TY  - JOUR
AB  - Background: Adjuvant radiotherapy (RT) of left sided breast cancer is increasingly performed in deep inspiration breath hold (DIBH). This technique requires active involvement and compliance of patients as well as pulmonary endurance. Since previous studies focused on female patients with a median age under 65 years to test practicability of DIBH and advantages in comparison to free breathing (FB), DIBH in elderly patients over 65 years remains mostly underexplored. This study aims to evaluate attitudes and feasibility of DIBH in elderly breast cancer patients. Methods: First a 14-item survey of 100 female breast cancer patients aged ≥65 years was conducted to assess their attitudes toward DIBH and their breath-hold capability. Secondly, we performed a matched-pair analyses using pooled data from the prospective GATTUM and B-REST trials to compare respiratory and dosimetric parameters during DIBH between patients aged ≥65 years (n = 30) and <65 years (n = 30). Results: According to the survey large majority of patients were interested in DIBH: 98 % stated that age should not be a criterion when selecting patients for DIBH, and 66 were able to hold their breath > 20 s. Based on the matched-pair analyses of the GATTUM and B-Rest trials, no significant differences were observed regarding breath hold amplitude, duration and stability, and in DIBH-induced dose reduction to organs at risk between elderly (≥65) (n = 30) and younger patients (n = 30). Conclusion: Based on our results age alone should not be used as a criterion for excluding patients from DIBH in the treatment of left-sided breast cancer.
AU  - Moser, R.*
AU  - Buchecker, L.M.*
AU  - Bohlen, J.M.*
AU  - Düsberg, M.*
AU  - Aigner, M.*
AU  - Mayr, N.A.
AU  - Nano, J.*
AU  - Behzadi, S.T.*
AU  - Kiesl, S.*
AU  - Duma, M.N.*
AU  - Oechsner, M.*
AU  - Combs, S.E.*
AU  - Borm, K.J.*
C1  - 74161
C2  - 57274
CY  - Elsevier House, Brookvale Plaza, East Park Shannon, Co, Clare, 00000, Ireland
TI  - Assessment of the impact of age on DIBH in radiotherapy based on the prospective GATTUM and B-REST trials.
JO  - Clin. Transl. Radiat. Oncol.
VL  - 53
PB  - Elsevier Ireland Ltd
PY  - 2025
SN  - 2405-6308
ER  - 

TY  - JOUR
AB  - Background and purpose: In a relevant number of primary breast cancer patients, lymphatic drainage to the contralateral internal mammary nodes (cIMN) is being observed. Nevertheless, so far lymphatic drainage pathway to the cIMN is largely neglected during adjuvant radiotherapy. Materials and methods: This study evaluated the incidental dose to the cIMN for 120 volumetric modulated arc therapy (VMAT) treatment plans for node positive breast in dependence of internal mammary node irradiation (IMNI) and deep inspiration breath hold (DIBH). Additionally, incidental dose distribution to the cIMN based on the field design in the MA20, EORTC22922/10925 and AMAROS trials was assessed. Results: The incidental dose (Dmean ± SD) to the cIMN-CTV was 13.0 (±4.7) Gy with a maximum dose of < 30 Gy in 113/120 cases. If IMNI was included (n = 80), the Dmean to the cIMN-CTV was significantly higher compared to no IMNI, but still comparably low (n = 40; 14.3 Gy vs. 9.6 Gy; p = 0.0001). Furthermore, the dose in the cIMN during free breathing (n = 80) was higher compared to DIBH (n = 40; 13.9 Gy vs. 11.2 Gy; p = 0.002). Simulated treatment plans based on the randomized RNI trials revealed neglectable dose coverage of the cIMN (Dmean 1.0–1.8 Gy) for all protocols. Conclusion: Neither in the randomized RNI trials nor during contemporary treatment techniques clinically relevant dose distribution to the cIMN was observed. Further studies are warranted to assess the potential impact of intended irradiation of cIMN in high-risk patients.
AU  - Behzadi, S.T.*
AU  - Duesberg, M.*
AU  - Moser, R.*
AU  - Duma, M.N.*
AU  - Oechsner, M.*
AU  - Kiesl, S.*
AU  - Nano, J.*
AU  - Combs, S.E.
