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Varnava M, Tashiro M, Okamoto M, Ando K, Kubo N, Kawamura H, Onishi M, Shibuya K, Kumazawa T, Ohtaka T, Ohno T. Dose-Volume Constraints for Thoracic, Abdominal, and Pelvic Carbon Ion Radiotherapy: A Literature Review. Cancer Med 2025; 14:e70840. [PMID: 40156204 PMCID: PMC11953175 DOI: 10.1002/cam4.70840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 03/18/2025] [Accepted: 03/20/2025] [Indexed: 04/01/2025] Open
Abstract
BACKGROUND Applying dose-volume constraints is extremely important in ensuring the safe use of radiotherapy. However, constraints for carbon ion radiotherapy (CIRT) have not been established yet. This review aims to summarize dose-volume constraints for thoracic, abdominal, and pelvic CIRT that have been identified through previous research based on the Japanese models for relative biological effectiveness (RBE). RESULTS Constraints are reported for the lungs, liver, stomach, gastrointestinal tract, rectum, sigmoid, bladder, nerves, rib, femoral head, sacrum, and skin. The constraints are classified into hard and soft to aid in determining whether priority should be given to the target coverage or organ-at-risk (OAR) sparing during treatment planning. CONCLUSIONS Further research is necessary to verify the applicability of the reported constraints and to identify constraints for the OARs that have not been investigated yet.
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Affiliation(s)
- Maria Varnava
- Gunma University Heavy Ion Medical CenterMaebashiGunmaJapan
| | | | - Masahiko Okamoto
- Gunma University Heavy Ion Medical CenterMaebashiGunmaJapan
- Department of Radiation OncologyGunma University Graduate School of MedicineMaebashiJapan
| | - Ken Ando
- Gunma University Heavy Ion Medical CenterMaebashiGunmaJapan
- Department of Radiation OncologyGunma University Graduate School of MedicineMaebashiJapan
| | - Nobutero Kubo
- Gunma University Heavy Ion Medical CenterMaebashiGunmaJapan
- Department of Radiation OncologyGunma University Graduate School of MedicineMaebashiJapan
| | - Hidemasa Kawamura
- Gunma University Heavy Ion Medical CenterMaebashiGunmaJapan
- Department of Radiation OncologyGunma University Graduate School of MedicineMaebashiJapan
| | - Masahiro Onishi
- Gunma University Heavy Ion Medical CenterMaebashiGunmaJapan
- Department of Radiation OncologyGunma University Graduate School of MedicineMaebashiJapan
| | - Kei Shibuya
- Gunma University Heavy Ion Medical CenterMaebashiGunmaJapan
- Department of Radiation OncologyGunma University Graduate School of MedicineMaebashiJapan
| | - Takuya Kumazawa
- Gunma University Heavy Ion Medical CenterMaebashiGunmaJapan
- Department of Radiation OncologyGunma University Graduate School of MedicineMaebashiJapan
| | - Takeru Ohtaka
- Gunma University Heavy Ion Medical CenterMaebashiGunmaJapan
- Department of Radiation OncologyGunma University Graduate School of MedicineMaebashiJapan
| | - Tatsuya Ohno
- Gunma University Heavy Ion Medical CenterMaebashiGunmaJapan
- Department of Radiation OncologyGunma University Graduate School of MedicineMaebashiJapan
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Ma J, Dragojevic S, Remmes NB, Mendelson NL, Kloeber JA, Ebner DK, Wu Z, Gunn HJ, Merrell KW, Hallemeier CL, Haddock MG, Jethwa KR, Lou Z, Mutter RW, Callaghan CM. Linear energy transfer optimized proton therapy for rectal cancer. Radiother Oncol 2025; 207:110850. [PMID: 40101854 DOI: 10.1016/j.radonc.2025.110850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Revised: 03/10/2025] [Accepted: 03/13/2025] [Indexed: 03/20/2025]
Abstract
PURPOSE To evaluate the feasibility and utility of an LET-optimized proton treatment planning algorithm in locally advanced rectal cancer and to assess whether the degree of LET-optimization achieved in clinical plans improves efficacy and toxicity in preclinical models. MATERIALS AND METHODS A series of five rectal cancer patients treated with standard 25 fraction clinical proton plans were re-planned using an LET-optimization treatment planning algorithm and evaluated for dosimetric endpoints. LET-optimized plans were generated using an algorithm which iteratively increases the weights of higher LET spots in GTV and lower LET in OARs. Murine and in vitro preclinical models of tumor efficacy and normal tissue toxicity were evaluated using comparable LETd range to that achieved in clinical LET-optimized plans. RESULTS LET-optimized proton plans increased dose-averaged LET (LETd) in the GTV and LET-weighted dose in the GTV, and CTV5625cGy V100% coverage. At the same time, LET-optimization also decreased mean LET-weighted dose to bladder and small bowel, as well as small bowel V30Gy(cc) compared to standard proton plans. Optimizing the LETd to a volume of GTV-3 mm further increased LETd compared to total GTV. LET-optimization in preclinical models increased tumor efficacy in colorectal cancer cell lines in vitro and decreased small bowel radiation enteropathy in murine models of normal tissue toxicity. CONCLUSIONS LET-optimized proton plans increased LETd in gross tumor while maintaining or improving target coverage and OAR sparing, with acceptable plan robustness. Preclinical models demonstrated that comparable LET-optimization may increase tumor efficacy and decrease normal tissue toxicity in rectal cancer.
