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PURPOSE/OBJECTIVE(S): Along with breast-conserving surgery (BCS), adjuvant radiotherapy (RT) of patients with early breast cancer plays a crucial role in the oncologic treatment concept. Conventionally, irradiation is carried out with the aid of tangentially arranged fields. However, more modern and more complex radiation techniques such as IMRT (intensity-modulated radio therapy) are used more frequently, as they improve dose conformity and homogeneity and, in some cases, achieve better protection of adjacent risk factors. The use of this technique has implications for the incidental- and thus unintended- irradiation of adjacent loco regional lymph drainage in axillary lymph node levels I-III and internal mammary lymph nodes (IMLNs). A comparison of a homogeneous "real-life" patient collective, treated with helical tomotherapy (TT), patients treated with 3D conformal RT conventional tangentially arranged fields (3DCRT) and deep inspiration breath hold (3DCRT-DIBH), was conducted. MATERIALS/METHODS: This study included 90 treatment plans after BCS, irradiated in our clinic from January 2012 to August 2016 with TT (n = 30) and 3D-CRT (n = 30), 3DCRT DIBH (n = 30). PTVs were contoured at different time points by different radiation oncologists (> 7). TT was performed with a total dose of 50.4 Gy and a single dose of 1.8 Gy with a simultaneous integrated boost (SIB) to the tumor cavity (TT group). Patients irradiated with 3DCRT/3DCRT DIBH received 50 Gy à 2 Gy and a sequential boost. Contouring of lymph drainage routes was performed retrospectively according to RTOG guidelines. RESULTS: Average doses (DMean) in axillary lymph node Level I/Level II/Level III were 31.6 Gy/8.43 Gy/2.38 Gy for TT, 24.0 Gy/11.2 Gy/3.97 Gy for 3DCRT and 24.7 Gy/13.3 Gy/5.59 Gy for 3DCRT-DIBH patients. Internal mammary lymph nodes (IMLNs) Dmean were 27.8 Gy (TT), 13.5 Gy (3DCRT), and 18.7 Gy (3DCRT-DIBH). Comparing TT to 3DCRT-DIBH dose varied significantly in all axillary lymph node levels and the IMLNs. Comparing TT to 3DCRT significant dose difference in Level I and IMLNs was observed. CONCLUSION: Dose applied to locoregional lymph drainage pathways varies comparing tomotherapy plans to conventional tangentially arranged fields. Studies are warranted whether dose variations influence loco-regional spread and must have implications for target volume definition guidelines.

Purpose: In elderly patients with esophageal cancer (EC), esophagectomy is associated with an increased mortality, and therefore these patients are often treated with definite (chemo) radiation. The purpose of this study was to assess the toxicity and efficiency of definite radio(chemo) therapy in patients >75 years compared with definite radio(chemo) therapy in patients 75 years were treated with definite radio(chemo) therapy for EC. We compared baseline parameters, efficiency and toxicity rates of these patients to 39 patients

Background: While neoadjuvant chemoradiation therapy (nCRT) with subsequent surgery is the treatment of choice for patients with locally advanced or node-positive squamous cell carcinoma of the esophagus (SCC) suitable for surgery, patients who are unsuitable for surgery or who refuse surgery should be treated with definite chemoradiation therapy (dCRT). Purpose of this study was to compare toxicity and oncologic outcome of dCRT with either cisplatin and 5-fluoruracil (CDDP/5FU) or carboplatin and paclitaxel (Carb/TAX) in patients with SCC.Methods: Twenty-two patients who received dCRT with carboplatin (AUC2, weekly) and paclitaxel (50 mg per square meter of body-surface area, weekly) were retrospectively compared to 25 patients who were scheduled for dCRT with cisplatin (20 mg/m(2)/d) and 5-fluoruracil (500 mg/m(2)/d) on day 1-5 and day 29-33. For the per-protocol (PP) analysis, PP treatment was defined as complete radiation therapy with at least 54Gy and at least three complete cycles of Carb/TAX or complete radiation therapy with at least 54Gy and at least one complete cycle of CDDP/5FU. While patients who were scheduled for dCRT with Carb/TAX received a significantly higher total radiation dose (median dose 59.4Gy vs. 54Gy, p < 0.001) than patients who were scheduled for dCRT with CDDP/5FU, no significant differences were seen for other parameters (age, sex, TNM-stage, grading and tumor extension).Results: Forty-seven patients (25 patients treated with CDDP/5FU and 22 patients treated with Carb/TAX) were evaluated for the intention-to-treat (ITT) analysis and 41 of 47 patients (23 patients treated with CDDP/5FU and 18 patients treated with Carb/TAX) were evaluated for the PP analysis. Severe myelotoxicity (>= III degrees) was seen in 52% (CDDP/5FU) and 55% of patients (Carb/TAX), respectively (p = 1.000). In the univariate binary logistic regression analysis, patients age was the only factor associated with an increased risk of >= III degrees myelotoxicity (hazard ratio 1.145, 95% CI 1.035; 1.266; p = 0.009). Regarding treatment efficiency, no significant differences were seen for overall survival (OS) and freedom from relapse (FFR) between both treatment groups.Conclusion: Myelotoxicity and oncologic outcome under dCRT were not different for patients with SCC of the esophagus treated with either CDDP/5FU or Carb/TAX. The putative equivalence of dCRT with Carb/TAX in this setting should be further investigated in prospective trials. However, our data reveal that the risk of significant myelotoxicity increases with patient age and therefore other chemotherapy regimens might be evaluated in elderly patients.

