N Willich

Publications (126)328.29 Total impact

• Article: Pelvic Ewing sarcomas : Three-dimensional conformal vs. intensity-modulated radiotherapy.

  F S Mounessi, P Lehrich, U Haverkamp, N Willich, T Bölling, H T Eich
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  ABSTRACT: PURPOSE: The goal of the present work was to assess the potential advantage of intensity-modulated radiotherapy (IMRT) over three-dimensional conformal radiotherapy (3D-CRT) planning in pelvic Ewing's sarcoma. PATIENTS AND METHODS: A total of 8 patients with Ewing sarcoma of the pelvis undergoing radiotherapy were analyzed. Plans for 3D-CRT and IMRT were calculated for each patient. Dose coverage of the planning target volume (PTV), conformity and homogeneity indices, as well as further parameters were evaluated. RESULTS: The average dose coverage values for PTV were comparable in 3D-CRT and IMRT plans. Both techniques had a PTV coverage of V(95) > 98 % in all patients. Whereas the IMRT plans achieved a higher conformity index compared to the 3D-CRT plans (conformity index 0.79 ± 0.12 vs. 0.54 ± 0.19, p = 0.012), the dose distribution across the target volumes was less homogeneous with IMRT planning than with 3D-CRT planning. This difference was statistically significant (homogeneity index 0.11 ± 0.03 vs. 0.07 ± 0.0, p = 0.035). For the bowel, D(mean) and D(1%), as well as V(2) to V(60) were reduced in IMRT plans. For the bladder and the rectum, there was no significant difference in D(mean). However, the percentages of volumes receiving at least doses of 30, 40, 45, and 50 Gy (V(30) to V(50)) were lower for the rectum in IMRT plans. The volume of normal tissue receiving at least 2 Gy (V(2)) was significantly higher in IMRT plans compared with 3D-CRT, whereas at high dose levels (V(30)) it was significantly lower. CONCLUSION: Compared to 3D-CRT, IMRT showed significantly better results regarding dose conformity (p = 0.012) and bowel sparing at dose levels above 30 Gy (p = 0.012). Thus, dose escalation in the radiotherapy of pelvic Ewing's sarcoma can be more easily achieved using IMRT.
  Strahlentherapie und Onkologie 02/2013; · 3.56 Impact Factor
• Article: Die intraoperative Radiotherapie als Bestandteil multimodaler Therapiekonzepte bei epithelialen Tumoren des Gastrointestinaltrakts

  M. Brüwer, S. Hesselmann, U. Schäfer, N. Willich, N. Senninger
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  ABSTRACT: Durch intraoperative Strahlentherapie (IORT) wird unter maximaler Schonung der umliegenden strahlensensiblen Organe die Strahlendosis im Tumorbett lokal erhöht. Mit diesem Verfahren als Bestandteil eines multimodalen Therapieregimes konnten sowohl die Lokalrezidivrate als auch die Überlebensrate gegenüber konventionellen Therapieregimen beim fortgeschrittenen primären Rectumcarcinom und Carcinomrezidiv verbessert werden. Dagegen ist bisher nur in wenigen Studien über eine verbesserte Überlebensrate durch zusätzliche IORT beim fortgeschrittenen Magencarcinom berichtet worden. Beim Pankreascarcinom wird durch IORT die lokale Tumorkontrolle, nicht aber die Überlebensrate verbessert, da häufig Leber- und Peritonealmetastasen auftreten. Für das Oesophaguscarcinom liegen zur Zeit nur unzureichende Daten vor. Surgery alone often fails to achieve local control in advanced gastrointestinal tumors. With multimodal therapy approaches, both local tumor control and long-term survival appear to be improved. Intraoperative radiation therapy (IORT) is an attempt to achieve higher doses of irradiation while dose-limiting structures are surgically displaced. It has been shown previously that both local tumor control and long-term survival are improved in patients undergoing surgery combined with IORT for both primary and recurrent rectal carcinoma. In advanced gastric carcinoma, IORT has achieved optimistic survival results in a few studies. In locally advanced pancreatic cancer, an apparent improvement in local control has been noted with IORT, but survival has not been prolonged because of a high incidence of both liver and peritoneal metastases. The data concerning IORT for esophageal carcinoma are not yet sufficient to allow judgement.
  Der Chirurg 04/2012; 71(6):682-691. · 0.70 Impact Factor
• Article: Thyroid function in paediatric and young adult patients after sarcoma therapy: a report from the Late Effects Surveillance System.

