Search

Highlights • Carbon-photon radiotherapy requires an elaborate and time-consuming planning process. • An established planning workflow includes independent optimization stages. • A bias-dose strategy may yield favorable cumulative dose distributions. • Follow-up studies will assess robustness and impact on tumor control., Background and purpose Combined photon intensity-modulated radiotherapy (IMRT) and sequential dose-escalated carbon ion beam therapy (IBT) is a technically advanced treatment option for head and neck malignancies. We proposed and evaluated an integrated planning strategy as opposed to an established and largely separated planning workflow. Materials and methods Ten patients with representative malignancies of the head and neck region underwent combined carbon-photon radiotherapy (RT) in our facilities. Clinical plans were created according to the separated workflow with independent optimization stages for both modalities. Experimental plans incorporated the existing carbon IBT dose distribution into the optimization stage of a step-and-shoot photon IMRT (bias dose planning). Results Cumulative dose distributions showed statistically significant differences between the two planning strategies and were predominantly in favor of the integrated approach. As such, target irradiation was generally maintained or even improved in a subset of metrics, while normal tissue sparing was widely enhanced; for instance, in the ipsilateral temporal lobe with median Dmean of −16% (p

Denise Bernhardt,1–3 Florian Sterzing,1–4,5 Sebastian Adeberg,1–4 Klaus Herfarth,1–3 Sonja Katayama,1,3 Robert Foerster,1,3,6Juliane Hoerner-Rieber,1,3 Laila König,1,3 Juergen Debus,1–4 Stefan Rieken1,3 1Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany; 2Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg, Germany; 3Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany; 4Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; 5Department of Radiation Oncology, Klinikum Kempten, Kempten, Germany; 6Department of Radiation Oncology, University Hospital of Zürich, Zürich, Switzerland Background: Treatment of patients with pelvic adenoid cystic carcinoma (ACC) remains a challenge owing to the rarity of the disease, the lack of data, and the relative radioresistance of these tumors.Case reports: This case series presents the results of three patients with recurrent or inoperable pelvic ACC treated with intensity-modulated radiotherapy (IMRT) plus carbon ion (C12) boost. Patients received C12 therapy at a dose of 3Gray equivalents (GyE) (relative biological effectiveness [RBE]) per fraction up to 24GyE RBE, followed by 50GyE of photon IMRT in 25 fractions.Conclusion: IMRT plus C12 ion boost as a definitive or adjuvant treatment for pelvic ACCs seems to be a promising therapeutic option. No unexpected toxicity was detected and the observed toxicity remained consistently low. The initial treatment response is promising and similar to that experienced for head and neck ACCs. Keywords: ACC of Bartholin’s gland, adenoid cystic carcinoma, ACC of the prostate, ion therapy, IMRT, tomotherapy, particle irradiation, carbon ion

BACKGROUND: Radical local treatment of pulmonary metastases is practiced with increasing frequency due to acknowledgment and better understanding of oligo-metastatic disease. This study aimed to develop a nomogram predicting overall survival (OS) after stereotactic body radiotherapy (SBRT) for pulmonary metastases. PATIENTS AND METHODS: A multi-institutional database of 670 patients treated with SBRT for pulmonary metastases was used as training cohort. Cox regression analysis with bidirectional variable elimination was performed to identify factors to be included into the nomogram model to predict 2-year OS. The calibration rate of the nomogram was assessed by plotting the actual Kaplan-Meier 2-year OS against the nomogram predicted survival. The nomogram was externally validated using two separate monocentric databases of 145 and 92 patients treated with SBRT for pulmonary metastases. RESULTS: The median follow up of the trainings cohort was 14.3months, the 2-year and 5-year OS was 52.6% and 23.7%, respectively. Karnofsky performance index, type of the primary tumor, control of the primary tumor, maximum diameter of the largest treated metastasis and number of metastases (1 versus >1) were significant prognostic factors in the Cox model (all pBACKGROUND: Radical local treatment of pulmonary metastases is practiced with increasing frequency due to acknowledgment and better understanding of oligo-metastatic disease. This study aimed to develop a nomogram predicting overall survival (OS) after stereotactic body radiotherapy (SBRT) for pulmonary metastases.PATIENTS AND METHODS: A multi-institutional database of 670 patients treated with SBRT for pulmonary metastases was used as training cohort. Cox regression analysis with bidirectional variable elimination was performed to identify factors to be included into the nomogram model to predict 2-year OS. The calibration rate of the nomogram was assessed by plotting the actual Kaplan-Meier 2-year OS against the nomogram predicted survival. The nomogram was externally validated using two separate monocentric databases of 145 and 92 patients treated with SBRT for pulmonary metastases.RESULTS: The median follow up of the trainings cohort was 14.3months, the 2-year and 5-year OS was 52.6% and 23.7%, respectively. Karnofsky performance index, type of the primary tumor, control of the primary tumor, maximum diameter of the largest treated metastasis and number of metastases (1 versus >1) were significant prognostic factors in the Cox model (all pCONCLUSIONS: A nomogram for prediction of OS after SBRT for pulmonary metastases was generated and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting.KEY MESSAGE: A nomogram for prediction of overall survival after stereotactic body radiotherapy (SBRT) for pulmonary metastases was developed and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting.

