Volker Budach
Research interests
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InterestsRadiotherapy, Head and Neck Cancer, soft tissue sarcomas, Intensity-Modulated Radiotherapy, Conformal Radiotherapy, High-Energy Radiotherapy
Publications
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4.59Impact points
Monitoring of Circulating Tumor Cells and Their Expression of EGFR/Phospho-EGFR During Combined Radiotherapy Regimens in Locally Advanced Squamous Cell Carcinoma of the Head and Neck.
International journal of radiation oncology, biology, physics. 05/2012;
PURPOSE: The numbers of circulating tumor cells (CTCs) and their expression/activation of epidermal growth factor receptor (EGFR) during the course of combined chemo- or bioradiotherapy regimens as potential biomarkers of treatment efficacy in squamous cell carcinoma of the head and neck (SCCHN) wer... [more] PURPOSE: The numbers of circulating tumor cells (CTCs) and their expression/activation of epidermal growth factor receptor (EGFR) during the course of combined chemo- or bioradiotherapy regimens as potential biomarkers of treatment efficacy in squamous cell carcinoma of the head and neck (SCCHN) were determined. METHODS AND MATERIALS: Peripheral blood samples from SCCHN patients with locally advanced stage IVA/B disease who were treated with concurrent radiochemotherapy or induction chemotherapy followed by bioradiation with cetuximab were included in this study. Using flow cytometry, the absolute number of CTCs per defined blood volume as well as their expression of EGFR and its phosphorylated form (pEGFR) during the course of treatment were assessed. RESULTS: Before treatment, we detected ≥1 CTC per 3.75 mL blood in 9 of 31 patients (29%). Basal expression of EGFR was detected in 100% and pEGFR in 55% of the CTC+ cases. The frequency of CTC detection was not influenced by induction chemotherapy. However, the number of CTC+ samples significantly increased after radiotherapy. This radiation-induced increase in CTC numbers was less pronounced when radiotherapy was combined with cetuximab compared to its combination with cisplatin/5-fluorouracil. The former treatment regimen was also more effective in reducing pEGFR expression in CTCs. CONCLUSIONS: Definitive radiotherapy regimens of locally advanced SCCHN can increase the number of CTCs and might thus contribute to a systemic spread of tumor cells. Further studies are needed to evaluate the predictive value of the radiation-induced increase in CTC numbers and the persistent activation of the EGFR signalling pathway in individual CTC+ cases.
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4.59Impact points
Contribution of (68)Ga-DOTATOC PET/CT to Target Volume Delineation of Skull Base Meningiomas Treated With Stereotactic Radiation Therapy.
International journal of radiation oncology, biology, physics. 05/2012;
PURPOSE: To investigate the potential impact of (68)Ga-DOTATOC positron emission tomography ((68)Ga-DOTATOC-PET) in addition to magnetic resonance imaging (MRI) and computed tomography (CT) for retrospectively assessing the gross tumor volume (GTV) delineation of meningiomas of the skull base in pat... [more] PURPOSE: To investigate the potential impact of (68)Ga-DOTATOC positron emission tomography ((68)Ga-DOTATOC-PET) in addition to magnetic resonance imaging (MRI) and computed tomography (CT) for retrospectively assessing the gross tumor volume (GTV) delineation of meningiomas of the skull base in patients treated with fractionated stereotactic radiation therapy (FSRT). METHODS AND MATERIALS: The study population consisted of 48 patients with 54 skull base meningiomas, previously treated with FSRT. After scans were coregistered, the GTVs were first delineated with MRI and CT data (GTV(MRI/CT)) and then by PET (GTV(PET)) data. The overlapping regions of both datasets resulted in the GTV(common), which was enlarged to the GTV(final) by adding volumes defined by only one of the complementary modalities (GTV(MRI/CT-added) or GTV(PET-added)). We then evaluated the contribution of conventional imaging modalities (MRI, CT) and (68)Ga-DOTATOC-PET to the GTV(final), which was used for planning purposes. RESULTS: Forty-eight of the 54 skull base lesions in 45 patients showed increased (68)Ga-DOTATOC uptake and were further analyzed. The mean GTV(MRI/CT) and GTV(PET) were approximately 21 cm(3) and 25 cm(3), with a common volume of approximately 15 cm(3). PET contributed a mean additional GTV of approximately 1.5 cm(3) to the common volume (16% ± 34% of the GTV(common)). Approximately 4.5 cm(3) of the GTV(MRI/CT) was excluded from the contribution to the common volume. The resulting mean GTV(final) was significantly smaller than both the GTV(MRI/CT) and the GTV(PET). Compared with the initial GTV(MRI/CT), the addition of (68)Ga-DOTATOC-PET resulted in more than 10% modification of the size of the GTV(final) in 32 (67%) meningiomas CONCLUSIONS: (68)Ga-DOTATOC-PET/CT seems to improve the target volume delineation in skull base meningiomas, often leading to a reduction of GTV compared with results from conventional imaging (MRI and CT).
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1.26Impact points
Interfraction rotation of the prostate as evaluated by kilovoltage X-ray fiducial marker imaging in intensity-modulated radiotherapy of localized prostate cancer.
