Fritz K W Schaefer

University Medical Center Schleswig-Holstein, Kiel, Schleswig-Holstein, Germany

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Publications (60)142.97 Total impact

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    ABSTRACT: Background: Imatinib is a tyrosine kinase inhibitor of BCR-ABL, ABL, PDGFR-α and -β, KIT, and DDR. In solid tumors, it inhibits proliferation and invasiveness and facilitates higher intratumoral cytotoxic drug concentrations. Vinorelbine has good tolerability and efficacy in metastatic breast cancer (MBC). This study evaluates the safety and efficacy of imatinib and vinorelbine in combination. Methods: In a prospective, open-label, phase I/II trial, 400 mg imatinib p.o. daily (corrected from 600 mg) was combined with an escalating dose of vinorelbine i.v. weekly in four dose levels of 10, 15, 20, and 25 mg/m(2) (each n ≥ 5) to treat patients with MBC (expressing PDGFR-α and/or -β, and/or KIT). The last patient of each level was treated for >28 days, before enrolment for the next dose level started. Study endpoints were feasibility and tolerability, incidence of hematological and nonhematological toxicity, and clinical efficacy (data cutoff: November 18, 2011). A total of 33 patients have been enrolled, and all dose levels have been fully recruited. One patient is still on study medication. A translational subprotocol is ongoing. Results: All 33 included patients are evaluable for safety (32 within the ITT population). Eleven patients were excluded early from the study (progressive disease, toxicity, and withdrawal of consent). Twenty-two patients participated in the study for >28 days ('ITT >28'). Within the ITT population, the response rate [complete response (CR) and partial response (PR)] was 9.4% (n = 3), the clinical benefit rate (CBR; CR+PR+stable disease) 50% (n = 16), and the median time to progression (TTP) 155 days. A total of 21.3% of the patients were on study medication for >6 months, and 15.2% for >12 months (mean 140 days, range 15-643). Within 'ITT >28', the response rate was 13.6%, CBR 72.7%, and median TTP 176 days. The response was independent of the receptor status (PDGFR-α, -β, and KIT). Toxicities were as follows (safety population): 21.6% severe leukopenia, 9.1% severe neutropenia (with 1 febrile neutropenia), 1 case of bowel perforation, 36% diarrhea (3% severe), 84.8% nausea (severe 15.2%), 48.5% vomiting (severe 9.1%), 27.3% infections (severe 6.1%), 12.1% peripheral neuropathy (severe 9.1%), and 36.4% dyspnea (3% severe). Four patients on trial died (nondrug-related). Conclusion: The combination of imatinib and vinorelbine in MBC appeared to be feasible and tolerable. A CBR of 50% (ITT) in pretreated patients suggests that this combination may be active. Although toxicities were frequent, they appeared to be manageable. © 2014 S. Karger AG, Basel.
    Oncology 08/2014; 87(5):300-310. · 2.17 Impact Factor
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    ABSTRACT: Local treatment of breast cancer with tumor-free surgical margins is the standard procedure in the treatment of T1 and small T2 breast cancers. Surgery is followed by radiation therapy, and adjuvant systemic therapy is offered depending on primary tumor characteristics, such as tumor size, grade of differentiation, number of involved axillary lymph nodes, the status of estrogen (ER) and progesterone (PR) receptors, and the expression of the human epidermal growth factor 2 (HER2) receptor. Although this approach implies a higher risk of ipsilateral breast tumor recurrence, the total risk of recurrence is low (1% per year), with rates of overall survival similar to that after radical procedures. The most peripheral part of epithelial tumors, the tumor margin, is the part which is most likely to remain in loco after surgical resection. Thus, understanding the biology of the invasion front is important as these tumor cells have been reported to lose epithelial properties, such as cohesiveness and keratin expression, and to acquire features of mesenchymal cells. The parallel appearance of tumor cells in different states of cell dedifferentiation implicates a dynamic equilibrium that is determined by the induction of epithelial-mesenchymal transition (EMT). EMT has been suggested to be of prime importance for tissue and vessel invasion. Furthermore, features of EMT are associated with the activity of tumor stem cells (TSC). TSC exist in breast cancer and their appearance varies depending on the used marker profile. Consequently, intratumoral heterogeneity is reflected by the grade of EMT activation. A specific function at the invasion front is hypothesized but has not yet been proven. Nevertheless, the molecular differentiation between the tumor center and the invasion front enhances the importance of tumor-free surgical margins.
