Stephanie E Combs

Technische Universität München, München, Bavaria, Germany

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Publications (213)671.73 Total impact

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    ABSTRACT: The primary objective was to assess the different reasons for refusal of surgical resection (SR) in patients with esophageal squamous cell cancer (ESCC), who were initially planned for neoadjuvant radiochemotherapy (N-RCT) + SR, but SR was not performed after N-RCT. From 1988 to 2011, 311 patients with ESCC were treated with N-RCT in a tertiary referral center for esophageal diseases. Fifty-three patients were analyzed who received RCT with 40-45 Gy and concomitant chemotherapy in neoadjuvant intention, but in whom the treatment was stopped or switched to definitive RCT due to progression, patient decision, or new findings. The reasons for refusal of SR for these 53 patients were as follows: (1) patients' or physicians' preference for the planned treatment was changed during the N-RCT, such that RCT was continued to a curative dose without a break (group 1, n = 23, 44%); (2) patients were restaged after 4 weeks, and the tumor board decided to continue RCT because R0 resection was unlikely and/or patients were medically unfit (group 2, n = 15, 28%); (3) patients refused continuation of any treatment (group 3, n = 15, 28%). Refusal of SR was significantly more likely in patients with longitudinal tumor dimension >8 cm and those with an Eastern Cooperative Oncology Group performance status score of 2. Median follow-up time from the start of N-RCT was 57 months (range 1-137 months). The survival rates at 2 and 5 years were 36 ± 7% and 27 ± 7%, respectively. Group 1 had significantly longer survival. The planned N-RCT+SR could not be completed in a considerable number of patients in a tertiary referral center. More strict selection criteria for multimodality treatment including SR could spare some of these patients an incomplete treatment and probably lead to increased utilization of definitive RCT.
    04/2015; DOI:10.5301/tj.5000266
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    ABSTRACT: The purpose of the study was to evaluate the effect of radiation therapy and chemoradiation with gemcitabine (GEM) after R1 resection in patients with pancreatic adenocarcinoma (PAC). We performed a retrospective analysis of 25 patients who were treated with postoperative radiotherapy (RT) or chemoradiation (CRT) after surgery with microscopically positive resection margins for primary pancreatic cancer (PAC). Median age was 60 years (range 34 to 74 years), and there were 17 male and 8 female patients. Fractionated RT was applied with a median dose of 49.6 Gy (range 36 to 54 Gy). Eight patients received additional intraoperative radiotherapy (IORT) with a median dose of 12 Gy. Median overall survival (mOS) of all treated patients was 22 months (95% confidence interval (CI) 7.9 to 36.1 months) after date of resection and 21.1 months (95% CI 7.6 to 34.6 months) after start of (C)RT. Median progression-free survival (mPFS) was 13.0 months (95% CI 0.93 to 25 months). Grading (G2 vs. G3, P = 0.005) and gender (female vs. male, P = 0.01) were significantly correlated with OS. There was a significant difference in mPFS between male and female patients (P = 0.008). A total of 11 from 25 patients experienced local tumour progression, and 19 patients were diagnosed with either locoregional or distant failure. We demonstrated that GEM-based CRT can be applied in analogy to neoadjuvant protocols in the adjuvant setting for PAC patients at high risk for disease recurrence after incomplete resection. Patients undergoing additive CRT have a rather good OS and PFS compared to historical control patient groups.