  M Paulides, H G Dörr, W Stöhr, S Bielack, E Koscielniak, T Klingebiel, H Jürgens, T Bölling, N Willich, R Sauer, T Langer, J D Beck
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  ABSTRACT: The role of chemotherapy in thyroid sequelae after cancer treatment has not been studied systematically, especially in sarcoma patients. The aim of this study was to determine the incidence of post-therapeutic thyroid disorders and their contributing factors in a cohort of paediatric sarcoma patients. Late effects of sarcoma treatment have been collected prospectively within the Late Effects Surveillance System (LESS) in Germany, Austria and Switzerland since 1998. We studied 340 relapse-free paediatric patients (median age at diagnosis 12.2 [interquartile range (IQR) = 7.3-15.6 years] treated for osteosarcoma, soft tissue sarcoma or Ewing's sarcoma within the COSS-96, CWS-96/CWS-2002P or EICESS-92/EURO-E.W.I.N.G.-99 therapy trials. In addition to polychemotherapy, 127 patients were irradiated (mean cumulative dose 47 +/- 9.7 Gy), including 51 patients with irradiation to the head/neck region. Median follow-up was 24.6 (IQR = 11.9-44.9) months. We reviewed the results of yearly examinations of serum TSH and fT4 levels and thyroid ultrasound examinations. The incidence of thyroid disorders was 37% (19/51, 95% CI 24-52%) in patients with head/neck irradiation, and 11% (32/289, 95% CI 8-15%) in patients without irradiation to the head/neck. Thyroid disorders were more frequent in patients treated with idarubicin (P = 0.027) and trofosfamide (P = 0.016). We also found a significant association between raised TSH levels and treatment with trofosfamide (P = 0.008) or idarubicin (P = 0.037) (n = 250). The incidence of thyroid disorders in the head/neck-irradiated group was high. Even without head/neck irradiation, we found an increased proportion of patients with thyroid disorders, possibly as a result of chemotherapy.
  Clinical Endocrinology 06/2007; 66(5):727-31. · 3.17 Impact Factor
• Chapter: Primäre gastrointestinale Non-Hodgkin-Lymphome

  P. Koch, N. Willich, W. E. Berdel
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  ABSTRACT: Definition: Primäre gastrointestinale Non-Hodgkin-Lymphome (GI-NHL) zählen zur Gruppe extralymphatischer* NHL. Sie definieren sich dadurch, daß Symptome oder Läsionen zur Diagnose führen, und lassen sich so von einer sekundären Beteiligung des Magen-Darm-Trakts im Rahmen der Generalisation eines nodalen NHL abgrenzen.
  12/2005: pages 3066-3085;
• Article: [Plantar fasciitis and radiotherapy. Clinical and radiobiological treatment results].

  O Micke, M H Seeegenschmiedt, R Mücke, A de Vries, U Schäfer, N Willich
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  ABSTRACT: Patients with plantar fasciitis and pain refractory to conventional therapy are treated with low-dose radiotherapy (RT), but no conclusive evidence-based and radiobiological studies had been performed. In 2001 the German Cooperative Group on Radiotherapy for Benign Diseases (GCG-BD) carried out a study by mailing a standardized questionnaire. A total of 136 institutions treated 3621 patients/year with chronic or refractory pain. The median total dose was 6 Gy (median single dose: 1 Gy); 76 institutions reported data of their clinical evaluation of a total of 7947 patients. Pain relief lasting for at least 3 months was reported in 70% and persistent pain relief in 65%. There were no acute or chronic radiogenic side effects observed. The radiobiological studies showed a significant increase of granulocyte function at 1.5 Gy and a significant decrease at 3.5 and 4.0 Gy. These results may provide a possible explanation for a local anti-inflammatory effect of low-dose RT. RT may be an excellent alternative for patients with contraindications to long-term treatment with steroids or NSAID.
  Der Orthopäde 07/2005; 34(6):579-91. · 0.51 Impact Factor
• Article: Guidelines on radioiodine therapy for differentiated thyroid carcinoma: impact on clinical practice.