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Affiliation(s)
- Jiasen Ma
- Mayo Clinic Department of Radiation Oncology, Rochester, MN, USA.
| | - Sonja Dragojevic
- Mayo Clinic Department of Radiation Oncology, Rochester, MN, USA
| | | | | | - Jake A Kloeber
- Mayo Clinic Medical Scientist Training Program, Mayo Clinic, Rochester, MN, USA
| | - Daniel K Ebner
- Mayo Clinic Department of Radiation Oncology, Rochester, MN, USA
| | - Zheming Wu
- Mayo Clinic Department of Oncology, Rochester, MN, USA
| | - Heather J Gunn
- Mayo Clinic Department of Quantitative Health Sciences, Scottsdale, AZ, USA
| | | | | | | | - Krishan R Jethwa
- Mayo Clinic Department of Radiation Oncology, Rochester, MN, USA
| | - Zhenkun Lou
- Mayo Clinic Department of Molecular Pharmacology and Experimental Therapeutics, Rochester, MN, USA
| | - Robert W Mutter
- Mayo Clinic Department of Radiation Oncology, Rochester, MN, USA; Mayo Clinic Department of Molecular Pharmacology and Experimental Therapeutics, Rochester, MN, USA
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Ono T, Sato H, Miyasaka Y, Hagiwara Y, Yano N, Akamatsu H, Harada M, Ichikawa M. Correlation between dose-volume parameters and rectal bleeding after 12 fractions of carbon ion radiotherapy for prostate cancer. World J Radiol 2024; 16:256-264. [PMID: 39086610 PMCID: PMC11287435 DOI: 10.4329/wjr.v16.i7.256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 07/08/2024] [Accepted: 07/10/2024] [Indexed: 07/24/2024] Open
Abstract
BACKGROUND Carbon ion radiotherapy (CIRT) is currently used to treat prostate cancer. Rectal bleeding is a major cause of toxicity even with CIRT. However, to date, a correlation between the dose and volume parameters of the 12 fractions of CIRT for prostate cancer and rectal bleeding has not been shown. Similarly, the clinical risk factors for rectal bleeding were absent after 12 fractions of CIRT. AIM To identify the risk factors for rectal bleeding in 12 fractions of CIRT for prostate cancer. METHODS Among 259 patients who received 51.6 Gy [relative biological effectiveness (RBE)], in 12 fractions of CIRT, 15 had grade 1 (5.8%) and nine had grade 2 rectal bleeding (3.5%). The dose-volume parameters included the volume (cc) of the rectum irradiated with at least x Gy (RBE) (Vx) and the minimum dose in the most irradiated x cc normal rectal volume (Dx). RESULTS The mean values of D6cc, D2cc, V10 Gy (RBE), V20 Gy (RBE), V30 Gy (RBE), and V40 Gy (RBE) were significantly higher in the patients with rectal bleeding than in those without. The cutoff values were D6cc = 34.34 Gy (RBE), D2cc = 46.46 Gy (RBE), V10 Gy (RBE) = 9.85 cc, V20 Gy (RBE) = 7.00 cc, V30 Gy (RBE) = 6.91 cc, and V40 Gy (RBE) = 4.26 cc. The D2cc, V10 Gy (RBE), and V20 Gy (RBE) cutoff values were significant predictors of grade 2 rectal bleeding. CONCLUSION The above dose-volume parameters may serve as guidelines for preventing rectal bleeding after 12 fractions of CIRT for prostate cancer.