    World Journal of Surgical Oncology 04/2015; 13(1):149. DOI:10.1186/s12957-015-0560-3 · 1.20 Impact Factor
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    ABSTRACT: Heat shock protein 70 (Hsp70) is frequently overexpressed in tumor cells. An unusual cell surface localization could be demonstrated on a large variety of solid tumors including lung, colorectal, breast, squamous cell carcinomas of the head and neck, prostate and pancreatic carcinomas, glioblastomas, sarcomas and hematological malignancies, but not on corresponding normal tissues. A membrane (m)Hsp70-positive phenotype can be determined either directly on single cell suspensions of tumor biopsies by flow cytometry using cmHsp70.1 monoclonal antibody or indirectly in the serum of patients using a novel lipHsp70 ELISA. A mHsp70-positive tumor phenotype has been associated with highly aggressive tumors, causing invasion and metastases and resistance to cell death. However, natural killer (NK), but not T cells were found to kill mHsp70-positive tumor cells after activation with a naturally occurring Hsp70 peptide (TKD) plus low dose IL-2 (TKD/IL-2). Safety and tolerability of ex vivo TKD/IL-2 stimulated, autologous NK cells has been demonstrated in patients with metastasized colorectal and NSCLC in a phase I clinical trial. Based on promising clinical results of the previous study, a phase II randomized clinical study was initiated in 2015. The primary objective of this multicenter proof-of-concept trial is to examine whether an adjuvant treatment of NSCLC patients after platinum based radiochemotherapy with TKD/IL-2 activated, autologous NK cells is clinically effective. As a mHsp70-positive tumor phenotype is associated with poor clinical outcome only mHsp70-positive tumor patients will be recruited into the trial. The primary endpoint of this study will be the comparison of the progression-free survival of patients treated with ex vivo activated NK cells compared to patients who were treated with radiochemotherapy alone. As secondary endpoints overall survival, toxicity, quality-of-life and biological responses will be determined in both study groups.
    Frontiers in Immunology 04/2015; 6:162. DOI:10.3389/fimmu.2015.00162
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    ABSTRACT: The physical and biological properties of ion-beams offer various advantages in comparison to conventional radiotherapy, though uncertainties concerning quality assurance are still left. Due to the inverted depth dose profile, range accuracy is of paramount importance. We investigated the range deviations between planning simulation and post-fractional PET/CT measurement from particle therapy in primary glioblastoma. 20 patients with glioblastoma undergoing particle therapy at our institution were selected. 10 received a proton-boost, 10 a carbon-ion-boost in addition to standard treatment. After two fractions, we performed a PET/CT-scan of the brain. We compared the resulting range deviation based on the Most-likely-shift method between the two measurements, and the measurements with corresponding expectations, calculated with the Monte-Carlo code FLUKA. A patient's two measurements deviated by 0.7mm (±0.7mm). Overall comparison between measurements and simulation resulted in a mean range deviation of 3.3mm (±2.2mm) with significant lower deviations in the (12)C-arm. The used planning concepts display the actual dose distributions adequately. The carbon ion group's results are below the used PTV safety margins (3mm). Further adjustments to the simulation are required for proton irradiations. Some anatomical situations require particular attention to ensure highest accuracy and safety. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Radiotherapy and Oncology 04/2015; 115(2). DOI:10.1016/j.radonc.2015.03.022 · 4.86 Impact Factor
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    ABSTRACT: During radiation treatment, movement of the target and organs at risks as well as tumor response can significantly influence dose distribution. This is highly relevant in patients with pancreatic cancer, where organs at risk lie in close proximity to the target. Data sets of 10 patients with locally advanced pancreatic cancer were evaluated. Gross tumor volume deformation was analyzed. Dose changes to organs at risk were determined with focus on kidneys both without adaptive radiotherapy compensation and with replanning based on weekly acquired computed tomography scans. During irradiation, gross tumor volume changes between 0% and 26% and moves within a radius of 5 to 16 mm. Required maximal dose to organs at risk for kidneys can be met with the current practice of matching computed tomography scans during treatment and adjusting patient position accordingly. Comparison of the mean doses and V15, V20 volumes demonstrated that weekly replanning could bring a significant dose sparing of the left kidney. Manual matching with focus on bony structures can lead to overall acceptable positioning of patients during treatment. Thus, tolerance doses of organs at risk, such as the kidneys, can be met. With adequate margins, normal tissue constraints to organs at risk can be kept as well. Adaptive radiotherapy approaches (in this case with weekly rescanning) reduced dose to organs at risk, which may be especially important for hypofractionated approaches. © The Author(s) 2015.
