Final results from the prospective phase III WSG-ARA trial: impact of adjuvant darbepoetin alfa on event-free survival in early breast cancer.

BACKGROUND: WSG-ARA plus trial evaluated the effect of adjuvant darbepoetin alfa (DA) on outcome in node positive primary breast cancer (BC). PATIENTS AND METHODS: One thousand two hundred thirty-four patients were randomized to chemotherapy either with DA (DA+; n = 615) or without DA (DA-; n = 619). DA (500 µg q3w) was started at hemoglobin (Hb) levels <13.0 g/dl (<12 g/dl after DA label amendment) and stopped at Hb levels ≥14.0 g/dl (12 g/dl after label amendment). Primary efficacy end point was event-free survival (EFS); secondary end points were toxicity, quality of life (QoL) and overall survival (OS). RESULTS: Venous thrombosis (DA+: 3.0%, DA-: 1.0%; P = 0.013) was significantly higher for DA+, but not pulmonary embolism (0.3% in both arms). Median Hb levels were stable in DA+ (12.6 g/dl) and decreased in DA- (11.7 g/dl). Hb levels >15 g/dl were reported in 0.8% of cycles. QoL parameters did not significantly differ between arms. At 39 months, DA had no significant impact on EFS (DA+: 89.3%, DA-: 87.5%; Plog-rank = 0.55) or OS (DA+: 95.5%, DA-: 95.4%; Plog-rank = 0.77). CONCLUSIONS: DA treatment did not impact EFS or OS in routine adjuvant BC treatment.

Randomized phase 2 trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine: the TREAT study.

BACKGROUND: Adjuvant chemotherapy is beneficial in non-small-cell lung cancer (NSCLC). However, balancing toxicity and efficacy mandates improvement. PATIENTS AND METHODS: Patients with completely resected stages IB-pT3N1 NSCLC were randomly assigned to either four cycles cisplatin (C: 50 mg/m(2) day (d)1 + 8) and vinorelbine (V: 25 mg/m(2) d1, 8, 15, 22) q4 weeks or four cycles cisplatin (75 mg/m(2) d1) and pemetrexed (Px: 500 mg/m(2) d1) q3 weeks. Primary objective was the clinical feasibility rate (no grade (G)4 neutropenia/thrombocytopenia or thrombocytopenia with bleeding, no G3/4 febrile neutropenia or non-hematological toxicity; no premature withdrawal/death). Secondary objectives were drug delivery and efficacy. RESULTS: One hundred and thirty two patients were randomized (stages: 38% IB, 10% IIA, 47% IIB, 5% pT3pN1; histology: 43% squamous, 57% non-squamous). The feasibility rates were 95.5% (cisplatin and pemetrexed, CPx) and 75.4% (cisplatin and vinorelbine, CVb) (P = 0.001); hematological G3/4 toxic effects were 10% (CPx) and 74% (CVb) (P < 0.001), non-hematological toxic effects were comparable (33% and 31%, P = 0.798). Delivery of total mean doses was 90% of planned with CPx, but 66% (cisplatin) and 64% (vinorelbine) with CVb (P < 0.0001). The median number of cycles [treatment time (weeks)] was 4 for CPx (11.2) and 3 for CVb (9.9). Time to withdrawal from therapy differed significantly between arms favoring CPx (P < 0.001). CONCLUSION: Adjuvant chemotherapy with CPx is safe and feasible with less toxicity and superior dose delivery compared with CVb.

In vivo chemosensitivity-adapted preoperative chemotherapy in patients with early-stage breast cancer: the GEPARTRIO pilot study.

