TY  - JOUR
AB  - Background: The purpose of this study was to estimate the additional risk of side effects attributed to internal mammary node irradiation (IMNI) as part of regional lymph node irradiation (RNI) in breast cancer patients and to compare it with estimated overall survival (OS) benefit from IMNI. Material and methods: Treatment plans (n = 80) with volumetric modulated arc therapy (VMAT) were calculated for 20 patients (4 plans per patient) with left-sided breast cancer from the prospective GATTUM trial in free breathing (FB) and in deep inspiration breath hold (DIBH). We assessed doses to organs at risk ((OARs) lung, contralateral breast and heart) during RNI with and without additional IMNI. Based on the OAR doses, the additional absolute risks of 10-year cardiac mortality, pneumonitis, and secondary lung and breast cancer were estimated using normal tissue complication probability (NTCP) and risk models assuming different age and risk levels. Results: IMNI notably increased the mean OAR doses. The mean heart dose increased upon IMNI by 0.2–3.4 Gy (median: 1.9 Gy) in FB and 0.0–1.5 Gy (median 0.4 Gy) in DIBH. However, the estimated absolute additional 10-year cardiac mortality caused by IMNI was <0.5% for all patients studied except 70-year-old high risk patients (0.2–2.4% in FB and 0.0–1.1% in DIBH). In comparison to this, the published oncological benefit of IMNI ranges between 3.3% and 4.7%. The estimated additional 10-year risk of secondary cancer of the lung or contralateral breast ranged from 0–1.5% and 0–2.8%, respectively, depending on age and risk levels. IMNI increased the pneumonitis risk in all groups (0–2.2%). Conclusion: According to our analyses, the published oncological benefit of IMNI outweighs the estimated risk of cardiac mortality even in case of (e.g., cardiac) risk factors during VMAT. The estimated risk of secondary cancer or pneumonitis attributed to IMNI is low. DIBH reduces the estimated additional risk of IMNI even further and should be strongly considered especially in patients with a high baseline risk.
AU  - Borm, K.J.*
AU  - Simonetto, C.
AU  - Kundrát, P.
AU  - Eidemüller, M.
AU  - Oechsner, M.*
AU  - Düsberg, M.*
AU  - Combs, S.E.
C1  - 59585
C2  - 48856
CY  - 2-4 Park Square, Milton Park, Abingdon Or14 4rn, Oxon, England
SP  - 1201-1209
TI  - Toxicity of internal mammary irradiation in breast cancer. Are concerns still justified in times of modern treatment techniques?
JO  - Acta Oncol.
VL  - 59
IS  - 10
PB  - Taylor & Francis Ltd
PY  - 2020
SN  - 0284-186X
ER  - 

TY  - JOUR
AB  - Purpose: This study aimed to evaluate whether an early beginning of the adjuvant stereotactic radiotherapy after macroscopic complete resection of 1-3 brain metastases is essential or whether longer intervals between surgery and radiotherapy are feasible.Material and methods: Sixty-six patients with 69 resection cavities treated with HFSRT after macroscopic complete resection of 1-3 brain metastases between 2009 and 2016 in our institution were included in this study. Overall survival, local recurrence and locoregional recurrence were evaluated depending on the time interval from surgery to the start of radiation therapy.Results: Patients that started radiotherapy within 21 days from surgery had a significantly decreased OS compared to patients treated after a longer interval from surgery (p < .01). There was no significant difference between patients treated ≥ 34 and 22-33 days from surgery (p = .210). In the univariate analysis, local control was superior for patients starting treatment 22-33 days from surgery compared to a later start (p = .049). This effect did not prevail in a multivariate model. There was no significant difference between patients treated within 21 days and patients treated more than 33 days after surgery (p = .203). Locoregional control was not influenced by RT timing (p = .508).Conclusion: A short delay in the start of radiotherapy does not seem to negatively impact the outcome in patients with resected brain metastases. We even observed an unexpected reduction in OS in patients treated within 21 days from surgery. Further studies are needed to define the optimal timing of postoperative radiotherapy to the resection cavity.
AU  - Scharl, S.*
AU  - Kirstein, A.
AU  - Kessel, K.A.
AU  - Diehl, C.*
AU  - Oechsner, M.*
AU  - Straube, C.*
AU  - Meyer, B.*
AU  - Zimmer, C.*
AU  - Combs, S.E.
C1  - 56699
C2  - 47249
CY  - 2-4 Park Square, Milton Park, Abingdon Or14 4rn, Oxon, England
SP  - 1714-1719
TI  - Stereotactic irradiation of the resection cavity after surgical resection of brain metastases - when is the right timing?
JO  - Acta Oncol.
VL  - 58
IS  - 12
PB  - Taylor & Francis Ltd
PY  - 2019
SN  - 0284-186X
ER  - 

