Frank B Zimmermann

Universitätsspital Basel, Bâle, Basel-City, Switzerland

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Publications (65)150.48 Total impact

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    ABSTRACT: In radiotherapy the normal tissue reaction is often a limiting factor for radiation treatment. Still there is no screening method, which predicts normal tissue reaction on radiotherapy, especially in comparison to tumor tissue, and therefore allows tailoring of the radiation dose to each patient. Here, we present a case of severe radiation-related side effects. We applied classical cytogenetic techniques (Giemsa-banding and staining of centromeric regions), the comet assay as well as multicolor fluorescence hybridization on peripheral blood lymphocytes of this patient in order to determine the radio-sensitivity on the DNA level and to correlate these findings with the clinical outcome. Our investigations revealed abnormalities on chromosome 9, deficiencies in the DNA-repair capacity after radiation exposure and a high number of radiation induced chromosomal aberrations. A detected high amount of residual damage two or three hours after radiation exposure and repair as well as the high number of chromosomal aberrations (ChAs) suggests a correlation between repair capacity and radiation induced ChAs. We concluded that the detected abnormalities might serve as a genetic basis for the radio-sensitive phenotype of this patient. Taken together this report strengthens the idea that intensive DNA genomic analysis of individual patients can serve as the basis for more favourable treatment of cancer patients.
    Current Genomics 09/2012; 13(6):426-32. · 2.87 Impact Factor
  • M W Gross, F B Zimmermann
    Strahlentherapie und Onkologie 01/2012; 188(1):94-5. · 2.73 Impact Factor
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    ABSTRACT: Several retrospective analyses have suggested that obese men with prostate cancer treated with external beam radiotherapy (EBRT) have outcomes inferior to those of normal-weight men. However, a recently presented analysis for the first time challenged this association between body mass index (BMI) and treatment failure. It is therefore important to provide further data on this issue. This was a retrospective analysis of 564 men treated with risk-adapted conformal EBRT at a single institution. Low-risk patients received EBRT alone, and the other patients received EBRT plus endocrine treatment. In addition, high-risk patients were treated to higher EBRT doses (74 Gy). A rectal balloon catheter for internal immobilization, which can be identified on portal images, was used in 261 patients (46%). Thus, localization did not rely on bony landmarks alone in these cases. The median BMI was 26, and 15% of patients had BMI≥30. Neither univariate nor multivariate analyses detected any significant impact of BMI on biochemical relapse, prostate cancer-specific survival, or overall survival. The 5-year biochemical relapse rate was 21% and prostate cancer-specific survival 96%. The present analysis of a large cohort of consecutively treated patients suggests that efforts to reduce prostate movement and geographic miss might result in comparable outcomes in obese and normal-weight patients.
    International journal of radiation oncology, biology, physics 09/2011; 81(1):16-22. · 4.59 Impact Factor
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    ABSTRACT: To prospectively assess the intestinal symptoms and fecal continence in patients who had undergone conformal radiotherapy (CRT) for prostate cancer. A total of 78 men who had undergone definitive CRT for prostate cancer were evaluated. The patients were assessed before, during (treatment Weeks 4 and 6), and 2, 12, and 24 months after CRT completion. The intestinal symptoms and fecal continence were evaluated with comprehensive standardized questionnaires. The intestinal symptoms were mostly intermittent, with only a small minority of patients affected daily. Defecation pain, fecal urge, and rectal mucous discharge increased significantly during therapy. Defecation pain and rectal mucous discharge had returned to baseline levels within 8 weeks and 1 year after CRT, respectively. However, fecal urge remained significantly elevated for ≤1 year and then returned toward the pretreatment values. The prevalence of rectal bleeding was significantly elevated 2 years after CRT. Fecal continence deteriorated during CRT and remained impaired at 1 year after treatment. Incontinence was mostly minor, occurring less than once per week and predominantly affecting incontinence for gas. Intestinal symptoms and fecal incontinence increased during prostate CRT. Except for rectal bleeding, the intestinal symptoms, including fecal incontinence, returned to baseline levels within 1-2 years after CRT. Thus, the rate of long-term late radiation-related intestinal toxicity was low.
