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Sati Akbaba - One of the best experts on this subject based on the ideXlab platform.
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treatment outcome of 227 patients with sinonasal adenoid cystic carcinoma acc after intensity modulated radiotherapy and active Raster Scanning carbon ion boost a 10 year single center experience
Cancers, 2019Co-Authors: Sati Akbaba, Kristin Lang, Thomas Held, Tobias Forster, Dina Ahmed, Andreas Mock, Suzan Bahadir, Mustafa Syed, Juliane Hoernerrieber, P A FederspilAbstract:We aimed to evaluate the treatment outcome of primary and postoperative bimodal radiotherapy (RT) including intensity modulated photon radiotherapy (IMRT) and carbon ion radiotherapy (CIRT) for sinonasal adenoid cystic carcinoma (ACC) patients. Medical records of 227 consecutive patients who received either a primary (n = 90, 40%) or postoperative (n = 137, 60%; R2, n = 86, 63%) IMRT with doses between 48 and 56 Gy in 1.8 or 2 Gy fractions and active Raster-Scanning carbon ion boost with 18 to 24 Gy (RBE, relative biological effectiveness) in 3 Gy (RBE) fractions between 2009 and 2019 up to a median total dose of 80 Gy (EQD2, equivalent dose in 2 Gy single dose fractions, range 71–80 Gy) were reviewed. Results: Median follow-up was 50 months. In univariate and multivariate analysis, no significant difference in local control (LC) could be shown between the two treatment groups (p = 0.33). Corresponding 3-year LC rates were 79% for primary bimodal RT and 82% for postoperative bimodal RT, respectively. T4 stage (p = 0.002) and solid histology (p = 0.005) were identified as independent prognostic factors for decreased LC. Significant worse long-term treatment tolerance was observed for postoperatively irradiated patients with 17% vs. 6% late grade 3 toxicity (p < 0.001). Primary radiotherapy including IMRT and carbon ion boost for dose-escalation results in adequate LC with less long-term grade 3 toxicity compared to postoperative bimodal radiotherapy in sinonasal ACC patients. The high rate of macroscopic tumor disease in the postoperative group makes the interpretation of the beneficial results in LC for primary RT difficult.
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treatment outcome of a combined dose escalated treatment regime with helical tomotherapy and active Raster Scanning carbon ion boost for adenocarcinomas of the head and neck
Frontiers in Oncology, 2019Co-Authors: Sati Akbaba, Thomas Held, Klaus Herfarth, Stefan Rieken, Tobias Forster, Andreas Mock, Juliane Hoernerrieber, Sonja Katayama, Christian Freudlsperger, Peter PlinkertAbstract:Introduction: Data regarding treatment and survival outcome of patients with adenocarcinoma of the head and neck are limited to case reports and case series. As a consequence of lacking evidence, treatment guidelines do not exist. We aimed to analyze the effect of a bimodal irradiation regime with intensity modulated radiotherapy (IMRT) and carbon ion boost on local control (LC) and survival in adenocarcinoma patients for a large patient collective. Materials and Methods: Patient records of eighty consecutive patients treated between 2009 and 2018 were analyzed retrospectively and Kaplan-Meier estimates for LC, overall survival (OS) and progression-free survival (PFS) were compared among patients with salivary gland adenocarcinoma (SGAC), salivary duct adenocarcinoma (SDAC), and intestinal-type adenocarcinoma (ITAC) according to the World Health Organization (WHO). Prognostic factors were identified using the log-rank test and cox-regression modeling. Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE). Results: Median follow-up was 41 months. The 3-year and estimated 5-year Kaplan-Meier rates for all patients were 83 and 75% for LC, 74 and 50% for OS and 60 and 53% for PFS, respectively. While bimodal RT for ITAC resulted in a significantly decreased 3-year LC rate of 50 vs. 93% for each SGAC and SDAC (p < 0.01), no statistical significant survival differences could be identified across the three groups regarding OS (p = 0.08) and PFS (p = 0.063). 3-year OS was 88% for SGAC, 78% for SDAC and 67% for ITAC and 3-year PFS was 72% for SGAC, 53% for SDAC and 44% for ITAC, respectively. Nevertheless, in subgroup analysis, OS for ITAC was significantly worse compared to SGAC (p = 0.024). In multivariate analysis, bilateral tumor side (vs. unilateral) solely could be identified as independent negative prognostic factor for LC (p < 0.01). Treatment was well-tolerated with 21% acute (n = 17) and 25% (n = 20) late grade ≥3 toxicities. Conclusion: Radiotherapy including active Raster-Scanning carbon ion boost for relatively radio resistant adenocarcinomas of the head and neck resulted in favorable survival outcome for salivary gland and salivary duct adenocarcinomas with moderate toxicity. However, local control and prognosis for bilateral intestinal-type adenocarcinomas (ITAC) seem to remain low even after dose-escalation.