Background: With the advance of modern irradiation techniques, the role of radiotherapy (RT) for intracranial meningioma has increased significantly throughout the past years. Despite that tumor's generally favorable outcome with local control rates of up to 90% after ten years, progression after RT does occur. In those cases, re-irradiation is often difficult due to the limited radiation tolerance of the surrounding tissue. The aim of this analysis is to determine the value of particle therapy with its better dose conformity and higher biological efficacy for re-irradiating recurrent intracranial meningioma. It was performed within the framework of the "clinical research group heavy ion therapy" and funded by the German Research Council (DFG, KFO 214). Methods: Forty-two patients treated with particle RT (protons (n = 8) or carbon ions (n = 34)) for recurrent intracranial meningioma were included in this analysis. Location of the primary lesion varied, including skull base (n = 31), convexity (n = 5) and falx (n = 6). 74% of the patients were categorized high-risk according to histology with a WHO grading of II (n = 25) or III (n = 6), in the remaining cases histology was either WHO grade I (n = 10) or unknown (n = 1). Median follow-up was 49,7 months. Results: In all patients, re-irradiation could be performed safely without interruptions due to side effects. No grade IV or V toxicities according to CTCAE v4.0 were observed. Particle RT offered good overall local control rates with 71% progression-free survival (PFS) after 12 months, 56,5% after 24 months and a median PFS of 34,3 months (95% CI 11,7-56,9). Histology had a significant impact on PFS yielding a median PFS of 25,7 months (95% CI 5,8-45,5) for high-risk histology (WHO grades II and III) while median PFS was not reached for low-risk tumors (WHO grade I) (p = 0,03). Median time to local progression was 15,3 months (Q1-Q3 8,08-34,6). Overall survival (OS) after re-irradiation was 89,6% after 12 months and 71,4% after 24 months with a median OS of 61,0 months (95% CI 34,2-87,7). Again, WHO grading had an effect, as median OS for low-risk patients was not reached whereas for high-risk patients it was 45,5 months (95% CI 35,6-55,3). Conclusion: Re-irradiation using particle therapy is an effective method for the treatment of recurrent meningiomas. Interdisciplinary decision making is necessary to guarantee best treatment for every patient.

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.

Following publication of the original article [1], the authors reported that for one of the authors, Stephanie E. Combs, the middle name was accidentally omitted. They also reported that for two of the authors, Daniel Habermehl and Stephanie E. Combs, two affiliations were accidentally omitted. In this Correction the incorrect and correct author name are shown and the two omitted affiliations are listed.

Background: The aim of the thesis is to improve treatment plans of carbon ion irradiation by integrating the tissues' specific α/β-values for patients with locally advanced pancreatic cancer (LAPC). Material and Methods: Five patients with LAPC were included in this study. By the use of the treatment planning system Syngo RT Planning (Siemens, Erlangen, Germany) treatment plans with carbon ion beams have been created. Dose calculation was based on α/β-values for both organs at risk (OAR) and the tumor. Twenty-five treatment plans and thirty-five forward calculations were created. With reference to the anatomy five field configurations were included. Single Beam Optimization (SBO) and Intensity Modulated Particle Therapy (IMPT) were used for optimization. The plans were analyzed with respect to both dose distributions and individual anatomy. The plans were evaluated using a customized index. Results: With regard to the target, a field setup with one single posterior field achieves the highest score in our index. Field setups made up of three fields achieve good results in OAR sparing. Nevertheless, the field setup with one field is superior in complex topographic conditions. But, allocating an α/β-value of 2 Gy to the spinal cord leads to critical high maximum doses in the spinal cord. The evaluation of dose profiles showed significant dose peaks at borders of the α/β-gradient, especially in case of a single posterior field. Conclusion: Optimization with specific α/β-values allows a more accurate view on dose distribution than previously. A field setup with one single posterior field achieves good results in case of difficult topographic conditions, but leads to high maximum doses to the spinal cord. So, field setups with multiple fields seem to be more adequate in case of LAPC, being surrounded by highly radiosensitive normal tissues.

Aims and background Primary liver cancer is the fourth leading cause of cancer-related death worldwide and is still associated with a poor prognosis. Hepatocellular carcinoma and cholangiocarcinoma are known to cause bone metastasis resulting in pain, neurologic impairment and risk of fracture. Palliative radiotherapy is the treatment of choice in symptomatic bone lesions and is usually performed as percutaneous fractionated radiotherapy. Methods and study design From June 1987 to December 2009, 41 patients (median age, 64 years) with bone metastasis received radiotherapy in our department. The analyzed patients were treated for 67 sites of bone lesions. We analyzed the applied fractionation schedules and the preferred sites of metastasis and symptoms, evaluated the therapeutic outcome in terms of symptomatic improvement, and described the prognosis of these patients. Results Main indication for palliative radiotherapy was pain in 94% of all cases. Most frequent radiation protocols were 10 × 3 Gy (20 patients) and 20 × 2 Gy (19 patients). Median applied overall dose was 39 Gy (range, 4–48 Gy) and median single dose was 2.5 Gy (range, 1.8–4 Gy). The median duration of the radiotherapeutic treatment was 15 days (range, 2–24 days) and in 12 cases treatment was discontinuated. The overall response rate to palliative radiotherapy in bone metastasis was 77%. Median overall survival in both cholangiocarcinoma and hepatocellular carcinoma patients was 4.2 months after initiation of radiotherapy (range, 0.2–38.9). Conclusions Considering the poor prognosis of patients with bone metastasis in hepatocellular carcinoma and cholangiocarcinoma, with a poor median survival of 3.7–5.0 months according to our study and existing literature, shorter radiotherapy schedules or even single-fraction irradiation can be considered.