  M Biermann, M K Pixberg, U Dörr, M Dietlein, H Schlemmer, J Grimm, T Zajic, U Nestle, S Ladner, S Sepehr-Rezai, S Rosenbaum, C Puskás, P Fostitsch, A Heinecke, A Schuck, N Willich, K W Schmid, H Dralle, O Schober
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  ABSTRACT: For the examination of the impact on clinical practice of the guidelines for differentiated thyroid carcinoma (DTC), treatment data from the ongoing Multicenter Study Differentiated Thyroid Carcinoma (MSDS) were analyzed. Patients were randomized to adjuvant external beam radiotherapy (RTx) or no RTx in addition to standard therapy in TNM stages pT4 pN0/1/x M0/x (UICC, 5th ed. 1997). All patients were to receive the same treatment regimen consisting of thyroidectomy, ablative radioiodine therapy (RIT), and a diagnostic 131I whole-body scintigraphy (WBS) 3-4 months after RIT. Of 339 eligible patients enrolled between January 2000 and March 2004, 273 could be analyzed. Guideline recommendations by the German Society for Nuclear Medicine from 1999 and 1992 were complied with within 28% and 82% with regard to the interval between surgery and RIT (4 vs. 4-6 weeks), in 33% and 84% with regard to 131I activity for RIT (1-3 vs. 1-4 GBq; +/- 10%), and in 16% and 60% with regard to 131I activity for WBS (100-300 vs. 100-400 MBq; +/- 10%). The 1999 guideline revision appears to have had little impact on clinical practice. Further follow-up will reveal if guideline compliance had an effect on outcomes.
  Nuklearmedizin 02/2005; 44(6):229-34, 236-7. · 1.28 Impact Factor
• Article: Heterogeneity of radiation induced apoptosis in Ewing Tumor cell lines characterized on a single cell level.

  S Könemann, T Bölling, A Kolkmeyer, D Riesenbeck, S Hesselmann, J Vormoor, N Willich, A Schuck
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  ABSTRACT: The objective of this study was to investigate heterogeneity of radiation induced apoptosis on a single cell level. Two Ewing tumor cell lines were characterized in vitro before and 24 and 72 h after radiation with 5 Gy by multiparametric flow cytometry. Annexin V, 7-AAD and fluorescence conjugated antibodies that were directed against HLA-ABC, CD11a and CD62L were used. Based on these markers radiation induced apoptosis was quantified, multiple apoptotic subpopulations were identified and a characteristic individual apoptotic profile was characterized. The characterization of HLA-ABC, CD11a and CD62L was informative to detect subpopulations of apoptotic cells. The observed heterogeneity and the identification of multiple apoptotic subpopulations reflect the complexity and diversity of biology of radiation induced cell death. This might be an indication for co-existing apoptotic pathways or it might represent sequential steps of the apoptotic cascade.
  APOPTOSIS 02/2005; 10(1):177-84. · 4.79 Impact Factor
• Article: Radiojodtherapie des Schilddrüsenkarzinoms

  M. Biermann, M. K. Pixberg, B. Riemann, A. Schuck, N. Willich, O. Schober
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  ABSTRACT: Die hoch dosierte Radiojodtherapie wird gem den Leitlinien der Deutschen Krebsgesellschaft bei allen differenzierten Schilddrsenkarzinomen zur Ablation des nach Thyroidektomie verbliebenen Schilddrsenrestgewebes durchgefhrt. Einzige Ausnahme ist das auf die Schilddrse beschrnkte unifokale papillre Mikrokarzinom 1cm ohne Lymphknoten oder Fernmetastasen. Durch die Sterilisation (pr-)maligner Zellen im Schilddrsenrestgewebe oder in zervikalen Lymphknoten wird die lokoregionre Rezidivrate im Gegensatz zur ausschlielichen chirurgischen Therapie wirksam auf unter 10% in 10Jahren gesenkt. Eine effektive Therapie Jod speichernder Metastasen ist ebenfalls mglich. Durchfhrung der Therapie und Nachsorge sollten aufgrund der Seltenheit des Krankheitsbilds spezialisierten Zentren vorbehalten bleiben.According to the current guidelines of the German Cancer Society, high-dose radioiodine therapy is obligatory in all cases of differentiated thyroid carcinoma to ablate the thyroid remnant after thyroidectomy. The only exception is made in the case of unifocal papillary microcarcinomas 1cm that are confined to the thyroid gland with no lymph node involvement or distant metastases. By sterilizing (pre)malignant cells in the thyroid remnant or in cervical lymph nodes, radioiodine therapy can reduce locoregional recurrence rates to under 10% in 10years, in contrast to surgery alone. It is also effective against distant metastases that take up radioiodine. Owing to the low incidence of the disease, radioiodine therapy and patient follow-up should be restricted to specialized centres.
  Der Onkologe 12/2004; 11(1):70-77. · 0.17 Impact Factor
• Article: Strahlentherapie des Schilddrüsenkarzinoms