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results of a combination treatment with intensity modulated radiotherapy and active Raster Scanning carbon ion boost for adenoid cystic carcinoma of the minor salivary glands of the nasopharynx
Oral Oncology, 2019Co-Authors: Sati Akbaba, Kristin Lang, Thomas Held, Peter Plinkert, Stefan Rieken, Dina Ahmed, Juliane Hoernerrieber, Matthias Mattke, K Herfarth, J DebusAbstract:Abstract Objectives We aimed to present the first clinical results for adenoid cystic carcinoma (ACC) of the nasopharynx after primary radiotherapy (RT) with the focus on local control (LC) and patterns of recurrence. Materials and methods We retrospectively analyzed 59 patients with ACC of the nasopharynx, who were treated with bimodal radiotherapy (RT) consisting of intensity modulated radiotherapy and carbon ion boost at the Heidelberg Ion-Beam Therapy Center between 2009 and 2018. The patients had predominantly inoperable (n = 42, 72%) or incompletely resected (n = 17, 29%) tumors. Kaplan-Meier estimates and the log-rank (Mantel-Cox) test were used for univariate and multivariate analyses. Results The median follow-up was 32 months. At last follow-up, 67% of the patients were still alive (n = 39/58), of whom 74% were free of progression (n = 29/39). The 2-year LC, distant progression-free survival (DPFS) and overall survival (OS) were 83%, 81%, 87% and the estimated 5-year LC, DPFS and OS were 49%, 54%, 69%, respectively. LC was significantly inferior in patients with large tumor volumes (gross tumor volume, GTV > 100 cc, p = 0.020) and T4 tumors (p = 0.021). The majority of the recurrences occurred at the margin, where critical structures were spared (n = 11/19, 58%). Overall, grade 3 toxicity was moderate with 12% acute and 8% late side effects. Conclusion Bimodal RT including active Raster-Scanning carbon ion boost for nasopharyngeal ACC resulted in adequate LC and OS rates with moderate toxicity. T4 stage, large tumor volume and the necessary dose sparing in critical structures, i.e. optic nerves, brain stem and orbit, negatively affected LC.
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bimodal radiotherapy with active Raster Scanning carbon ion radiotherapy and intensity modulated radiotherapy in high risk nasopharyngeal carcinoma results in excellent local control
Cancers, 2019Co-Authors: Sati Akbaba, Kristin Lang, Thomas Held, Klaus Herfarth, Peter Plinkert, Stefan Rieken, Tobias Forster, P A Federspil, Matthias Hafner, Jurgen DebusAbstract:Background: In this analysis, we aimed to present the first results of carbon ion radiotherapy (CIRT), which is known for its conformal dose distribution and increased biological effectiveness in the treatment of high-risk nasopharyngeal carcinoma (NPC). Methods: We retrospectively analyzed twenty-six consecutive patients who had been treated at our center with CIRT for high-risk NPC between 2009 and 2018. Carbon ion (C12) boost was applied in a bimodal setting combined with intensity-modulated radiotherapy (IMRT) base plan. The median cumulative total dose was 74 Gy (RBE), and patients with inoperable (n = 17, 65%) or incompletely resected (n = 7, 27%) tumors were included in the analysis. Overall, 81% received concomitant chemotherapy (n = 21). Results: The median follow-up time was 40 months (range 10–97 months) for all patients. At the last follow-up, 92% of the patients were still alive. We could identify excellent tumor response with complete tumor remission (CR) in 60% (n = 15/25), partial tumor remission (PR) in 20% (n = 5/25), and stable disease (SD) in 12% (n = 3/25) of the patients according to the RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Despite unfavorable tumor characteristics, only one patient showed a locally in-field recurrence after 56 months (4%) and another patient a locoregional recurrence in the unilateral cervical lymph nodes after 21 months (4%). The 2-year local control (LC), distant progression-free survival (DPFS), and overall survival (OS) were 95%, 93%, and 100% and the estimated 5-year LC, DPFS, and OS were 90%, 86%, and 86%, respectively. Overall, treatment was tolerated well with 20% acute and 16% chronic grade 3 side effects. No toxicity greater than grade 3 occurred. Conclusion: Bimodal radiotherapy including IMRT and active Raster-Scanning CIRT for high-risk nasopharyngeal cancer is a safe treatment method resulting in moderate toxicity and excellent local control. A larger patient number and longer follow-up time would be necessary to strengthen the current findings.
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Carbon-ion radiotherapy in accelerated hypofractionated active Raster-Scanning technique for malignant lacrimal gland tumors: feasibility and safety.
Cancer management and research, 2019Co-Authors: Sati Akbaba, Kristin Lang, Thomas Held, Klaus Herfarth, J. Rieber, Peter Plinkert, Gerd U. Auffarth, Stefan Rieken, Juergen Debus, Sebastian AdebergAbstract:Introduction We evaluated treatment outcomes of CIRT in an active Raster-Scanning technique alone or in combination with IMRT for lacrimal gland tumors. Methods A total of 24 patients who received CIRT for a malignant lacrimal gland tumor at the HIT between 2009 and 2018 were analyzed retrospectively for LC, OS, and distant progression-free survival (DPFS) using Kaplan-Meier estimates. Toxicity was assessed according to the CTCAE version 5. Results Median follow-up was 30 months and overall median LC, OS, and DPFS 24 months, 36 months, and 31 months, respectively. Two-year LC, OS, and DPFS of 93%, 96%, and 87% with CIRT was achieved for all patients. Local failure occurred only in patients with ACC and after a median follow-up of 30 months after the completion of RT (n=5, 21%; P=0.09). We identified a significant negative impact of a macroscopic tumor disease, which was diagnosed on planning CT or MRI before RT, on LC (P=0.026). In contrast, perineural spread (P=0.661), T stage (P=0.552), and resection margins in operated patients (P=0.069) had no significant impact on LC. No grade ≥3 acute or grade >3 chronic toxicity occurred. Late grade 3 side effects were identified in form of a wound-healing disorder 3 months after RT in one patient and temporal lobe necrosis 6 months after RT in another (n=2, 8%). Conclusion Accelerated hypofractionated active Raster-Scanning CIRT for relative radio-resistant malignant lacrimal gland tumors results in adequate LC rates and moderate acute and late toxicity. Nevertheless, LC for ACC histology remains challenging and risk factors for local recurrence are still unclear. Further follow-up is necessary to evaluate long-term clinical outcome.