    Minerva ginecologica 08/2013; 65(4):363-383.
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    ABSTRACT: Objective: To prospectively analyze duplex sonography, CTA, and MRA with respect to stenosis grading of the celiac trunk (TC) and the superior mesenteric artery (SMA), with DSA as the reference.Materials & Methods: 52 subjects were enrolled (mean age: 71). The image quality was graded: 1-insufficient, 2-bad, 3-moderate, 4-good or 5-excellent. Stenosis was graded: 1 (< 25 %), 2 (25 - < 50 %), 3 (50 - 75 %) or 4 (75 %). Two-sided chi-square tests were used to check for correlation of stenosis grading between modalities. The weighted Cohen's kappa was calculated to assess the strength of correlation. With a threshold of 50 % for non-relevant stenosis vs. relevant stenosis, the sensitivity, specificity, PPV, NPV, and accuracy were calculated.Results: The mean image quality was 3.8 ± 0.7, 3.1 ± 1.0, 4.4 ± 0.7, and 3.8 ± 0.9 for DSA, duplex sonography, CTA, and MRA, respectively. For both TC and SMA, stenosis grading reached a significant level of correlation between each noninvasive modality with DSA (p < 0.001, each). The weighted Cohen's kappa for duplex sonography/CTA/MRA was 0.94/0.93/0.74, respectively, for the TC and 0.64/0.91/0.56, respectively, for the SMA. Highest sensitivity/specificity/NPV/PPV/accuracy were found for CTA with 100 %/95 %/85 %/100 %/96 % for the TC and with na/98 %/na/100 %/98 %, respectively, for the SMA.Conclusion: CTA provided the best image quality, reached the highest level of agreement and significance in correlation in stenosis grading, and offered the best diagnostic accuracy.
    RöFo - Fortschritte auf dem Gebiet der R 06/2013; · 2.76 Impact Factor
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    ABSTRACT: Purpose: To determine the benefit of ShearWave™ Elastography (SWE™) in the ultrasound characterization of BI-RADS® 3 breast lesions in a diagnostic population.Materials and Methods: 303 BI-RADS® 3 lesions (mean size: 13.2 mm, SD: 7.5 mm) from the multicenter BE1 prospective study population were analyzed: 201 (66 %) had cytology or core biopsy, and the remaining 102 had a minimum follow-up of one year; 8 (2.6 %) were malignant. 7 SWE features were evaluated with regard to their ability to downgrade benign BI-RADS® 3 masses. The performance of each SWE feature was assessed by evaluating the number of lesions correctly reclassified and the impact on cancer rates within the new BI-RADS® 3' lesion group. Results: No malignancies were found with an E-color "black to dark blue", which allowed the downgrading of 110/303 benign masses (p < 0.0001), with a non-significant increase in BI-RADS® 3' malignancy rate from 2.6 % to 4.1 %. E-max ≤ 20kPa (2.6 m/s) was able to downgrade 48/303 (p < 0.0001) lesions with a lower increase in BI-RADS® 3' malignancy rate (3.1 %). No other SWE features were useful for reclassifying benign BI-RADS® 3 lesions.Conclusion: Applying simple reclassification rules, SWE assessment of the maximum stiffness of lesions allowed the downgrading of a sub-group of benign BI-RADS® 3 lesions. This was accompanied by a non-significant increase in the malignancy rate in the new BI-RADS® 3 class.