AU  - Borm, K.J.*
C1  - 71476
C2  - 56129
CY  - Elsevier House, Brookvale Plaza, East Park Shannon, Co, Clare, 00000, Ireland
TI  - Incidental dose distribution to contralateral internal mammary nodes in breast cancer patients undergoing adjuvant radiotherapy.
JO  - Clin. Transl. Radiat. Oncol.
VL  - 48
PB  - Elsevier Ireland Ltd
PY  - 2024
SN  - 2405-6308
ER  - 

TY  - JOUR
AB  - BACKGROUND AND PURPOSE: The PRIDE trial (NOA-28; ARO-2022-12; NCT05871021) is scheduled to start recruitment in October 2023. Its primary objective is to enhance median overall survival (OS), compared to historical median OS rates, in patients with methylguanine methlyltransferase (MGMT) promotor unmethylated glioblastoma by incorporating isotoxic dose escalation to 75 Gy in 30 fractions. To achieve isotoxicity and counteract the elevated risk of radiation necrosis (RN) associated with dose-escalated regimens, the addition of protective concurrent bevacizumab (BEV) serves as an innovative approach. The current study aims to assess the dosimetric feasibility of the proposed concept. MATERIALS AND METHODS: A total of ten patients diagnosed with glioblastoma were included in this dosimetric analysis. Delineation of target volumes for the reference plans adhered to the ESTRO-EANO 2023 guideline. The experimental plans included an additional volume for the integrated boost. Additionally, the 60 Gy-volume was reduced by using a margin of 1.0 cm instead of 1.5 cm. To assess the risk of symptomatic RN, the Normal Tissue Complication Probability (NTCP) was calculated and compared between the reference and experimental plans. RESULTS: Median NTCP of the reference plan (NTCPref) and of the experimental plan (NTCPex) were 0.24 (range 0.11-0.29) and 0.42 (range 0.18-0.54), respectively. NTCPex was a median of 1.77 (range 1.60-1.99) times as high as the NTXPref. In a logarithmic comparison, the risk of RN is enhanced by a factor of median 2.00 (range 1.66-2.35). The defined constraints for the organs at risk were feasible. CONCLUSION: When considering the potential protective effect of BEV, which we hypothesized might reduce the risk of RN by approximately two-fold, achieving isotoxicity with the proposed dose-escalated experimental plan for the PRIDE trial seems feasible.
AU  - Bodensohn, R.*
AU  - Fleischmann, D.F.*
AU  - Maier, S.H.*
AU  - Anagnostatou, V.*
AU  - Garny, S.*
AU  - Nitschmann, A.*
AU  - Büttner, M.*
AU  - Mücke, J.*
AU  - Schönecker, S.*
AU  - Unger, K.
AU  - Hoffmann, E.J.*
AU  - Paulsen, F.*
AU  - Thorwarth, D.*
AU  - Holzgreve, A.*
AU  - Albert, N.L.*
AU  - Corradini, S.*
AU  - Tabatabai, G.*
AU  - Belka, C.*
AU  - Niyazi, M.*
C1  - 69061
C2  - 53838
CY  - Elsevier House, Brookvale Plaza, East Park Shannon, Co, Clare, 00000, Ireland
TI  - Dosimetric feasibility analysis and presentation of an isotoxic dose-escalated radiation therapy concept for glioblastoma used in the PRIDE trial (NOA-28; ARO-2022-12).
JO  - Clin. Transl. Radiat. Oncol.
VL  - 45
PB  - Elsevier Ireland Ltd
PY  - 2024
SN  - 2405-6308
ER  - 

TY  - JOUR
AB  - BACKGROUND: Most clinical studies failed to elicit a strong antitumor immune response and subsequent systemic tumor regression after radiation therapy (RT), even in combination with the immune checkpoint inhibitors (ICI) anti-CTLA4 or anti-PD1. Mechanistically, type I interferon (IFN-I) activation is essential for the development of such abscopal effects (AE); however, mechanisms driving or limiting IFN-I activation are ill defined. Groundbreaking discoveries have shown that antibiotics (ABx) can affect oncological outcomes and that microbiota-derived metabolites can modulate systemic antitumor immunity. Recent studies have demonstrated that the bacterial metabolites desaminotyrosine (DAT) and indole-3-carboxaldehyde (ICA) can enhance IFN-I activation in models of inflammatory diseases. MATERIALS AND METHODS: The subcutaneous bilateral MC38 tumor model is a widely used experimental tool to study the AE in mice. We applied it to explore the influence of broad-spectrum ABx, DAT and ICA on the AE after radioimmunotherapy (RIT). We performed 1x8 Gy of the primary tumor ± anti-CTLA4 or anti-PD1, and ± daily oral application of ABx or metabolites. RESULT: Combinatory ABx had neither a significant effect on tumor growth of the irradiated tumor nor on tumor progression of the abscopal tumor after RIT with anti-CTLA4. Furthermore, DAT and ICA did not significantly impact on the AE after RIT with anti-CTLA4 or anti-PD1. Surprisingly, ICA even appears to reduce outcomes after RIT with anti-CTLA4. CONCLUSION: We did not find a significant impact of combinatory ABx on the AE. Experimental application of the IFN-I-inducing metabolites DAT or ICA did not boost the AE after combined RIT. Additional studies are important to further investigate whether the intestinal microbiota or specific microbiota-derived metabolites modulate the AE.