    International journal of radiation oncology, biology, physics 10/2010; 79(5):1373-80. · 4.59 Impact Factor
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    ABSTRACT: Erratum to: Strahlenther Onkol 2010;186:1–6 (DOI 10.1007/s00066-009-2026-4) Strahlenther Onkol 2010;186:7–17 (DOI 10.1007/s00066-009-1995-7) Strahlenther Onkol 2010;186:18–23 (DOI 10.1007/s00066-009-2025-5) Strahlenther Onkol 2010;186:24–9 (DOI 10.1007/s00066-009-2049-x) Strahlenther Onkol 2010;186:30–5 (DOI 10.1007/s00066-009-2037-1) Strahlenther Onkol 2010;186:36–9 (DOI 10.1007/s00066-009-2019-3) Strahlenther Onkol 2010;186:46–52 (DOI 10.1007/s00066-009-2023-7)
    Strahlentherapie und Onkologie 02/2010; 186(2). · 2.73 Impact Factor
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    ABSTRACT: To prospectively assess quality of life (QoL) in patients receiving conformal radiation therapy (CRT) for prostate cancer. 78 men with definitive CRT for prostate cancer were entered into the study. Patients were assessed before CRT, at 40 and 60 Gy, and 2, 12 and 24 months after the end of treatment. QoL was assessed using the EORTC Quality of Life Questionnaire C30 and the prostate module PR25. Changes in mean QoL scores with time of >or= 10 points were considered clinically relevant. Global QoL did not change statistically significant during CRT and was slightly above baseline levels during follow-up. CRT had a statistically significant negative short-term impact on role functioning, fatigue, and PR25 urinary symptoms. The scores recovered within 2 months to 1 year after CRT. Emotional functioning and social functioning scores slightly increased during and after CRT. Role functioning decreased by > 10 points at 60 Gy and urinary symptoms decreased by > 10 points at 40 and 60 Gy. All other differences were < 10 points. A high number of concomitant diseases and having no children were negative pretreatment predictors for long-term global QoL. Definitive CRT for prostate cancer does not compromise global QoL during therapy and up to 2 years after treatment. It has a limited negative effect on role functioning, urinary symptoms and, to a lesser extent, on fatigue with restitution within 2 months to 1 year after treatment.
    Strahlentherapie und Onkologie 01/2010; 186(1):46-52. · 2.73 Impact Factor
  • Strahlentherapie Und Onkologie - STRAHLENTHER ONKOL. 01/2010; 186(1):46-52.
  • Frank Zimmermann
    Swiss medical weekly: official journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology 10/2009; 139(35-36):494-5. · 1.88 Impact Factor
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    ABSTRACT: Information on a patient's prognosis is important for the clinical decision-making process. This study explored the capacity of quantitative ultrasound imaging to increase prognostic information. High-resolution B-scan and colour-coded duplex-sonography of the neck was prospectively applied to 50 HNSCC-patients stage IVA-B 05/99-01/02 before definite radio-(chemo-)therapy. Every lymph node >1.5 cm was scored for the following Malignancy Criteria: Inhomogeneity, Surface-irregularity, Missing hilar sign, Spherical form, Matting, Aberrant intranodal vessels, Infiltration of surrounding tissue, Intranodal cystic necrosis. Median Overall Survival (OS) was 1 year. High MMCC (Maximal Malignancy Criteria Count in a single node) predicted a poor outcome with a median OS of 8.1 months (MMCC=7-8, n=24) vs. 24.7 months for low MMCC (1-6, n=26, p=0.0004, logrank). Estimated 1- and 3-year-OS was 25% and 8% for high vs. 69% and 41% for low MMCC. Ten out of eleven living patients (follow-up 2.3-5.3 years) had a low MMCC. Of the clinical parameters determined, only pre-treatment hemoglobin levels <12 g/dl and treatment less radical than chemoradiation to 70 Gy predicted poor OS (univariate p=0.04 and 0.02, respectively). In multivariate Cox analysis, MMCC continued to significantly predict for OS (p=0.002) and Disease-Free Survival (p=0.002). Quantification of nodal ultrasonography offers valuable prognostic information for the conservative management of HNSCC.