    Technology in cancer research & treatment 03/2015; DOI:10.1177/1533034615577515 · 1.94 Impact Factor
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    ABSTRACT: Photon irradiation has been repeatedly suspected of increasing tumor cell motility and promoting locoregional recurrence of disease. This study was set up to analyse possible mechanisms underlying the potentially radiation-altered motility in medulloblastoma cells. Medulloblastoma cell lines D425 and Med8A were analyzed in migration and adhesion experiments with and without photon and carbon ion irradiation. Expression of integrins was determined by quantitative FACS analysis. Matrix metalloproteinase concentrations within cell culture supernatants were investigated by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using Student's t-test. Both photon and carbon ion irradiation significantly reduced chemotactic medulloblastoma cell transmigration through 8-μm pore size membranes, while simultaneously increasing adherence to fibronectin- and collagen I- and IV-coated surfaces. Correspondingly, both photon and carbon ion irradiation downregulate soluble MMP9 concentrations, while upregulating cell surface expression of proadhesive extracellular matrix protein-binding integrin α5. The observed phenotype of radiation-altered motility is more pronounced following carbon ion than photon irradiation. Both photon and (even more so) carbon ion irradiation are effective in inhibiting medulloblastoma cell migration through downregulation of matrix metalloproteinase 9 and upregulation of proadhesive cell surface integrin α5, which lead to increased cell adherence to extracellular matrix proteins. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.
    Journal of Radiation Research 03/2015; 56(3). DOI:10.1093/jrr/rru120 · 1.69 Impact Factor
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    ABSTRACT: To evaluate long-term clinical outcome and determine prognostic factors for local-control, hearing preservation and cranial nerve toxicity in 449 patients treated for 451 vestibular schwannomas (VS) with radiosurgery (n=169; 38%) or fractionated stereotactic radiotherapy (FSRT; n=291; 62%). 245 patients were male (55%), and 204 were female (45%). Median age was 60years (range 17-88years). Median tumor diameter was 15mm. For FSRT, a median dose of 57.6Gy in median single doses of 1.8Gy was applied. For SRS, median dose was 13Gy. The median follow-up time was 67months. Local control was 97% at 36months, 95% at 60months, and 94% at 120months with no difference between FSRT and SRS (p=0.39). "Useful hearing" was present 46%. After RT, "useful hearing" was preserved in 85% of the patients. Loss of useful hearing was observed in the FSRT group in 14%, and in the SRS group in 16% of the patients. For patients treated with SRS ⩽13Gy, useful hearing deterioration was 13%. For trigeminal and facial nerve toxicity, there was no difference between FSRT and SRS. Supported by this large multicentric series, both SRS and FSRT can be recommended for the treatment of VS. SRS application is limited by tumor size, and is associated with a steep dose-response-curve. When chosen diligently based on tumor volume, pre-treatment characteristics and volume-dependent dose-prescription in SRS (⩽13Gy), both treatments may be considered equally effective. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Radiotherapy and Oncology 02/2015; 87(2). DOI:10.1016/j.radonc.2015.01.011 · 4.86 Impact Factor
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    ABSTRACT: Curative treatment of pediatric cancer not only focuses on long-term survival, but also on reducing treatment-related side effects. Advantages of particle therapy are mainly due to their physical ability of significantly reducing integral dose. Methods. Between January 2009 and December 2012, we treated 83 pediatric patients (aged 21 and younger) at the Heidelberg Ion Therapy Center at University Hospital of Heidelberg (HIT). In total 56 patients (67%) received proton irradiation, while 25 (30%) patients were treated with carbon ions (C12). Two patients received both treatments (3%). Treatment toxicity was analyzed retrospectively and documented according to the CTCAE/RTOG classification. In a second step, treatment toxicity from ion therapy was analyzed in comparison to treatment toxicity during photon irradiation of a comparable historical group of 19 pediatric patients. Results. In all patients, particle therapy was tolerated well (median follow-up time 3.7 months), children (20 patients) with at least two follow-up visits showed a median follow-up time of 10.2 months. During the first two months patients mainly suffered from radiogenic skin reaction (63%), mucositis (30%), headache and dizziness (35%) as well as nausea and vomiting (13%). Severe toxicity reaction (grade II-IV) was only seen in patients who had intensive simultaneous chemotherapy or who had undergone several operations in the irradiated area before radiotherapy (18%). Treatment toxicity during ion therapy was comparable to treatment toxicity from photon irradiation of a historical group. Conclusions. In comparison to conventional therapy, patients with particle therapy do not suffer from increased acute treatment-related toxicity during the first months. More experience with particle therapy will be needed during the next years to help to thoroughly evaluate the high potential of ion therapy.