Medical dosimetry : official journal of the American Association of Medical Dosimetrists. 04/2012;
To quantify the daily rotation of the prostate during a radiotherapy course using stereoscopic kilovoltage (kV) x-ray imaging and intraprostatic fiducials for localization and positioning correction. From 2005 to 2009, radio-opaque fiducial markers were inserted into 38 patients via perineum into th... [more] To quantify the daily rotation of the prostate during a radiotherapy course using stereoscopic kilovoltage (kV) x-ray imaging and intraprostatic fiducials for localization and positioning correction. From 2005 to 2009, radio-opaque fiducial markers were inserted into 38 patients via perineum into the prostate. The ExacTrac/Novalis Body X-ray 6-day image acquisition system (ET/NB; BrainLab AG, Feldkirchen, Germany) was used to determine and correct the target position. During the first period in 10 patients we recorded all rotation errors but used only Y (table) for correction. For the next 28 patients we used for correction all rotational coordinates, i.e., in addition Z (superior-inferior [SI] or roll) and X (left-right [LR] or tilt/pitch) according to the fiducial marker position by use of the Robotic Tilt Module and Varian Exact Couch. Rotation correction was applied above a threshold of 1° displacement. The systematic and random errors were specified. Overall, 993 software-assisted rotational corrections were performed. The interfraction rotation errors of the prostate as assessed from the radiodense surrogate markers around the three axes Y, Z, and X were on average 0.09, -0.52, and -0.01° with standard deviations of 2.01, 2.30, and 3.95°, respectively. The systematic uncertainty per patient for prostate rotation was estimated with 2.30, 1.56, and 4.13° and the mean random components with 1.81, 2.02, and 3.09°. The largest rotational errors occurred around the X-axis (pitch), but without preferring a certain orientation. Although the error around Z (roll) can be compensated on average by a transformation with 4 coordinates, a significant error around X remains and advocates the full correction with 6 coordinates. Rotational errors as assessed via daily stereoscopic online imaging are significant and dominate around X. Rotation possibly degrades the dosimetric coverage of the target volume and may require suitable strategies for correction.
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3.03Impact points
A simple multicolor flow cytometry protocol for detection and molecular characterization of circulating tumor cells in epithelial cancers.
Cytometry. Part A : the journal of the International Society for Analytical Cytology. 03/2012;
Circulating tumor cells (CTCs) might not only serve as prognostic marker but could also be useful for monitoring treatment efficacy. A multicolor flow cytometry protocol for their detection and molecular characterization in peripheral blood was developed which consisted of erythrocyte lysis followed... [more] Circulating tumor cells (CTCs) might not only serve as prognostic marker but could also be useful for monitoring treatment efficacy. A multicolor flow cytometry protocol for their detection and molecular characterization in peripheral blood was developed which consisted of erythrocyte lysis followed by staining of cells with fluorochrome-labeled antibodies against CD45 and the epithelial markers EpCam and cytokeratin 7/8. For reducing the number of events acquired by flow cytometry, an electronic threshold for the fluorescent signals from the epithelial markers was applied. After establishment of the protocol by using spiking experiments, its suitability to determine the absolute number of CTCs as well as their expression of epidermal growth factor receptor (EGFR) and its phosphorylated form (phospho-EGFR) in blood samples from patients with squamous cell carcinoma of the head and neck (SCCHN) was validated. Spiking experiments demonstrated an excellent recovery (mean 85%) and a linear performance (R(2) = 0.98) of the protocol. Sensitivity and specificity were comparable to our former protocol using immunomagnetic CTC pre-enrichment. The analysis of 33 SCCHN patient samples revealed the presence of CTCs in 33.3% of cases with a mean ± SD of 1.5 ± 0.5 CTCs per 3.75 ml blood. EGFR was expressed in 100% and phospho-EGFR in 36.4% of the CTC+ cases. We have established a simple and sensitive multicolor flow cytometry protocol for detection of CTCs in patients with epithelial cancers including SCCHN which will allow their detailed molecular characterization. © 2012 International Society for Advancement of Cytometry.
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Magnetic resonance imaging, computed tomography, and 68Ga-DOTATOC positron emission tomography for imaging skull base meningiomas with infracranial extension treated with stereotactic radiotherapy - a case series.
Head & face medicine. 01/2012; 8(1):1.
ABSTRACT: Magnetic resonance imaging (MRI) and computed tomography (CT) with 68Ga-DOTATOC positron emission tomography (68Ga-DOTATOC-PET) were compared retrospectively for their ability to delineate infracranial extension of skull base (SB) meningiomas treated with fractionated stereotactic radiothe... [more] ABSTRACT: Magnetic resonance imaging (MRI) and computed tomography (CT) with 68Ga-DOTATOC positron emission tomography (68Ga-DOTATOC-PET) were compared retrospectively for their ability to delineate infracranial extension of skull base (SB) meningiomas treated with fractionated stereotactic radiotherapy. Fifty patients with 56 meningiomas of the SB underwent MRI, CT, and 68Ga-DOTATOC PET/CT prior to fractionated stereotactic radiotherapy. The study group consisted of 16 patients who had infracranial meningioma extension, visible on MRI ± CT (MRI/CT) or PET, and were evaluated further. The respective findings were reviewed independently, analyzed with respect to correlations, and compared with each other. Within the study group, SB transgression was associated with bony changes visible by CT in 14 patients (81%). Tumorous changes of the foramen ovale and rotundum were evident in 13 and 8 cases, respectively, which were accompanied by skeletal muscular invasion in 8 lesions. We analysed six designated anatomical sites of the SB in each of the 16 patients. Of the 96 sites, 42 had infiltration that was delineable by MRI/CT and PET in 35 cases and by PET only in 7 cases. The mean infracranial volume that was delineable in PET was 10.1 ± 10.6 cm3, which was somewhat larger than the volume detectable in MRI/CT (8.4 ± 7.9 cm3). 68Ga-DOTATOC-PET allows detection and assessment of the extent of infracranial meningioma invasion. This method seems to be useful for planning fractionated stereotactic radiation when used in addition to conventional imaging modalities that are often inconclusive in the SB region.
