Frank Zimmermann

Universität Basel, Bâle, Basel-City, Switzerland

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Publications (49)183.28 Total impact

  • H. Geinitz · R. Thamm · C. Scholz · C. Heinrich · M. Keller · R. Busch · M. Molls · F. Zimmermann ·

    European Journal of Cancer 09/2011; 47. DOI:10.1016/S0959-8049(11)71980-3 · 5.42 Impact Factor
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    ABSTRACT: Previous studies demonstrated that chemotherapy-induced changes in tumor glucose metabolism measured with (18)F-FDG PET identify patients who benefit from preoperative chemotherapy and those who do not. The prognosis for chemotherapy metabolic nonresponders is poorer than for metabolic responders. Therefore, we initiated this prospective trial to improve the clinical outcome of metabolic nonresponders using a salvage neoadjuvant radiochemotherapy. Fifty-six patients with locally advanced adenocarcinomas of the esophagogastric junction were included. Tumor glucose uptake was assessed by (18)F-FDG PET before chemotherapy and 14 d after initiation of chemotherapy. PET nonresponders received salvage neoadjuvant radiochemotherapy, whereas metabolic responders received neoadjuvant chemotherapy for 3 mo before surgery. Thirty-three patients were metabolic responders, and 23 were nonresponders. Resection was performed on 54 patients. R0 resection rate was 82% (95% confidence interval [CI], 66%-91%) in metabolic responders and 70% (95% CI, 49%-84%) in metabolic nonresponders (P = 0.51). Major histologic remissions were observed in 12 metabolic responders (36%; 95% CI, 22%-53%) and 6 nonresponders (26%; 95% CI, 13%-46%). One-year progression-free rate was 74% ± 8% in PET responders and 57% ± 10% in metabolic nonresponders (log rank test, P = 0.035). One-year overall survival was comparable between the groups (∼80%), and 2-y overall survival was estimated to be 71% ± 8% in metabolic responders and 42% ± 11% in PET nonresponders (hazard ratio, 1.9; 95% CI, 0.87-4.24; P = 0.10). This prospective study showed the feasibility of a PET-guided treatment algorithm. However, by comparing the groups of nonresponding patients in the current trial and the previous published MUNICON (Metabolic response evalUatioN for Individualisation of neoadjuvant Chemotherapy in Esophageal and esophagogastric adeNocarcinoma) I trial, increased histopathologic response was observed after salvage radiochemotherapy, but the primary endpoint of the study to increase the R0 resection rate was not met. The prognosis of the subgroup of PET nonresponders remains poor, indicating their different tumor biology.
    Journal of Nuclear Medicine 08/2011; 52(8):1189-96. DOI:10.2967/jnumed.110.085803 · 6.16 Impact Factor
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    ABSTRACT: To report patterns of failure of stereotactic body radiation therapy (SBRT) in inoperable patients with histologically confirmed stage I NSCLC. Ninety-two inoperable patients (median age: 75 years) with clinically staged, histologically proven T1 (n=31) or T2 (n=61), N0, M0 non-small cell lung cancer (NSCLC) were included in this study. Treatment consisted of 3-5 fractions with 7-15 Gy per fraction prescribed to the 60% isodose. Freedom from local recurrence at 1, 3 and 5 years was 89%, 83% and 83%, respectively. All 10 local failures were observed in patients with T2 tumors. Isolated regional recurrence was observed in 7.6%. The crude rate of distant progression was 20.7%. Overall survival at 1, 3, and 5 years was 79%, 38% and 17% with a median survival of 29 months. Disease specific survival at 1, 3, and 5 years was 93%, 64% and 48%. Karnofsky performance status, T stage, gross tumor volume and tumor location had no significant impact on overall and disease specific survival. SBRT was generally well tolerated and all patients completed therapy as planned. SBRT for stage I lung cancer is very well tolerated in this patient cohort with significant cardiopulmonal comorbidity and results in excellent local control rates, although a considerable portion develops regional and distant metastases.
    Radiotherapy and Oncology 07/2011; 101(2):245-9. DOI:10.1016/j.radonc.2011.06.009 · 4.36 Impact Factor
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    ABSTRACT: The present study evaluates the incidence of (11)C-choline PET/CT positive findings in patients with recurrent prostate cancer referred for salvage radiotherapy (SRT) and the influence on the definition of the planning target volume (PTV). Thirty-seven patients treated with radical prostatectomy and referred to SRT to the prostatic fossa because of biochemical relapse, were analysed retrospectively. All patients underwent (11)C-choline PET/CT before radiotherapy. The influence of PET/CT on the extent of the PTV was analysed. The median total follow up after SRT was 51.2 months. 11/37 (30%) patients had a positive finding in the (11)C-choline PET/CT, 5 (13%) outside of the prostatic fossa (iliac lymph nodes), implicating an extension of the PTV. Patients with positive (11)C-choline PET/CT had a significant higher PSA value than patients with no pathologic uptake (p=0.03). Overall, at the end of follow up 56% of the patients had a PSA ≤ 0.2ng/ml and 44% had a biochemical relapse of prostate cancer. (11)C-choline PET/CT detects abnormalities outside of the prostatic fossa in 13% of patients referred for SRT because of biochemical relapse after radical prostatectomy, affecting the extent of the PTV. Prospective studies need to be implemented to evaluate the benefit of SRT with a PTV based on (11)C-choline PET/CT.