TY  - JOUR
AB  - Flatworms of the species Schmidtea mediterranea are immortal-adult animals contain a large pool of pluripotent stem cells that continuously differentiate into all adult cell types. Therefore, single-cell transcriptome profiling of adult animals should reveal mature and progenitor cells. By combining perturbation experiments, gene expression analysis, a computational method that predicts future cell states from transcriptional changes, and a lineage reconstruction method, we placed all major cell types onto a single lineage tree that connects all cells to a single stem cell compartment. We characterized gene expression changes during differentiation and discovered cell types important for regeneration. Our results demonstrate the importance of single-cell transcriptome analysis for mapping and reconstructing fundamental processes of developmental and regenerative biology at high resolution.
AU  - Dapper, H.*
AU  - Habl, G.*
AU  - Hirche, C.*
AU  - Münch, S.*
AU  - Oechsner, M.*
AU  - Mayinger, M.*
AU  - Sauter, C.*
AU  - Combs, S.E.
AU  - Habermehl, D.
C1  - 52864
C2  - 44323
CY  - 1200 New York Ave, Nw, Washington, Dc 20005 Usa
SP  - 825-830
TI  - Dosimetric quantification of the incidental irradiation of the "true' (deep) ano-inguinal lymphatic drainage of anal cancer patients not described in conventional contouring guidelines.
JO  - Acta Oncol.
VL  - 57
IS  - 6
PB  - Amer Assoc Advancement Science
PY  - 2018
SN  - 0284-186X
ER  - 

TY  - JOUR
AB  - Background: Re-irradiation (Re-RT) is offered widely in clinical routine, and has been established as a key element in the treatment of recurrent gliomas. At our center, generally re-resection is performed widely by an experienced neurosurgical team. Thus, Re-RT mostly offered to patients with macroscopic residuals or irresectable lesions, is applied later compared to other centers. Therefore, we sought to validate the Combs Prognostic Score developed in 2012 using our independent patient cohort. Patients and methods: We included 199 patients treated from 2002 until April 2016 for recurrent glioma at the Department of Radiation Oncology at the Klinikum Rechts der Isar, Munich. Different concepts of Re-RT were applied. Results: Median follow-up after Re-RT was 2.5 months. Median overall survival (OS) after Re-RT was 7.9 months for WHO IV gliomas, 11.3 months for WHO III gliomas, and 13.6 months for low-grade gliomas (WHO I/II). Univariate analyses confirmed the prognostic factors primary histology (p = 0.001), age (p = 0.002), and time between primary radiotherapy and Re-RT (p < 0.001). We also tested Karnofsky Performance Score (KPS), gender, and neurological symptoms before Re-RT as well as planning target volume and found only KPS also significant at p < 0.001. Comparing the prognostic score groups, the outcome was highly statistically significant at p < 0.001. Conclusion: In our analysis, we validated the Combs Prognostic Score. Validation in this independent large patient cohort confirms the significance of the score for glioma recurrences. Thus, the role of the Combs Prognostic Score might be an essential component of future clinical decision making and patient stratification.
AU  - Kessel, K.A.
AU  - Hesse, J.*
AU  - Straube, C.*
AU  - Zimmer, C.*
AU  - Schmidt-Graf, F.*
AU  - Schlegel, J.*
AU  - Meyer, B.*
AU  - Combs, S.E.
C1  - 50352
C2  - 42389
CY  - Abingdon
SP  - 422-426
TI  - Validation of an established prognostic score after re-irradiation of recurrent glioma.
JO  - Acta Oncol.
VL  - 56
IS  - 3
PB  - Taylor & Francis Ltd
PY  - 2017
SN  - 0284-186X
ER  - 