Stefan Rieken - One of the best experts on this subject based on the ideXlab platform.
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treatment outcome of a combined dose escalated treatment regime with helical tomotherapy and active Raster Scanning carbon ion boost for adenocarcinomas of the head and neck
Frontiers in Oncology, 2019Co-Authors: Sati Akbaba, Thomas Held, Klaus Herfarth, Stefan Rieken, Tobias Forster, Andreas Mock, Juliane Hoernerrieber, Sonja Katayama, Christian Freudlsperger, Peter PlinkertAbstract:Introduction: Data regarding treatment and survival outcome of patients with adenocarcinoma of the head and neck are limited to case reports and case series. As a consequence of lacking evidence, treatment guidelines do not exist. We aimed to analyze the effect of a bimodal irradiation regime with intensity modulated radiotherapy (IMRT) and carbon ion boost on local control (LC) and survival in adenocarcinoma patients for a large patient collective. Materials and Methods: Patient records of eighty consecutive patients treated between 2009 and 2018 were analyzed retrospectively and Kaplan-Meier estimates for LC, overall survival (OS) and progression-free survival (PFS) were compared among patients with salivary gland adenocarcinoma (SGAC), salivary duct adenocarcinoma (SDAC), and intestinal-type adenocarcinoma (ITAC) according to the World Health Organization (WHO). Prognostic factors were identified using the log-rank test and cox-regression modeling. Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE). Results: Median follow-up was 41 months. The 3-year and estimated 5-year Kaplan-Meier rates for all patients were 83 and 75% for LC, 74 and 50% for OS and 60 and 53% for PFS, respectively. While bimodal RT for ITAC resulted in a significantly decreased 3-year LC rate of 50 vs. 93% for each SGAC and SDAC (p < 0.01), no statistical significant survival differences could be identified across the three groups regarding OS (p = 0.08) and PFS (p = 0.063). 3-year OS was 88% for SGAC, 78% for SDAC and 67% for ITAC and 3-year PFS was 72% for SGAC, 53% for SDAC and 44% for ITAC, respectively. Nevertheless, in subgroup analysis, OS for ITAC was significantly worse compared to SGAC (p = 0.024). In multivariate analysis, bilateral tumor side (vs. unilateral) solely could be identified as independent negative prognostic factor for LC (p < 0.01). Treatment was well-tolerated with 21% acute (n = 17) and 25% (n = 20) late grade ≥3 toxicities. Conclusion: Radiotherapy including active Raster-Scanning carbon ion boost for relatively radio resistant adenocarcinomas of the head and neck resulted in favorable survival outcome for salivary gland and salivary duct adenocarcinomas with moderate toxicity. However, local control and prognosis for bilateral intestinal-type adenocarcinomas (ITAC) seem to remain low even after dose-escalation.
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results of a combination treatment with intensity modulated radiotherapy and active Raster Scanning carbon ion boost for adenoid cystic carcinoma of the minor salivary glands of the nasopharynx
Oral Oncology, 2019Co-Authors: Sati Akbaba, Kristin Lang, Thomas Held, Peter Plinkert, Stefan Rieken, Dina Ahmed, Juliane Hoernerrieber, Matthias Mattke, K Herfarth, J DebusAbstract:Abstract Objectives We aimed to present the first clinical results for adenoid cystic carcinoma (ACC) of the nasopharynx after primary radiotherapy (RT) with the focus on local control (LC) and patterns of recurrence. Materials and methods We retrospectively analyzed 59 patients with ACC of the nasopharynx, who were treated with bimodal radiotherapy (RT) consisting of intensity modulated radiotherapy and carbon ion boost at the Heidelberg Ion-Beam Therapy Center between 2009 and 2018. The patients had predominantly inoperable (n = 42, 72%) or incompletely resected (n = 17, 29%) tumors. Kaplan-Meier estimates and the log-rank (Mantel-Cox) test were used for univariate and multivariate analyses. Results The median follow-up was 32 months. At last follow-up, 67% of the patients were still alive (n = 39/58), of whom 74% were free of progression (n = 29/39). The 2-year LC, distant progression-free survival (DPFS) and overall survival (OS) were 83%, 81%, 87% and the estimated 5-year LC, DPFS and OS were 49%, 54%, 69%, respectively. LC was significantly inferior in patients with large tumor volumes (gross tumor volume, GTV > 100 cc, p = 0.020) and T4 tumors (p = 0.021). The majority of the recurrences occurred at the margin, where critical structures were spared (n = 11/19, 58%). Overall, grade 3 toxicity was moderate with 12% acute and 8% late side effects. Conclusion Bimodal RT including active Raster-Scanning carbon ion boost for nasopharyngeal ACC resulted in adequate LC and OS rates with moderate toxicity. T4 stage, large tumor volume and the necessary dose sparing in critical structures, i.e. optic nerves, brain stem and orbit, negatively affected LC.