AU  - Felchle, H.*
AU  - Gissibl, J.*
AU  - Lansink Rotgerink, L.*
AU  - Nefzger, S.M.*
AU  - Walther, C.N.*
AU  - Timnik, V.R.*
AU  - Combs, S.E.
AU  - Fischer, J.C.*
C1  - 70234
C2  - 55451
CY  - Elsevier House, Brookvale Plaza, East Park Shannon, Co, Clare, 00000, Ireland
TI  - Influence of intestinal microbial metabolites on the abscopal effect after radiation therapy combined with immune checkpoint inhibitors.
JO  - Clin. Transl. Radiat. Oncol.
VL  - 46
PB  - Elsevier Ireland Ltd
PY  - 2024
SN  - 2405-6308
ER  - 

TY  - JOUR
AB  - Purpose: In prostate cancer, the indication to irradiate the pelvic lymphatic pathways in clinical node-negative patients is solely based on clinical nomograms. To define biological risk patterns of lymphatic spread, we studied DNA-methylation and genomic copy number in primary tumors and corresponding lymph nodes metastases. Methods/Patients: DNA-methylation and genomic copy number profiles of primary tumors (PT) and paired synchronous lymph node metastases (LN) from Gleason Score (GS)-6/7a (n = 20 LN-positive, n = 20 LN-negative) and GS-9/10 patients (LN-positive n = 20) after prostatectomy and lymphonodectomy were analyzed. Results: GS-6/7a pN0 PTs and GS-6/7a pN1 PTs differed in histone H3K27me3/H3K9me3 mediated methylation. PTs compared to LNs, in both, GS-6/7a pN1 and GS-9/10 pN1 patients showed large differences in DNA-methylation mediated by histones H3K4me1/2, in addition to copy number changes of chromosomal regions 11q13.1, 14q11.2 and 15q26.1. Between GS-6/7a pN1 and GS-9/10 pN1 patients, methylation levels differed more when comparing LNs than PTs. 16q21-22.1 was specifically lost in GS-9/10 pN0 PTs. Immune system-related pathways characterized the differences between PTs and LNs in both GS-6/7a pN1 and GS-9/10 pN1 patients. Comparing PTs and LKs between GS-6/7a pN1 and GS-9/10 pN1 patients revealed altered transmembrane and G-protein-coupled receptor signaling. Conclusions: Our data suggest that progression of prostate cancer, including lymphatic spread, is associated with histone-mediated DNA-methylation and we hypothesize a methylation signature predicting lymphatic spread in GS-6/7a patients from primary tumors. Lymphatic spread in GS-6/7a patients, flanked by DNA-methylation and CNA alterations, appears to be more complex than in GS-9/10 patients, in whom the primary tumors already appear to bear lymph node metastasis-enabling alterations.
AU  - Unger, K.
AU  - Hess J.
AU  - Link, V.*
AU  - Buchner, A.*
AU  - Eze, C.*
AU  - Li, M.*
AU  - Stief, C.*
AU  - Kirchner, T.*
AU  - Klauschen, F.*
AU  - Zitzelsberger, H.
AU  - Niyazi, M.*
AU  - Ganswindt, U.*
AU  - Schmidt-Hegemann, N.S.*
AU  - Belka, C.
C1  - 67382
C2  - 54015
CY  - Elsevier House, Brookvale Plaza, East Park Shannon, Co, Clare, 00000, Ireland
TI  - DNA-methylation and genomic copy number in primary tumors and corresponding lymph node metastases in prostate cancer from patients with low and high Gleason score.