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3.78Impact points
Simultaneous chemoradiation with cisplatin in a patient with recurrent cervical cancer undergoing hemodialysis: analysis of cisplatin concentrations in serum and dialysate and therapy-related acute toxicity.
Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al]. 11/2011; 187(12):831-4.
To prove the feasibility and toxicity of platinum-based chemoradiation in a patient with recurrent cervical cancer undergoing concomitant hemodialysis. We report a patient with a renal transplant because of chronic renal failure who then underwent radical hysterectomy and lymphadenectomy due to cerv... [more] To prove the feasibility and toxicity of platinum-based chemoradiation in a patient with recurrent cervical cancer undergoing concomitant hemodialysis. We report a patient with a renal transplant because of chronic renal failure who then underwent radical hysterectomy and lymphadenectomy due to cervical cancer FIGO stage IB1. One year after primary therapy, a 53 × 54 × 68 mm vaginal stump recurrence was treated by total translevatoric exenteration with lymphadenectomy, explantation of the transplant, and the right residual kidney. Because of microscopically involved margins, chemoradiation was recommended. Radiation was performed to the tumor region and pelvic lymph nodes up to 50.4 Gy. A boost was given to the clip-marked region to 66.6 Gy. Neurological, gastrointestinal and genitourinary toxicity was evaluated once a week, while hematological toxicity twice per week. Samples to evaluate cisplatin concentrations were taken from blood and dialysate. The patient completed chemoradiation with 5 cisplatin applications with a decreased dose (20 mg/m(2)) without any high grade toxicity. Hemodialysis was performed three times a week. Within 30 min after cisplatin application, the cisplatin serum concentration reached the highest level with 1,179.6 µg/l and showed nearly stable concentrations over 120 min. There was an accumulation of cisplatin from week 1 (100%) to week 5 of application (219%). The corresponding concentration in the dialysate also showed a rapid increase within the first hour of hemodialysis and decreased to 50% within 2 h. Cisplatin application with a modified dose (20 mg/m(2)) is feasible and safe in a patient with cervical carcinoma undergoing chemoradiation and hemodialysis.
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4.59Impact points
Helical tomotherapy versus conventional intensity-modulated radiation therapy for primary chemoradiation in cervical cancer patients: an intraindividual comparison.
International journal of radiation oncology, biology, physics. 10/2011; 81(2):424-30.
To compare intensity-modulated radiotherapy (IMRT) delivered by helical tomotherapy (HT) with conventional IMRT for primary chemoradiation in cervical cancer patients. Twenty cervical cancer patients undergoing primary chemoradiation received radiation with HT; 10 patients underwent pelvic irradiati... [more] To compare intensity-modulated radiotherapy (IMRT) delivered by helical tomotherapy (HT) with conventional IMRT for primary chemoradiation in cervical cancer patients. Twenty cervical cancer patients undergoing primary chemoradiation received radiation with HT; 10 patients underwent pelvic irradiation (PEL) and 10 extended-field irradiation (EXT). For treatment planning, the simultaneously integrated boost (SIB) concept was applied. Tumor, pelvic, with or without para-aortic lymph nodes were defined as planning target volume A (PTV-A) with a prescribed dose of 1.8/50.4 Gy (28 fractions). The SIB dose for the parametrium (PTV-B), was 2.12/59.36 Gy. The lower target constraints were 95% of the prescribed dose in 95% of the target volume, and the upper dose constraint was 107%. The irradiated small-bowel volumes were kept as low as possible. For every HT plan, a conventional IMRT plan was calculated and compared with regard to dose-volume histogram, conformity index and conformity number, and homogeneity index. Both techniques allowed excellent target volume coverage and sufficient SB sparing. Conformity index and conformity number results for both PTV-A and PTV-B, homogeneity index for PTV-B, and SB sparing for V45, V50, Dmax, and D1% were significantly better with HT. SB sparing was significantly better for conventional IMRT at low doses (V10). Both HT and conventional IMRT provide optimal treatment of cervical cancer patients. The HT technique was significantly favored with regard to target conformity, homogeneity, and SB sparing. Randomized trials are needed to assess the oncological outcome, toxicity, and clinical relevance of these differences.
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17.79Impact points
Randomized phase III trial of sequential adjuvant chemoradiotherapy with or without erythropoietin Alfa in patients with high-risk cervical cancer: results of the NOGGO-AGO intergroup study.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 08/2011; 29(28):3791-7.