TY  - JOUR
AB  - BACKGROUND: The evidence concerning the cost-effectiveness of UGT1A1*28 genotyping is ambiguous and does not allow drawing valid conclusions for Germany. This study evaluates the cost-effectiveness of UGT1A1 genotyping in patients with metastatic colorectal cancer undergoing irinotecan-based chemotherapy compared to no testing from the perspective of the German statutory health insurance. MATERIAL AND METHODS: A decision-analytic Markov model with a life time horizon was developed. No testing was compared to two genotype-dependent therapy strategies: 1) dose reduction by 25%; and 2) administration of a prophylactic G-CSF growth factor analog for homozygous and heterozygous patients. Probability, quality of life and cost parameters used in this study were based on published literature. Deterministic and probabilistic sensitivity analyses were performed to account for parameter uncertainties. RESULTS: Strategy 1 dominated all remaining strategies. Compared to no testing, it resulted in only marginal QALY increases (0.0002) but a cost reduction of €580 per patient. Strategy 2 resulted in the same health gains but increased costs by €10 773. In the probabilistic analysis, genotyping and dose reduction was the optimal strategy in approximately 100% of simulations at a threshold of €50 000 per QALY. Deterministic sensitivity analysis shows that uncertainty for this strategy originated primarily from costs for irinotecan-based chemotherapy, from the prevalence of neutropenia among heterozygous patients, and from whether dose reduction is applied to both homozygotes and heterozygotes or only to the former. CONCLUSION: This model-based synthesis of the most recent evidence suggests that pharmacogenetic UGT1A1 testing prior to irinotecan-based chemotherapy dominates non-personalized colon cancer care in Germany. However, as structural uncertainty remains high, these results require validation in clinical practice, e.g. based on a managed-entry agreement.
AU  - Butzke, B.
AU  - Oduncu, F.S.*
AU  - Severin, F.
AU  - Pfeufer, A.
AU  - Heinemann, V.*
AU  - Giessen-Jung, C.*
AU  - Stollenwerk, B.
AU  - Rogowski, W.H.
C1  - 45382
C2  - 37342
CY  - Abingdon
SP  - 318-328
TI  - The cost-effectiveness of UGT1A1 genotyping before colorectal cancer treatment with irinotecan from the perspective of the German statutory health insurance.
JO  - Acta Oncol.
VL  - 55
IS  - 3
PB  - Taylor & Francis Ltd
PY  - 2016
SN  - 0284-186X
ER  - 

TY  - JOUR
AB  - Background: Meningiomas are usually slow growing, well circumscribed intracranial tumors. In symptom-free cases observation with close follow-up imaging could be performed. Symptomatic meningiomas could be surgically removed and/or treated with radiotherapy. The study aimed to evaluate the volumetric response of intracranial meningiomas at different time points after photon, proton, and a mixed photon and carbon ion boost irradiation. Patients and methods: In Group A 38 patients received proton therapy (median dose: 56 GyE in 1.8–2 GyE daily fractions) or a mixed photon/carbon ion therapy (50 Gy in 2 Gy daily fractions with intensity modulated radiotherapy (IMRT) and 18 GyE in 3 GyE daily dose carbon ion boost). Thirty-nine patients (Group B) were treated by photon therapy with IMRT or fractionated stereotactic radiotherapy technique (median dose: 56 Gy in 1.8–2 Gy daily fractions). The delineation of the tumor volume was based on the initial, one- and two-year follow-up magnetic resonance imaging and these volumes were compared to evaluate the volumetric tumor response. Results: Significant tumor volume shrinkage was detected at one- and at two-year follow-up both after irradiation by particles and by photons. No significant difference in tumor volume change was observed between photon, proton or combined photon plus carbon ion boost treated patients. WHO grade and gender appear to be determining factors for tumor volume shrinkage. Conclusion: Significant volumetric shrinkage of meningiomas could be observed independently of the applied radiation modality. Long-term follow-up is recommended to evaluate further dynamic of size reduction and its correlation with outcome data.
AU  - Mozes, P.*
AU  - Dittmar, J.O.*
AU  - Habermehl, D.*
AU  - Tonndorf-Martini, E.*
AU  - Hideghety, K.*
AU  - Dittmar, A.*
AU  - Debus, J.*
AU  - Combs, S.E.
C1  - 50135
C2  - 42176
CY  - Abingdon
SP  - 1-7
TI  - Volumetric response of intracranial meningioma after photon or particle irradiation.
JO  - Acta Oncol.
VL  - 2
IS  - 3
PB  - Taylor & Francis Ltd
PY  - 2016
SN  - 0284-186X
ER  - 

TY  - JOUR
AU  - Kummermehr, J.C.
C1  - 10396
C2  - 20589
SP  - 981-988
TI  - Tumour stem cells : The evidence and the ambiguity.
JO  - Acta Oncol.
VL  - 40
PY  - 2002
SN  - 0284-186X
ER  -