    Acta oncologica (Stockholm, Sweden) 01/2015; 54(7):1-7. DOI:10.3109/0284186X.2014.998273 · 3.71 Impact Factor
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    ABSTRACT: To assess the association between dosimetric factors of the lung and incidence of intra- and postoperative mortality among esophageal cancer (EC) patients treated with neoadjuvant radiochemotherapy (N-RCT) followed by surgery (S). Inclusion criteria were: age < 85 years, no distant metastases at the time of diagnosis, no induction chemotherapy, conformal radiotherapy, total dose ≤ 50.4 Gy, and available dose volume histogram (DVH) data. One-hundred thirty-five patients met our inclusion criteria. Median age was 62 years. N-RCT consisted of 36 - 50.4 Gy (median 45 Gy), 1.8 - 2 Gy per fraction. Concomitant chemotherapy consisted of 5-Fluoruracil (5-FU) and cisplatin in 113 patients and cisplatin and taxan-derivates in 15 patients. Seven patients received a single cytotoxic agent. In 130 patients an abdominothoracal and in 5 patients a transhiatal resection was performed. The following dosimetric parameters were generated from the total lung DVH: mean dose, V5, V10, V15, V20, V30, V40, V45 and V50. The primary endpoint was the rate of intra- and postoperative mortality (from the start of N-RCT to 60 days after surgical resection). A total of ten postoperative deaths (7%) were observed: 3 within 30 days (2%) and 7 between 30 and 60 days after surgical intervention (5%); no patient died during the operation. In the univariate analysis, weight loss (≥10% in 6 months prior to diagnosis, risk ratio: 1.60, 95%CI: 0.856-2.992, p=0.043), Eastern Cooperative Oncology Group-performance status (ECOG 2 vs. 1, risk ratio: 1.931, 95%CI: 0.898-4.150, p=0.018) and postoperative pulmonary plus non-pulmonary complications (risk ratio: 2.533, 95%CI: 0.978-6.563, p=0.004) were significantly associated with postoperative mortality. There was no significant association between postoperative mortality and irradiated lung volumes. Lung V45 was the only variable which was significantly associated with higher incidence of postoperative pulmonary plus non-pulmonary complications (Exp(B): 1.285, 95%CI 1.029-1.606, p=0.027), but not with the postoperative pulmonary complications (Exp(B): 1.249, 95%CI 0.999-1.561, p=0.051). Irradiated lung volumes did not show relevant associations with intra- and postoperative mortality of patients treated with moderate dose (36 - 50.4 Gy) conventionally fractionated conformal radiotherapy combined with widely used radiosensitizers. Postoperative mortality was significantly associated with greater weight loss, poor performance status and development of postoperative complications, but not with treatment-related factors. Limiting the volume of lung receiving higher radiation doses appears prudent because of the observed association with risk of postoperative complications.
    Journal of Cancer 01/2015; 6(3):254-60. DOI:10.7150/jca.10796 · 2.64 Impact Factor
  • Radiotherapy and Oncology 12/2014; 111:S152-S153. DOI:10.1016/S0167-8140(15)30495-3 · 4.86 Impact Factor
  • Radiotherapy and Oncology 12/2014; 111:S10-S11. DOI:10.1016/S0167-8140(15)31191-9 · 4.86 Impact Factor
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    ABSTRACT: To investigate the impact of HPV status in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received surgery and cisplatin-based postoperative radiochemotherapy. For 221 patients with locally advanced squamous cell carcinoma of the hypopharynx, oropharynx or oral cavity treated at the 8 partner sites of the German Cancer Consortium, the impact of HPV DNA, p16 overexpression and p53 expression on outcome were retrospectively analysed. The primary endpoint was loco-regional tumour control; secondary endpoints were distant metastases and overall survival. In the total patient population, univariate analyses revealed a significant impact of HPV16 DNA positivity, p16 overexpression, p53 positivity and tumour site on loco-regional tumour control. Multivariate analysis stratified for tumour site showed that positive HPV 16 DNA status correlated with loco-regional tumour control in patients with oropharyngeal carcinoma (p=0.02) but not in the oral cavity carcinoma group. Multivariate evaluation of the secondary endpoints in the total population revealed a significant association of HPV16 DNA positivity with overall survival (p<0.01) but not with distant metastases. HPV16 DNA status appears to be a strong prognosticator of loco-regional tumour control after postoperative cisplatin-based radiochemotherapy of locally advanced oropharyngeal carcinoma and is now being explored in a prospective validation trial. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Radiotherapy and Oncology 12/2014; 113(3):317-323. DOI:10.1016/j.radonc.2014.11.011 · 4.86 Impact Factor