This open-label, randomized phase III study was designed to investigate the effects of erythropoietin alfa (EPO) in addition to adjuvant chemotherapy and pelvic radiotherapy (CRT) in patients with stage IB to II cervical cancer who had undergone radical hysterectomy. Two hundred fifty-seven patients... [more] This open-label, randomized phase III study was designed to investigate the effects of erythropoietin alfa (EPO) in addition to adjuvant chemotherapy and pelvic radiotherapy (CRT) in patients with stage IB to II cervical cancer who had undergone radical hysterectomy. Two hundred fifty-seven patients were randomly assigned to four cycles of carboplatin/ifosfamide chemotherapy followed by external-beam pelvic radiotherapy (CRT group) or four cycles of carboplatin/ifosfamide chemotherapy and EPO followed by pelvic radiotherapy and EPO (CRT + EPO group). The primary end point was recurrence-free survival (RFS). Secondary end points included overall survival (OS), change in hemoglobin levels, and safety, including thromboembolic events. The estimated 5-year RFS rates were 78% for patients receiving CRT + EPO and 70% for patients receiving CRT. There was no statistically significant difference in RFS, although a trend favoring patients treated with CRT + EPO was observed (hazard ratio [HR], 0.66; 95% CI, 0.39 to 1.12; log-rank P = .06). Exploratory analyses suggest a benefit with CRT + EPO for patients with stage IB to IIA disease (HR, 0.39; 95% CI, 0.18 to 0.85; P = .014) or patients with complete resection (HR, 0.55; 95% CI, 0.31 to 0.98; P = .039). OS was similar in both groups (HR, 0.88; 95% CI, 0.51 to 1.50; log-rank P = .63). Patients treated with EPO maintained higher hemoglobin levels throughout CRT. No significant differences in safety profiles were observed between the two groups. Incidence of thrombovascular events was low (2%) and comparable between both groups. This study confirms that EPO can be added safely to CRT in patients with cervical cancer, but it failed to demonstrate a significant benefit in RFS and OS.
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4.34Impact points
Epithelial-mesenchymal-transition induced by EGFR activation interferes with cell migration and response to irradiation and cetuximab in head and neck cancer cells.
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 06/2011; 101(1):158-64.
The role of epithelial-mesenchymal transition (EMT) in the poor outcome of EGFR-overexpressing SCCHN was evaluated. SCCHN cell lines were characterized for their cell morphology and expression of EGFR and the EMT-associated factors E-cadherin, vimentin and Snail1. The migratory potential of cells wa... [more] The role of epithelial-mesenchymal transition (EMT) in the poor outcome of EGFR-overexpressing SCCHN was evaluated. SCCHN cell lines were characterized for their cell morphology and expression of EGFR and the EMT-associated factors E-cadherin, vimentin and Snail1. The migratory potential of cells was assessed in motility assays. Response to irradiation and cetuximab was determined using clonogenic survival assays. High basal expression of E-cadherin but low to absent vimentin expression could be observed in all SCCHN cell lines. Although E-cadherin expression levels did not change after treatment with EGF we observed a significant change in cell morphology resembling EMT. SCCHN cells with high basal levels of Snail1 resulting from constitutive EGFR activation were characterized by mesenchymal-like morphology, elevated migratory potential, reduced sensitivity to irradiation and cetuximab but increased sensitivity to the combined treatment. Autocrine activation of EGFR leading to EMT is associated with a metastatic phenotype and reduced sensitivity of SCCHN cells to single-modality treatment with cetuximab or irradiation. The potential of Snail1 as biomarker for selection of patients who will mostly benefit from a combination of cetuximab and radiotherapy has to be evaluated in future clinical studies.
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6.75Impact points
Expression of amphiregulin and EGFRvIII affect outcome of patients with squamous cell carcinoma of the head and neck receiving cetuximab-docetaxel treatment.
Clinical cancer research : an official journal of the American Association for Cancer Research. 06/2011; 17(15):5197-204.
Constitutive activation of epidermal growth factor receptor (EGFR) as a result of gene amplification, mutation, or overexpression of its ligands has been associated with response to EGFR targeting strategies. The role of these molecular mechanisms for the responsiveness of squamous cell carcinoma of... [more] Constitutive activation of epidermal growth factor receptor (EGFR) as a result of gene amplification, mutation, or overexpression of its ligands has been associated with response to EGFR targeting strategies. The role of these molecular mechanisms for the responsiveness of squamous cell carcinoma of the head and neck (SCCHN) to cetuximab-containing regimens remains unknown. Tumor biopsies from 47 patients, enrolled in a single-arm phase II multicenter study for second-line treatment of recurrent or metastatic SCCHN with cetuximab and docetaxel, were analyzed by immunohistochemistry for expression of EGFR, its deletion variant III (EGFRvIII) and its ligand amphiregulin (AREG). The relation between expression levels and disease control rate (DCR) was evaluated by logistic regression. Association between expression levels, progression-free survival (PFS), and overall survival (OS) was determined by Kaplan-Meier analysis, log-rank test, and uni- and multivariate Cox regression analysis. High expression of EGFR, EGFRvIII, and AREG was detected in 73%, 17%, and 45% of SCCHN cases, respectively. Expression levels of EGFR had no impact on PFS or OS. High expression levels of EGFRvIII were significantly associated with reduced DCR and shortened PFS (HR: 3.3, P = 0.005) but not with OS. Patients with high AREG expression in tumor cells had significantly shortened OS (HR: 2.2, P = 0.002) and PFS (HR 2.2, P = 0.019) compared with patients with low expression score. Multivariate Cox analysis revealed an independent association of AREG and EGFRvIII with PFS but only AREG was an independent prognosticator of OS. High EGFRvIII and AREG expression levels identify SCCHN patients who are less likely to benefit from combination treatment with cetuximab and docetaxel.