BACKGROUND: Response to the first two cycles of preoperative chemotherapy might differentiate subgroups of breast cancer patients with high or minimal chances for a pathologic complete response (pCR) and may be used as an in vivo chemosensitivity test. METHODS: Breast cancer patients were treated with two cycles of TAC (docetaxel 75 mg/m(2), doxorubicin 50 mg/m(2), cyclophosphamide 500 mg/m(2) every 21 days). Patients whose tumors showed a response received four more cycles. Patients whose tumors did not respond were randomized to four additional cycles TAC or NX (vinorelbine 25 mg/m(2) days 1 and 8, capecitabine 2000 mg/m(2) days 1-14, every 21 days). The primary end point was pCR at surgery. RESULTS: Two hundred and eighty-five patients showed a clinical response, in 73.0% after two cycles, in 88.4% at surgery, and a pCR was seen in 17.9%. Breast conservation was possible in 72.2%. Responding patients obtained a pCR in 22.6% whereas non-responding patients reached a pCR in 7.3% and 3.1% with TAC or NX, respectively. Grade III/IV neutropenia and febrile neutropenia were observed during TAC in 70.2% and 13.5%, respectively. Significantly less toxicity were observed with NX. CONCLUSION: Early response to TAC can reliably identify patients with a high chance of achieving a pCR. New effective treatments need to be explored for patients without an early response.

Perfusion CT in patients with advanced bronchial carcinomas: a novel chance for characterization and treatment monitoring?

Advanced bronchial carcinomas by means of perfusion and peak enhancement using dynamic contrast-enhanced multislice CT are characterized. Twenty-four patients with advanced bronchial carcinoma were examined. During breathhold, after injection of a contrast-medium (CM), 25 scans were performed (1 scan/s) at a fixed table position. Density-time curves were evaluated from regions of interest of the whole tumor and high- and low-enhancing tumor areas. Perfusion and peak enhancement were calculated using the maximum-slope method of Miles and compared with size, localization (central or peripheral) and histology. Perfusion of large tumors (> 50 cm3) averaged over both the whole tumor (P = 0.001) and the highest enhancing area (P = 0.003) was significantly lower than that of smaller ones. Independent of size, central carcinomas had a significantly (P = 0.04) lower perfusion (mean 27.9 ml/min/100 g) than peripheral ones (mean 66.5 ml/min/100 g). In contrast, peak enhancement of central and peripheral carcinomas was not significantly different. Between non-small-cell lung cancers and small-cell lung cancers, no significant differences were observed in both parameters. In seven tumors, density increase after CM administration started earlier than in the aorta, indicating considerable blood supply from pulmonary vessels. Tumor perfusion was dependent on tumor size and localization, but not on histology. Furthermore, perfusion CT disclosed blood supply from both pulmonary and/or bronchial vessels in some tumors.

[Fluoroscopy based surgical navitation vs. mechanical guidance system for percutaneous interventions. A controlled prospective study exemplified by distal locking of intramedullary nails]. / Fluoroskopiebasierte chirurgische Navigation vs. mechanisches Zielsystem für perkutane Eingriffe. Eine kontrollierte prospektive Studie am Beispiel der distalen Verriegelung von Marknägeln.

The aim of this study was to directly compare mechanically based targetting and surgical navigation when applied for percutaneous osteosynthesis. The distal locking procedure of intramedullary nails was used as the clinical model for a controlled prospective study. A total of 50 patients were included in two groups. In group 1, the distal locking was done with a mechanical aiming device while in group 2 this was done using a fluoroscopy based surgical navigation system. The target parameters were the precision attained, the necessary operation and fluoroscopy times as well as the number and severity of intra-operative problems. The drill-bit failed to pass through the interlocking hole in one patient with mechanical guidance and in two patients with surgical navigation. The average procedure time for distal locking with mechanical guidance was 6.9 minutes compared with 37.6 minutes with surgical navigation. An additional 44 minutes were required before skin incision and after skin closure as setup time for the navigation system. There was no significant difference in the fluoroscopy time or in the number of intra-operative technical problems. Surgical navigation increased the demand for resources but failed to improve the precision of distal locking compared with mechanical guidance. Further clinical studies are required to determine to what degree these results, using a special model, relate to other applications.

Accuracy of tumor size measurement in breast cancer using MRI is influenced by histological regression induced by neoadjuvant chemotherapy.