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    ABSTRACT: Sublethal doses of photon irradiation (IR) are suspected to increase tumor cell migration and support locoregional recurrence of disease, which has already been shown in other cell lines. This manuscript describes the effect of photon and carbon-ion IR on WHO class I meningioma cell migration and provides an approach to the underlying cellular mechanisms. Meningioma cells were gained operatively at the university hospital in Homburg/Saar, Germany. For migration, membranes (8-µm pore sizes) were coated with collagen I, with collagen IV, and with fibronectin. Cells were analyzed in migration experiments with or without serum stimulation, with or without photon and carbon IR 24 h prior to experiments, and with or without integrin antibodies. Fluorescence-activated cell sorting (FACS) analyses of the integrins ανβ1, ανβ3, and ανβ5 were performed without IR and 6, 12 and 24 h after IR. Enzyme-linked immunosorbent assay (ELISA) analyses of matrix metalloproteinases (MMP)-2 and MMP-9 were realized with and without IR after cells were cultured on collagen I, collagen IV, or fibronectin for 24 h. Cells and supernatants for FACS and ELISA were stored at - 18 °C. The significance level was set at 5 % using both Student's t test and two-way ANOVA. Migration of meningioma cells was serum-inducible (p < 0.001). It could be increased by photon IR (p < 0.02). The integrins ανβ1 and ανβ5 showed a 21 and 11 % higher expression after serum stimulation (not significant), respectively, and ανβ1 expression was raised by 14 % (p = 0.0057) after photon IR. Antibody blockage of the integrins ανβ1 and ανβ5 inhibited serum- and photon-induced migration. Expression of MMP-2 and MMP-9 remained unchanged after both IR and fetal bovine serum (FBS). Carbon-ion IR left both integrin expression and meningioma cell migration unaffected. Photon but not carbon-ion IR promotes serum-based meningioma cell migration. Fibronectin receptor integrin ανβ1 signaling can be identified as an important mechanism for serum- and photon-induced migration of WHO class I meningioma cells.
    Strahlentherapie und Onkologie 12/2014; DOI:10.1007/s00066-014-0778-y · 2.73 Impact Factor
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    ABSTRACT: Aim of this study was to evaluate the relative biological effectiveness (RBE) of carbon (12C) and oxygen ion (16O)-irradiation applied in the raster-scanning technique at the Heidelberg Ion beam Therapy center (HIT) based on clonogenic survival in hepatocellular carcinoma cell lines compared to photon irradiation. Four human HCC lines Hep3B, PLC, HepG2 and HUH7 were irradiated with photons, 12C and 16O using a customized experimental setting at HIT for in-vitro trials. Cells were irradiated with increasing physical photon single doses of 0, 2, 4 and 6 Gy and heavy ionsingle doses of 0, 0.125, 0.5, 1, 2, 3 Gy (12C and 16O). SOBP-penetration depth and extension was 35 mm +/-4 mm and 36 mm +/-5 mm for carbon ions and oxygen ions respectively. Mean energy level and mean linear energy transfer (LET) were 130 MeV/u and 112 keV/um for 12C, and 154 MeV/u and 146 keV/um for 16O. Clonogenic survival was computated and realtive biological effectiveness (RBE) values were defined. For all cell lines and both particle modalities α- and β-values were determined. As expected, α-values were significantly higher for 12C and 16O than for photons, reflecting a steeper decline of the initial slope of the survival curves for high-LET beams. RBE-values were in the range of 2.1-3.3 and 1.9-3.1 for 12C and 16O, respectively. Both irradiation with 12C and 16O using the rasterscanning technique leads to an enhanced RBE in HCC cell lines. No relevant differences between achieved RBE-values for 12C and 16O were found. Results of this work will further influence biological-adapted treatment planning for HCC patients that will undergo particle therapy with 12C or 16O.