  A. Schuck, M. Biermann, O. Schober, N. Willich
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  ABSTRACT: Beim differenzierten Schilddrsenkarzinom besteht bei nicht Organkapsel berschreitendem Tumorwachstum und adquater Operation keine Indikation zur postoperativen Bestrahlung. Bei Patienten mit Organkapsel berschreitendem Wachstum wird nach vollstndiger Resektion der Nutzen einer zustzlichen perkutanen Radiotherapie kontrovers diskutiert. Die MSDS-Studie (Multizenterstudie Differenziertes Schilddrsenkarzinom), die eine Randomisierung genau zu dieser Fragestellung durchfhrte, musste aufgrund der mangelnden Rekrutierung vorzeitig beendet werden. Beim anaplastischen Schilddrsenkarzinom wird die vollstndige Resektion angestrebt. Die postoperative Bestrahlung ist dann obligat. Bei Therapieprotokollen mit zustzlicher Adriamycingabe konnten erhhte lokale Kontroll- und berlebensraten beobachtet werden. Bei medullrem Schilddrsenkarzinom und inkompletter Tumorresektion geht eine additive Radiotherapie mit einer verbesserten lokalen Kontrolle einher. Bei nicht Radiojod speichernden Metastasen des Schilddrsenkarzinoms wird die Radiotherapie im Bereich des Knochens bei Schmerzen, Frakturgefahr oder Myelonkompression eingesetzt.In patients with differentiated thyroid cancer and organ-confined tumor, no radiotherapy is performed after appropriate surgery. Following complete resection in patients with extracapsular extension, the value of external beam radiotherapy is controversial. The MSDS trial (Multicenter Trial Differentiated Thyroid Cancer) randomized the use of external beam radiotherapy but had to close because of insufficient recruitment. In anaplastic thyroid cancer, complete resection is the goal and postoperative radiotherapy is compulsory. In treatment protocols with additional Adriamycin-containing chemotherapy, improved local control and survival have been reported. In medullary thyroid cancer and incomplete tumor resection, additional radiotherapy can improve local control. In metastases without radioiodine uptake, radiotherapy is indicated in bone metastases with pain, at risk for pathologic fracture, or with myelon compression.
  Der Onkologe 12/2004; 11(1):87-92. · 0.17 Impact Factor
• Article: [PET/CT in radiotherapy].

  M Weckesser, S Könemann, M Brinkmann, N Willich, O Schober
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  ABSTRACT: Combining positron emission tomography (PET) and X-ray computed tomography (CT) with simultaneous acquisition may improve diagnostic accuracy in oncology. Moreover this combination holds considerable promise in radiotherapy. Metabolic information may be used in decision making in radiotherapy and in planning target volumes. Furthermore early evaluation of treatment efficacy becomes possible. New tracers for the assessment of tumour hypoxia or apoptosis in clinical routine are currently being developed. These tracers may yield high relevance in radiotherapy. Hybrid scanners facilitate patient handling and shorten the duration of acquisition. Furthermore fusion accuracy is optimal. Prospective studies have to be conducted to show that the new technology improves patient care in terms of efficiency and quality.
  Der Radiologe 12/2004; 44(11):1096-104. · 0.61 Impact Factor
• Article: Treatment of advanced Hodgkin's disease with COPP/ABV/IMEP versus COPP/ABVD and consolidating radiotherapy: final results of the German Hodgkin's Lymphoma Study Group HD6 trial.