    Radiotherapy and Oncology 10/2007; 85(1):48-57. · 4.86 Impact Factor
  • Frank B. Zimmermann, Alexandros Papachristofilou
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    ABSTRACT: Kasuistik Vor 5 Jahren wurde bei einem männlichen 39-jährigen Patienten ein frühes Rektumkarzinom diagnostiziert, das mittels anteriorer Rektumresektion behandelt wurde. Aufgrund des lokal begrenzten Stadiums ohne Befall lokoregionärer Lymphknoten (pT2 pN0 cM0 R0) wurde keine adjuvante Therapie durchgeführt. Hinweise auf eine genetische Disposition zur Entwicklung eines kolorektalen Karzinoms hatten sich nicht gefunden. Die Kontrolluntersuchungen und die letzte Rektoskopie vor 3 Monaten hatten bislang keinen Hinweis auf ein Rezidiv der Erkrankung ergeben. Jetzt stellt sich der Patient mit Schmerzen bei der Defäkation bei seinem Hausarzt vor. Der rektale Tastbefund ist unauffällig, die Untersuchung wird allerdings vom Patienten als sehr schmerzhaft empfunden. Der Hausarzt überweist den Patienten zu einem niedergelassenen Gastroenterologen. Dieser führt eine Rektoskopie und eine Koloskopie durch, die keinen pathologischen Befund erbringen. In der Endosonographie zeigt sich allerdings eine rechtsseitige extraluminale Raumforderung in Höhe der Anastomose. Unter endosonographischer Kontrolle wird die Raumforderung punktiert. In der zytologischen Aufarbeitung finden sich Zellen eines Adenokarzinoms, passend zu einem Rezidiv des bekannten Rektumkarzinoms. Der Patient wird in ein onkologisches Zentrum zum Staging und zur Klärung des therapeutischen Vorgehens eingewiesen. Im Rahmen der Staginguntersuchungen wird eine [18F]-2-Fluoro-2-desoxy-D-Glucose-Positronenemissionstomographie/Computertomographie (FDG-PET/CT) durchgeführt, bei der sich keine Hinweise auf eine regionale und eine distante Metastasierung ergeben (Abbildung 1). Der Rezidivtumor zeigt hingegen einen deutlich erhöhten FDG-Uptake. Es finden sich keine Hinweise auf eine Infiltration des Beckenbodens bzw. des knöchernen Beckens. Somit liegt ein lokal begrenztes und damit prinzipiell resektables Karzinomrezidiv vor (rcT3 cN0 cM0). Der Empfehlung der interdisziplinären Tumorkonferenz zur präoperativen Radiochemotherapie (RCT) mit nachfolgender abdominoperinealer Resektion stimmt der Patient in Kenntnis der kurativen Intention zu. Aufgrund des extraluminalen Rezidivs und des geringen Alters des Patienten wird eine kombinierte RCT (3D-geplante Strahlentherapie des Beckens mit 5 × 1,8 Gy pro Woche bis 45 Gy Gesamtdosis; Oxaliplatin mit 85 mg/m2/d an den Tagen 1, 15, 29; 5-Fluorouracil 300 mg/m2/d an den Tagen 1–5, 8–12, 15–19, 22–26, 29–33) durchgeführt. Die Therapie wird insgesamt bis auf leichte Pollakisurie gut vertragen. Nennenswerte hämatologische und intestinale Toxizitäten werden nicht beobachtet. Eine in der 4. Therapiewoche durchgeführte FDG-PET/CT-Untersuchung des Beckens zeigt bereits einen rückläufigen Tumor im Sinne eines guten, frühen Ansprechens auf die Therapie. 4 Wochen nach Ende der RCT stellt sich der Patient zum Restaging und zur Planung der Operation erneut vor. In der FDG-PET/CT finden sich weder in der Computertomographie noch in der FDG-PET Hinweise auf einen makroskopischen Tumorrest. Es liegt bildgebend eine komplette Remission vor (Abbildung 3). Aufgrund der vorausgegangenen anterioren Rektumresektion wird eine perineale Rektumamputation (Operation nach Miles) durchgeführt. Der postoperative Verlauf ist weitgehend komplikationslos. Der Patient erhält intraoperativ ein Descendostoma. In der histopathologischen Aufarbeitung findet sich ein Typ T3 pN0 extraluminales Rektumkarzinomrezidiv mit deutlichen regressiven Veränderungen nach neoadjuvanter RCT (vitales Tumorgewebe in 3% des gesamten resezierten Tumors). Der Tumor ist mit ausreichendem Sicherheitssaum operiert. Die bisherigen Verlaufskontrollen über 2 Jahre nach Therapie des Rezidivtumors zeigen keinen Hinweis auf ein erneutes Tumorrezidiv oder Fernmetastasen.