    PLoS ONE 12/2014; 9(12):e113591. DOI:10.1371/journal.pone.0113591 · 3.53 Impact Factor
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    ABSTRACT: This study was undertaken to examine the impact of radiation dose on pathological complete response (pCR) rates following neoadjuvant radiochemotherapy (N-RCT) for squamous cell esophageal cancer (ESCC). From 1988 to 2011, 218 patients were treated with 30-30.6 Gy (1.8-2 Gy per fraction), 39.6-40 Gy (1.8-2 Gy per fraction) or 44-45 Gy (1.8-2 Gy per fraction) and concomitant cisplatin ± 5-fluorouracil (5-FU), oxaliplatin + 5-FU or 5-FU alone. The most commonly used concomitant chemotherapy was continuous infusion of 5-FU-alone with a dose of 300 mg/m(2)/day during the whole course of treatment (n=111). To eliminate the dispersing effect of potentially different efficacy levels of these drug regimens on pCR, we excluded patients with regimens other than 5-FU-alone. Histomorphological regression grade 1a (0% residual tumor), 1b (<10% residual tumor), 2 (10-50% residual tumor) and 3 (>50% residual tumor) was observed in 26 (23%), 24 (22%), 36 (32%) and 25 (23%) patients, respectively. pCR was observed in 9 out of 71 (13%) patients treated with 30 Gy-30.6 Gy, 13 of 34 (38%) patients treated with 39.6-40 Gy and 4 of 6 (67%) patients treated with 44-45 Gy (p=0.001). Median follow-up time from the start of N-RCT was 191 months (range=2-262 months). The estimated 5-year overall survival (OS) was 33% for the whole cohort. OS at 5 years was 58% for patients with pCR compared to 25% for patients with less favorable response to N-RCT (p=0.009), respectively. The dose of radiation correlates significantly with the likelihood of achieving a pCR in stage II/III squamous cell esophageal cancer patients. Prospective randomized trials are required to definitively evaluate the impact of application of higher radiation doses on efficacy and safety/tolerability in the context of N-RCT on the clinical outcomes. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
    Anticancer research 12/2014; 34(12):7255-61. · 1.87 Impact Factor
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    ABSTRACT: Interplay effects may limit the applicability of scanned ion beam therapy for moving tumors even if the motion amplitude is reduced by techniques such as gating or abdominal compression (AC). We investigate the potential of enhanced pencil beam overlap to mitigate residual motion interplay effects in scanned ion beam therapy. Eight patients with hepato cellular carcinoma were selected who were either treated under AC (5 clinical target volumes (CTVs)) or with gating (6 CTVs). We performed 4D dose calculations for treatment plans with variable beam parameters (lateral raster spacing, beam full-width-at-half-maximum (FWHM), iso-energy slice spacing, gating window (GW)) and assessed under- and overdose (V95 and V107), dose homogeneity (HI=D5-D95), and dose volume histograms. The influence of the beam parameters on HI was studied by multivariate regression models. Motion amplitude and FWHM had the largest impact on dose homogeneity, while decreased iso-energy slice spacing and lateral raster spacing had a much smaller or no significant effect, respectively. The multivariate regression models including FWHM, motion amplitude, and IES-spacing explained 86%, 42%, and 71% of the observed variance for AC, 30% and 50% GW, respectively. Residual motion in scanned carbon ion therapy of liver tumors can lead to considerable dose heterogeneities. Using an increased beam spot size dose degradation can be significantly mitigated. Especially for large tumors, increasing the beam spot size is an efficient motion mitigation option readily available at most scanning facilities. Copyright © 2014. Published by Elsevier Ireland Ltd.