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bimodal radiotherapy with active Raster Scanning carbon ion radiotherapy and intensity modulated radiotherapy in high risk nasopharyngeal carcinoma results in excellent local control
Cancers, 2019Co-Authors: Sati Akbaba, Kristin Lang, Thomas Held, Klaus Herfarth, Peter Plinkert, Stefan Rieken, Tobias Forster, P A Federspil, Matthias Hafner, Jurgen DebusAbstract:Background: In this analysis, we aimed to present the first results of carbon ion radiotherapy (CIRT), which is known for its conformal dose distribution and increased biological effectiveness in the treatment of high-risk nasopharyngeal carcinoma (NPC). Methods: We retrospectively analyzed twenty-six consecutive patients who had been treated at our center with CIRT for high-risk NPC between 2009 and 2018. Carbon ion (C12) boost was applied in a bimodal setting combined with intensity-modulated radiotherapy (IMRT) base plan. The median cumulative total dose was 74 Gy (RBE), and patients with inoperable (n = 17, 65%) or incompletely resected (n = 7, 27%) tumors were included in the analysis. Overall, 81% received concomitant chemotherapy (n = 21). Results: The median follow-up time was 40 months (range 10–97 months) for all patients. At the last follow-up, 92% of the patients were still alive. We could identify excellent tumor response with complete tumor remission (CR) in 60% (n = 15/25), partial tumor remission (PR) in 20% (n = 5/25), and stable disease (SD) in 12% (n = 3/25) of the patients according to the RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Despite unfavorable tumor characteristics, only one patient showed a locally in-field recurrence after 56 months (4%) and another patient a locoregional recurrence in the unilateral cervical lymph nodes after 21 months (4%). The 2-year local control (LC), distant progression-free survival (DPFS), and overall survival (OS) were 95%, 93%, and 100% and the estimated 5-year LC, DPFS, and OS were 90%, 86%, and 86%, respectively. Overall, treatment was tolerated well with 20% acute and 16% chronic grade 3 side effects. No toxicity greater than grade 3 occurred. Conclusion: Bimodal radiotherapy including IMRT and active Raster-Scanning CIRT for high-risk nasopharyngeal cancer is a safe treatment method resulting in moderate toxicity and excellent local control. A larger patient number and longer follow-up time would be necessary to strengthen the current findings.
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Carbon-ion radiotherapy in accelerated hypofractionated active Raster-Scanning technique for malignant lacrimal gland tumors: feasibility and safety.
Cancer management and research, 2019Co-Authors: Sati Akbaba, Kristin Lang, Thomas Held, Klaus Herfarth, J. Rieber, Peter Plinkert, Gerd U. Auffarth, Stefan Rieken, Juergen Debus, Sebastian AdebergAbstract:Introduction We evaluated treatment outcomes of CIRT in an active Raster-Scanning technique alone or in combination with IMRT for lacrimal gland tumors. Methods A total of 24 patients who received CIRT for a malignant lacrimal gland tumor at the HIT between 2009 and 2018 were analyzed retrospectively for LC, OS, and distant progression-free survival (DPFS) using Kaplan-Meier estimates. Toxicity was assessed according to the CTCAE version 5. Results Median follow-up was 30 months and overall median LC, OS, and DPFS 24 months, 36 months, and 31 months, respectively. Two-year LC, OS, and DPFS of 93%, 96%, and 87% with CIRT was achieved for all patients. Local failure occurred only in patients with ACC and after a median follow-up of 30 months after the completion of RT (n=5, 21%; P=0.09). We identified a significant negative impact of a macroscopic tumor disease, which was diagnosed on planning CT or MRI before RT, on LC (P=0.026). In contrast, perineural spread (P=0.661), T stage (P=0.552), and resection margins in operated patients (P=0.069) had no significant impact on LC. No grade ≥3 acute or grade >3 chronic toxicity occurred. Late grade 3 side effects were identified in form of a wound-healing disorder 3 months after RT in one patient and temporal lobe necrosis 6 months after RT in another (n=2, 8%). Conclusion Accelerated hypofractionated active Raster-Scanning CIRT for relative radio-resistant malignant lacrimal gland tumors results in adequate LC rates and moderate acute and late toxicity. Nevertheless, LC for ACC histology remains challenging and risk factors for local recurrence are still unclear. Further follow-up is necessary to evaluate long-term clinical outcome.
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the relative biological effectiveness for carbon and oxygen ion beams using the Raster Scanning technique in hepatocellular carcinoma cell lines
PLOS ONE, 2014Co-Authors: Daniel Habermehl, Stefan Rieken, Jurgen Debus, K Ilicic, Sarah Dehne, Lena Orschiedt, S Brons, Thomas Haberer, Klausjosef Weber, Stephanie E CombsAbstract:Background 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. Methods 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. Results 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. Conclusion 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.
Jurgen Debus - One of the best experts on this subject based on the ideXlab platform.