The aim of this study was to evaluate whether regressive changes after neoadjuvant chemotherapy for breast cancer affect the accuracy of preoperative MRI measurements of tumor size. Thirty-one patients with breast cancer underwent MRI before and after neoadjuvant treatment. Besides pre- and post-contrast T1-weighted MRI, dynamic MRI with high temporal resolution (turbo-FLASH) was performed. Contrast enhancement in dynamic MRI was quantified using a pharmacokinetic two-compartment model, where two parameters, amplitude and k(ep), were calculated and color coded on transversal parameter maps. Considering the conventional MR images, tumor diameters were measured on the color maps and compared with histological tumor size. Histological regression was scored on a five-point scale regarding cytopathic effects, reactive changes, and tumor cell reduction. The correlation between tumor sizes measured by MRI and histopathology was 0.83 ( p<0.0007) in 12 tumors without regressive changes (score 0), and 0.48 ( p<0.051) in 17 tumors with regressive changes scored 1 or 2, without any tendency for systematic over- or underestimation. In two cases without residual tumor (score 4), MRI likewise showed no signs of persistent tumor. The decrease of the contrast enhancement parameters was significantly more marked in tumors with signs of histological regression than in those without. Whenever MRI is used to judge the response of breast cancer to chemotherapy, the reader must be aware that therapy-induced changes may cause significant over- or underestimation of tumor size. We saw a high precision only when there was either no response - according to histological criteria - or when the tumor had regressed completely.

Evaluation of neoadjuvant chemotherapeutic response of breast cancer using dynamic MRI with high temporal resolution.

The aim of this study was to evaluate changes in both size and contrast enhancement of breast tumors during neoadjuvant chemotherapy, using dynamic MRI with high temporal resolution. Patients with advanced breast cancer (n=21) underwent a 1.5-T MRI scan prior to and following neoadjuvant chemotherapy with four cycles. Dynamic contrast enhancement was measured using a fast turbo-FLASH sequence and quantified using a two-compartment model with the parameters k(ep) and amplitude. Image analysis was done on images overlayed with a color map of parameters. The correlation between tumor diameter measured by histopathology and MRI was 0.7 (p<0.003). A reduction of tumor size after chemotherapy of more than 25% was associated with a decrease of both analyzed contrast enhancement parameters (k(ep): p<0.002; amplitude: p<0.006), where k(ep) began to drop already after the first cycle of chemotherapy (p<0.008). A clear reduction of tumor size was only noted after the third cycle (p<0.008). In patients without tumor regression there was also a trend towards an early reduction of contrast enhancement. We assume that MRI with high temporal resolution and color mapping is a novel tool to assess therapeutic effects of neoadjuvant chemotherapy in breast tumors, which deserves further prospective evaluation.

Calcification in coronary arteries as quantified by CT scans correlated with tobacco consumption in patients with inoperable non-small cell lung cancer treated with three-dimensional radiotherapy.

It has been shown that radiological manifestations of coronary artery sclerosis are an indirect measure of co-morbidity and predictive of survival. The aim of the present study is to evaluate the outcome and side effects after three-dimensional (3D) radiotherapy in patients with unresectable non-small cell lung cancer (NSCLC) stage I, II and IIIA, depending on coronary artery calcification, Karnofsky performance index (KI) and co-morbidity. Between 1993 and 1999, 89 patients with unresectable NSCLC were treated with 3D-radiotherapy. The median age was 66.6 years and median KI 80%. All patients had 3D-treatment planning, based on CT scans. The median total dose was 60 Gy in 2 Gy fractions five times a week. The mean follow-up period was 13.2 months and mean survival time 12.2 months. Significant prognostic factors for improved survival were KI and tumour stage. Patients with a KI<90% had a median survival of 6.5 months compared with 14 months, in patients with KI>/==" BORDER="0">90% (p<0.001). NSCLC stage I+II showed a significantly longer median survival than patients with NSCLC stage IIIA (16.5 months versus 7 months, p<0.004). A significant correlation was seen between pack-years and coronary artery calcification (p<0.05) and between age and marked coronary artery calcification. The incidence of calcification was 67% in smokers (>/==" BORDER="0">20 pack-years) and 43/58 in patients >60 years (p<0.007). Side effects, e.g. pneumonitis, did not correlate with coronary artery calcification but correlated with chronic obstructive lung disease in 19/89 patients. Conventional CT scans for 3D-treatment planning are able to detect coronary artery calcification. There is a significant correlation between age, KI, tobacco consumption and vascular calcification. Although there was a trend to worse overall survival, coronary artery calcification was not a significant predictor of progression-free and overall survival.

