Andreas Meyer

Hannover Medical School, Hanover, Lower Saxony, Germany

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Publications (35)199.13 Total impact

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    ABSTRACT: To retrospectively assess the incidence and time course of renal dysfunction in children (< or = 16 years) following total- body irradiation (TBI) before allogeneic stem cell transplantation (SCT). Between 1986 and 2003, 92 children (median age, 11 years; range, 3-16 years) underwent TBI before allogeneic SCT. 43 of them had a minimum follow-up of 12 months (median, 51 months; range, 12-186 months) and were included into this analysis. Conditioning regimen included chemotherapy and fractionated TBI with 12 Gy (n = 26) or 11.1 Gy (n = 17). In one patient, renal dose was limited to 10 Gy by customized renal shielding due to known nephropathy prior to SCT. Renal dysfunction was defined as an increase of serum creatinine > 1.25 times the upper limit of age-dependent normal. Twelve children (28%) experienced an episode of renal dysfunction after a median of 2 months (range, 1-10 months) following SCT. In all but one patient renal dysfunction was transient and resolved after a median of 8 months (range, 3-16 months). One single patient developed persistent renal dysfunction with onset at 10 months after SCT. None of these patients required dialysis. The actuarial 3-year freedom from persistent renal toxicity for children surviving > 12 months after SCT was 97.3%. The incidence of persistent renal dysfunction after fractionated TBI with total doses < or = 12 Gy was very low in this analysis.
    Strahlentherapie und Onkologie 11/2009; 185(11):751-5. · 4.16 Impact Factor
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    ABSTRACT: Prostate cancer (PrCa) is the most frequently diagnosed cancer in males in developed countries. To identify common PrCa susceptibility alleles, we previously conducted a genome-wide association study in which 541,129 SNPs were genotyped in 1,854 PrCa cases with clinically detected disease and in 1,894 controls. We have now extended the study to evaluate promising associations in a second stage in which we genotyped 43,671 SNPs in 3,650 PrCa cases and 3,940 controls and in a third stage involving an additional 16,229 cases and 14,821 controls from 21 studies. In addition to replicating previous associations, we identified seven new prostate cancer susceptibility loci on chromosomes 2, 4, 8, 11 and 22 (with P = 1.6 x 10(-8) to P = 2.7 x 10(-33)).
    Nature Genetics 09/2009; 41(10):1116-21. · 35.21 Impact Factor
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    ABSTRACT: The purpose of this study was the evaluation of the feasibility and outcome of definitive radio-chemotherapy without split-course technique but with individualised short treatment interruption in anal cancer patients. Between 1993 and 2008, 101 patients with anal cancer were treated in our institution with definitive radio-chemotherapy with individualised short treatment interruptions. Treatment was halted independent of dose in case of acute grade 3 toxicities and started again until improvement. Short interruption was defined as completing treatment without exceeding six cumulative treatment days beyond a scheduled plan; otherwise, it was defined as prolonged interruption. Median overall treatment time was 47 days corresponding to an interruption of six cumulative treatment days. Fifty-one patients (50%) had treatment interruption of <or=6 days. No acute grade 4 toxicities were observed. One fatality occurred during treatment due to ileus-like symptoms according to acute grade 5 toxicity. After a median follow-up of 56 months, the 5-year actuarial rates for local control comparing patients with short vs. prolonged treatment interruption were 78% vs. 81% (p = 0.904) and, for colostomy-free survival, 83% vs. 85% (p = 0.784), respectively. Definitive radio-chemotherapy with short individualised treatment interruption shows high local control and colostomy-free survival rates.
    International Journal of Colorectal Disease 09/2009; 24(12):1421-8. · 2.24 Impact Factor
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    ABSTRACT: Transforming growth factor beta1 gene (TGFB1) variant Leu10Pro (L10P) has previously been implicated in prostate cancer risk and radiation-induced side-effects. We investigated whether prevalence of this polymorphism is increased in prostate cancer patients and whether carriers are at increased risk for treatment-related side effects. A series of 445 consecutive patients treated for early-stage prostate cancer receiving definitive I-125 brachytherapy (permanent seed implantation) between 10/2000 and 10/2007 at our institution and a comparison group of 457 healthy male control individuals were screened for TGFB1 L10P (869T>C) polymorphism. Morbidity was assessed prospectively and compared between carriers versus non-carriers using International Prostate Symptom Score (IPSS), disease-specific Quality-of-Life single question added to the IPSS and International Index of Erectile Function with its subgroups. The Leu/Leu genotype was found in 150 patients (34%) versus 180 controls (39%), the Pro/Pro genotype in 75 patients (17%) versus 65 controls (14%) and the Leu/Pro genotype in 220 patients (49%) versus 212 controls (46%) without any statistically significant differences between the two groups. There was a trend towards an increased prevalence of the L10P substitution among patients with a per allele odds ratio of 1.19 (95% CI 0.99-1.44; P = 0.08). After a median follow-up of 18 months (range 1-60 months) there were no statistically significant differences regarding morbidity. TGFB1 polymorphism L10P is not strongly associated with prostate cancer risk. After 18 months, there was no evidence for increased adverse radiotherapy responses in heterozygote or rare homozygote carriers. Longer follow-up may be necessary to detect a statistically significant difference.