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rapid effective dose calculation for Raster Scanning 4he ion therapy with the modified microdosimetric kinetic model mmkm
Physica Medica, 2021Co-Authors: Benedikt Kopp, T Tessonnier, Jurgen Debus, Thomas Haberer, S Mein, J Besuglow, Semi Ben Harrabi, E Heim, Amir Abdollahi, Andrea MairaniAbstract:Abstract Purpose To develop and verify effective dose (DRBE) calculation in 4He ion beam therapy based on the modified microdosimetric kinetic model (mMKM) and evaluate the bio-sensitivity of mMKM-based plans to clinical parameters using a fast analytical dose engine. Methods Mixed radiation field particle spectra (MRFS) databases have been generated with Monte-Carlo (MC) simulations for 4He-ion beams. Relative biological effectiveness (RBE) and DRBE calculation using MRFS were established within a fast analytical engine. Spread-out Bragg-Peaks (SOBPs) in water were optimized for two dose levels and two tissue types with photon linear-quadratic model parameters αph, βph, and (α/β)ph to verify MRFS-derived database implementation against computations with MC-generated mixed-field α and β databases. Bio-sensitivity of the SOBPs was investigated by varying absolute values of βph, while keeping (α/β)ph constant. Additionally, dose, dose-averaged linear energy transfer, and bio-sensitivity were investigated for two patient cases. Results Using MRFS-derived databases, dose differences ≲2% in the plateau and SOBP are observed compared to computations with MC-generated databases. Bio-sensitivity studies show larger deviations when altering the absolute βph value, with maximum D50% changes of ~5%, with similar results for patient cases. Bio-sensitivity analysis indicates a greater impact on DRBE varying (α/β)ph than βph in mMKM. Conclusions The MRSF approach yielded negligible differences in the target and small differences in the plateau compared to MC-generated databases. The presented analyses provide guidance for proper implementation of RBE-weighted 4He ion dose prescription and planning with mMKM. The MRFS-DRBE calculation approach using mMKM will be implemented in a clinical treatment planning system.
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bimodal radiotherapy with active Raster Scanning carbon ion radiotherapy and intensity modulated radiotherapy in high risk nasopharyngeal carcinoma results in excellent local control
Cancers, 2019Co-Authors: Sati Akbaba, Kristin Lang, Thomas Held, Klaus Herfarth, Peter Plinkert, Stefan Rieken, Tobias Forster, P A Federspil, Matthias Hafner, Jurgen DebusAbstract:Background: In this analysis, we aimed to present the first results of carbon ion radiotherapy (CIRT), which is known for its conformal dose distribution and increased biological effectiveness in the treatment of high-risk nasopharyngeal carcinoma (NPC). Methods: We retrospectively analyzed twenty-six consecutive patients who had been treated at our center with CIRT for high-risk NPC between 2009 and 2018. Carbon ion (C12) boost was applied in a bimodal setting combined with intensity-modulated radiotherapy (IMRT) base plan. The median cumulative total dose was 74 Gy (RBE), and patients with inoperable (n = 17, 65%) or incompletely resected (n = 7, 27%) tumors were included in the analysis. Overall, 81% received concomitant chemotherapy (n = 21). Results: The median follow-up time was 40 months (range 10–97 months) for all patients. At the last follow-up, 92% of the patients were still alive. We could identify excellent tumor response with complete tumor remission (CR) in 60% (n = 15/25), partial tumor remission (PR) in 20% (n = 5/25), and stable disease (SD) in 12% (n = 3/25) of the patients according to the RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Despite unfavorable tumor characteristics, only one patient showed a locally in-field recurrence after 56 months (4%) and another patient a locoregional recurrence in the unilateral cervical lymph nodes after 21 months (4%). The 2-year local control (LC), distant progression-free survival (DPFS), and overall survival (OS) were 95%, 93%, and 100% and the estimated 5-year LC, DPFS, and OS were 90%, 86%, and 86%, respectively. Overall, treatment was tolerated well with 20% acute and 16% chronic grade 3 side effects. No toxicity greater than grade 3 occurred. Conclusion: Bimodal radiotherapy including IMRT and active Raster-Scanning CIRT for high-risk nasopharyngeal cancer is a safe treatment method resulting in moderate toxicity and excellent local control. A larger patient number and longer follow-up time would be necessary to strengthen the current findings.
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the relative biological effectiveness for carbon and oxygen ion beams using the Raster Scanning technique in hepatocellular carcinoma cell lines
PLOS ONE, 2014Co-Authors: Daniel Habermehl, Stefan Rieken, Jurgen Debus, K Ilicic, Sarah Dehne, Lena Orschiedt, S Brons, Thomas Haberer, Klausjosef Weber, Stephanie E CombsAbstract:Background 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. Methods 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. Results 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. Conclusion 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.