  M Sieber, H Tesch, B Pfistner, U Rueffer, U Paulus, R Munker, R Hermann, G Doelken, P Koch, J Oertel, [......], A Engert, M Loeffler, V Diehl, R P Mueller, N Willich, R Fischer, M L Hansmann, H Stein, T Schober, B Koch
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  ABSTRACT: The purpose of this study was to compare the efficacy of the hybrid chemotherapeutic regimen COPP/ABV/IMEP (cyclophosphamide-vincristine-procarbazine-prednisone-doxorubicin-bleomycin-vinblastine-ifosfamide-methotrexate-etoposide) (CAI) with that of the standard regimen COPP/ABVD (COPP/ABV, dacarbacine) (CA) in the treatment of advanced-stage Hodgkin's disease (HD). Between January 1988 and January 1993, 588 eligible patients with HD in stages IIIB and IV were randomly assigned to a treatment or control group. The treatment group received four cycles of CAI over a complete cycle duration of 43 days. The control group received four cycles of CA over 57 days. Both groups then received consolidating radiotherapy. Five hundred and eighty-four patients were suitable for arm comparison. Patients in each group were similar in age, sex, histological subtype and clinical risk factors. Complete remission rates, overall survival and freedom from treatment failure at 7 years were similar for the two groups: 77% versus 78%, 73% versus 73% and 54% versus 56% for CAI and CA, respectively. Differences in acute chemotherapy-related toxicity were significant, however. Prognostic factor analysis confirmed the relevance of the International Prognostic Index and revealed that stage IVB, low hemoglobin, low lymphocyte count, high age and male gender were associated with a poor prognosis The rapidly alternating hybrid CAI did not give superior results when compared with the standard regimen CA in advanced-stage HD.
  Annals of Oncology 03/2004; 15(2):276-82. · 6.43 Impact Factor
• Article: Late urologic effects after adjuvant irradiation in stage I endometrial carcinoma.

  R Herwig, F Bruns, H Strasser, Germar M Pinggera, O Micke, P Rehder, C Gozzi, N Willich, L Hertle
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  ABSTRACT: To evaluate the incidence and type of incontinence after external beam radiotherapy (RT) and brachytherapy. Distinct late effects on the urinary bladder can occur and are frequently mild after adjuvant RT for Stage I endometrial carcinoma. Not all side effects that impair quality of life (eg, urinary incontinence) are classified in the commonly used grading system. Forty-one patients were evaluated for newly occurred urinary incontinence after adjuvant RT. The mean follow-up was 64.8 months, and the mean age was 62.1 years. The validated incontinence score from Gaudenz was used. Additionally, quality-of-life questions were asked. Overall, 22 (53.7%) of 41 patients complained of urinary incontinence. Urge incontinence was classified in 45.5% (10 of 22 patients) and stress urinary incontinence in 54.5% (12 of 22 patients). The onset of stress urinary incontinence after brachytherapy can be explained by anatomic findings, such as adverse affects to the nerve supply of the rhabdosphincter. According to our results, the exposure to additional external beam RT can cause urge incontinence. Patients and doctors must be aware that urinary incontinence, with an occurrence rate of more than 50%, represents the most common side effect after surgery and RT for Stage I endometrial carcinoma. We conclude that, depending on the type of RT, a stress incontinence rate of 24.4% and an urge incontinence rate of 29.2% is possible.
  Urology 03/2004; 63(2):354-8. · 2.43 Impact Factor
• Article: PET-CT in der Strahlentherapie

  M. Weckesser, S. Könemann, M. Brinkmann, N. Willich, O. Schober
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  ABSTRACT: Die gleichzeitige Kombination von Positronenemissionstomographie (PET) und Computertomographie (CT) kann gegenber der Summe der einzelnen Verfahren die Diagnostik von Tumorerkrankungen verbessern. Darber hinaus besteht ein hohes Potenzial fr den Einsatz in der Strahlentherapie. Neben der Indikationsstellung und der Therapieplanung knnen metabolische Informationen auch verwendet werden, um den Therapieerfolg frhzeitig zu berprfen. Klinische Verfahren zur Darstellung therapierelevanter Tumoreigenschaften, wie der Oxygenierung oder des Einsetzens von Apoptose, werden zurzeit entwickelt. Der Einsatz von Hybridgerten erleichtert und beschleunigt Arbeitsablufe und bietet die in der Strahlentherapie besonders wichtige hohe Fusionsgenauigkeit. Prospektive Studien sind erforderlich, um nachzuweisen, dass die neue Technologie zu einer Verbesserung von Effizienz und Qualitt der Patientenversorgung fhrt.Combining positron emission tomography (PET) and X-ray computed tomography (CT) with simultaneous acquisition may improve diagnostic accuracy in oncology. Moreover this combination holds considerable promise in radiotherapy. Metabolic information may be used in decision making in radiotherapy and in planning target volumes. Furthermore early evaluation of treatment efficacy becomes possible. New tracers for the assessment of tumour hypoxia or apoptosis in clinical routine are currently being developed. These tracers may yield high relevance in radiotherapy. Hybrid scanners facilitate patient handling and shorten the duration of acquisition. Furthermore fusion accuracy is optimal. Prospective studies have to be conducted to show that the new technology improves patient care in terms of efficiency and quality.
  Der Radiologe 01/2004; 44(11):1096-1104. · 0.61 Impact Factor
• Article: Multicenter study differentiated thyroid carcinoma (MSDS). Diminished acceptance of adjuvant external beam radiotherapy.