    Radiotherapy and Oncology 05/2011; 99(2):193-200. DOI:10.1016/j.radonc.2011.05.005 · 4.36 Impact Factor
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    ABSTRACT: This study attempts to improve our understanding of the role of salvage radiotherapy (SRT) in patients with prostate-specific antigen (PSA) relapse after radical prostatectomy with regard to biochemical control, rate of distant metastasis, and survival. We performed a retrospective analysis of 96 men treated with conformal prostate bed SRT (median, 64.8 Gy) at a single institution (median follow-up, 70 months). The majority had intermediate- or high-risk prostate cancer. Fifty-four percent underwent a resection with positive margins (R1 resection). The median time interval between surgery and SRT was 22 months. After SRT, 66% of patients reached a PSA nadir of less than 0.2 ng/mL. However, the 5-year biochemical no evidence of disease rate was 35%. Seminal vesicle involvement was predictive for a significantly lower biochemical no evidence of disease rate. All patients with a preoperative PSA level greater than 50 ng/mL relapsed biochemically within 2 years. The 5-year distant metastasis rate was 18%, the 5-year prostate cancer-specific survival rate was 90%, and the 5-year overall survival rate was 88%. Significantly more distant metastases developed in patients with a PSA nadir greater than 0.05 ng/mL after SRT, and they had significantly inferior prostate cancer-specific and overall survival rates. Resection status (R1 vs. R0) was not predictive for any of the endpoints. Men with postoperative PSA relapse can undergo salvage treatment by prostate bed radiotherapy, but durable PSA control is maintained only in about one-third of the patients. Despite a high biochemical failure rate after SRT, prostate cancer-specific survival does not decrease rapidly.
    International journal of radiation oncology, biology, physics 04/2011; 82(5):1930-7. DOI:10.1016/j.ijrobp.2011.03.003 · 4.26 Impact Factor
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    ABSTRACT: To evaluate the current status of stereotactic body radiotherapy (SBRT) and identify both advantages and disadvantages of its use in developing countries, a meeting composed of consultants of the International Atomic Energy Agency was held in Vienna in November 2006. Owing to continuous developments in the field, the meeting was extended by subsequent discussions and correspondence (2007-2010), which led to the summary presented here. The advantages and disadvantages of SBRT expected to be encountered in developing countries were identified. The definitions, typical treatment courses, and clinical results were presented. Thereafter, minimal methodology/technology requirements for SBRT were evaluated. Finally, characteristics of SBRT for developing countries were recommended. Patients for SBRT should be carefully selected, because single high-dose radiotherapy may cause serious complications in some serial organs at risk. Clinical experiences have been reported in some populations of lung cancer, lung oligometastases, liver cancer, pancreas cancer, and kidney cancer. Despite the disadvantages expected to be experienced in developing countries, SBRT using fewer fractions may be useful in selected patients with various extracranial cancers with favorable outcome and low toxicity.
    International journal of radiation oncology, biology, physics 03/2011; 79(3):660-9. DOI:10.1016/j.ijrobp.2010.10.004 · 4.26 Impact Factor
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    ABSTRACT: For patients with early stage non-small cell lung cancer (NSCLC) unsuitable for resection local high-dose radiotherapy is the treatment of choice. In modern series even with escalated conformal radiotherapy local control rates of about 55% remain disappointing. Within the last years, stereotactic radiotherapy has been shown an effective treatment approach for early stage malignant lung tumors, combining the accurate focal dose delivery by stereotactic techniques with the biological advantages of dose escalated hypofractionated radiotherapy. Typical treatment regimens include three to five fractions over 1-2 weeks or 1 single fraction as radiosurgery. With adequate staging procedures including FDG-PET-CT scan and a low probability of subclinical involvement of unsuspicious locoregional lymph nodes, the concept is to irradiate the primary T1/2 tumor alone. Recent data report local control rates of up to 90%, with favorable results especially for patients in good general condition. Less than 10% of all patients develop isolated tumor recurrences in regional lymph nodes. Three-year survival is significantly improved to more than 80% when biological effective doses of more than 100 Gy are applied to patients in good conditions. Systemic tumor recurrence still is a major problem, making an additional systemic chemotherapy interesting for selected patients after hSRT, such as those younger than 75 years.
    Frontiers of radiation therapy and oncology 01/2010; 42:94-114. DOI:10.1159/000262465