JO  - Clin. Transl. Radiat. Oncol.
VL  - 39
PB  - Elsevier Ireland Ltd
PY  - 2023
SN  - 2405-6308
ER  - 

TY  - JOUR
AB  - Purpose: To establish stable in vitro growth of keratinocytes from very small biopsy specimens and successfully apply new test systems to determine their radiosensitivity. Materials and Methods: Oral mucosa biopsies (diameter: 1.7 mm) from 15 subjects were immobilized with custom-made cups onto culture plates. Outgrowing cells were tested for cytokeratin 5/14 and Ki67, expanded, radiated at different doses, and seeded onto circumscribed areas before being allowed to spread centrifugally. In this newly developed spreading assay, cell-covered areas were measured by image analysis. For statistical analysis, a linear mixed regression model was used; additionally, results were correlated to the radiation dose applied. Colony forming efficiency (CFE) was used to validate the results. DNA damage repair was analysed by gammaH2AX and 53BP1 foci quantification using immunofluorescence microscopy 24 h and 96 h after irradiation. Results: Stable keratinocyte growth continued for up to 7 weeks in 14 biopsies. Cells spread reliably from an initial 16.6 mm2 up to a median of 119.2 mm2 (range: 54.4–290). Radiated cells spread to only 100.7 mm2 (2 Gy; range: 55.3–266.7); 73.2 mm2 (4 Gy; 15–240.4); 47 mm2 (6 Gy; 2–111.9), and 22.7 mm2 (8 Gy; 0–80). Similarly, CFE decreased from 0.223 (0 Gy) to 0.0028 (8 Gy). Using an individual donor as a random factor, cell spread correlated with CFE, where radiation dose was the main driver (decrease by 0.50, adjusted for area). Upon irradiation with 6 Gy, radiation-induced DNA damage was increased after 24 h in all samples, and even after 96 h in 5 out of 7 samples, as detected by a higher number of gammaH2AX/53BP1 foci in irradiated cells (mean 3.7 for 24 h; mean 0.6 for 96 h). Conclusion: In vitro propagation of keratinocytes derived from a small biopsy is feasible. Radiation impairs cellular migration and proliferation, and the newly described spreading assay allows ranking for cellular radioresistance. The keratinocyte model also supports classical functional assays such as clonogenic survival and DNA double strand repair. The clinical relevance awaits upcoming investigations.
AU  - Thomsen, A.R.*
AU  - Aldrian, C.*
AU  - Luka, B.*
AU  - Hornhardt, S.*
AU  - Gomolka, M.*
AU  - Moertl, S.*
AU  - Hess J.
AU  - Zitzelsberger, H.
AU  - Heider, T.*
AU  - Schlueter, N.*
AU  - Rau, S.*
AU  - Monroy Ordonez, B.*
AU  - Schäfer, H.*
AU  - Rücker, G.*
AU  - Henke, M.*
C1  - 64691
C2  - 52411
SP  - 51-56
TI  - Biopsy-derived oral keratinocytes – A model to potentially test for oral mucosa radiation sensitivity.
JO  - Clin. Transl. Radiat. Oncol.
VL  - 34
PY  - 2022
SN  - 2405-6308
ER  - 

TY  - JOUR
AB  - Purpose: To develop and validate a CT-based radiomics signature for the prognosis of loco-regional tumour control (LRC) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated by primary radiochemotherapy (RCTx) based on retrospective data from 6 partner sites of the German Cancer Consortium - Radiation Oncology Group (DKTK-ROG). Material and methods: Pre-treatment CT images of 318 patients with locally advanced HNSCC were collected. Four-hundred forty-six features were extracted from each primary tumour volume and then filtered through stability analysis and clustering. First, a baseline signature was developed from demographic and tumour-associated clinical parameters. This signature was then supplemented by CT imaging features. A final signature was derived using repeated 3-fold cross-validation on the discovery cohort. Performance in external validation was assessed by the concordance index (C-Index). Furthermore, calibration and patient stratification in groups with low and high risk for loco-regional recurrence were analysed. Results: For the clinical baseline signature, only the primary tumour volume was selected. The final signature combined the tumour volume with two independent radiomics features. It achieved moderately good discriminatory performance (C-Index [95% confidence interval]: 0.66 [0.55–0.75]) on the validation cohort along with significant patient stratification (p = 0.005) and good calibration. Conclusion: We identified and validated a clinical-radiomics signature for LRC of locally advanced HNSCC using a multi-centric retrospective dataset. Prospective validation will be performed on the primary cohort of the HNprädBio trial of the DKTK-ROG once follow-up is completed.