  M Biermann, M K Pixberg, A Schuck, A Heinecke, W Köpcke, K W Schmid, H Dralle, N Willich, O Schober
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  ABSTRACT: The Multicenter Study Differentiated Thyroid Carcinoma (MSDS) is an ongoing study in Germany, Austria, and Switzerland on the clinical benefit of adjuvant external beam radiotherapy (RTx) for locally invasive differentiated thyroid carcinoma (DTC) in TNM stages pT4 pN0/1/x M0/x (5th ed. 1997). MSDS was designed as a prospective randomized trial. Patients receive thyroidectomy, radioiodine therapy (RIT) to ablate the thyroid remnant, and TSH-suppressive L-thyroxine therapy with or without RTx after documented elimination of cervical iodine-131 uptake (http://msds-studie.uni-muenster.de). 311 patients were enrolled between January 2000 and March 2003. 279 patients met the trial's inclusion criteria. 45 consented to randomization, of whom 17 were randomized into treatment arm A (RTx) and 18 into arm B (no RTx). Advised by the trial's independent Data Monitoring and Safety Committee, the MSDS steering committee decided to terminate randomization in April 2003 and continue MSDS as a prospective cohort study. 23 of the 234 patients in the observation arm of the trial were prescribed RTx by their physicians. Thus, 14% of the trial cohort were randomized or assigned to receive RTx (in-tention-to-treat analysis). In contrast, at least 44% of all patients with pT4 papillary DTC in Germany in the nation-wide PCES study underwent RTx in 1996 (p <0.001, chi(2)-test). Acceptance of external beam RTx as a treatment modality for DTC has receded to a degree that accrual of a sufficient number of patients for a randomized trial has been impossible. Observation of the trial cohort is continued in order to assess clinical event rates with and without RTx and chronic RTx toxicity.
  Nuklearmedizin 01/2004; 42(6):244-50. · 1.28 Impact Factor
• Article: Time- and dose-dependent changes of intracellular cytokine and cytokine receptor profile of Ewing tumour subpopulations under the influence of ionizing radiation.

  S Könemann, T Bölling, J Malath, A Kolkmeyer, K Janke, D Riesenbeck, S Hesselmann, R Diallo, J Vormoor, N Willich, A Schuck
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  ABSTRACT: Cytokines and their corresponding cell surface receptors are involved in intercellular signalling pathways and in the radioresistance of normal and malignant cells. The aim was the characterization of the expression of intracellular cytokines, their receptors and apoptosis-associated markers under the influence of radiation. Two Ewing tumours were characterized in vitro before and 4, 24 and 72 h after radiation with 5 and 10 Gy, and in vivo 4, 6 and 15 days after radiation with 5 and 30 Gy by five parameter flow cytometry. Direct fluorescence-conjugated antibodies directed against intracellular cytokines (interferon-gamma, tumour necrosis factor [TNF]-alpha, interleukin 1) and their receptors (CD119, CD120a, CD121a) were used. Annexin V and 7-amino-actinomycin D were used to identify radiation-induced apoptosis. Inter- and intra-individual heterogeneities were identified by the expression of cytokine receptors and the intracellular cytokine profile before radiation. Time- and dose-dependent up-regulation of the cytokines TNF-alpha and interleukin 1 were found in vitro. In vivo, an up-regulation of CD120a and CD121a was detectable on tumour cell subpopulations. For interferon-gamma and CD119, no changes were seen. The observed radiation-induced changes of cytokine and receptor profile are an indication for complex intercellular interactions in view of radioresistance-associated mechanisms between cell populations within one individual tumour. The observed heterogeneous response on radiation might have therapeutic implications for an individualized therapy based on combined radiation and cytokine modulation, defined by flow cytometric characterization of markers potentially informative for radioresistance.
  International Journal of Radiation Biology 12/2003; 79(11):897-909. · 2.28 Impact Factor
• Article: Lymphangiolipoma of the lower extremity: 5-year radiological follow-up after radiotherapy treatment.