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2.75Impact points
Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme.
Journal of neuro-oncology. 06/2011; 103(2):317-24.
Therapy options at the time of recurrence of glioblastoma multiforme are often limited. We investigated whether treatment with a new intratumoral thermotherapy procedure using magnetic nanoparticles improves survival outcome. In a single-arm study in two centers, 66 patients (59 with recurrent gliob... [more] Therapy options at the time of recurrence of glioblastoma multiforme are often limited. We investigated whether treatment with a new intratumoral thermotherapy procedure using magnetic nanoparticles improves survival outcome. In a single-arm study in two centers, 66 patients (59 with recurrent glioblastoma) received neuronavigationally controlled intratumoral instillation of an aqueous dispersion of iron-oxide (magnetite) nanoparticles and subsequent heating of the particles in an alternating magnetic field. Treatment was combined with fractionated stereotactic radiotherapy. A median dose of 30 Gy using a fractionation of 5 × 2 Gy/week was applied. The primary study endpoint was overall survival following diagnosis of first tumor recurrence (OS-2), while the secondary endpoint was overall survival after primary tumor diagnosis (OS-1). Survival times were calculated using the Kaplan-Meier method. Analyses were by intention to treat. The median overall survival from diagnosis of the first tumor recurrence among the 59 patients with recurrent glioblastoma was 13.4 months (95% CI: 10.6-16.2 months). Median OS-1 was 23.2 months while the median time interval between primary diagnosis and first tumor recurrence was 8.0 months. Only tumor volume at study entry was significantly correlated with ensuing survival (P < 0.01). No other variables predicting longer survival could be determined. The side effects of the new therapeutic approach were moderate, and no serious complications were observed. Thermotherapy using magnetic nanoparticles in conjunction with a reduced radiation dose is safe and effective and leads to longer OS-2 compared to conventional therapies in the treatment of recurrent glioblastoma.
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3.78Impact points
Adjuvant chemoradiation after laparoscopically assisted vaginal radical hysterectomy (LARVH) in patients with cervical cancer: oncologic outcome and morbidity.
Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al]. 06/2011; 187(6):344-9.
Compared to laparotomic surgery, laparoscopically assisted radical vaginal hysterectomy (LARVH) offers decreased blood loss during surgery and faster convalescence of the patient postoperatively, while at the same time delivering similar oncologic results. However, there is no data on outcome and to... [more] Compared to laparotomic surgery, laparoscopically assisted radical vaginal hysterectomy (LARVH) offers decreased blood loss during surgery and faster convalescence of the patient postoperatively, while at the same time delivering similar oncologic results. However, there is no data on outcome and toxicity of LARVH followed by (chemo)radiation. A total of 55 patients (range 28-78 years) with cervical cancer on FIGO stages IB1-IIIA (Tables 1 and 2) with risk factors were submitted to either external beam radiotherapy alone [EBRT, n = 8 (14%), including paraaortic irradiation, n = 4 (2.2%); EBRT and brachytherapy (BT), n = 33 (60%); BT alone, n = 14 (25.5%)] or chemoradiation after LARVH. At a median follow-up of 4.4 years, the 5-year disease-free survival (DFS) was 81.8% with 84.5% overall survival (OS). Acute grade 3 side effects were seen in 4 patients. These were mainly gastrointestinal (GI) and genitourinary (GU) symptoms. Grade 4 side effects were not observed. With similar oncologic outcome data and mostly mild side effects, LARVH followed by (chemo)radiation is a valid alternative in the treatment of cervical cancer patients.
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4.59Impact points
Helical tomotherapy with simultaneous integrated boost after laparoscopic staging in patients with cervical cancer: analysis of feasibility and early toxicity.
International journal of radiation oncology, biology, physics. 05/2011; 82(2):e137-43.