  • Fuel and Energy Abstracts 11/2009; 75(3). DOI:10.1016/j.ijrobp.2009.07.391
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    ABSTRACT: Evaluation of late side effects and biochemical control (bNED) 5 years after three-dimensional radiotherapy with moderate, risk-adapted dose escalation. From 03/1999 to 07/2002, 486 patients have been registered in the prospective Austrian-German multicenter phase II trial (AUGE). 399 (82%) localized prostate cancer patients (T1-3 Nx/N0 M0) were evaluated. The low- and intermediate-risk groups were treated with 70 Gy, the high-risk group with 74 Gy, respectively. Additional hormonal therapy (HT) was recommended for intermediate- and high-risk group patients. Late toxicity (EORTC/RTOG) and bNED (ASTRO and Phoenix) were prospectively assessed. Median follow-up was 65 months. Distribution concerning risk groups (low-, intermediate-, high-risk group) showed 29%, 50% and 21% of patients, respectively. HT was given in 87% of patients. The 5-year actuarial rates of late side effects grade > or = 2 for 70 Gy/74 Gy were 28%/30% (gastrointestinal; p = 0.73) and 19%/34% (urogenital; p = 0,06). The 5-year actuarial bNED rate stratified by risk groups (low-, intermediate-, high-risk group) was 74%, 66% and 50% (ASTRO), and 81%, 80% and 60% (Phoenix), respectively. Within multivariate analysis T-stage and initial prostate specific antigen were significant factors influencing bNED (ASTRO) whereas Gleason Score and duration of HT were not. Dose escalation within standard three-dimensional conformal radiotherapy (3D-CRT) up to a level of 74 Gy did not result in significantly increased gastrointestinal side effects, whereas urogenital side effects showed an increase close to significance. However, the total number of patients with severe toxicity was low. To achieve high tumor control rates with acceptable treatment-related morbidity, local doses of at least 74 Gy should be considered, in particular for intermediate- or high-risk patients applying 3D-CRT.
    Strahlentherapie und Onkologie 03/2009; 185(2):94-100. DOI:10.1007/s00066-009-1970-3 · 2.91 Impact Factor
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    ABSTRACT: Oxaliplatin and 5-fluorouracil have a significant activity in locally advanced oesophageal squamous cell cancer (OSCC). However, their optimal dosage and efficacy when combined with concurrent radiotherapy as neoadjuvant treatment are unknown. This non-randomised, phase I/II study aimed to define the maximum tolerated dose (MTD) and assessed the histopathological tumour response rate to neoadjuvant oxaliplatin in weekly escalating doses (40, 45, 50 mg m(-2)) and continuous infusional 5-fluorouracil (CI-5FU; 225 mg m(-2)) plus concurrent radiotherapy. Patients had resectable OSCC. Resection was scheduled for 4-6 weeks after chemoradiotherapy. During phase I (dose escalation; n=19), weekly oxaliplatin 45 mg m(-2) plus CI-5FU 225 mg m(-2) was established as the MTD and was the recommended dosage for phase II. Oesophageal mucositis was the dose-limiting toxicity at higher doses. During phase II, histopathological responses (<10% residual tumour cells within the specimen) were observed in 10 of 16 patients (63%; 95% confidence interval: 39-82%). Overall, 16 of the 25 patients (64%) who underwent resection had a histopathological response; tumour-free resection (R0) was achieved in 80%. Neoadjuvant weekly oxaliplatin 45 mg m(-2) plus CI-5FU 225 mg m(-2) with concurrent radiotherapy provides promising histological response rates and R0 resection rates in locally advanced OSCC.
    British Journal of Cancer 10/2008; 99(7):1020-6. DOI:10.1038/sj.bjc.6604659 · 4.84 Impact Factor
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    R Rosenberg · H Nekarda · F Zimmermann · K Becker · F Lordick · H Hofler · M Molls · J R Siewert ·
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    ABSTRACT: Recent studies showed improved local control after preoperative radiochemotherapy (RCTX) in patients with locally advanced rectal carcinoma, but failed to demonstrate a survival benefit. Our aims were to determine outcome and impact of histopathological response after preoperative RCTX. One hundred four patients with uT3 rectal carcinoma were treated with preoperative RCTX of 45 Gy and continuous 5-FU infusion between 1997 and 2001 (group I). Histopathological response was evaluated in all specimens after tumor resection. Group II consisted of 114 patients with uT3 rectal carcinoma treated with postoperative RCTX between 1988 and 1997. Group I showed a 6.1% 5-year local recurrence rate compared to 15.3% in group II (P = 0.023). Overall survival rates did not differ significantly between both groups (P = 0.225). Histopathological responders had a significantly improved 5-year overall survival with 89.1 (7.8)% compared to 68.7 (6.7)% of the non-responders (P = 0.008) and were identified as an independent prognostic factor. Significant improvement of overall survival was observed for histopathological tumor responders after neoadjuvant radiochemotherapy. Our protocol of preoperative radiochemotherapy confirms the results of the multi-center studies in regard to local control and overall survival.
    Journal of Surgical Oncology 02/2008; 97(1):8-13. · 3.24 Impact Factor
  • H. Geinitz · F. Zimmermann · R. Thamm · S. Kerndl · N. Prause · C. Scholz · C. Winkler · M. Keller · R. Busch · M. Molls ·