    Ultraschall in der Medizin 06/2013; 34(3):254-259. · 4.12 Impact Factor
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    ABSTRACT: The clinical part of these Guidelines and Recommendations produced under the auspices of the European Federation of Societies for Ultrasound in Medicine and Biology EFSUMB assesses the clinically used applications of all forms of elastography, stressing the evidence from meta-analyses and giving practical advice for their uses and interpretation. Diffuse liver disease forms the largest section, reflecting the wide experience with transient and shear wave elastography . Then follow the breast, thyroid, gastro-intestinal tract, endoscopic elastography, the prostate and the musculo-skeletal system using strain and shear wave elastography as appropriate. The document is intended to form a reference and to guide clinical users in a practical way.
    Ultraschall in der Medizin 04/2013; · 4.12 Impact Factor
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    ABSTRACT: The technical part of these Guidelines and Recommendations, produced under the auspices of EFSUMB, provides an introduction to the physical principles and technology on which all forms of current commercially available ultrasound elastography are based. A difference in shear modulus is the common underlying physical mechanism that provides tissue contrast in all elastograms. The relationship between the alternative technologies is considered in terms of the method used to take advantage of this. The practical advantages and disadvantages associated with each of the techniques are described, and guidance is provided on optimisation of scanning technique, image display, image interpretation and some of the known image artefacts.
    Ultraschall in der Medizin 04/2013; 34(2):169-84. · 4.12 Impact Factor
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  • F Schäfer
    European journal of radiology 12/2012; · 2.65 Impact Factor
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    ABSTRACT: Purpose: To analyze the efficacy of interventions in acute dysfunctional hemodialysis fistulas, if intervention is performed immediately as recommended by European Best Practice Guidelines for Hemodialysis. Materials and Methods: Over 3 years, all (n = 280) patients with an acute dysfunctional hemodialysis fistula were immediately referred to angiography, irrespective of the time of day. Angiography and, if possible, interventional revision (n = 241) were performed. Three groups of interest were established: interventionalist's experience (high/low), time of day (routine hours: 7 am-4 pm/emergency hours: 4 pm-7 am), lesion type (stenosis/fibrosclerotic occlusion/thrombotic occlusion/combined stenosis+thrombotic occlusion). For statistical analysis corresponding success rates, chi-square tests (p < 0.025) and logistic regression analysis (p < 0.05) were calculated. Results: The total success rate was 62 % (149/241). The success rates were: interventionalist experience high/low 71 % (79/111)/54 % (70/130), p = 0.022; time of day routine/emergency hours 68 % (93/136)/53 % (56/105), p = 0.017; lesion type stenosis/fibrosclerotic occlusion/thrombotic occlusion/combined stenosis+occlusion 82 % (94/104)/39 % (13/33)/18 % (6/33)/59 % (36/61), p < 0.001. Relevant variables due to logistic regression analysis were high experience and the lesion types stenosis and combined stenosis+occlusion with odds ratios 2.300 (p = 0.012), 12.053 (p < 0.001), 3.189 (p = 0.003). Conclusion: Unrestricted implementation of immediate interventions in acute dysfunctional hemodialysis fistulas requires permanent availability of experienced interventionalists. The lesion types fibrosclerotic occlusion and thrombotic occlusion offer poor success rates for interventional revision.