  F Bruns, W Steitz, P Schueller, U Schaefer, N Willich, O Micke
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  ABSTRACT: This report describes a lymphangiolipoma located in the extremity in a young woman. Radiotherapy effectively controlled recurrent lymphangiolipoma of the left upper leg that had been judged inoperable by limb-sparing surgical resection. In the case presented here, a dose of 50 Gy in 25 fractions over 5 weeks was employed without long-term complications after 5-year follow-up.
  British Journal of Radiology 10/2002; 75(897):767-71. · 1.31 Impact Factor
• Article: Radiotherapy in the treatment of locoregional relapses of breast cancer.

  A Schuck, S Könemann, B Matthees, C E Rübe, G Reinartz, S Hesselmann, O Micke, U Schäfer, N Willich
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  ABSTRACT: Locoregional recurrences of breast cancer are associated with considerable morbidity and frequently present with concurrent metastatic disease. Yet patients without systemic spread can be treated with curative intent. In a retrospective analysis, the results of treatment of these patients have been evaluated at our institution. Between 1987 and 1996, 113 patients with locoregional breast cancer relapse, without systemic manifestation, received irradiation after local tumour excision. 13 patients (11.5%) had already received radiotherapy as part of their primary treatment. In these cases, only the area involved was treated. In all other patients, the chest wall and the ipsilateral lymph nodes were irradiated. Median dose was 50 Gy (range 20-65 Gy). Median follow-up was 4.4 years. 76 patients (67.3%) presented with chest wall recurrence only, 25 patients (22.1%) with nodal relapse only and 12 patients (10.6%) with combined relapses. 93% of patients had local control of disease after treatment. Local control rate after 5 years was 59%. 63 patients (55.8%) died within the follow-up interval, 45 patients (39.8%) owing to metastases, 4 patients (3.5%) owing to local failure and 8 patients (7%) owing to causes unrelated to tumour. Overall survival after 5 years was 43%. In multivariate analysis, positive hormone receptor status, small tumours on relapse and chest wall relapses alone were associated with improved survival. Radical local therapy is necessary in order to achieve and maintain local control and to prevent secondary dissemination in patients with only local recurrence of breast cancer.
  British Journal of Radiology 09/2002; 75(896):663-9. · 1.31 Impact Factor
• Article: Case report: Kasabach-Merritt syndrome: a review of the therapeutic options and a case report of successful treatment with radiotherapy and interferon alpha.

  S Hesselmann, O Micke, T Marquardt, S Baas, J H Bramswig, E Harms, N Willich
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  ABSTRACT: We describe the successful treatment of a neonate with Kasabach-Merritt syndrome who received local irradiation and interferon alpha therapy after failure of corticosteroid treatment. A male neonate, born after an uneventful pregnancy, had a huge haemangioma involving the upper right cervical region as well as severe thrombocytopenia. He was treated with corticosteroids, interferon alpha and radiotherapy. Prednisolone therapy (5 mg kg(-1) day(-1)) was started at 41 days of age. No therapeutic effect was observed after 2 weeks. At this time the tumour size had increased dramatically, platelet counts had decreased progressively and coagulation abnormalities had developed. Because corticosteroid therapy had been ineffective and the child was in a life-threatening condition, irradiation was delivered up to a total dose of 9.5 Gy in five fractions. Simultaneously, prednisolone therapy was slowly decreased and interferon alpha therapy (3 million U m(-2) day(-1)) was started and continued for 6 weeks. After irradiation with 9.5 Gy and beginning interferon alpha therapy, the tumour decreased in size and coagulation parameters normalized within 4 weeks. 6 months later, platelet counts and coagulation parameters were still normal. The tumour had further decreased in size. No acute severe side effects were observed. Radiation therapy combined with interferon alpha treatment is an alternative treatment modality when high dose corticoid steroid therapy has been ineffective in patients with Kasabach-Merritt syndrome, despite the risks of growth delay and secondary malignancy. In children showing no response to corticosteroids, radiotherapy and/or interferon alpha should be considered in Kasabach-Merritt syndrome.
  British Journal of Radiology 03/2002; 75(890):180-4. · 1.31 Impact Factor
• Article: CT simulation in nodal positive breast cancer.