    coloproctology 10/2007; 29(5):273-292.
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    ABSTRACT: Anfang März 2005 erfolgt bei einer 73-jährigen, adipösen Patientin (163 cm, 79 kg) eine gynäkologische Früherkennungsuntersuchung. Hierbei wird eine pathologische Raumforderung im Analkanal getastet. Auf Nachfragen gibt die Patientin an, seit 3 Monaten wiederholt Blutauflagerungen des Stuhlgangs zu haben. Aus der Vorgeschichte sind eine chronische Nierenerkrankung ersten Grades, eine arterielle Hypertonie und eine Cholezystektomie vor 7 Jahren bekannt. Die Patientin stellt sich eine Woche später bei ihrem Hausarzt vor, der den Tastbefund der Frauenärztin bestätigt. Die durchgeführten Laboruntersuchungen zeigen regelrechte Befunde für Blutbild, Differentialblutbild, Gerinnung und Elektrolyte. Das Kreatinin liegt bei 1,3 mg/dl, die AP (alkalische Phosphatase) und die GGT (γ-Glutamyltransferase) sind wie seit Jahren gering erhöht. Die weiterführenden Untersuchungen (Rektoskopie inkl. Biopsie, histopathologische Befundung, Koloskopie, Sonographie des Oberbauchs, Röntgen des Thorax in zwei Ebenen) bestätigen die Verdachtsdiagnose eines Analkarzinoms. Zur Beschreibung der Ausdehnung des Analkanalkarzinoms erfolgt eine Kernspintomographie, die einen Tumor von 6 cm in kraniokaudaler und 1,9 cm in axialer Ausdehnung zeigt (Abbildungen 1a und 1b). Es finden sich multiple vergrößerte Lymphknoten beidseits entlang der A. iliaca interna und links inguinal (Abbildung 1c). Das resultierende Tumorstadium lautet: Plattenepithelkarzinom G3 des Analkanals, cT3 cN3 cM0. Der in der Röntgenaufnahme verbreiterte Herzschatten führt zur Vorstellung beim Kardiologen, der nach EKG, Ergometrie und Echokardiographie eine Umstellung der antihypertensiven Medikation vornimmt, aber keine Kontraindikation gegenüber einer Operation oder einer 5-Fluorouracil-(5-FU-)haltigen Chemotherapie sieht. Die Patientin wird einem Radioonkologen vorgestellt, der gemeinsam mit dem internistischen Onkologen und einem Chirurgen die Indikation zur primären, definitiven Radiochemotherapie stellt. Dabei erhält die Patientin zwei Zyklen Mitomycin C und 5-FU sowie eine Strahlentherapie des Primärtumors bis 59,4 Gy und der befallenen Lymphknoten bis 54,0 Gy Gesamtdosis. Die radiologisch unauffälligen pelvinen Lymphknoten werden bis zu 45,0 Gy bestrahlt. Eine Verlaufskontrolle mittels Kernspintomographie (Abbildungen 2a bis 2c) und Rektoskopie zeigt bereits 6 Wochen nach Abschluss der Radiochemotherapie eine gute Tumorremission, so dass auf Biopsien verzichtet wird. Die Patientin verbleibt in der engmaschigen, interdisziplinären Nachsorge, die zunächst in 6-wöchigen Intervallen vorgenommen wird.
    coloproctology 01/2007; 29(1):23-36.