    EJC Supplements 09/2007; 5(4):293-294. DOI:10.1016/S1359-6349(07)71116-3 · 9.39 Impact Factor
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    ABSTRACT: To evaluate the Vienna Rectoscopy Score (VRS) as a feasible and effective tool for detecting and classifying pathologic changes in the rectal mucosa after radiotherapy (RT) for prostate cancer, and, also, to correlate its findings with the European Organization for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) score for late rectal toxicity. A total of 486 patients with localized prostate cancer underwent external-beam RT up to 70 or 74 Gy within an Austrian-German prospective multicenter trial. In 166 patients, voluntary rectal sigmoidoscopy was performed before and at 12 and/or 24 months after RT. Pathologic findings such as telangiectasia, congested mucosa, and ulcers were graded (Grades 0-3) and summarized according to the VRS. Late rectal side effects (EORTC/RTOG) were documented and correlated with the corresponding VRS. Before RT, 99% had a VRS score of 0. The median follow-up was 40 months. Overall, a late rectal side effects grade or score 1-3 was detected in 43% by EORTC/RTOG compared with 68% by VRS (p < 0.05). Grades 0, 1, 2, and 3 late rectal side effects were found using EORTC/RTOG in 57%, 11%, 28%, and 3%, respectively; the corresponding percentages were 32%, 22%, 32%, and 14% for a VRS of 0, 1, 2, and 3, respectively. A significant coherence between the VRS and EORTC/RTOG was found (p < 0.01). The VRS is a feasible and effective tool for describing and classifying pathologic findings in the rectal mucosa after RT within a multicenter trial. The VRS and EORTC/RTOG showed a high coherence. However the VRS was significantly more sensitive.
    International Journal of Radiation OncologyBiologyPhysics 01/2007; 67(1):78-83. DOI:10.1016/j.ijrobp.2006.08.055 · 4.26 Impact Factor
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    Frank Zimmermann · Björn Brücher ·