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high control rate in patients with chondrosarcoma of the skull base after carbon ion therapy first report of long term results
Cancer, 2014Co-Authors: Matthias Uhl, Klaus Herfarth, Thomas Welzel, Jan Oelmann, Gregor Habl, Alexandra D Jensen, Malte Ellerbrock, Thomas Haberer, Matthias Mattke, Jurgen DebusAbstract:BACKGROUND The current study was performed to evaluate the safety and effectiveness of irradiation with carbon ions using Raster Scanning as well as prognostic factors in patients with skull base chondrosarcomas. METHODS Between 1998 and 2008, 79 patients with chondrosarcoma of the skull base were treated using carbon ions in Raster Scanning. The applied median total dose was 60 gray equivalent (GyE) at 3 GyE per fraction. Local control and overall survival (OS) were evaluated using the Kaplan-Meier method. Long-term toxicity was quantitatively assessed using questionnaires. RESULTS The median follow-up after irradiation was 91 months (range, 3 months-175 months). Within the follow-up, 10 patients developed local disease recurrence. The 3-year, 5-year, and 10-year local control rates were 95.9%, 88%, and 88%, respectively; the corresponding OS rates were 96.1%, 96.1%, and 78.9%, respectively. With a median follow-up of 110 months after first diagnosis, the corresponding 3-year, 5-year, and 10-year OS rates were 97.5%, 97.5%, and 91.5%, respectively. Age ≤ 45 years and boost volume ≤ 55 mL were associated with significantly better local control rates. We observed a clinically relevant improvement in cranial nerve deficits 7 to 10 years after treatment (range, 45.5%-53.3%) compared with the baseline (73.4%). During follow-up, none of the patients in the current study developed a secondary malignancy. CONCLUSIONS Carbon ion therapy is a safe and effective treatment in patients with chondrosarcoma of the skull base. For further evaluation, a prospective randomized phase 3 trial comparing protons versus carbon ions has been recruiting patients with low-grade and intermediate-grade chondrosarcoma of the skull base since 2009. Cancer 2014;120:1579–1585. © 2014 American Cancer Society.
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active Raster Scanning with carbon ions reirradiation in patients with recurrent skull base chordomas and chondrosarcomas
Strahlentherapie Und Onkologie, 2014Co-Authors: Matthias Uhl, Thomas Welzel, Jan Oelmann, Gregor Habl, Henrik Hauswald, Alexandra D Jensen, Malte Ellerbrock, Jurgen Debus, Klaus HerfarthAbstract:To evaluate the safety and efficacy of reirradiation with carbon ions in patients with relapse of skull base chordoma and chondrosarcoma. Reirradiation with carbon ions was performed on 25 patients with locally recurrent skull base chordoma (n = 20) or chondrosarcoma (n = 5). The median time between the last radiation exposure and the reirradiation with carbon ions was 7 years. In the past, 23 patients had been irradiated once, two patients twice. Reirradiation was delivered using the active Raster Scanning method. The total median dose was 51.0 GyE carbon ions in a weekly regimen of five to six fractions of 3 GyE. Local progression-free survival (LPFS) was evaluated using the Kaplan–Meier method; toxicity was evaluated using the NCI Common Terminology Criteria for Adverse Events (CTCAE v.4.03). The treatment could be finished in all patients without interruption. In 80 % of patients, symptom control was achieved after therapy. The 2-year-LPFS probability was 79.3 %. A PTV volume of 51 GyE was associated with a superior local control rate. The therapy was associated with low acute toxicity. One patient developed grade 2 mucositis during therapy. Furthermore, 12 % of patients had tympanic effusion with mild hypacusis (grade 2), while 20 % developed an asymptomatic temporal lobe reaction after treatment (grade 1). Only one patient showed a grade 3 osteoradionecrosis. Reirradiation with carbon ions is a safe and effective method in patients with relapsed chordoma and chondrosarcoma of the skull base.
John C Howell - One of the best experts on this subject based on the ideXlab platform.
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frequency modulated continuous wave lidar compressive depth mapping
Optics Express, 2018Co-Authors: Daniel J Lum, Samuel H Knarr, John C HowellAbstract:We present an inexpensive architecture for converting a frequency-modulated continuous-wave LiDAR system into a compressive-sensing based depth-mapping camera. Instead of Raster Scanning to obtain depth-maps, compressive sensing is used to significantly reduce the number of measurements. Ideally, our approach requires two difference detectors. Due to the large flux entering the detectors, the signal amplification from heterodyne detection, and the effects of background subtraction from compressive sensing, the system can obtain higher signal-to-noise ratios over detector-array based schemes while Scanning a scene faster than is possible through Raster-Scanning. Moreover, by efficiently storing only 2m data points from m < n measurements of an n pixel scene, we can easily extract depths by solving only two linear equations with efficient convex-optimization methods.
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frequency modulated continuous wave lidar compressive depth mapping
arXiv: Signal Processing, 2018Co-Authors: Daniel J Lum, Samuel H Knarr, John C HowellAbstract:We present an inexpensive architecture for converting a frequency-modulated continuous-wave LiDAR system into a compressive-sensing based depth-mapping system. Instead of Raster Scanning to obtain high-resolution depth-maps, compressive sensing is used to significantly reduce the number of measurements and computationally extract depths. Because our approach requires only one difference detector, the system can easily obtain higher signal-to-noise ratios over detector-array based detection schemes. Moreover, we also show how a single total-variation minimization and two fast least-squares minimizations, instead of a single complex nonlinear minimization, can efficiently recover high-resolution depth-maps with minimal computational overhead.