    RöFo - Fortschritte auf dem Gebiet der R 12/2012; · 2.76 Impact Factor
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    ABSTRACT: PURPOSE To determine potential impact of shear-wave elastography (SWE) on reclassification of sonographic BI-RADS 3 breast masses to BI-RADS 2. Previous reports indicate that upgrading BI-RADS 3 masses suspicious on SWE to biopsy (BI-RADS 4a) is appropriate. METHOD AND MATERIALS From 9/2008 to 9/2010, across 16 centers in Europe and USA, 1647 women with breast masses consented to repeat ultrasound and quantitative SWE imaging (SuperSonic Imagine, Aix, France). 1562 women/masses had acceptable reference standard (biopsy or 1-year follow-up imaging). 440 (28.2%) masses were BI-RADS 3 based on B-mode imaging, of which 310 (70.5%) had biopsy. Quantitative maximum elasticity (Emax) across three acquisitions was determined, with range set 0 (very soft) to 180 kPa (very stiff). Shape and homogeneity of the mass and surrounding tissue on SWE were also recorded. A nonparametric test for trend was performed across ordered categories. RESULTS Among 440 BI-RADS 3 masses, 11 (2.5%) were malignant (1 borderline phyllodes, 1 DCIS, 9 invasive; median invasive tumor size 9 mm). There were 72 (16%) BI-RADS 3 masses with Emax ≤ 20 kPa, all of which were benign; increasing Emax predicted increasing likelihood of malignancy, with 5/323 (1.6%) malignant among masses with 20<Emax<160 kPa, and 6/45 (13%) of masses with Emax 160 kPa or higher malignant (p<.001 across Emax categories). No other subset was reliably benign, with 4/318 (1.3%) BI-RADS 3 masses oval on SWE malignant, compared to 1/28 (4%) of round and 6/94 (6%) of irregular masses (p=.005). When the mass and surrounding tissue were homogeneous on SWE, 5/235 (2.1%) were malignant, compared to 1/149 (0.7%) of those reasonably homogeneous, and 5/56 (9%) of masses heterogeneous on SWE (p=.05). CONCLUSION Confirming earlier reports, it is possible to identify a subset of BI-RADS 3 masses which require biopsy, based on suspicious features on SWE, with malignancy rates of 5 to 13%; however, the vast majority can be safely followed. While very soft lesions on SWE were unlikely to be malignant, only a small percentage of BI-RADS 3 masses could be considered for downgrade to BI-RADS 2, and they would still require diagnostic follow-up: it is not clear that SWE should be used reduce short-term follow-up of probably benign lesions. CLINICAL RELEVANCE/APPLICATION BI-RADS 3 masses are common on breast ultrasound. Understanding the appropriate role of SWE for such masses is important for appropriate patient management.
    Radiological Society of North America 2012 Scientific Assembly and Annual Meeting; 11/2012
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    ABSTRACT: Hamartomas can occur in different areas of the breast, but they are rarely found in the breast. Myoid hamartomas with smooth muscle cells of the type described here are particularly unusual. The pathogenesis of this benign entity with its tendency to growth and recurrence is not clear. Excision is the therapy of choice. Capillary hemangiomas are rare vascular malformations of the breast which, in contrast to cavernous hemangiomas, usually remain clinically occult. It is important to differentiate these benign findings from malignant angiosarcoma. The possible heterogeneities between myoid hamartoma and capillary hemangioma using current breast imaging methods for the differential diagnosis (high-resolution ultrasound, duplex sonography, shear wave elastography, digital mammography, minimally invasive intervention) are discussed together with an overview of the literature.
    Geburtshilfe und Frauenheilkunde 05/2012; 72(5):412-418. · 0.85 Impact Factor
  • RöFo - Fortschritte auf dem Gebiet der R 05/2012; 184(S 01). · 1.96 Impact Factor
  • PD Dr. C. Schem, F.K.W. Schäfer
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    ABSTRACT: Die konventionelle Mammographie ist derzeit die einzige für die Erkennung von Brustkrebsvorstufen oder frühen Tumorstadien allgemein anerkannte Methode (1a LoE, Leitlinienadaptation). Sie ist die am besten erprobte und evaluierte diagnostische Untersuchungsmethode der Brust und wird eingesetzt zur Abklärung und Charakterisierung von Tastbefunden, zum lokalen Staging und zur Brustkrebsfrüherkennung. Dabei erweist sie sich als besonders effektiv. Prospektiv randomisierte Studien zeigen, dass mit der Einführung der Screeningmammographie als Röntgenreihenuntersuchung eine altersabhängige Brustkrebssterblichkeitsreduktion möglich ist (1b-1a LoE, Leitlinienadaptation). Die Mammographie hat sich auch technisch deutlich weiterentwickelt. Die Digitaltechnik einerseits und die ergänzenden Darstellungsmethoden, wie Sonographie, Tomosynthese und Magnetresonanztomographie komplettieren heute die diagnostischen Möglichkeiten. In dieser Übersichtsarbeit sollen der derzeitige Goldstandard und mögliche zukünftige Entwicklungen bei der Diagnostik des duktalen Carcinoma in situ dargestellt werden.