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Affiliation(s)
- Takashi Ono
- Department of Radiation Oncology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan
| | - Hiraku Sato
- Department of Radiation Oncology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan
| | - Yuya Miyasaka
- Department of Heavy Particle Medical Science, Yamagata University Graduate School of Medical Science, Yamagata 990-9585, Japan
| | - Yasuhito Hagiwara
- Department of Radiation Oncology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan
| | - Natsuko Yano
- Department of Radiation Oncology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan
| | - Hiroko Akamatsu
- Department of Radiation Oncology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan
| | - Mayumi Harada
- Department of Radiation Oncology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan
| | - Mayumi Ichikawa
- Department of Radiation Oncology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan
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Ndjembidouma BCM, James LG, Meye PO, Loembamouandza SY, Belembaogo E, Ben-Bolie GH. Assessment of rectal toxicities after radiation therapy for localized prostate cancer: experience of the Akanda Cancer Institute in Gabon. Rep Pract Oncol Radiother 2023; 28:636-645. [PMID: 38179290 PMCID: PMC10764052 DOI: 10.5603/rpor.97507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 10/18/2023] [Indexed: 01/06/2024] Open
Abstract
Background The purpose was to evaluate the incidence of acute and late rectal toxicities and their correlation with the clinical and dosimetric parameters of patients who underwent curative radiotherapy for localized prostate cancer at the Akanda Cancer Institute, Gabon. Materials and methods Between 2013 and 2021, a cohort of 46 patients with clinically localized stage cT1c-T4 prostate cancer was treated with three-dimensional conformal radiation therapy (3D-CRT) at the national cancer institute with doses ranging from 66 to 80 Gy. Post-radiation gastrointestinal (GI) toxicities were classified and graded according to the Common Terminology Criteria for Adverse Events CTCAE v4.0. Results In our study, 17.4% (8/46) developed acute GI. Grades 1 and 3 acute GI complications were seen in 13.0% (6/46) and 4.3% (2/46), respectively. No patient developed acute grade 2 or grade higher than 3 complications. Late GI side effects were limited. The median time to the development of late GI Grade ≥ 1 toxicities was 12 months (range: 9-19 months). 10.9% (5/46) had experience late GI. Among them, grade 1 and 2 were seen in 6.5% (3/46), and 4.3% (2/46), respectively. There was no grade 3 or higher complications. Statistically, we did not find any correlation between the presence of rectal toxicity and clinical factors or the presence of comorbidity. On the dosimetric level, the Mann-Whitney statistical test found a correlation between the presence of late GI toxicity and rectal volume irradiated at the prescribed dose (p = 0.02). Conclusion Despite the high radiation doses involved, our results showed an acceptable complication rate.
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Affiliation(s)
- Beaud Conrad Mabika Ndjembidouma
- Departement of Medical Physics and Radiotherapy, Akanda Cancer Institute, Libreville, Gabon
- Laboratory of Atomic, Molecular and Nuclear Physics, Department of Physics, Faculty of Science, University of Yaounde I, Yaounde, Cameroun
| | | | - Phillippe Ondo Meye
- General Directorate for Radiation Protection and Nuclear Safety, Ministery of Energy and Hydraulic Resources, Libreville Gabon
- Laboratory of Atomic, Molecular and Nuclear Physics, Department of Physics, Faculty of Science, University of Yaounde I, Yaounde, Cameroun
| | | | - Ernest Belembaogo
- Departement of Medical Physics and Radiotherapy, Akanda Cancer Institute, Libreville, Gabon
| | - Germain Hubert Ben-Bolie
- Laboratory of Atomic, Molecular and Nuclear Physics, Department of Physics, Faculty of Science, University of Yaounde I, Yaounde, Cameroun
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Momeni N, Ali Boroomand M, Roozmand Z, Namiranian N, Hamzian N. Normal tissue complication probability of acute eyelids erythema following radiotherapy of head and neck cancers and skull-base tumors. Phys Med 2023; 112:102621. [PMID: 37329741 DOI: 10.1016/j.ejmp.2023.102621] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 06/04/2023] [Accepted: 06/06/2023] [Indexed: 06/19/2023] Open
Abstract
PURPOSE Radiation therapy is broadly used as one of the main treatment methods for patients with head and neck cancers and skull base tumors. However, it can lead to normal tissue complications. Therefore, this study aimed to model normal tissue complication probability (NTCP) of eyelid skin erythema after radiation therapy. METHODS The dataset of 45 patients with head and neck and skull base tumors was prospectively collected from their dose-volume histograms (DVHs). Grade 1 + eyelid skin erythema based on the Common Terminology Criteria for Adverse Events (CTCAE 4.0) was evaluated as the endpoint after a three-month follow-up. The Lyman-Kutcher-Burman (LKB) radiobiological model was developed based on generalized equivalent uniform dose (gEUD). Model parameters were calculated by maximum likelihood estimation. Model performance was evaluated by ROC-AUC, Brier score and Hosmer-Lemeshow test. RESULTS After three months of follow-up, 13.33% of patients experienced eyelids skin erythema grade 1 or more. The parameters of the LKB model were: TD50 = 30 Gy, m = 0.14, and n = 0.10. The model showed good predictive performance with ROC-AUC = 0.80 (CI:0.66-0.94) and a Brier score of 0.20. CONCLUSIONS In this study, NTCP of eyelid skin erythema was modeled based on the LKB radiobiological model with good predictive performance.