  • Frank B. Zimmermann, Alexandros Papachristofilou
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    ABSTRACT: Kasuistik Teil 1 Ein 64-jähriger Patient klagt beim Hausarzt über schmerzhafte Obstipation sowie rektalen Schleim- und Blutabgang. In den letzten 3 Monaten habe er 20 kg abgenommen. Bei der digital-rektalen Untersuchung fällt dem Hausarzt eine verhärtete Raumforderung im Bereich des Enddarmes ca. 2 cm ab ano auf, und er überweist den Patienten an einen niedergelassenen Gastroenterologen, der einen Tumor mit einer nicht passierbaren Stenose 7 cm ab ano feststellt. Die Histologie der Probebiopsie ergibt ein mäßig differenziertes invasives Adenokarzinom, G2. Der Patient wird zur weiteren Diagnostik und Therapie in eine Klinik eingewiesen. Dort wird computertomographisch ein organ über schrei tendes Rektumkarzinom mit Infiltration des gesamten Mesorektums ohne Hinweise auf Invasion der Harnblase oder der Prostata festgestellt. Suspekte Lymphknoten finden sich pelvin und paraaortal. Kleine Leberläsionen werden sonographisch abgeklärt und entsprechen Zys ten. In einer FDG-PET-CT zeigt der Primärtumor einen intensiven FDG-Uptake ohne Hinweise auf Lymph knoten- oder Fernmetastasen (Abbildung 1). Der Fall wird im interdisziplinären Tumorboard zwischen Chirurgen, Radioonkologen, Hämatoonkologen, Radiologen und Nuklearmedizinern besprochen: Bei einem Rektumkarzinom cT3 cN0 cM0 G2 des unteren Drittels wird entschieden, dem Patienten eine neoadjuvante Radiochemotherapie zu empfehlen, um die Chancen auf eine R0-Resektion zu erhöhen. Aufgrund der Ausdehnung des Tumors bis zur Linea dentata ist nicht zu erwarten, dass ein kontinenzerhaltendes operatives Vorgehen möglich sein wird. Teil 2 4 Wochen nach Ende der simultanen Radiochemotherapie wird der Patient in der Chirurgischen Klinik erneut stationär aufgenommen und für die geplante Resektion vorbereitet: Eine MRT des Beckens zeigt eine partielle Remission des Tumors (Volumenabnahme > 50%) ohne Hinweise auf Infiltration benachbarter Organe. Lymphknotenmetastasen kommen nicht zur Darstellung. In der PET-CT ist eine verminderte FDG-Speicherung des Tumors zu verzeichnen (SUV-Wert-Abnahme 56%; Abbildung 2). Endoskopisch zeigt sich ebenfalls ein gutes Ansprechen des Tumors auf die neoadjuvante Behandlung. Es findet sich allerdings weiterhin eine Ausdehnung bis nahe an die Linea dentata, so dass die Indikation zur abdominoperinealen Resektion (Operation nach Miles) gestellt wird. Der Patient verbringt postoperativ drei Tage auf der Intensivstation und wird aufgrund von Wundheilungsstörungen, die eine Narbeneröffnung und offene Wundbehandlung im Bereich der Sakralhöhlen notwendig machen, erst am 25. postoperativen Tag entlassen. Eine stationäre Anschlussheilbehandlung wird veranlasst. Das postoperative Tumorstadium lautet pT3 pN0(0/9) cM0 G2 RX (aufgrund einer Präparatfragmentierung). Der Patient wird gemäß den Richtlinien des Tumorzentrums München in der Nachsorge untersucht ( cancercenter/rektum.pdf).
    coloproctology 01/2007; 29(4):215-224.