To demonstrate the feasibility and safety of the simultaneous integrated boost technique for dose escalation in combination with helical tomotherapy in patients with cervical cancer. Forty patients (International Federation of Gynecology and Obstetrics Stage IB1 pN1-IVA) underwent primary chemoradia... [more] To demonstrate the feasibility and safety of the simultaneous integrated boost technique for dose escalation in combination with helical tomotherapy in patients with cervical cancer. Forty patients (International Federation of Gynecology and Obstetrics Stage IB1 pN1-IVA) underwent primary chemoradiation with helical tomotherapy. Before therapy, 29/40 patients underwent laparoscopic pelvic and para-aortic lymphadenectomy. In 21%, 31%, and 3% of the patients, pelvic, pelvic and para-aortic, and skip metastases in the para-aortic region could be confirmed. All patients underwent radiation with 1.8-50.4 Gy to the tumor region and the pelvic (para-aortic) lymph node region (planning target volume-A), and a simultaneous boost with 2.12-59.36 Gy to the boost region (planning target volume-B). The boost region was defined using titan clips during laparoscopic staging. In all other patients, standardized borders for the planning target volume-B were defined. High-dose-rate brachytherapy was performed in 39/40 patients. The mean biologic effective dose to the macroscopic tumor ranged from 87.5 to 97.5 Gy. Chemotherapy consisted of weekly cisplatin 40 mg/m(2). Dose-volume histograms and acute gastrointestinal, genitourinary, and hematologic toxicity were evaluated. The mean treatment time was 45 days. The mean doses to the small bowel, rectum, and bladder were 28.5 ± 6.1 Gy, 47.9 ± 3.8 Gy, and 48 ± 3 Gy, respectively. Hematologic toxicity Grade 3 occurred in 20% of patients, diarrhea Grade 2 in 5%, and diarrhea Grade 3 in 2.5%. There was no Grade 3 genitourinary toxicity. All patients underwent curettage 3 months after chemoradiation, which confirmed complete pathologic response in 38/40 patients. The concept of simultaneous integrated boost for dose escalation in patients with cervical cancer is feasible, with a low rate of acute gastrointestinal and genitourinary toxicity. Whether dose escalation can be translated into improved outcome will be assessed after a longer follow-up time.
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2.95Impact points
Pifithrin-α as a potential cytoprotective agent in radiotherapy: protection of normal tissue without decreasing therapeutic efficacy in glioma cells.
Radiation research. 11/2010; 174(5):601-10.
Activation of p53 has been causally linked to normal tissue damage after irradiation. Pifithrin-α (PFT-α), a specific inhibitor of p53, has been suggested as a combinatory agent in the treatment of p53-deficient tumors in which inhibition of p53 would not compromise therapeutic efficacy but would de... [more] Activation of p53 has been causally linked to normal tissue damage after irradiation. Pifithrin-α (PFT-α), a specific inhibitor of p53, has been suggested as a combinatory agent in the treatment of p53-deficient tumors in which inhibition of p53 would not compromise therapeutic efficacy but would decrease p53-mediated side effects in normal tissue. We tested this concept for radiotherapy of p53-deficient and -proficient glioma. We observed significant interaction of PFT-α with radiation-induced G(1) checkpoint activation and plating efficiency only in glioma cells expressing at least one wild-type allele of p53. This interaction was correlated with PFT-α-mediated inhibition of radiation-induced expression of the p53 target gene p21(Waf1). Despite inhibition of p53 function we did not observe significant changes in radiosensitivity after treatment with PFT-α in either p53-deficient or p53-proficient tumor cells. We confirmed these results in p53-proficient lung cancer cells. In contrast, PFT-α significantly increased the fraction of normal astrocytes and fibroblasts surviving irradiation; this was accompanied by improved DNA damage repair, speaking against an accumulation of cells with genetic lesions after PFT-α treatment. In conclusion, PFT-α might prove useful in protecting normal tissue from the side effects of radiotherapy without reducing the efficacy of treatment for both p53-proficient and -deficient tumors.
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17.79Impact points
Adjuvant gemcitabine alone versus gemcitabine-based chemoradiotherapy after curative resection for pancreatic cancer: a randomized EORTC-40013-22012/FFCD-9203/GERCOR phase II study.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 10/2010; 28(29):4450-6.
The role of adjuvant chemoradiotherapy (CRT) in resectable pancreatic cancer is still debated. This randomized phase II intergroup study explores the feasibility and tolerability of a gemcitabine-based CRT regimen after R0 resection of pancreatic head cancer. Within 8 weeks after surgery, patients w... [more] The role of adjuvant chemoradiotherapy (CRT) in resectable pancreatic cancer is still debated. This randomized phase II intergroup study explores the feasibility and tolerability of a gemcitabine-based CRT regimen after R0 resection of pancreatic head cancer. Within 8 weeks after surgery, patients were randomly assigned to receive either four cycles of gemcitabine (control arm) or gemcitabine for two cycles followed by weekly gemcitabine with concurrent radiation (50.4 Gy; CRT arm). The primary objective was to exclude a < 60% treatment completion and a > 40% rate of grade 4 hematologic or GI toxicity in the CRT arm with type I and II errors of 10%. Secondary end points were late toxicity, disease-free survival (DFS), and overall survival (OS). Between September 2004 and January 2007, 90 patients were randomly assigned (45:45). Patient characteristics were similar in both arms. Treatment was completed per protocol by 86.7% and 73.3% (80% CI, 63.1% to 81.9%; 95% CI, 58.1% to 85.4%) in the control and CRT arms, respectively, and grade 4 toxicity was 0% and 4.7% (two of 43; 80% CI, 1.2% to 11.9%), respectively. In the CRT arm, three patients experienced grade 3-related late toxicity. Median DFS was 12 months in the CRT arm and 11 months in the control arm. Median OS was 24 months in both arms. First local recurrence was less frequent in the CRT arm (11% v 24%). Adjuvant gemcitabine-based CRT is feasible, well-tolerated, and not deleterious; adding this treatment to full-dose adjuvant gemcitabine after resection of pancreatic cancer should be evaluated in a phase III trial.
