comprehensive local treatment. (ABSTR

The prognostic significance of the supraclavicular lymph node metastases in breast cancer patients.

PURPOSE: To define the patterns of failure and outcome of patients presenting supraclavicular lymph node involvement and the prognostic significance of supraclavicular lymph node involvement. METHODS AND MATERIALS: We reviewed the history of 795 breast cancer patients treated at the Department of Radiation Therapy, University of Würzburg between 1978 and 1988. The clinical and pathologic features of 21 patients who had ipsilateral supraclavicular lymph node metastases at primary diagnosis and 38 patients who presented supraclavicular lymph node recurrence during the course of disease were reviewed. These were compared with the features of 20 patients who initially had M1 status at primary diagnosis and 278 patients who had developed distant metastases in the follow-up period. Survival rates were calculated starting from the time of diagnosis of supraclavicular involvement respective of distant metastases. RESULTS: Survival from appearance of supraclavicular lymph node metastases at primary diagnosis or as a recurrence is not different from survival of patients presenting with a primary M1 stage or presenting distant metastases during the course of disease. Two and 5-year survival rates of patients with supraclavicular lymph node involvement at primary diagnosis were 52% and 34% compared to 50% and 16% 2- and 5-year survival rate of patients with supraclavicular lymph node involvement as a recurrence. Patients who presented a primary M1-status had 2- and 5-year survival rates of 56% and 24%. Survival of patients with distant metastases calculated from the onset of metastatic disease was similar to that of the other three groups with a 46% and 16% survival rate at 2 and 5 years. There was no difference in survival rates between the four groups. CONCLUSION: The prognostic significance of supraclavicular lymph node involvement at primary diagnosis or as a relapse is similar, both have the same significance as the first distant relapse and are characterized by a poor prognosis.

The influence of the radicality of resection and dose of postoperative radiation therapy on local control and survival in carcinomas of the upper aerodigestive tract.

PURPOSE: To evaluate dose concepts in postoperative irradiation of carcinomas of the upper aerodigestive tract according to the radicality of resection. PATIENTS AND METHODS: In a retrospective analysis, the charts of 257 patients with histologically-proven carcinoma of the upper aerodigestive tract (40 T1, 80 T2, 53 T3, 84 T4 tumors, with nodal involvement in 181 cases) were reviewed according to the radicality of resection and dose of irradiation administered. Sixty-four patients had tumor-free resection margins (> 3 mm), 66 patients had close resection margins (< 3 mm), and 101 patients had R1 resections, and 26 patients had R2 resections. A median dose of 56 Gy was applied to the primary tumor bed and the cervical lymphatics (2 Gy/fraction, 5 fractions/week). In cases of R1 or R2 resection, or of close margins (< 3 mm), the tumor bed or, respectively, tumor residuals were boosted with doses up to a median of 66 Gy. Locoregional tumor control and survival was investigated by uni- and multivariate analyses according to T-, N-stage, grade of resection, total dose of radiation, and presence or absence of extracapsular tumor spread and lymphangiosis carcinomatosa. RESULTS: An overall 3- and 5-year survival rate of 60% and 45%, respectively, was achieved. Rates for freedom from locoregional recurrence were 77% and 72% at 3 and 5 years, respectively. The survival rates according to the grade of resection at 5 years were 67% for patients resected with tumor-free margins, 59% for patients resected with close margins, 26% for patients with R1 resection, and 27% for patients with R2 resection. Within a median follow-up period of 4.7 years for living patients, a total of 67 recurrences (26%) were observed (in 9% of patients resected with tumor-free margins, in 27% with close margins, in 37% of R1 resected, and in 19% of R2 resected patients). Freedom from locoregional recurrence at 3 years was achieved in 100% of the patients resected with tumor-free margins, in 92% of patients resected with close surgical margins, in 87% of R1 and 69% of R2 resected patients. In multivariate Cox-regression analysis, the variables grade of resection (p = 0.00031) and total dose of irradiation (p = 0.0046) were found as factors influencing locoregional control. Variables influencing survival according to multivariate analysis are T-stage (p = 0.0057), N-stage (p = 0.024), grade of resection (p = 0.000015), total dose of irradiation (p < 0. 000000). Extracapsular tumor spread and lymphangiosis carcinomatosa are factors of borderline significance (p = 0.055, p = 0.066). CONCLUSION: In postoperative radiotherapy of head and neck carcinomas, doses adapted to the risk of locoregional recurrent disease should be applied. Patients with R1 and R2 resections should be treated with doses of more than 68 Gy (2 Gy/fraction, 5 fractions/week) (with close margins [< 3 mm] more than 66 Gy) to achieve an improvement in locoregional control and survival.