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    ABSTRACT: To describe an emerging concept of high-precision radiotherapy, a modality characterized by adaptation to patient and organ movements, which might occur between fractions or even during radiation delivery. Today's unprecedented technical capabilities to visualize the target volume and create conformal dose distributions allow for avoidance of critical structures or targeted treatment intensification within a conventionally imaged, anatomically defined tumor. The success of selective dose escalation depends on (1) correct staging and target volume identification, which can be improved by biological imaging, and (2) identification of biologically relevant subvolumes, which determine tumor control. Current efforts are directed at different methods, such as positron emission tomography and magnetic resonance spectroscopy, and integrating them into treatment planning. Early clinical trials assessing the safety and efficacy of image- and biology-guided radiotherapy are ongoing. The same modalities might be used to determine the individual tumor response during treatment and to adapt therapy. Temporal changes in tumor biology, which might represent both a challenge and a chance with regard to adaptation of treatment, need to be addressed in greater detail.
    Strahlentherapie und Onkologie 08/2006; 182(7):361-8. · 2.73 Impact Factor
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    ABSTRACT: This study was carried out in order to analyze the prevalence of late rectal and anal symptoms after conformal radiation therapy for prostate cancer and to assess their association with quality of life. Two-hundred and forty nine patients were interviewed at 24-111 months after definitive conformal radiation therapy of localized prostate cancer with a median dose of 70 Gy. Rectal symptoms and fecal incontinence were evaluated with standardized questionnaires. Quality of life was assessed with the EORTC Quality of Life Questionnaire-C30 and the prostate cancer module PR25. Rectal symptoms were mostly intermittent. Daily symptoms occurred in < or =5% of the patients. Incontinence was mostly mild with only 3% of the patients reporting daily incontinence episodes. Quality of life was comparable to that of the male German general population except that cognitive functioning and diarrhea were worse in the study population and pain was worse in the reference population. Global quality of life was associated with fecal incontinence, fecal urge, tenesmus, therapy for rectal symptoms and hormonal therapy for biochemical/clinical recurrence. Rectal symptoms and fecal incontinence after conformal radiation therapy for prostate cancer are mostly intermittent. Fecal incontinence, fecal urge and tenesmus are associated with lower global quality of life levels.
    Radiotherapy and Oncology 06/2006; 79(3):341-7. · 4.86 Impact Factor
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    ABSTRACT: Stereotactic Radiotherapy has the potential to produce high local control rates with low risk of severe lung toxicity. From December 2000 to January 2006, 68 inoperable patients (median age 76 years) with stage I NSCLC received definitive hSRT. A mean total dose of 37.5 Gy (24-40 Gy; 60%-isodose) in 3-5 fractions was applied. Immobilisation was carried out by means of a vacuum couch and low pressure foil (Medical Intelligence, Schwab München, Germany). Staging procedures were thoracic and abdominal CT-scan, FDG-PET and CT or MRI of the brain in all patients. Clinical target volume was the tumor as seen in lung windowing of CT and in FDG-PET. Organ movements (6-22 mm) and patient positioning in the couch (3-12 mm) were added as safety margin for the definition of the planning target volume (PTV), that was enclosed by the 60%-isodose. We observed four (6%) local tumor recurrences, resulting in an actuarial local tumor control rate of 96%, 88% and 88% after 1, 2 and 3 year follow-up. Nineteen patients died, with eight patients due to cancer (12%), two to local tumor progression alone. Cancer-specific survival is 96%, 82% and 73% at 1, 2 and 3 years. Eleven patients died from comorbidities, making a 53% overall 3-year survival. Fifty five percent of the patients were affected by mild acute and subacute side effects, with only 3% experiencing pneumonitis III degrees . Late effects were pneumonitis III degrees in 1%, rib fractures in 3%, and benign pleural effusion in 2 patients. Hypofractionated SRT is safe even in elderly patients with stage I NSCLC and significantly reduced lung capacity. It leads to high local control rates and should be offered to patients not amenable for curative resection.