    Der Gynäkologe 04/2012; 45(4).
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    European Congress of Radiology; 03/2012
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    ABSTRACT: To evaluate prospectively the correlation of scar-formations after vacuum-assisted biopsy with different systems and needle-sizes and interventional bleeding/post-interventional hematoma. Between 01/2008 and 12/2009, 479 patients underwent vacuum-assisted biopsy under stereotactic-guidance, using the Mammotome(®)-system with 11/8-gauge and ATEC(®)-system with 12/9-gauge, whereas in 178 cases with representative benign histology no surgical-biopsy after vacuum-assisted biopsy was performed and at least a 2-plane-follow-up-mammogram after 6 month post-vacuum-assisted biopsy was available. Bleeding during intervention, hematoma post-intervention and scar-tissue was scored as minimal and moderate/severe. Statistical analysis included Chi-Square-trend-test, p-value <0.05 was considered to be significant. Significantly more bleedings and post-interventional hematomas for 8-gauge-Mammotome(®)-system vs. 11-gauge-Mammotome(®)-system (41.9% vs. 8.4%, p<0.001/35.5% vs. 16.7%, p=0.029), no significant-differences for the ATEC(®)-systems 9-gauge vs. 12-gauge (26.9% vs. 29.7%, p=0.799/42.3% vs. 43.2%, p=0.596). 11-gauge-Mammotome(®)-system vs. ATEC(®)-12-gauge-system revealed significantly less bleedings/hematomas (8.4% vs. 29.7%, p=0.015/16.7% vs. 43.2%, p=0.001), no significant differences for the large-systems (p=0.135/p=0.352). Follow-up of Mammotome(®)-11/8-gauge-system system has shown 13.1/16.1% minimal scar-formation and 1.2/3.2% moderate/severe scars, whereas ATEC(®)-12/9-gauge-system has shown 10.8/3.8% minimal scar-formation and 0/11.5% moderate/severe scars, no significant differences. No significant difference was found when comparing Mammotome(®)-11/8-g-systems vs. ATEC(®)-12/9-g-systems (p=0.609/p=0.823). There was also no correlation between risk of scar-formation after occurrence of bleeding or hematoma with any examined VAB-system or any needle size in this study (p=0.800). Using larger needle-sizes significantly (Mammotome(®))/not significant for ATEC(®)) more interventional bleedings and post-interventional hematomas were detected, only a tendency concerning scar-formation.