AU  - Rabasco Meneghetti, A.*
AU  - Zwanenburg, A.*
AU  - Leger, S.*
AU  - Leger, K.*
AU  - Linge, A.*
AU  - Lohaus, F.*
AU  - Schreiber, A.*
AU  - Kalinauskaite, G.*
AU  - Tinhofer, I.*
AU  - Guberina, N.*
AU  - Guberina, M.*
AU  - Balermpas, P.*
AU  - Von der Grün, J.*
AU  - Ganswindt, U.
AU  - Belka, C.
AU  - Peeken, J.C.
AU  - Combs, S.E.
AU  - Böke, S.*
AU  - Zips, D.*
AU  - Löck, S.*
C1  - 60811
C2  - 49600
SP  - 62-70
TI  - Definition and validation of a radiomics signature for loco-regional tumour control in patients with locally advanced head and neck squamous cell carcinoma.
JO  - Clin. Transl. Radiat. Oncol.
VL  - 26
PY  - 2021
SN  - 2405-6308
ER  - 

TY  - JOUR
AB  - Introduction: Prospective clinical trials are essential to translate new therapy concepts or rather any scientific development into the medical routine. Besides a sophisticated trial protocol, the success of clinical trials depends on patient recruitment and participation. Patient recruitment remains a challenge and depends on several factors. To get a current picture of the patients’ attitude, we conducted the present survey. Methods: We designed a survey with seven questions, which was given to all oncological patients treated within a timeframe of three months between Mai and July 2017. Participation was voluntary and anonymous. The questionnaire mainly inquires patients’ participation in clinical trials in a university-based setting, their attitude towards clinical trials regarding risks and benefits, and their source of information in this context. Results: 771 patients (1:1 male/female) participated with a median age of 61 years (range 18–91 years) with a response rate of 71.5%. Of all, 17.8% (137/771) were participating in a clinical trial. The most mentioned reason was to serve medical progress and cancer research. Out of the patients not currently participating in a trial, 79 (12.7%, 79/623) refusers named the following main reasons: extensive travel time to the clinic, no therapeutic advantage, and too time-consuming. Out of the patients not offered to take part in a trial, 265 (51.0%, 265/520) would participate if offered. Of all patients, 8.3% (64/771) used the clinics' homepage as a source of information, of those 79.7% (51/64) were satisfied with its content. To enhance patient recruitment strategies, we asked how patients wish to be informed about possible trials: More than half (52.0%) of the questioned patients preferred an individual medical consultation with their physician. We further analyzed the trial participation depending on age, gender, unit, and tumor entity. We could show a significant influence of age (p < 0.001) but not for gender (p = 0.724). The trial participation was also significantly associated with the treating unit (p < 0.001) and tumor entity (p = 0.001). Conclusion: Patients are willing to participate in clinical trials. Better information strategies need to be implemented. Physicians need to be aware of running trials within their department and must counseling counsel patients effectively to improve recruitment. Trial concepts should keep in mind patients’ needs including an adequate number of appointments, positive risk-benefit profiles, and information material.
AU  - Kessel, K.A.
AU  - Vogel, M.M.E.*
AU  - Kessel, C.*
AU  - Bier, H.*
AU  - Biedermann, T.*
AU  - Friess, H.*
AU  - Herschbach, P.*
AU  - von Eisenhart-Rothe, R.*
AU  - Meyer, B.*
AU  - Kiechle, M.*
AU  - Keller, U.*
AU  - Peschel, C.*
AU  - Bassermann, F.*
AU  - Schmid, R.*
AU  - Schwaiger, M.*
AU  - Combs, S.E.
C1  - 54951
C2  - 45957
SP  - 44-49
TI  - Cancer clinical trials – Survey evaluating patient participation and acceptance in a university-based Comprehensive Cancer Center (CCC).
JO  - Clin. Transl. Radiat. Oncol.
VL  - 13
PY  - 2018
SN  - 2405-6308
ER  -