Comparison of B-mode and conventional colour/power Doppler ultrasound, contrast-enhanced Doppler ultrasound and spiral CT in the diagnosis of focal lesions of the liver: Results of a multicentre study.

AIM: In patients with lesions of the liver we compared diagnoses based on different methods of ultrasound as well as spiral CT with the final diagnosis reached at the time of the patient's discharge from hospital. METHOD: From records of a prospective multicentre study including 90 liver lesions investigated with B-mode baseline and conventional colour/power Doppler ultrasound, contrast-enhanced colour/power Doppler ultrasound and spiral-CT, we evaluated only those where diagnoses for all modalities were available, and where the diagnosis at discharge comprising all clinical, laboratory and imaging data as well as histologic proof was at least "highly probable". RESULTS: 60 lesions met the inclusion criteria. 20 lesions were ultimately diagnosed as benign, and 40 as malignant. With respect to the diagnosis of malignancy, sensitivity was 92.5 % (37/40) with B-mode and unenhanced conventional colour/power Doppler US ultrasound, 97.5 % (39/40) with contrast-enhanced colour/ power Doppler ultrasound, and 100 % with CT; the corresponding specificities were 65 % (13/20), 85 % (17/20) and 80 % (16/20). 4 of 7 false positive, and 2 of 3 false negative results in the unenhanced technique were diagnosed correctly with contrast-enhanced Doppler ultrasound. CONCLUSION: Compared to conventional ultrasound, contrast-enhanced Doppler ultrasound improved the diagnostic accuracy in 10 % of the cases. Its accuracy in our study was equal to that of CT.

[Multi-slice CT in the planning of nephron-sparing interventions for renal cell carcinoma: Prospective study correlated with histopathology]. / Multi-Slice-CT in der Planung der organerhaltenden Operation des Nierenzellkarzinoms: Prospektive histopathologisch korrelierte Studie.

OBJECTIVE: For nephron sparing surgery of renal cell carcinoma knowledge of the intrarenal extension of the tumor and infiltration of the renal pelvis, the intrarenal vessels and the perinephric fat is essential. This question is much more difficult to answer compared to the description of staging parameters. Aim of this study is to evaluate the value of multi-slice CT in planning of nephron sparing surgery. MATERIAL AND METHODS: In a prospective study 46 patients with suspected renal cell carcinoma underwent a triphasic multi-slice CT (unenhanced, delay 30 s and 120 s). A reconstructed slice thickness of 2 mm in the arterial and parenchymal phase was used to create volume rendered 3D-reconstructions. Based on the source data and multiplanar reconstructed images the extent of the renal cell carcinoma was assessed in terms of size, hilar infiltration, arterial and venous invasions, capsula infiltration and perirenal growth. The results of two blinded readers were correlated with histopathological staging and intraoperative findings. RESULTS: 36 carcinomas were evaluated histopathologically. 10 patients showed no renal cell carcinoma histopathologically. Multi-slice CT allowed us to diagnose the localization and size of all tumors correctly. Infiltration into perinephric fat was correctly excluded in 24/30 and 8/30 cases. Infiltration of the renal pelvis could be excluded in 17/24 and 12/24 cases. The state of venous infiltration could be correctly diagnosed in 29/30 and 27 /30 carcinomas. CONCLUSION: Despite of the high temporal and spatial resolution of multi-slice CT, which allows the delineation of intrarenal arteries as well as renal hilus and the veins, the evaluation of tumor infiltration into the renal hilus, the intrarenal vessels and the perinephric fat remains a diagnostic problem. For planning of nephron sparing surgery, a knowledge of the infiltration in these structures is essential.

Comparison of forward planned conformal radiation therapy and inverse planned intensity modulated radiation therapy for esthesioneuroblastoma.