    Multimodal Concepts for Integration of Cytotoxic Drugs, 2nd edited by J.Martin Brown, Minesh P Mehta, Carsten Nieder, 12/2006: chapter Applications in Esophageal and Gastric Cancer: pages 197-213; Springer Berlin Heidelberg., ISBN: 978-3-540-35662-2
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    ABSTRACT: Patients with localized prostate cancer are treated with 3D radiotherapy using a rectal balloon catheter for internal immobilization of the prostate, thereby reducing the radiation dose to the dorsal rectal wall. The purpose of the study was to investigate clinical feasibility and the influence of acute rectal side effects and pre-existing hemorrhoids on patients' acceptance of the rectal balloon catheter. 442 patients who underwent primary radiation therapy for localized prostate cancer were included in this prospective Austrian-German multicenter trial. The total radiation dose was either 70 Gy or 74 Gy. Acute rectal side effects were documented using the EORTC/RTOG grading score (European Organisation for Research and Treatment of Cancer/Radiation Therapy 225 Oncology Group) at weeks 2, 4 and 7 of radiation treatment. Within the same time intervals patients were interviewed about their tolerance of the rectal balloon catheter, evaluating five categories of acceptance (1 = no major complaints, 2 = pain at/during application, 3 = signs of blood at the balloon catheter after application but without any pain, 4 = signs of blood at the balloon catheter after application and pain, 5 = balloon application had to be stopped). Voluntary rectoscopy prior to radiotherapy was performed in 310 patients. 429/442 patients (97 %) were treated with the balloon catheter. No major complaints were reported in 79 % of the patients and no acute rectal side effects were seen in 52 % of the patients. Grade 1 side effects were seen in 31 % patients, Grade 2 in 17 % and Grade 3 in 0.5 %. Balloon use had to be stopped in only 4 % of the patients. There was significant correlation between balloon discomfort and rectal side effects (p < 0.01). The presence of hemorrhoids in 36 % patients prior to irradiation had no influence on balloon tolerance. The rectal balloon can be used in 3D radiotherapy of localized prostate cancer with a high degree of acceptance by the patients. Use of the balloon is safe within daily clinical treatment. Patients reporting acute rectal side effects experienced significantly more balloon discomfort, but the presence of hemorrhoids was not found to influence acceptance of the balloon.
    Wiener klinische Wochenschrift 06/2006; 118(7-8):224-9. DOI:10.1007/s00508-006-0588-z · 0.84 Impact Factor