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treatment outcome of 227 patients with sinonasal adenoid cystic carcinoma acc after intensity modulated radiotherapy and active Raster Scanning carbon ion boost a 10 year single center experience
Cancers, 2019Co-Authors: Sati Akbaba, Kristin Lang, Thomas Held, Tobias Forster, Dina Ahmed, Andreas Mock, Suzan Bahadir, Mustafa Syed, Juliane Hoernerrieber, P A FederspilAbstract:We aimed to evaluate the treatment outcome of primary and postoperative bimodal radiotherapy (RT) including intensity modulated photon radiotherapy (IMRT) and carbon ion radiotherapy (CIRT) for sinonasal adenoid cystic carcinoma (ACC) patients. Medical records of 227 consecutive patients who received either a primary (n = 90, 40%) or postoperative (n = 137, 60%; R2, n = 86, 63%) IMRT with doses between 48 and 56 Gy in 1.8 or 2 Gy fractions and active Raster-Scanning carbon ion boost with 18 to 24 Gy (RBE, relative biological effectiveness) in 3 Gy (RBE) fractions between 2009 and 2019 up to a median total dose of 80 Gy (EQD2, equivalent dose in 2 Gy single dose fractions, range 71–80 Gy) were reviewed. Results: Median follow-up was 50 months. In univariate and multivariate analysis, no significant difference in local control (LC) could be shown between the two treatment groups (p = 0.33). Corresponding 3-year LC rates were 79% for primary bimodal RT and 82% for postoperative bimodal RT, respectively. T4 stage (p = 0.002) and solid histology (p = 0.005) were identified as independent prognostic factors for decreased LC. Significant worse long-term treatment tolerance was observed for postoperatively irradiated patients with 17% vs. 6% late grade 3 toxicity (p < 0.001). Primary radiotherapy including IMRT and carbon ion boost for dose-escalation results in adequate LC with less long-term grade 3 toxicity compared to postoperative bimodal radiotherapy in sinonasal ACC patients. The high rate of macroscopic tumor disease in the postoperative group makes the interpretation of the beneficial results in LC for primary RT difficult.
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treatment outcome of a combined dose escalated treatment regime with helical tomotherapy and active Raster Scanning carbon ion boost for adenocarcinomas of the head and neck
Frontiers in Oncology, 2019Co-Authors: Sati Akbaba, Thomas Held, Klaus Herfarth, Stefan Rieken, Tobias Forster, Andreas Mock, Juliane Hoernerrieber, Sonja Katayama, Christian Freudlsperger, Peter PlinkertAbstract:Introduction: Data regarding treatment and survival outcome of patients with adenocarcinoma of the head and neck are limited to case reports and case series. As a consequence of lacking evidence, treatment guidelines do not exist. We aimed to analyze the effect of a bimodal irradiation regime with intensity modulated radiotherapy (IMRT) and carbon ion boost on local control (LC) and survival in adenocarcinoma patients for a large patient collective. Materials and Methods: Patient records of eighty consecutive patients treated between 2009 and 2018 were analyzed retrospectively and Kaplan-Meier estimates for LC, overall survival (OS) and progression-free survival (PFS) were compared among patients with salivary gland adenocarcinoma (SGAC), salivary duct adenocarcinoma (SDAC), and intestinal-type adenocarcinoma (ITAC) according to the World Health Organization (WHO). Prognostic factors were identified using the log-rank test and cox-regression modeling. Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE). Results: Median follow-up was 41 months. The 3-year and estimated 5-year Kaplan-Meier rates for all patients were 83 and 75% for LC, 74 and 50% for OS and 60 and 53% for PFS, respectively. While bimodal RT for ITAC resulted in a significantly decreased 3-year LC rate of 50 vs. 93% for each SGAC and SDAC (p < 0.01), no statistical significant survival differences could be identified across the three groups regarding OS (p = 0.08) and PFS (p = 0.063). 3-year OS was 88% for SGAC, 78% for SDAC and 67% for ITAC and 3-year PFS was 72% for SGAC, 53% for SDAC and 44% for ITAC, respectively. Nevertheless, in subgroup analysis, OS for ITAC was significantly worse compared to SGAC (p = 0.024). In multivariate analysis, bilateral tumor side (vs. unilateral) solely could be identified as independent negative prognostic factor for LC (p < 0.01). Treatment was well-tolerated with 21% acute (n = 17) and 25% (n = 20) late grade ≥3 toxicities. Conclusion: Radiotherapy including active Raster-Scanning carbon ion boost for relatively radio resistant adenocarcinomas of the head and neck resulted in favorable survival outcome for salivary gland and salivary duct adenocarcinomas with moderate toxicity. However, local control and prognosis for bilateral intestinal-type adenocarcinomas (ITAC) seem to remain low even after dose-escalation.
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results of a combination treatment with intensity modulated radiotherapy and active Raster Scanning carbon ion boost for adenoid cystic carcinoma of the minor salivary glands of the nasopharynx
Oral Oncology, 2019Co-Authors: Sati Akbaba, Kristin Lang, Thomas Held, Peter Plinkert, Stefan Rieken, Dina Ahmed, Juliane Hoernerrieber, Matthias Mattke, K Herfarth, J DebusAbstract:Abstract Objectives We aimed to present the first clinical results for adenoid cystic carcinoma (ACC) of the nasopharynx after primary radiotherapy (RT) with the focus on local control (LC) and patterns of recurrence. Materials and methods We retrospectively analyzed 59 patients with ACC of the nasopharynx, who were treated with bimodal radiotherapy (RT) consisting of intensity modulated radiotherapy and carbon ion boost at the Heidelberg Ion-Beam Therapy Center between 2009 and 2018. The patients had predominantly inoperable (n = 42, 72%) or incompletely resected (n = 17, 29%) tumors. Kaplan-Meier estimates and the log-rank (Mantel-Cox) test were used for univariate and multivariate analyses. Results The median follow-up was 32 months. At last follow-up, 67% of the patients were still alive (n = 39/58), of whom 74% were free of progression (n = 29/39). The 2-year LC, distant progression-free survival (DPFS) and overall survival (OS) were 83%, 81%, 87% and the estimated 5-year LC, DPFS and OS were 49%, 54%, 69%, respectively. LC was significantly inferior in patients with large tumor volumes (gross tumor volume, GTV > 100 cc, p = 0.020) and T4 tumors (p = 0.021). The majority of the recurrences occurred at the margin, where critical structures were spared (n = 11/19, 58%). Overall, grade 3 toxicity was moderate with 12% acute and 8% late side effects. Conclusion Bimodal RT including active Raster-Scanning carbon ion boost for nasopharyngeal ACC resulted in adequate LC and OS rates with moderate toxicity. T4 stage, large tumor volume and the necessary dose sparing in critical structures, i.e. optic nerves, brain stem and orbit, negatively affected LC.