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2.70Impact points
Regularized antenna profile adaptation in online hyperthermia treatment.
Medical physics. 10/2010; 37(10):5382-94.
Online optimization of annular-phased-array hyperthermia (HT) is based on planning tools and magnetic resonance (MR) thermometry. Until now, the method has been validated in phantoms. Further developments and extensions are required for clinical purposes. In particular, the problem of deducing the e... [more] Online optimization of annular-phased-array hyperthermia (HT) is based on planning tools and magnetic resonance (MR) thermometry. Until now, the method has been validated in phantoms. Further developments and extensions are required for clinical purposes. In particular, the problem of deducing the electric field distribution inside the patient from MR thermometry is ill-posed, which leads to an amplification of measurement errors. A method to overcome this difficulty is proposed. The authors utilized a regularized Gauss-Newton algorithm with a fast bioheat transfer equation (BHTE) approximation to identify the field parameters. To evaluate the method, simulations with patient models are conducted and a treatment data set obtained from a heat treatment performed in the hybrid HT-MR system at the Charité Medical School is used to visualize the error amplification. The regularization leads to a significantly improved accuracy of the predicted electric fields and temperatures compared to an unregularized approach. The BHTE approximation enables highly accurate temperature predictions in real-time. Regularization proves to be necessary to identify electromagnetic field parameters. The proposed method is able to reproduce measurements without overfitting to the noise in the MR measurements and results in an improved treatment planning.
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3.78Impact points
Helical tomotherapy in cervical cancer patients: simultaneous integrated boost concept: technique and acute toxicity.
Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al]. 09/2010; 186(10):572-9.
To evaluate the acute toxicity of simultaneous integrated boost (SIB) technique for dose escalation with helical tomotherapy (HT) in patients with locally advanced cervical cancer. 20 patients (FIGO IB1 pN1-IIIB) underwent primary chemoradiation. Prior to chemoradiation, a laparoscopic pelvic and pa... [more] To evaluate the acute toxicity of simultaneous integrated boost (SIB) technique for dose escalation with helical tomotherapy (HT) in patients with locally advanced cervical cancer. 20 patients (FIGO IB1 pN1-IIIB) underwent primary chemoradiation. Prior to chemoradiation, a laparoscopic pelvic and para-aortic lymphadenectomy was performed. A boost region was defined using titanium clips during staging for planning target volume (PTV-B). Patients were treated with five weekly fractions of 1.8 Gy to a total dose of 50.4 Gy to the tumor region and the pelvic (para-aortic) lymph node region (PTV-A), and five weekly fractions of 2.12 Gy to a total dose of 59.36 Gy to the PTV-B. Chemotherapy consisted of weekly cisplatin 40 mg/m(2). 19 patients underwent brachytherapy. Dose-volume histograms were evaluated and acute gastrointestinal (GI), genitourinary (GU), and hematologic toxicity were documented (CTCAE v3.0). Pelvic and para-aortic lymph node metastases were confirmed in nine and four patients, respectively. Five patients refused laparoscopic staging. The mean volume of PTV-A and PTV-B was 1,570 ± 404 cm(3) and 341 ± 125 cm(3), respectively. The mean dose to the bladder, rectum, and small bowel was 47.85 Gy, 45.76 Gy, and 29.71 Gy, respectively. No grade 4/5 toxicity was observed. Grade 2/3 hematologic toxicity occurred in 50% of patients and 5% experienced grade 3 diarrhea. There was no grade 3 GU toxicity. 19 patients underwent curettage 6-9 weeks after chemoradiation without any evidence of tumor. The concept of SIB for dose escalation in patients with locally advanced cervical cancer is feasible with a low rate of acute toxicity. Whether dose escalation can translate into improved outcome will be assessed after a longer follow-up.
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3.78Impact points
Residual translational and rotational errors after kV X-ray image-guided correction of prostate location using implanted fiducials.
Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al]. 09/2010; 186(10):544-50.
To evaluate the residual errors and required safety margins after stereoscopic kilovoltage (kV) X-ray target localization of the prostate in image-guided radiotherapy (IGRT) using internal fiducials. Radiopaque fiducial markers (FMs) have been inserted into the prostate in a cohort of 33 patients. T... [more] To evaluate the residual errors and required safety margins after stereoscopic kilovoltage (kV) X-ray target localization of the prostate in image-guided radiotherapy (IGRT) using internal fiducials. Radiopaque fiducial markers (FMs) have been inserted into the prostate in a cohort of 33 patients. The ExacTrac/Novalis Body™ X-ray 6d image acquisition system (BrainLAB AG, Feldkirchen, Germany) was used. Corrections were performed in left-right (LR), anterior-posterior (AP), and superior-inferior (SI) direction. Rotational errors around LR (x-axis), AP (y) and SI (z) have been recorded for the first series of nine patients, and since 2007 for the subsequent 24 patients in addition corrected in each fraction by using the Robotic Tilt Module™ and Varian Exact Couch™. After positioning, a second set of X-ray images was acquired for verification purposes. Residual errors were registered and again corrected. Standard deviations (SD) of residual translational random errors in LR, AP, and SI coordinates were 1.3, 1.7, and 2.2 mm. Residual random rotation errors were found for lateral (around x, tilt), vertical (around y, table), and longitudinal (around z, roll) and of 3.2°, 1.8°, and 1.5°. Planning target volume (PTV)-clinical target volume (CTV) margins were calculated in LR, AP, and SI direction to 2.3, 3.0, and 3.7 mm. After a second repositioning, the margins could be reduced to 1.8, 2.1, and 1.8 mm. On the basis of the residual setup error measurements, the margin required after one to two online X-ray corrections for the patients enrolled in this study would be at minimum 2 mm. The contribution of intrafractional motion to residual random errors has to be evaluated.