    World Journal of Urology 12/2008; 27(3):371-7. · 2.89 Impact Factor
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    ABSTRACT: A recent genome-wide association study found that genetic variants on chromosomes 3, 6, 7, 10, 11, 19 and X were associated with prostate cancer risk. We evaluated the most significant single-nucleotide polymorphisms (SNP) in these loci using a worldwide consortium of 13 groups (PRACTICAL). Blood DNA from 7,370 prostate cancer cases and 5,742 male controls was analyzed by genotyping assays. Odds ratios (OR) associated with each genotype were estimated using unconditional logistic regression. Six of the seven SNPs showed clear evidence of association with prostate cancer (P = 0.0007-P = 10(-17)). For each of these six SNPs, the estimated per-allele OR was similar to those previously reported and ranged from 1.12 to 1.29. One SNP on 3p12 (rs2660753) showed a weaker association than previously reported [per-allele OR, 1.08 (95% confidence interval, 1.00-1.16; P = 0.06) versus 1.18 (95% confidence interval, 1.06-1.31)]. The combined risks associated with each pair of SNPs were consistent with a multiplicative risk model. Under this model, and in combination with previously reported SNPs on 8q and 17q, these loci explain 16% of the familial risk of the disease, and men in the top 10% of the risk distribution have a 2.1-fold increased risk relative to general population rates. This study provides strong confirmation of these susceptibility loci in multiple populations and shows that they make an important contribution to prostate cancer risk prediction.
    Cancer Epidemiology Biomarkers &amp Prevention 09/2008; 17(8):2052-61. · 4.56 Impact Factor
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    ABSTRACT: Genetic susceptibility contributes to the risk of prostate cancer but the underlying genes are largely unknown. Polymorphic loci on chromosome 8q24 have emerged as possible risk factors for breast and prostate cancer from genome-wide association studies. We aimed to define the risks associated with two single nucleotide polymorphisms, rs1447295 and rs13281615, in a hospital-based series of prostate cancer patients treated with brachytherapy. We analyzed genomic DNA samples of 488 prostate cancer cases undergoing brachytherapy at Hannover Medical School, and of 462 male controls from the same location. Genotyping was performed using 5'-exonuclease allelic discrimination assays, and results were evaluated with chi(2) tests and logistic regression analyses. We investigated whether rs1447295 and rs13281615 are associated with disease risk in a hospital-based prostate cancer case-control series from Northern Germany. The rare allele of rs1447295 was observed at higher frequency among cases than among hospital-based controls (13.9% vs. 10.2%, P = 0.01), and there was a dose-dependent trend towards a higher prevalence of heterozygous and homozygous carriers among the prostate cancer patients (per allele OR 1.42, 95% CI 1.07; 1.87, P = 0.02). By contrast, the rare allele of rs13281615 did not predispose to prostate cancer (per allele OR 0.84, 95% CI 0.70; 1.00, P = 0.05). The distribution of combined 8q24 genotypes was significantly different between cases and controls (P = 0.01). Our results corroborate previous reports of 8q24 as a prostate cancer susceptibility locus and provide evidence for rs1447295 as a potentially important genetic marker. Further studies are required to confirm whether the adjacent breast cancer-associated variant rs13281615 may be inversely associated with prostate cancer risk.