    Acta Oncologica 02/2006; 45(7):796-801. · 3.71 Impact Factor
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  • Carsten Nieder, Frank B Zimmermann, Markus Adam, Michael Molls
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    ABSTRACT: Pentoxifylline (Ptx), a hemorrheologic methylxanthine derivative, is of interest in radiation oncology for several reasons. First, improvement of tumor perfusion might result in better oxygenation and thus radiosensitivity. In addition, the drug also influences cytokine-mediated inflammation. The role of cytokines in the progression of radiation reactions in both tumor and normal tissues therefore provides further opportunities to combine Ptx with ionising radiation in order to improve the therapeutic ratio. This review summarizes preclinical and clinical data in both tumor and normal tissues. Regarding radiosensitization of tumors, a large body of evidence suggests that Ptx improves tumor oxygenation and sensitizes p53 mutant tumors. However, these findings have not translated into positive clinical studies to date. None of three published clinical trials attempting to enhance the effectiveness of radiotherapy with Ptx had a satisfactory design. There is also little evidence to prove that Ptx reduces acute side effects of radiotherapy. The only possible exception is a small randomized trial of lung radiotherapy. Regarding established late sequelae, numerous non-randomized clinical trials described healing of soft tissue necrosis and improvement of trismus and fibrosis after several weeks of Ptx or Ptx plus vitamin E. However, is not unequivocally clear that the combination with vitamin E indeed is superior. The literature data suggest that radiation necrosis can be treated more effectively than fibrosis and that certain improvements might be functional and transient, with less influence on the chronic structural damage induced by ionising radiation. The ultimate individual outcome might depend, for example, on the stage of fibrosis progression, the size of the lesion and comorbid conditions such as diabetes and arteriosclerosis. Some of these factors will influence the actual amount of drug available in the targeted region. It is therefore necessary to evaluate Ptx in larger clinical trials with less baseline variation and to improve the recording of long-term results.
    Cancer Treatment Reviews 11/2005; 31(6):448-55. · 6.47 Impact Factor
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    ABSTRACT: To evaluate the impact of positron emission tomography (PET) on target volume delineation for radiation treatment planning. The data of the literature concerning the use of PET in target volume delineation are summarized. The following points are discussed for each tumor entity: biological background for the PET investigation, sensitivity and specificity of PET (with different tracers) in comparison to computed tomography (CT) and magnetic resonance imaging (MRI) and impact of PET on target volume definition. New PET tracers, which could visualize biological pathways, such as hypoxia, proliferation, angiogenesis, apoptosis and gene expression patterns, will also be discussed. The results of clinical studies on the integration of PET in target volume definition for lung, head-and-neck, genitourinary and brain tumors were analyzed. Fluorodeoxyglucose-(FDG-)PET has a significant impact on GTV (gross tumor volume) and PTV (planning target volume) delineation in lung cancer and can detect lymph node involvement and differentiate malignant tissue from atelectasis. In head-and-neck cancer, the value of FDG-PET for radiation treatment planning is still under investigation. For example, FDG-PET could be superior to CT and MRI in the detection of lymph node metastases and unknown primary cancer and in the differentiation of viable tumor tissue after treatment. Therefore, it might play an important role in GTV definition and sparing of normal tissue. Choline PET and acetate PET are promising tracers in the diagnosis of prostate cancer, but their validity in local tumor demarcation, lymph node diagnosis and detection of recurrence has to be defined in future clinical trials. FDG-PET seems to be particularly valuable in lymph node status definition in cervical cancer. In high-grade gliomas and meningiomas, methionine PET helps to define the GTV and differentiate tumor from normal tissue. For other entities like gastrointestinal cancer, lymphomas, sarcomas, etc., the data of the literature are yet insufficient. The imaging of hypoxia, cell proliferation, angiogenesis, apoptosis and gene expression leads to the identification of different areas of a biologically heterogeneous tumor mass that can individually be targeted using intensity modulated radiotherapy (IMRT). In addition, a biological dose distribution can be generated, the socalled dose painting. However, systematic experimental and clinical trials are necessary to validate this hypothesis. Regarding treatment planning in radiotherapy, PET offers advantages in terms of tumor delineation and the description of biological processes. To define the real impact of this investigation in radiation treatment planning, subsequent experimental, clinical and cost-benefit analyses are required.