Carcinoma of the external auditory canal and middle ear.

PURPOSE: To evaluate therapeutic modalities used at our institutions regarding local control, disease-free survival and actuarial survival in carcinoma of the external auditory canal and middle ear, in an attempt to provide guidelines for therapy. METHODS AND MATERIALS: A series of 27 patients with carcinoma of the external auditory canal and middle ear treated between 1978 and 1997 in our institutions were analyzed with particular reference to tumor size and its relation to surrounding tissues, patterns of neck node involvement, surgical procedures, and radiation techniques employed. Clinical endpoints were freedom from local failure, overall survival, and disease-free survival. The median follow-up was 2.7 years (range 0.1-17.9 years). RESULTS: Treatment by surgery and radiotherapy resulted in an overall 5-year survival rate of 61%. According to the Pittsburgh classification, the actuarial 5-year survival rate for early disease (T1 and T2 tumors) was 86%, for T3 tumors 50%, and T4 stages 41%. Patients with tumors limited to the external auditory canal had a 5-year survival rate of 100%, patients with tumor invasion of the temporal bone 63%, and patients with tumor infiltration beyond the temporal bone 38%. The rate of freedom from local recurrence was 50% at 5 years. Unresectability by dural and cerebral infiltration, and treatment factors such as complete resection or resection with tumor beyond surgical margins are of prognostic relevance. All patients with dural invasion died within 2.2 years. The actuarial 5-year survival rate of patients with complete tumor resection was 100%, but 66% in patients with tumor beyond surgical margins. 192Iridium high-dose-rate (HDR) afterloading brachytherapy based on three-dimensional computed tomography (3D CT)-treatment planning was an effective tool in management of local recurrences following surgery and a full course of external beam radiotherapy. CONCLUSION: Surgical resection followed by radiotherapy adapted to stage of disease and grade of resection is the preferred treatment of cancer of the external auditory canal and middle ear.

CT simulation in stereotactic brain radiotherapy--analysis of isocenter reproducibility with mask fixation.

BACKGROUND AND PURPOSE: CT verification and measurement of isocenter deviation using repeated mask fixation in linac-based stereotactic high dose radiotherapy of brain metastases were performed in this study. MATERIALS AND METHODS: For stereotactic radiotherapy of brain metastases a commercial head mask fixation device based on thermoplastic materials (BrainLAB) was used. A two-step planning-treatment procedure was performed. Immediately before treatment the patient was relocated in the mask and a verification CT scan of the radiopaque marked isocenter was performed and if necessary its position was corrected. The verification procedure is described in detail. Twenty-two CT verifications in 16 patients were analyzed. Deviations were measured separately for each direction. A 3D-deviation vector was calculated. Additionally the average amount of deviation in each of the three dimensions was calculated. RESULTS: The mean deviation and standard deviation (SD) of the isocenter was 0.4 mm (SD 1.5 mm) in the longitudinal direction, -0.1 mm (SD 1.8 mm) in the lateral direction and 0.1 mm (SD 1.2 mm) in the anterior-posterior direction. The mean three-dimensional distance (3D-vector) between the verified and the corrected isocenter was 2.4 mm (SD 1.3 mm). The average deviation (without consideration of direction) was 1.1 mm (SD 1.1 mm), 1.3 mm (SD 1.3 mm) and 0.8 mm (SD 0.9 mm) in the longitudinal, lateral and sagittal directions, respectively. No correlation was found between 3D-deviation and the distance of the isocenter from the reference plane nor between deviation and the position of metastases in the brain (central versus peripheral or between different lobes), or the date of treatment. CONCLUSION: Reproducibility of the isocenter using the presented mask fixation is in the range of positioning reproducibility reported for other non-invasive fixation devices for stereotactic brain treatment. Our results underline the importance of CT verification as a quality assurance method in stereotactic radiotherapy. Under the condition of a preceding CT verification the mask can be used for single dose stereotactic radiotherapy. For fractionated stereotactic irradiation of small target volumes we recommend repeated CT verifications to assure reproducibility.