The purpose of this study was to compare dose distribution of inverse planned intensity modulated radiation therapy (IMRT) with that of conformal radiation therapy (SCRT) in the treatment of esthesioneuroblastoma, and to report initial clinical results. 13 patients with esthesioneuroblastoma were planned both with IMRT and SCRT using complete three-dimensional data sets. A target dose of 60 Gy was prescribed. We performed a detailed dose volume histogram analysis. Dose coverage was equal in both plans while dose distribution was more conformal to the target volume with IMRT. Mean and maximum dose of the brain stem, chiasm, optic nerves and orbits were lower using IMRT than SCRT. The reduction was significant regarding orbit and optic nerve (p<0.05). IMRT was superior in sparing of organs at risk compared with SCRT. The additional sparing by IMRT was positively correlated to the size of the target volume, which was evident with target volumes above 200 cm3. Treatment time was approximately 20 minutes per fraction using IMRT compared with 15 minutes per fraction using SCRT. We conclude that IMRT is both feasible and a valuable tool for more conformal dose distribution in the treatment of esthesioneuroblastoma and to spare organs at risk that are in critical relationship to the tumour. This advantage could be seen especially well in complex shaped target volumes above 200 cm3. Thus, using IMRT, risk of complications may be minimized and local tumour control may be increased.

Systemic chemotherapy with epirubicin for treatment of advanced or multifocal hepatocellular carcinoma.

BACKGROUND: The purpose of this retrospective study was to determine the response rate and effect on survival of chemotherapy with epirubicin in non-resectable advanced hepatocellular carcinoma (HCC). METHODS: Fifty-two patients with non-resectable disease were treated with epirubicin. A treatment cycle consisted of 20 mg/m(2) i.v. on days 1, 8 and 15 and was repeated every 4 weeks to a maximum dose of 1,000 mg/m(2). Forty-four patients were eligible for analysis. RESULTS: Out of 44 patients, 1 (2.3%) achieved a complete response, 3 (6.8%) had partial responses and 16 (36%) had stable disease (SD). For patients with successful disease control (complete and partial responders and patients with SD), the median survival was 16.2 months; for non-responders, it was 6.1 months (p < 0.003). Eight (88.9%) of 9 patients with alpha-fetoprotein (AFP) levels <50 microg/l achieved successful disease control compared to 12 (34.9%) out of 35 patients with initially elevated AFP (p < 0.0001). CONCLUSION: Epirubicin appears to be an active therapeutic option for patients with non-resectable HCC. Especially the subgroup of patients with low levels of AFP may benefit from this treatment.

Proton MR spectroscopic evaluation of suspicious brain lesions after stereotactic radiotherapy.

BACKGROUND AND PURPOSE: The radiologic assessment of suspicious brain lesions after stereotactic radiotherapy of brain tumors is difficult. The purpose of our study was to define parameters from single-voxel proton MR spectroscopy that provide a probability measure for differentiating neoplastic from radiation-induced, nonneoplastic lesions. METHODS: Seventy-two lesions in 56 patients were examined using a combined MR imaging and MR spectroscopy protocol (point-resolved spectroscopy, TE = 135 ms). Signal intensities of cholines, creatines, N-acetyl aspartate, and the presence of lactate and lipid resonances were correlated to final diagnoses established by clinical and MR imaging follow-up, positron emission tomography studies, or biopsy/surgery. Statistical analysis was performed using the t test, linear discriminant analysis, and k nearest-neighbor method. RESULTS: Significantly increased signal intensity ratios I(tCho)/I(tCr) (P <.0001) and I(tCho)/I(NAA) (P <.0001) were observed in neoplastic (n = 34) compared with nonneoplastic lesions (n = 32) and contralateral normal brain (n = 33). Analysis of I(tCho)/I(tCr) and I(tCho)/I(NAA) data yielded correct retrospective classification as neoplastic and nonneoplastic in 82% and 81% of the lesions, respectively. Neither I(NAA)/I(tCr) nor signal intensitities of lactate or lipids were useful for differential diagnosis. CONCLUSION: Metabolic information provided by proton MR spectroscopy is useful for the differentiation of neoplastic and nonneoplastic brain lesions after stereotactic radiotherapy of brain tumors.

High efficacy of fractionated stereotactic radiotherapy of large base-of-skull meningiomas: long-term results.