    Strahlentherapie und Onkologie 09/2005; 181(8):483-99. · 2.73 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate if conformal radiation therapy for localized prostate cancer with doses of 70 Gy is well tolerated in patients aged 75 years or older, and if the side effects and the biochemical recurrence free (bNED) survival are comparable to younger patients. Eighty patients>or=75 years received definitive conformal radiotherapy for prostate cancer. Acute and late side effects as well as bNED survival (ASTRO criteria) were compared to 221 patients younger than 75 years who were treated during the same period of time. Median dose to the prostate was 70 Gy in both groups. There were no significant differences in acute or late side effects between age groups. The frequency of grade III late symptoms was low and ranged between 0 and 4% for the evaluated symptoms irrespective of age group. Older patients had a better bNED survival than younger patients (bNED survival at 4 years: 76 vs. 61%, P=0.042). High-dose conformal radiation therapy for prostate cancer is well tolerated in patients aged 75 years or older. In terms of bNED survival radiation treatment is at least as effective as it is for younger patients.
    Radiotherapy and Oncology 07/2005; 76(1):27-34. · 4.86 Impact Factor
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    ABSTRACT: We reviewed our initial institutional experience with the use of stereotactic hypofractionated radiation therapy (SFRT) in patients with stage I non-small cell lung cancer (NSCLC). Thirty patients with inoperable stage I non-small cell lung cancer due to a severe chronic obstructive pulmonary disease (COPD) and/or chronic heart disease (Eastern Cooperative Oncology Group (ECOG) performance status of 0-2) were treated between December 2000 and October 2003 with SFRT in curative intent. Infiltration of locoregional lymph nodes and distant metastases were ruled out by computerized tomography (CT) scan of the brain, thorax, and abdomen, and by whole body FDG-positron emission tomography scan in all patients. Total RT doses ranged from 24.0 to 37.5 Gy, given in 3-5 fractions to the 60% isodose encompassing the planning target volume. Immobilization was carried out by a vacuum couch and a low-pressure foil. The clinical target volume was the tumor as it appeared in lung windowing on lung CT scan. Organ movements (caused by breathing; range, 6-22 mm) and reproducibility of patient positioning in the couch (range, 3-12 mm) were calculated by sequential CT and orthogonal films. The individual values were taken into account as a safety margin for the definition of the planning target volume (PTV). The median follow-up of living patients is 18 months (range, 6-38 months). As maximum response, there were 10 (33%) complete responses (CRs) and 14 (47%) partial responses (PRs), resulting in a total response rate of 80%. Stable disease was observed in 6 (20%) patients, while no patient experienced progressive disease. During follow-up, 2 (7%) local recurrences were observed (after 17 and 18 months, respectively). Of 5 (17%) patients who developed distant metastasis, 1 patient developed it in liver (3 months), another one in brain (6 months), and another one in the lung (36 months), while 2 patients developed it in mediastinal lymph nodes (after 8, and 11 months, respectively) only. Of 9 (30%) patients who have died, only 3 (10%) died of cancer, while 6 (20%) died of cancer-unrelated or unknown causes. Acute side effects were mild and affected 9 (33%) patients during the RT course (fatigue being the most frequent one in 6 patients). There were 22 acute events occurring in 19 (63%) patients during the first 3 months post-SFRT, the most frequent one being pneumonitis observed in 14 (46%) patients. However, there was only one (3%) grade 3 acute toxicity and no patient experienced greater than grade 3 toxicity during this study. One (3%) patient experienced rib fracture as the late event. SFRT is a feasible and safe treatment method in inoperable patients with stage I NSCLC having reduced lung capacity. Longer follow-up is necessary to get robust data on late toxicity as well as survival.
    Lung Cancer 05/2005; 48(1):107-14. · 3.74 Impact Factor

Publication Stats

652 Citations
150.48 Total Impact Points


  • 2009–2012
    • Universitätsspital Basel
      Bâle, Basel-City, Switzerland
  • 1996–2010
    • Technische Universität München
      • Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie
      München, Bavaria, Germany
  • 1997–2004
    • Deutsches Herzzentrum München
      München, Bavaria, Germany