Three dimensional variability in patient positioning using bite block immobilization in 3D-conformal radiation treatment for ENT-tumors.

BACKGROUND AND PURPOSE: The aim of this prospective study was to analyze the three-dimensional (3D) reproducibility of the isocenter position and of patient positioning with the use of bite block immobilization by means of a simple verification procedure for a complex beam arrangement applied for ENT-tumors. MATERIALS AND METHODS: We analyzed the positioning data of 29 consecutive patients treated for ENT-tumors at the Department of Radiotherapy and Oncology of the University of Wurzburg. A total of 136 treatment sessions were analyzed. Patients were positioned and immobilized using an individualized bite block system and a head and neck support. A complex beam arrangement was applied combining two offset rotational and two oblique wedge fields on a 5 MV linear accelerator. Orthogonal verification films were taken once weekly. Four to six film pairs per patient were obtained (during 4-6 weeks) with a mean number of 4.7 film pairs per patient. These were compared to the corresponding orthogonal simulator films taken during primary simulation. Deviations of the verified isocenter from the isocenter on the simulator film were measured and analyzed in three dimensions in terms of overall, systematic and random categories. A 3D-deviation vector was calculated from these 3D data as well as a 2D-deviation vector (for comparison with literature data) from the lateral verification films. RESULTS: The overall setup deviation showed standard deviations (SD) of 2.5, 2.7 and 3.1 mm along the cranio-caudal, anterior-posterior and medio-lateral axes, respectively. The random component ranged from SD 1.9 to 2.1 mm and the systematic component ranged from SD 1.8 to 2.2 mm. The mean length of the 3D-vector was 3.1 mm for the systematic as well as the random component. Ninety percent of 3D systematic and random deviations were less than 5 mm. The mean length of the 2D-vector was 2.4 mm for the random component and 2.2 mm for the systematic component. Ninety percent of 2D-random and systematic variations were less than 4 mm. CONCLUSIONS: The presented individualized bite block immobilization device provides an accurate and reproducible patient positioning for 3D-conformal radiation therapy in the head and neck. Random and systematic deviations in each of the three directions are in the range of +/-4 mm (2 SD, comprising 95% of the deviations) and are within the range or even less than deviations described for most thermoplastic or PVC-mask fixation devices. These deviations should be taken into account during definition of planning target volume in head and neck tumors.

Prenatal diagnosis of trisomy 4 mosaicism.

Trisomy 4 mosaicism is rare. To our knowledge only two cases of prenatally diagnosed trisomy 4 mosaicism have been reported. One case resulted in a normal liveborn male, the other resulted in an abnormal liveborn female. The karyotype of our case at the time of amniocentesis was 47,XY,+4[3]/ 46,XY[33] and resulted in a normal liveborn male. FISH analysis using an alpha satellite chromosome 4 probe was performed to confirm the cytogenetic findings. Follow-up chromosome analysis of cord blood, peripheral blood, foreskin, and umbilical cord fibroblasts showed a normal 46,XY male karyotype in all cells. FISH analysis of cord blood, umbilical cord fibroblasts, and amniotic fluid cells demonstrated two signals in 246 nuclei (i.e., 46,XY) and three signals in six nuclei (i.e., 47,XY,+4). Here we describe the present case of trisomy 4 mosaicism, the literature is reviewed, and the significance of this finding is discussed.

Prenatal diagnosis of a fetus with two balanced de novo chromosome rearrangements.

Two apparently balanced chromosome rearrangements were identified in a 17-week fetus by analysis of cultured amniocytes. The fetal karyotype was 46,XX,t(2;16) (q33;q24), inv(7)(p15q11.23). Parental karyotypes were normal, indicating a de novo origin of both chromosome rearrangements in the fetus. The risk of phenotypic abnormality from a de novo reciprocal translocation of inversion has been estimated at approximately 7% [Warburton, 1991]. The risk of abnormality in this fetus was estimated to be a minimum of 14%, based on the additive risk of each rearrangement, equivalent to 3.5% per chromosome breakpoint. The pregnancy was terminated because of the risk of abnormality and the detection of intrauterine growth retardation by ultrasound. In the absence of additional experience, the minimum presumed risk of phenotypic abnormality for de novo, multiple or complex chromosome rearrangements identified prenatally may be estimated as the additive risk of the number of chromosome breakpoints involved.