    Urologic Oncology 08/2008; 27(4):373-6. · 3.65 Impact Factor
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    ABSTRACT: To look at differences between fractionation schedules regarding established prognostic factors in patients treated with whole-brain radiotherapy (WBRT) for metastasis and actual survival. One hundred and forty-six patients with brain metastases treated with WBRT with three different fractionation schedules with respect to the single dose (SD) 20 x 2.0 Gy (SD2), 15 x 2.5 Gy (SD2.5) and 10 x 3 Gy (SD3) were included. The median overall survival in the SD2, SD2.5 and SD3 groups was 10.3, 10.3 and 5.5 months (p = 0.005) while in recursive partitioning analysis (RPA) classes I, II and III it was 16.7, 8.1 and 3.7 months, respectively (p < 0.0001). Statistically significant variables for overall survival were age (< 60 years, p < 0.0001) and primary site (breast, p = 0.049) in the univariate analysis, and age (p = 0.003) and RPA class (p < 0.0001) in the multivariate analysis. The dose fractionation schedule for WBRT of metastases adequately reflected the clinical estimate of more favourable prognosis. Reduced single doses due to neurocognitive decline may be considered in patients with RPA class I.
    Anticancer research 01/2008; 28(6B):3965-9. · 1.71 Impact Factor
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    ABSTRACT: Prostate cancer is associated with defective DNA strand break repair after DNA damage leading to genetic instability and prostate cancer progression. The ATM (ataxia-telangiectasia mutated) gene product is known to play an important role in cell cycle regulation and maintenance of genomic integrity. We investigated whether the prevalence of the ATM missense substitution P1054R is increased in a hospital-based series of prostate cancer patients and whether carriers are at increased risk for treatment-related side effects. A consecutive series of 261 patients treated for early-stage prostate cancer with I-125 brachytherapy (permanent seed implantation) between 10/2000 and 04/2006 at our institution and a comparison group of 460 male control individuals were screened for the presence of the P1054R variant. Outcome of therapy regarding morbidity was assessed prospectively and compared between carriers vs. non-carriers with the International Prostate Symptom Score (IPSS), a Quality-of-Life-index (QoL) and the International Index of Erectile Function (IIEF-15) with its subgroups (IIEF-5 and EF). The proportion of carriers of the P1054R variant was significantly higher among prostate cancer patients than in the general population (25 out of 261 vs. 22 out of 460; OR 2.1; 95% CI 1.2-3.8, p<0.01). A subgroup of the carriers additionally harboured the ATM missense variant F858L that was associated with a similar risk (OR=2.2; 95% CI 1.1-4.6; p=0.03). After a mean follow-up of 18 months there were no statistically significant differences regarding IPSS (p=0.48), QoL (p=0.61), IIEF-15 score (p=0.78), IIEF-5 score (p=0.83), and EF score (p=0.80), respectively. The ATM missense variant P1054R confers an about twofold increased risk for prostate cancer in our series. The subgroup of patients with the second-site variant F858L is not at significantly higher risk. After 18 months, there was no evidence for an increased adverse radiotherapy response in P1054R carriers.
    Radiotherapy and Oncology 06/2007; 83(3):283-8. · 4.52 Impact Factor
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    ABSTRACT: Women carrying mutations in the CHEK2 gene are at an increased breast cancer risk. Data about outcome and prognosis for these patients after standard multimodality treatment are scarce at present. One-hundred and fifty (150) patients with non-metastasized early-stage breast cancer (T1-2) receiving postoperative radiotherapy following breast-conservative surgery at our department were included in this analysis. Carriers were identified using mutation-specific restriction enzyme-based screening assays in previous investigations. Twenty-five breast cancer patients were heterozygous for one of three CHEK2 gene mutations (I157T, n=13; 1100delC, n=10; IVS2+1G>A, n=2). The comparison group consisted of 125 early-stage breast cancer patients without a CHEK2 gene mutation (non-carriers). Median follow-up was 87 months for the total cohort of patients. Local recurrences occurred in 13 patients (carriers, 3 (12%); non-carriers, 10 (8%)) and distant metastases occurred in 27 patients (carriers, 8 (32%); non-carriers, 19 (15%)). Twenty-five patients had deceased (carriers, 8 (32%); non-carriers, 17 (14%)) with all but 3 deaths related to breast cancer. Actuarial 7-year local relapse-free survival was 86% in carriers versus 90% in non-carriers (p=0.48). Actuarial metastasis-free, disease-free and overall survival at 7 years were 64% vs. 84% (p=0.045), 59% vs. 78% (p=0.07) and 69% vs. 87% (p=0.10), respectively. In a multivariate step-wise Cox regression analysis presence of a CHEK2 mutation remained a borderline significant discriminator for metastasis-free survival (p=0.048; OR=0.4; 95% CI 0.2-1.0) next to T-stage (p=0.001; OR 0.3; 95% CI 0.1-0.6). Heterozygosity for a germline CHEK2 mutation appears to represent an adverse prognostic factor in patients with early-stage breast cancer. If confirmed in larger studies these data may serve as a basis for future surveillance and treatment strategies taking into account individual germline mutational status.