    European journal of radiology 02/2012; 81(5):e739-45. · 2.65 Impact Factor
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    ABSTRACT: To determine whether adding shear-wave (SW) elastographic features could improve accuracy of ultrasonographic (US) assessment of breast masses. From September 2008 to September 2010, 958 women consented to repeat standard breast US supplemented by quantitative SW elastographic examination in this prospective multicenter institutional review board-approved, HIPAA-compliant protocol. B-mode Breast Imaging Reporting and Data System (BI-RADS) features and assessments were recorded. SW elastographic evaluation (mean, maximum, and minimum elasticity of stiffest portion of mass and surrounding tissue; lesion-to-fat elasticity ratio; ratio of SW elastographic-to-B-mode lesion diameter or area; SW elastographic lesion shape and homogeneity) was performed. Qualitative color SW elastographic stiffness was assessed independently. Nine hundred thirty-nine masses were analyzable; 102 BI-RADS category 2 masses were assumed to be benign; reference standard was available for 837 category 3 or higher lesions. Considering BI-RADS category 4a or higher as test positive for malignancy, effect of SW elastographic features on area under the receiver operating characteristic curve (AUC), sensitivity, and specificity after reclassifying category 3 and 4a masses was determined. Median participant age was 50 years; 289 of 939 (30.8%) masses were malignant (median mass size, 12 mm). B-mode BI-RADS AUC was 0.950; eight of 303 (2.6%) BI-RADS category 3 masses, 18 of 193 (9.3%) category 4a lesions, 41 of 97 (42%) category 4b lesions, 42 of 57 (74%) category 4c lesions, and 180 of 187 (96.3%) category 5 lesions were malignant. By using visual color stiffness to selectively upgrade category 3 and lack of stiffness to downgrade category 4a masses, specificity improved from 61.1% (397 of 650) to 78.5% (510 of 650) (P<.001); AUC increased to 0.962 (P=.005). Oval shape on SW elastographic images and quantitative maximum elasticity of 80 kPa (5.2 m/sec) or less improved specificity (69.4% [451 of 650] and 77.4% [503 of 650], P<.001 for both), without significant improvement in sensitivity or AUC. Adding SW elastographic features to BI-RADS feature analysis improved specificity of breast US mass assessment without loss of sensitivity.
    Radiology 02/2012; 262(2):435-49. · 6.21 Impact Factor
  • F K Schaefer, M Fürst, P J Schaefer
    RöFo - Fortschritte auf dem Gebiet der R 01/2012; 184(1):59-60. · 2.76 Impact Factor
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    ABSTRACT: To demonstrate the structure and process quality of quality-assured mamma diagnostics (QuaMaDi) by means of quality indicators as defined in the European Guidelines for Quality Assurance in Breast Cancer Screening and Diagnosis and in the National Guideline on Early Detection of Cancer in Germany. Furthermore, spatial differences and changes in the chronological sequence were analyzed. We used administrative data as documented in the time period 2006 - 2009 in QuaMaDi in Schleswig-Holstein (SH), Germany, and analyzed quality indicators as defined in the abovementioned guidelines (absolute and relative frequencies, 95 % confidence intervals). Each year approximately 6 % of all women age 20 or older living in SH are examined using QuaMaDi. Only minor differences regarding age and clinical data were seen between the patients in the four regions of SH. Reference values for the quality indicators are largely reached (i. e., proportion of women with breast density ACR 3 or 4 plus additional ultrasound = 96.2 %; proportion with repeated mammography = 0.2 %). Spatial differences are only minor. In the chronological sequence, quality indicators improve, if they did not reach the reference values in the beginning, or indicate a high and constant quality. With regard to those quality indicators that were computable, reference values as defined in the guidelines were reached in 9 of 12 cases. In one case the difference between the observed value and the reference values is system-immanent and in another case the difference is less than four percentage points (reference value 90 %).
    RöFo - Fortschritte auf dem Gebiet der R 12/2011; 184(2):113-21. · 2.76 Impact Factor

Publication Stats

784 Citations
142.97 Total Impact Points


  • 2007–2013
    • University Medical Center Schleswig-Holstein
      • Department of Pediatrics
      Kiel, Schleswig-Holstein, Germany
  • 2012
    • Magee-Womens Hospital
      Pittsburgh, Pennsylvania, United States
    • Universitätsklinikum Schleswig - Holstein
      • Klinik für Gynäkologie und Geburtshilfe (Kiel)
      Kiel, Schleswig-Holstein, Germany
  • 2002–2008
    • Christian-Albrechts-Universität zu Kiel
      • UKSH Klinik für Diagnostische Radiologie
      Kiel, Schleswig-Holstein, Germany
  • 2005
    • Municipal Hospital of Lüneburg
      Luneberg, Lower Saxony, Germany