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4.95Impact points
Caffeine confers radiosensitization of PTEN-deficient malignant glioma cells by enhancing ionizing radiation-induced G1 arrest and negatively regulating Akt phosphorylation.
Molecular cancer therapeutics. 02/2010; 9(2):480-8.
PTEN mutations are frequently found in malignant glioma and can result in activated phosphatidylinositol-3-kinase/Akt survival signaling associated with resistance to radiotherapy. Strategies to interfere with aberrant PI3K/Akt activity are therefore being developed to improve the therapeutic effica... [more] PTEN mutations are frequently found in malignant glioma and can result in activated phosphatidylinositol-3-kinase/Akt survival signaling associated with resistance to radiotherapy. Strategies to interfere with aberrant PI3K/Akt activity are therefore being developed to improve the therapeutic efficacy of radiotherapy in patients with malignant glioma. The methylxanthine caffeine has been described as a PI3K inhibitor and is also known to sensitize cells to ionizing radiation. However, a direct association between these two caffeine-mediated effects has not been reported yet. Therefore, we asked whether caffeine or its derivative pentoxifylline differentially affect the radiosensitivity of malignant gliomas with different PTEN status. As models, we used the radiosensitive EA14 malignant glioma cell line containing wild-type PTEN and the radioresistant U87MG malignant glioma cell line harboring mutant PTEN. Our study revealed that caffeine and pentoxifylline radiosensitized PTEN-deficient but not PTEN-proficient glioma cells. Radiosensitization of PTEN-deficient U87MG cells by caffeine was significantly correlated with the activation of the G(1) DNA damage checkpoint that occurred independently of de novo synthesis of p53 and p21. The p53 independency was also confirmed by a significant caffeine-mediated radiosensitization of the glioma cell lines T98G and U373MG that are deficient for both PTEN and p53. Furthermore, caffeine-mediated radiosensitization was associated with the inhibition of Akt hyperphosphorylation in PTEN-deficient cells to a level comparable with PTEN-proficient cells. Our data suggest that the methylxanthine caffeine or its derivative pentoxifylline are promising candidate drugs for the radiosensitization of glioma cells particularly with PTEN mutations.
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Heterotopic Ossification And Functional Status Of The Hip Joint Following Total Hip Arthroplasty And Postoperative Prophylactic Irradiation
Journal of Orthopaedics. 01/2010;
Background and purpose: Heterotopic ossification (HO) is one of the major complications following total hip arthroplasty (THA). The aim of this study is to evaluate HO and functional status (FS) of the hip joint 5 years after THA and prophylactic postoperative irradiation with a single dose of 7 Gy.... [more] Background and purpose: Heterotopic ossification (HO) is one of the major complications following total hip arthroplasty (THA). The aim of this study is to evaluate HO and functional status (FS) of the hip joint 5 years after THA and prophylactic postoperative irradiation with a single dose of 7 Gy. Methods: We analyzed a random sample of 100 patients 5 years after THA and postoperative radiotherapy with a single dose of 7 Gy. Brooker score (BS) was used to classify the radiographic signs of HO and Harris-Hip Score (HHS) to assess the FS of the hip joint. The range of motion was assessed in all directions and was measured in degrees.Results: 51% of patients had radiographic evidence of HO; mean HHS 84.8 ± 16.5 points. Height (p = 0.025) and weight (p = 0.008) correlated positively with the extent of HO. Men developed significantly higher BS than women (p = 0.009). Duration of surgery correlated with HHS (p = 0.026). In the category BS 0 vs. BS 1 for the range of motion in degrees, there were significant correlations for flexion (p = 0.05), adduction (p = 0.03) and sum of motions (p = 0.04) in favour of BS 0. In the category BS 0 vs. BS 1,2,3,4, there were significant correlations for flexion (p = 0.07), adduction (p = 0.05), and sum of motions (p = 0.05) in favour of BS 0. For the range of motion in points (HHS), no significant correlations with all categories of HO were found. Conclusion: Mild HO of BS 1 can deteriorate the range of motion after THA significantly. The sum of motion in degrees has been proved a more sensitive tool for assessing the clinical outcome than the range of motion in points according to HHS or the total HHS.
Following (22)
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Marc Peeters
University of Antwerpen -
Konrad Klinghammer
Charité Universitätsmedizin Berlin -
Jean-Luc Van Laethem
Université Libre de Bruxelles -
Andreas Jordan
Charité Universitätsmedizin Berlin -
Karin Haustermans
Katholieke Universiteit Leuven
Topics (2)