PURPOSE: Large skull-base meningiomas are difficult to treat due to their proximity or adherence to critical structures. We analyzed the long-term results of patients with skull-base meningiomas treated by a new approach with high-precision fractionated stereotactic radiotherapy. PATIENTS AND METHODS: One hundred eighty-nine patients with benign meningiomas were treated with conformal fractionated stereotactic radiotherapy between 1985 and 1998. Patients were undergoing a course of radiotherapy either as primary treatment, following subtotal resection, or for recurrent disease. The median target volume was 52.5 mL (range, 5.2 to 370 mL). The mean radiation dose was 56.8 Gy (+/- 4.4 Gy). Follow-up examinations, including magnetic resonance imaging, were performed at 6-month intervals thereafter. RESULTS: The median follow-up period was 35 months (range, 3 months to 12 years). Overall actuarial survival for patients with World Health Organization (WHO) grade I meningiomas was 97% after 5 years and 96% after 10 years. Local tumor failure was observed in three of 180 patients with WHO grade I tumors and was significantly higher in two of nine patients with WHO grade II tumors. A volume reduction of more than 50% was observed in 26 patients (14%). Preexisting cranial nerve symptoms resolved completely in 28% of the patients. Clinically significant treatment-induced toxicity was seen in 1.6% of the patients. No treatment-related deaths occurred. CONCLUSION: The results of this study demonstrate that fractionated stereotactic radiotherapy is safe and effective in the therapy of subtotally resected or unresectable meningiomas. The overall morbidity and incidence subacute and late side effects of this conformal radiotherapy approach were low.

Fibroadenomas: computer-assisted quantitative evaluation of contrast-enhanced power Doppler features and correlation with histopathology.

We aimed to evaluate whether the histopathologic variability of fibroadenomas accounts for their varied appearance in contrast enhanced power Doppler (PD). Forty patients with fibroadenomas (aged 19 to 61 years) underwent power Doppler ultrasound (US) prior to and following IV bolus injection of a microbubble contrast agent. A 3-min computer-assisted assessment of the color pixel density (CPD) was used for objective evaluation of the increase in color Doppler signals. Enhancement characteristics were correlated to histopathologic features of microvessel density and epithelial hyperplasia, patient's age, tumor size, use of exogenous hormones and menopausal status. Epithelial hyperplasia was diagnosed in 19 patients. Compared to baseline values, patients with epithelial hyperplasia showed a significant increase in mean CPD following contrast media administration (p < 0.01). There was a significant correlation to patient's age (p < 0.0001) and tumor size (p < 0.0001), but not to the use of exogenous hormones and menopausal status. Microvessel counts did not show a significant correlation to CPD at baseline (p = 0.07) or with CPD on contrast enhanced PD (p = 0.13), or with patient age (p = 0.43) or tumor size (p = 0.34). Intratumoral epithelial hyperplasia, primarily occurring in young patients, may contribute to the differential diagnostic overlap in some fibroadenomas and thus limit the ability of PD to distinguish between benign and malignant masses on the basis of enhancement characteristics.

[Imaging the smallest tumor vessels using color Doppler ultrasound in an experiment]. / Darstellbarkeit kleinster Tumorgefässe mit Hilfe der Farbdopplersonographie im Experiment.

PURPOSE: We present an experimental, statistical approach to estimate the size required for small vessels to become detectable with color Doppler sonography. MATERIALS AND METHODS: A murine experimental tumor was examined with color Doppler sonography after injection of 1.5 ml of the contrast medium Levovist. Histologically, we measured vessel diameters inside the tumor as well as other, clearly identifiable locations. RESULTS: With color Doppler at a transmit frequency of 7 MHz, vessels were only detected in the tumor's environment, but not inside. From the 95% quantiles of the vessel diameter distribution found histologically, we estimate that vessels 80-140 microns in diameter or above may be detectable with color Doppler sonography, while vessels 40 microns in diameter or smaller are indetectable. CONCLUSIONS: Although a direct sonographic--histologic correlation is impossible for small vessels, a systematic assessment of the size distribution in clearly identifiable regions permits to estimate the sensitivity of color Doppler to detect blood flow in small vessels. According to our results, capillary blood flow is indetectable, and precapillary vessels may be detected only under optimal conditions.

[Radiation exposure of the patient by intraoperative imaging of intramedullary osteosyntheses]. / Strahlenexposition des Patienten durch intraoperative Bildgebung bei Marknagelosteosynthesen.