    Radiotherapy and Oncology 11/2014; 113(2). DOI:10.1016/j.radonc.2014.11.020 · 4.86 Impact Factor
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    ABSTRACT: The purpose of this work is to report the long-term outcomes of three-dimensional conformal radio(chemo)therapy in the curative management of esophageal squamous cell carcinoma (ESCC). A retrospective analysis of patients treated with radio(chemo)therapy between 1988 and 2011 at Klinikum rechts der Isar, Technische Universität München was performed. In all, 168 patients received radio(chemo)therapy for ESCC in curative intention. The median follow-up time was 91 months (range 1-212 months). There were 128 men and 40 women with a median age of 63 years. Selection criteria for radio(chemo)therapy were unfit for surgery and/or unresectable primary tumor (n = 146, 87 %) or patients' choice (n = 22, 13 %). The majority of the patients received a combination of cisplatin and 5-fluorouracil chemotherapy with 54 Gy in 30 fractions of radiotherapy. The median overall survival (OS) was 20 months (95 % confidence interval 17-23 months). The OS at 2 and 5 years for the whole cohort was 41 ± 4 % and 22 ± 3 %, respectively. Forty patients (24 %) suffered an in-field recurrence. The most common acute nonhematologic toxicity >grade 2 was dysphagia in 35 % of the patients. Acute hematologic toxicity > grade 2 was recorded in 14 % of the patients. There was no grade 5 toxicity observed during the study. Poor ECOG performance status (0-1 vs. 2-3, HR = 1.70, p = 0.002) and weight loss ≥ 10 % before the start of therapy (HR = 1.99, p = 0.001) were among the factors significantly associated with poor OS in multivariate analysis. Three-dimensional conformal definitive radio(chemo)therapy is well tolerated and leads to long-term survival in more than 20 % of patients with advanced disease and/or contraindication to surgery. However, 24 % in-field recurrence remains a major concern. Prospective trials are warranted to assess if a well-tailored conformal radiochemotherapy can improve the local control and obviate the need for surgical resection in patients with good general condition and potentially resectable tumors.
    Strahlentherapie und Onkologie 11/2014; 191(2). DOI:10.1007/s00066-014-0779-x · 2.73 Impact Factor
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    ABSTRACT: Background Locally recurrent rectal cancer remains a dreaded event because curative resection is unlikely to be performed in a large number of cases. Carbon ion radiotherapy offers physical and biologic advantages. A high precise local dose deposition and sparing of normal tissue is possible. This work summarizes our experience on feasibility and early toxicity of carbon ion radiotherapy in previously irradiated and operated patients. Methods Between 2010 and 2013, a total of 19 patients with a median age of 62 years (range 14–76 years) received carbon ion irradiation to treat locally recurrent rectal cancer at the Heidelberg Ion Beam Therapy Center (HIT). All patients had a history of surgery and pelvic radiotherapy of at least 50.4 Gy. Median dose was 36 Gy [relative biologic efficacy (RBE)] [range 36–51 Gy(RBE)], and median planning target volume was 456 ml (range 75–1,597 ml). Some patients were treated in the recruiting phase I/II of the PANDORA study (NCT01528683). Results Median follow-up was 7.8 months. Four patients were diagnosed with local relapse after carbon ion radiotherapy, and three patients developed distant metastases. Estimated mean local progression-free survival was 20.6 months by the Kaplan–Meier estimator. Two patients had preexisting rectovaginal fistula, and another patient had a preexisting presacral localized abscess formation in which the local relapse took place. No grade III or higher toxicities were observed. Conclusions Our first experiences in a pretreated patient group with a dismal prognosis are encouraging, and therapy-related side effects are mild. Longer follow-up is required to determine possible late effects and long-term disease control.
    Annals of Surgical Oncology 11/2014; 22(6). DOI:10.1245/s10434-014-4219-z · 3.94 Impact Factor

Publication Stats

3k Citations
671.73 Total Impact Points

Institutions

  • 2014–2015
    • Technische Universität München
      München, Bavaria, Germany
    • Zentrum für Strahlentherapie und Radioonkologie
      Bremen, Bremen, Germany
  • 2004–2014
    • German Cancer Research Center
      • Division of Clinical Cooperation Unit Radiation Oncology
      Heidelburg, Baden-Württemberg, Germany
  • 2002–2014
    • Universität Heidelberg
      • • Department of Radiation Oncology
      • • Institute of Anatomy and Cell Biology
      • • Interdisciplinary Center for Neurosciences
      Heidelburg, Baden-Württemberg, Germany
  • 2013
    • Ludwig-Maximilians-University of Munich
      München, Bavaria, Germany
    • Lilly Deutschland GmbH
      Homburg vor der Höhe, Hesse, Germany
  • 2012
    • Strahlentherapie Radioonkologie Freising
      Freysing, Bavaria, Germany