    Radiotherapy and Oncology 04/2007; 82(3):349-53. · 4.52 Impact Factor
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    ABSTRACT: We report on a rare case of small cell cancer located at the anal canal. A 41-year old woman presented with locally advanced small cell anal cancer and simultaneous hepatic and pulmonal deposits. Due to metastatic disease, chemotherapy with etoposide and cisplatin was performed with mixed response after four cycles of chemotherapy. After application of two additional chemotherapy cycles, locally progressive disease occurred causing symptomatic bowel obstruction. Pelvic irradiation was started and, several days later, additional irradiation of cerebral metastases was initiated due to rapid progression of distant disease. Despite adequate local treatment the patient's condition further deteriorated and irradiation was stopped. The patient died 10 months after initial diagnosis due to rapid tumor progression. In patients with metastatic small cell anal cancer chemotherapy remains the mainstay of therapy. Radiotherapy exerts additional activity and remains a prime choice to gain local control and ameliorate symptoms. Careful histopathological examination, together with immunohistochemistry, is needed to determine the therapeutic strategy to be followed.
    Anticancer research 01/2007; 27(2):1047-50. · 1.71 Impact Factor
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    ABSTRACT: Permanent interstitial brachytherapy represents the most conformal form of radiation therapy of the prostate and the number of patients with prostate cancers treated with permanent radioactive implants is increasing world wide. In the meanwhile long-term data on tumor control and treatment morbidity become available. Biochemical and clinical tumor control appears to be as effective as after radical prostatectomy or external beam radiation therapy in early prostate cancer. The risk of postreatment urinary incontinence and bowel dysfunction is low and erectile function can be preserved in the majority of patients. However, prostate brachytherapy requires a careful selection of patients as pretreatment factors predict for long-term outcome. The need for combined modality approaches in intermediate and high-risk patients remains controversely discussed. The continous refinement of intraoperative planning techniques and the elucidation of the etiology of urinary, sexual, and bowel dysfunction should result in further improvements in biochemical outcomes and decreased morbidity. Improved and standardized postimplantation evaluation will make outcome data more reliable and comparable.
    World Journal of Urology 09/2006; 24(3):289-95. · 2.89 Impact Factor
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    ABSTRACT: The aim of this retrospective analysis was to evaluate feasibility and effectiveness of definitive chemoradiotherapy without split-course technique in anal cancer patients. From 1993 to 2003, 81 patients were treated; 13 were excluded due to various chemotherapeutic regimes, thus 68 patients were analysed. In case of acute grade 3 toxicities, treatment was halted until improvement or resolution independent of dose. Short interruption was defined as completing treatment without exceeding eight cumulative treatment days beyond scheduled plan, other patients were considered to have had prolonged interruption. Median follow-up was 46 months. Median overall treatment time was 53 days corresponding to an interruption of eight cumulative treatment days. Thirty-five patients (51%) had treatment interruption of <or=8 days. No acute grade 4 toxicities were observed; one fatality occurred during treatment due to ileus-like symptoms according to acute grade 5 toxicity. Comparing patients with short vs. prolonged interruption 5-year actuarial rates for local control were 85% vs. 81% (p = 0.605) and for colostomy-free survival 85% vs. 87% (p = 0.762), respectively. Chemoradiotherapy with short individualised treatment interruptions seems to be feasible with acceptable acute or late toxicities. Treatment is highly effective in terms of local control and colostomy-free survival.
    Acta Oncologica 02/2006; 45(6):728-35. · 2.87 Impact Factor
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    ABSTRACT: An analysis was performed to determine whether a cranial reduction of the portals to the T11/T12 junction instead of the common T10/T11 junction would alter the outcome of patients with stage I seminoma. Of 163 consecutive patients with newly diagnosed testicular seminoma referred to the authors' institution between April 1992 and April 1999, 80 patients with stage I seminoma were treated with cranially reduced para-aortic treatment fields reaching from the top of T12 to the bottom of L4. Median total dose was 20.0 Gy (range, 19.8-27.2 Gy). Patients were followed-up by the use of CT in regular intervals. After a median follow-up of 7.1 years (range, 4.1-11.1 years), four patients (5%) had relapsed resulting in an actuarial 5-year relapse-free survival of 95%. No patients relapsed within the cranially reduced treatment volume above the top of T12. The cranial reduction of the para-aortic treatment fields resulted in a median reduction of treatment volume of 16% (range, 13-21%). The achieved median reduction in treatment volume of 16% appears to be relevant and is not associated with an increased relapse rate. This approach is recommended in analogy to the surgical approach in NSGCT to further minimize the risk of radiation-related late effects.