  E Horst, A Schuck, C Moustakis, U Schaefer, O Micke, H L Kronholz, N Willich
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  ABSTRACT: A variety of solutions are used to match tangential fields and opposed lymph node fields in irradiation of nodal positive breast cancer. The choice is depending on the technical equipment which is available and the clinical situation. The CT simulation of a non-monoisocentric technique was evaluated in terms of accuracy and reproducibility. The field match parameters were adjusted virtually at CT simulation and were compared with parameters derived mathematically. The coordinate transfer from the CT simulator to the conventional simulator was analyzed in 25 consecutive patients. The angles adjusted virtually for a geometrically exact coplanar field match corresponded with the angles calculated for each set-up. The mean isocenter displacement was 5.7 mm and the total uncertainty of the coordinate transfer was 6.7 mm (1 SD). Limitations in the patient set-up became obvious because of the steep arm abduction necessary to fit the 70 cm CT gantry aperture. Required modifications of the arm position and coordinate transfer errors led to a significant shift of the marked matchline of > 1.0 cm in eight of 25 patients (32%). The virtual CT simulation allows a precise and graphic definition of the field match parameters. However, modifications of the virtual set-up basically due to technical limitations were required in a total of 32% of cases, so that a hybrid technique was adapted at present that combines virtual adjustment of the ideal field alignment parameters with conventional simulation.
  Strahlentherapie und Onkologie 11/2001; 177(10):511-6. · 3.56 Impact Factor
• Article: Low-dose radiation is sufficient for the noninvolved extended-field treatment in favorable early-stage Hodgkin's disease: long-term results of a randomized trial of radiotherapy alone.

  E Dühmke, J Franklin, M Pfreundschuh, S Sehlen, N Willich, U Rühl, R P Müller, P Lukas, A Atzinger, U Paulus, [......], H Kirchner, A Emminger, R Greil, E Fritsch, P Koch, A Drochtert, O Brosteanu, D Hasenclever, M Loeffler, V Diehl
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  ABSTRACT: To show that radiotherapy (RT) dose to the noninvolved extended field (EF) can be reduced without loss of efficacy in patients with early-stage Hodgkin's disease (HD). During 1988 to 1994, pathologically staged patients with stage I or II disease who were without risk factors (large mediastinal mass, extranodal lesions, massive splenic disease, elevated erythrocyte sedimentation rate, or three or more involved areas) were recruited from various centers. All patients received 40 Gy total fractionated dose to the involved field areas but were randomly assigned to receive either 40 Gy (arm A) or 30 Gy (arm B) total fractionated dose for the clinically noninvolved EF. No chemotherapy was given. RT films were prospectively reviewed for protocol violations and recurrences retrospectively related to the applied RT. Of 382 recruited patients, 376 were eligible for randomized comparison, 190 in arm A and 186 in arm B. Complete remission was attained in 98% of patients in each arm. With a median follow-up of 86 months, 7-year relapse-free survival (RFS) rates were 78% (arm A) and 83% (arm B) (P =.093). The upper 95% confidence limit for the possible inferiority of arm B in RFS was 4%. Corresponding overall survival rates were 91% (arm A) and 96% (arm B) (P =.16). The most common causes of death (n = 27) were cardiorespiratory disease/pulmonary embolisms (seven), second malignancy (six), and HD (five). Protocol violation was associated with significantly poorer RFS. Nonirradiated nodes were involved in 42 of 52 reviewed relapses, infield areas in 18, marginal areas in 17, and extranodal sites in 16. EF-RT alone attains good survival rates in favorable early-stage HD. The 30-Gy dose is adequate for clinically noninvolved areas. Protocol violation worsens the subsequent prognosis. Relapse patterns suggest that systemic therapy can reduce the 20% long-term relapse rate.
  Journal of Clinical Oncology 07/2001; 19(11):2905-14. · 18.37 Impact Factor