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bimodal radiotherapy with active Raster Scanning carbon ion radiotherapy and intensity modulated radiotherapy in high risk nasopharyngeal carcinoma results in excellent local control
Cancers, 2019Co-Authors: Sati Akbaba, Kristin Lang, Thomas Held, Klaus Herfarth, Peter Plinkert, Stefan Rieken, Tobias Forster, P A Federspil, Matthias Hafner, Jurgen DebusAbstract:Background: In this analysis, we aimed to present the first results of carbon ion radiotherapy (CIRT), which is known for its conformal dose distribution and increased biological effectiveness in the treatment of high-risk nasopharyngeal carcinoma (NPC). Methods: We retrospectively analyzed twenty-six consecutive patients who had been treated at our center with CIRT for high-risk NPC between 2009 and 2018. Carbon ion (C12) boost was applied in a bimodal setting combined with intensity-modulated radiotherapy (IMRT) base plan. The median cumulative total dose was 74 Gy (RBE), and patients with inoperable (n = 17, 65%) or incompletely resected (n = 7, 27%) tumors were included in the analysis. Overall, 81% received concomitant chemotherapy (n = 21). Results: The median follow-up time was 40 months (range 10–97 months) for all patients. At the last follow-up, 92% of the patients were still alive. We could identify excellent tumor response with complete tumor remission (CR) in 60% (n = 15/25), partial tumor remission (PR) in 20% (n = 5/25), and stable disease (SD) in 12% (n = 3/25) of the patients according to the RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Despite unfavorable tumor characteristics, only one patient showed a locally in-field recurrence after 56 months (4%) and another patient a locoregional recurrence in the unilateral cervical lymph nodes after 21 months (4%). The 2-year local control (LC), distant progression-free survival (DPFS), and overall survival (OS) were 95%, 93%, and 100% and the estimated 5-year LC, DPFS, and OS were 90%, 86%, and 86%, respectively. Overall, treatment was tolerated well with 20% acute and 16% chronic grade 3 side effects. No toxicity greater than grade 3 occurred. Conclusion: Bimodal radiotherapy including IMRT and active Raster-Scanning CIRT for high-risk nasopharyngeal cancer is a safe treatment method resulting in moderate toxicity and excellent local control. A larger patient number and longer follow-up time would be necessary to strengthen the current findings.
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Carbon-ion radiotherapy in accelerated hypofractionated active Raster-Scanning technique for malignant lacrimal gland tumors: feasibility and safety.
Cancer management and research, 2019Co-Authors: Sati Akbaba, Kristin Lang, Thomas Held, Klaus Herfarth, J. Rieber, Peter Plinkert, Gerd U. Auffarth, Stefan Rieken, Juergen Debus, Sebastian AdebergAbstract:Introduction We evaluated treatment outcomes of CIRT in an active Raster-Scanning technique alone or in combination with IMRT for lacrimal gland tumors. Methods A total of 24 patients who received CIRT for a malignant lacrimal gland tumor at the HIT between 2009 and 2018 were analyzed retrospectively for LC, OS, and distant progression-free survival (DPFS) using Kaplan-Meier estimates. Toxicity was assessed according to the CTCAE version 5. Results Median follow-up was 30 months and overall median LC, OS, and DPFS 24 months, 36 months, and 31 months, respectively. Two-year LC, OS, and DPFS of 93%, 96%, and 87% with CIRT was achieved for all patients. Local failure occurred only in patients with ACC and after a median follow-up of 30 months after the completion of RT (n=5, 21%; P=0.09). We identified a significant negative impact of a macroscopic tumor disease, which was diagnosed on planning CT or MRI before RT, on LC (P=0.026). In contrast, perineural spread (P=0.661), T stage (P=0.552), and resection margins in operated patients (P=0.069) had no significant impact on LC. No grade ≥3 acute or grade >3 chronic toxicity occurred. Late grade 3 side effects were identified in form of a wound-healing disorder 3 months after RT in one patient and temporal lobe necrosis 6 months after RT in another (n=2, 8%). Conclusion Accelerated hypofractionated active Raster-Scanning CIRT for relative radio-resistant malignant lacrimal gland tumors results in adequate LC rates and moderate acute and late toxicity. Nevertheless, LC for ACC histology remains challenging and risk factors for local recurrence are still unclear. Further follow-up is necessary to evaluate long-term clinical outcome.