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Affiliation(s)
- Nastaran Momeni
- Department of Medical Physics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mohammad Ali Boroomand
- Clinical oncology department, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Zahra Roozmand
- Department of Medical Physics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Nasim Namiranian
- Diabetes research center of Alikhani, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Nima Hamzian
- Department of Medical Physics, School of Medicine, Shahid Sadoughi Universi of Medical Sciences, Yazd, Iran.
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Held T, Tessonnier T, Franke H, Regnery S, Bauer L, Weusthof K, Harrabi S, Herfarth K, Mairani A, Debus J, Adeberg S. Ways to unravel the clinical potential of carbon ions for head and neck cancer reirradiation: dosimetric comparison and local failure pattern analysis as part of the prospective randomized CARE trial. Radiat Oncol 2022; 17:121. [PMID: 35804448 PMCID: PMC9264522 DOI: 10.1186/s13014-022-02093-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Accepted: 06/30/2022] [Indexed: 11/21/2022] Open
Abstract
Background Carbon ion radiotherapy (CIRT) yields biophysical advantages compared to photons but randomized studies for the reirradiation setting are pending. The aim of the current project was to evaluate potential clinical benefits and drawbacks of CIRT compared to volumetric modulated arc therapy (VMAT) in recurrent head and neck cancer. Methods Dose-volume parameters and local failure patterns of CIRT compared to VMAT were evaluate in 16 patients from the randomized CARE trial on head and neck cancer reirradiation. Results Despite an increased target dose, CIRT resulted in significantly reduced organ at risk (OAR) dose across all patients (− 8.7% Dmean). The dose-volume benefits were most pronounced in the brainstem (− 20.7% Dmax) and the optic chiasma (− 13.0% Dmax). The most frequent local failure was type E (extraneous; 50%), followed type B (peripheral; 33%) and type A (central; 17%). In one patient with type A biological and/or dosimetric failure after CIRT, mMKM dose recalculation revealed reduced target coverage. Conclusions CIRT resulted in highly improved critical OAR sparing compared to VMAT across all head and neck cancer reirradiation scenarios despite an increased prescription dose. Local failure pattern analysis revealed further potential CIRT specific clinical benefits and potential pitfalls with regard to image-guidance and biological dose-optimization. Supplementary Information The online version contains supplementary material available at 10.1186/s13014-022-02093-4.
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Affiliation(s)
- Thomas Held
- Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. .,Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany. .,National Center for Tumor Diseases (NCT), Heidelberg, Germany. .,Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. .,Heidelberg Ion Beam Therapy Center (HIT), Heidelberg, Germany.
| | - Thomas Tessonnier
- Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.,Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany.,National Center for Tumor Diseases (NCT), Heidelberg, Germany.,Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Heidelberg Ion Beam Therapy Center (HIT), Heidelberg, Germany
| | - Henrik Franke
- Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.,Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany.,National Center for Tumor Diseases (NCT), Heidelberg, Germany
| | - Sebastian Regnery
- Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.,Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany.,National Center for Tumor Diseases (NCT), Heidelberg, Germany
| | - Lukas Bauer
- Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.,Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany.,National Center for Tumor Diseases (NCT), Heidelberg, Germany
| | - Katharina Weusthof
- Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.,Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany.,National Center for Tumor Diseases (NCT), Heidelberg, Germany
| | - Semi Harrabi
- Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.,Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany.,National Center for Tumor Diseases (NCT), Heidelberg, Germany.,Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Heidelberg Ion Beam Therapy Center (HIT), Heidelberg, Germany.,German Cancer Consortium (DKTK), partner site Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Klaus Herfarth
- Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.,Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany.,National Center for Tumor Diseases (NCT), Heidelberg, Germany.,Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Heidelberg Ion Beam Therapy Center (HIT), Heidelberg, Germany.,German Cancer Consortium (DKTK), partner site Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Andrea Mairani
- Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.,Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany.,National Center for Tumor Diseases (NCT), Heidelberg, Germany.,Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Heidelberg Ion Beam Therapy Center (HIT), Heidelberg, Germany.,German Cancer Consortium (DKTK), partner site Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Medical Physics, National Centre of Oncological Hadrontherapy (CNAO), Pavia, Italy
| | - Jürgen Debus
- Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.,Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany.,National Center for Tumor Diseases (NCT), Heidelberg, Germany.,Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Heidelberg Ion Beam Therapy Center (HIT), Heidelberg, Germany.,German Cancer Consortium (DKTK), partner site Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Sebastian Adeberg
- Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.,Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany.,National Center for Tumor Diseases (NCT), Heidelberg, Germany.,Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Heidelberg Ion Beam Therapy Center (HIT), Heidelberg, Germany.,German Cancer Consortium (DKTK), partner site Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany
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