  • Clinical Oncology 06/2006; 18(5):424-424. DOI:10.1016/j.clon.2006.03.011 · 3.40 Impact Factor
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    ABSTRACT: The objectives of this study were to investigate histomorphologic features as a response classification after neoadjuvant radiochemotherapy (RTx/CTx) and to correlate the results with clinical outcome parameters (e.g., postoperative morbidity and mortality, recurrence, and survival) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Three hundred eleven patients with histologically proven, locally advanced, intrathoracic ESCC (clinical T3 or T4, N0-N+, M0) located at or above the level of the tracheal bifurcation underwent preoperative, combined, simultaneous RTx/CTx followed by esophagectomy. Response to RTx/CTx was classified by the quantification of residual tumor cells. A histopathologic response was defined as <10% residual tumor cells found within the specimen compared with a histopathologic nonresponse, which was characterized by >10% residual tumor cells. A histopathologic response was correlated significantly with complete tumor resection status (R0 resection) (P .0001), histopathologic tumor (ypT) category (P <.0001), lymph node involvement (P <.0001), lymphatic vessel invasion (P <.001), and survival (P <.0001). A multivariate Cox regression analysis revealed that histopathologic response classification according to the percentage of residual tumor cells was an independent prognostic factor (P <.0001). Nonresponders had greater postoperative pulmonary morbidity (P = .01), a greater 30-day mortality rate (P = .02), and a dismal survival rate compared to histopathologic responders (P <.0001). Histopathologic response evaluation based on the quantification of residual tumor cells provided meaningful information for the assessment of outcomes among patients with ESCC who have underwent neoadjuvant RTx/CTx. The current results indicated that histopathologic responders may represent a subgroup of patients who benefit from neoadjuvant therapy followed by surgery.
    Cancer 05/2006; 106(10):2119-27. DOI:10.1002/cncr.21850 · 4.89 Impact Factor
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    ABSTRACT: To identify endoscopic pathological findings prior to radiotherapy and a possible correlation with acute or chronic rectal side effects after three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer. Between 03/99 and 07/02, a total of 298 patients, who consented in a voluntary rectoscopy prior to radiotherapy were included into the analysis. Patients were treated with a total dose of either 70 or 74 Gy. Pathological rectoscopic findings like hemorrhoids, polyps or diverticula were documented. Acute and late rectal side effects were scored using the EORTC/RTOG score. The most frequent pathological endosopic findings were hemorrhoids (35%), polyps (24%) and diverticula (13%). Rectal toxicity was mostly low to moderate. Grade 0/1 cumulative acute and late rectal side effects were 82 and 84%, grade 2 were 18 and 17%, respectively. We could not identify any correlation between preexisting pathological findings and rectal side effects by statistical analysis. There is no evidence that prostate cancer patients presenting with endoscopic verified pathological findings in the rectal mucosa at diagnosis are at an increased risk to develop rectal side effects when treated with 3D-CRT of the prostatic region.
    Radiotherapy and Oncology 02/2006; 78(1):36-40. DOI:10.1016/j.radonc.2005.10.009 · 4.36 Impact Factor
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    Brücher BLDM · Becker K · Lordick F · Fink U · Sarbia M · Stein HJ · Busch R · Zimmermann F · Molls M · Höfler H · Siewert JR ·

    Langenbecks Archiv für Chirurgie. Supplement. Kongressband. Deutsche Gesellschaft für Chirurgie. Kongress 01/2006;

  • International Journal of Radiation OncologyBiologyPhysics 10/2005; 63. DOI:10.1016/j.ijrobp.2005.07.539 · 4.26 Impact Factor

Publication Stats

970 Citations
183.28 Total Impact Points


  • 2011
    • Universität Basel
      Bâle, Basel-City, Switzerland
    • Universitätsspital Basel
      Bâle, Basel-City, Switzerland
  • 2001-2011
    • University of Technology Munich
      • • Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie
      • • Nuklearmedizinische Klinik und Poliklinik
      München, Bavaria, Germany
  • 2002-2006
    • Deutsches Herzzentrum München
      München, Bavaria, Germany
    • University of Greifswald
      • Department of Surgery
      Griefswald, Mecklenburg-Vorpommern, Germany