MATERIAL AND METHOD: 39 patients with pertrochanteric femur fracture (n = 32) or lower leg fracture (n = 7) were treated with closed intramedullary nailing. The related radiation exposure of the patients was calculated. RESULTS: Osteosynthesis of pertrochanteric fractures took less fluoroscopic time than osteosynthesis of lower leg fractures. The effective dose was 14 mSv for nailing osteosynthesis of proximal pertrochanteric fractures and less than 0.1 mSv for osteosynthesis of distal lower leg fractures. CONCLUSION: Radiation exposure of the patient due to intraoperative fluoroscopic imaging during osteosynthesis can be estimated based on the data given above. Intraoperative observations imply, consequent application of radiation protection by the orthopaedic surgeons may reduce intraoperative radiation exposure even more.

Changes of tumor vascularity during gene therapy monitored with color Doppler US.

Using contrast-enhanced color Doppler (CD) sonography, we assessed alterations of tumor blood flow induced in 25 murine Morris hepatomas transfected with a gancyclovir- (GCV-)sensitizing Herpes simplex virus thymidine kinase (HSVtk) suicide gene in combination with systemic GCV treatment and compared findings with a control tumor. CD measurements were quantified by the color pixel density (CPD) and the mean encoded flow velocity (mean color value, MCV), using computer-assisted image analysis, and compared with histologic arteriole counts. During 5 days, the tumor volume remained constant. In HSVtk-expressing tumors, the median CPD dropped from 16% at baseline to 5% on day 5 (p = 0.001), remaining constant in controls. The MCV decreased from 1.9 cm/s to 1.6 cm/s in the HSVtk-expressing tumors (p = 0.001) and rose from 1.8 cm/s to 2.0 cm/s in the controls (p = 0.002). In an accompanying histologic arteriole assay, we found no alterations attributable to treatment.

Relevance of sonographic B-mode criteria and computer-aided ultrasonic tissue characterization in differential/diagnosis of solid breast masses.

We aimed to evaluate the differential diagnostic value of a method of computer-assisted texture analysis in comparison to established ultrasonographic B-mode characteristics in the examination of solid breast masses. At two centers, 77 patients presenting with a solid mass on B-mode scan were studied at 7.5 MHz. Description of B-mode appearance included assessment of tumor shape, borders, presence of an echogenic rim, tissue architecture, internal echo structure, absorption and elasticity. For statistical pattern recognition, the following parameters were used: form factor, mean grey level, signal-to-noise ratio, mean gradient and correlation from the co-occurrence matrix. At center 1, the most decisive parameter for differential diagnosis was distortion of tissue architecture (sensitivity, SN, 83%; specificity, SP, 92%) and, at center 2, relation to the adjacent tissue (SN 93%, SP 92%). Among texture parameters, best discrimination was achieved for correlation from the co-occurrence matrix at center 1 (SN 58%, SP 73%) and for form factor at center 2 (SN 93%, SP 77%). Among sonographic criteria, the highest contribution to the diagnosis was found for an unsharp border (odds ratio, OR, 12.2), architectural distortion (OR, 8.6), fixation to skin or chest wall (OR, 9.0) and fixation to adjacent breast parenchyma (OR, 8.8), according to texture analysis for parameters form factor (OR 4.0) and correlation from the co-occurrence matrix (OR 4.7). Ultrasonographic texture analysis can be helpful as an additional parameter in differential diagnosis of breast tumors, but did not reach differential diagnostic accuracy of sonomorphologic features.

Ultrasonographic tissue characterization in monitoring tumor response to neoadjuvant chemotherapy in locally advanced breast cancer (work in progress).

A program of computer-assisted texture analysis was applied to evaluate its usefulness for objective description of changes in tumor architecture due to primary medical treatment in patients with locally advanced breast cancer. Changes in values of parameters of the statistical pattern recognition technique were compared to ultrasonographically depictable, subjectively recorded changes in echogenicity and echotexture (brightness, homogeneity) and reviewed with regard to histopathologic evaluation of tumor regression. Characteristic trends of defined quantitative texture parameters (mean gradient, mean gray value, contrast from the co-occurrence matrix) corresponded to visually depictable changes of the B-mode image and underlying histopathologic changes. The results indicate that quantitative texture analysis may aid in noninvasive monitoring of tumor response to neoadjuvant chemotherapy.