    Acta Oncologica 02/2005; 44(2):142-8. · 2.87 Impact Factor
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    ABSTRACT: We analyzed the clinical outcome of breast cancer patients carrying sequence variants in the ATM gene who received postoperative radiotherapy after breast conservative surgery to test whether an increased cellular radiosensitivity may translate into enhanced tumor cell killing and thereby result in an improvement of the therapeutic ratio. We investigated a cohort of 138 breast cancer patients who received adjuvant radiotherapy following breast conservative surgery for T1 and T2 tumors. Genomic DNA samples of these patients had previously been scanned for mutations in the ATM gene. Follow-up data were available in 135 patients, with a median follow-up of 87 months. Local relapse-free, metastasis-free and overall survival were compared between carriers and non-carriers of a sequence variant in the ATM gene. Twenty patients were found to carry a sequence variant in the ATM gene (truncating, 7; missense, 13). The actuarial 7-year local relapse-free survival of carriers vs. non-carriers were 88 vs. 94% (P=0.34). Actuarial metastasis-free and overall survival after 7 years were 63 vs. 85% (P=0.01) and 73 vs. 89% (P=0.055), respectively. However, the presence of a variant in the ATM gene did not remain a significant discriminator for metastasis-free survival in a multivariate Cox regression analysis (P=0.068). Our results do not support the hypothesis that breast cancer patients carrying a sequence variant in the ATM gene differentially benefit from postoperative radiotherapy. These findings have to be verified using larger number of cases to clarify the clinical consequences of sequence variants in the ATM gene.
    Radiotherapy and Oncology 10/2004; 72(3):319-23. · 4.52 Impact Factor
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    ABSTRACT: Background The quality of the interdisciplinary interface in oncological treatment between surgery, pathology and radiotherapy is mainly dependent on reliable anatomical three-dimensional (3D) allocation of specimen and their context sensitive interpretation which defines further treatment protocols. Computer-assisted preoperative planning (CAPP) allows for outlining macroscopical tumor size and margins. A new technique facilitates the 3D virtual marking and mapping of frozen sections and resection margins or important surgical intraoperative information. These data could be stored in DICOM format (Digital Imaging and Communication in Medicine) in terms of augmented reality and transferred to communicate patient’s specific tumor information (invasion to vessels and nerves, non-resectable tumor) to oncologists, radiotherapists and pathologists. Aim The purpose of this work was to develop, establish and clinically evaluate a novel, user-friendly, language independent and multidisciplinary tool to provide intraoperative collected data to the surgeon, oncologist, radiotherapist, pathologist and radiologist. Methods 19 Patients where operated with the support of computer assisted surgery. Time needed for preoperative planning including data transfer, dataset alignment, automatic and manual object segmentation, trajectories and additional safety checkups was measured in minutes. Accuracy of our set-up was recorded after registration. Finaly surgical time and Quality improvements were evaluated by comparison of hard and soft-tissue and the deviation of the correct position of the preplaned implants with the postoperative results was compared. Results Successful preoperative planning, import of image data suitable for navigation and intraoperative precise infrared-based navigation was obtained for all patients without any complications. The registration of patient data at the navigation system using screws as fiducial markers delivered a navigation accuracy with a mean deviation of 1.3 ± 0.6 mm in our cases. The novel method of intra-operative marking of specimen either frozen sections or surgical margins eases the storage and further use of intra-operative information. Image-guided navigation technique for head and neck oncologic surgery provides a precise, safe surgical method with real time excellent anatomic orientation. Conclusion Regarding the advantages of computer-assisted surgery, this technique will play a major part in craniofacial reconstructive surgery and will address widespread general methodological solutions that are of great interest in multidisciplinary oncologic treatment.
    Oral Oncology. 49:S28.

Publication Stats

674 Citations
199.13 Total Impact Points

Institutions

  • 2004–2013
    • Hannover Medical School
      • Clinic for Gynaecology and Obstretics
      Hanover, Lower Saxony, Germany
  • 2008–2011
    • Institute of Cancer Research
      Londinium, England, United Kingdom