Purpose: The radiation therapy treatment outcome of human papillomavirus–negative anal carcinoma may be improved by the biological effectiveness of carbon ions. However, abdominal tissue motion can compromise the precision of carbon ion therapy. This work aims to evaluate the dosimetric feasibility of carbon ion boost (CIB) therapy for anal carcinoma. Materials and Methods: An algorithm to generate computed tomographies based on daily magnetic resonance imaging data and deformable image registration was developed. By means of this algorithm, fractional computed tomography data for 54 treatment fractions for 3 different patients with anal carcinoma were derived. The dose for a sequential CIB (CIBseq) treatment plan was recalculated on the fractional computed tomography data and accumulated over the number of fractions. The resulting dose distributions were compared to standard intensity-modulated radiation therapy treatment with an integrated photon boost. Results: For the investigated patient cases, similar dosimetric results for CIBseq treatment and for intensity-modulated radiation therapy with an integrated photon boost were found. For CIBseq treatment, bladder-filling variation had the strongest influence on the dose distribution. However, the detrimental effects on the mean target dose remained below 1 Gy (RBE) as compared to photon therapy. Conclusion: This study shows the dosimetric feasibility of CIB therapy for anal carcinoma for the first time and gives reason for clinical exploitation of the enhanced biological effect of carbon ions for patients with human papillomavirus–negative anal cancer.

Purpose Many technological and methodical advances have made stereotactic body radiotherapy (SBRT) more accurate and more efficient during the last years. This study aims to investigate whether experience in SBRT and technological innovations also translated into improved local control (LC) and overall survival (OS). Methods and Materials A database of 700 patients treated with SBRT for lung metastases in 20 German centers between 1997 and 2014 was used for analysis. It was the aim of this study to investigate the impact of fluorodeoxyglucose positron-emission tomography (FDG-PET) staging, biopsy confirmation, image guidance, immobilization, and dose calculation algorithm, as well as the influence of SBRT experience, on LC and OS. Results Median follow-up time was 14.3 months (range, 0-131.9 months), with 2-year LC and OS of 81.2% (95% confidence interval [CI] 75.8%-85.7%) and 54.4% (95% CI 50.2%-59.0%), respectively. In multivariate analysis, all treatment technologies except FDG-PET staging did not significantly influence outcome. Patients who received pre-SBRT FDG-PET staging showed superior 1- and 2-year OS of 82.7% (95% CI 77.4%-88.6%) and 64.8% (95% CI 57.5%-73.3%), compared with patients without FDG-PET staging resulting in 1- and 2-year OS rates of 72.8% (95% CI 67.4%-78.8%) and 52.6% (95% CI 46.0%-60.4%), respectively ( P =.012). Experience with SBRT was identified as the main prognostic factor for LC: institutions with higher SBRT experience (patients treated with SBRT within the last 2 years of the inclusion period) showed superior LC compared with less-experienced centers ( P ≤.001). Experience with SBRT within the last 2 years was independent from known prognostic factors for LC. Conclusion Investigated technological and methodical advancements other than FDG-PET staging before SBRT did not significantly improve outcome in SBRT for pulmonary metastases. In contrast, LC was superior with increasing SBRT experience of the individual center.

Short-course preoperative radiotherapy (SCPRT) is an alternative method to chemoirradiation for patients with Stage II and III rectal cancer when no downsizing is needed, but there is still widespread reluctance to use this method because of fear of side effects from high-fraction doses. This paper reports on a single institution patient cohort of operated rectal cancer patients after SCPRT, evaluated for chronic adverse effects, local control, progression-free survival and overall survival. Altogether, 257 patients were treated with SCPRT and surgery including total mesorectal excision (92% total mesorectal excision = TME) between 2002 and 2009. Local control and survival were analyzed. Chronic adverse effects for 154 patients without local relapse were evaluated according to the NCI-CTCAE version 4.0 classification, with a median follow-up of 48 months. We found a 5-year disease-free survival (DFS) and overall survival (OS) of 71%. The 5-year estimated local control (LC) rate was 94%. A positive resection margin was found in 4% of the patients and was significantly correlated with decreased DFS, OS and LC. Chronic adverse effects were reported by 58% of the patients, of which 10% were Grade 3 toxicities. The most frequent Grade 2 toxicity was stool incontinence (13%). Sexual dysfunction was found in 36% of the patients (31% Grade 1 or 2, and only 5% Grade 3). SCPRT combined with TME produced excellent LC rates together with a low rate of high-grade chronic adverse effects.

The purpose of this study was to test the accuracy of a commercially available deformable image registration tool in a clinical situation. In addition, to demonstrate a method to evaluate the resulting transformation of such a tool to a reference defined by multiple experts. For 16 patients (seven head and neck, four thoracic, five abdominal), 30‐50 anatomical landmarks were defined on recognizable spots of a planning CT and a corresponding fraction CT. A commercially available deformable image registration tool, Velocity AI, was used to align all fraction CTs with the respective planning CTs. The registration accuracy was quantified by means of the target registration error in respect to expert‐defined landmarks, considering the interobserver variation of five observers. The interobserver uncertainty of the landmark definition in our data sets is found to be 1.2±1.1mm. In general the deformable image registration tool decreases the extent of observable misalignments from 4‐8 mm to 1‐4 mm for nearly 50% of the landmarks (to 77% in sum). Only small differences are observed in the alignment quality of scans with different tumor location. Smallest residual deviations were achieved in scans of the head and neck region (79%,≤4mm) and the thoracic cases (79%,≤4mm), followed by the abdominal cases (59%,≤4mm). No difference is observed in the alignment quality of different tissue types (bony vs. soft tissue). The investigated commercially available deformable image registration tool is capable of reducing a mean target registration error to a level that is clinically acceptable for the evaluation of retreatment plans and replanning in case of gross tumor change during treatment. Yet, since the alignment quality needs to be improved further, the individual result of the deformable image registration tool has still to be judged by the physician prior to application. PACS numbers: 87.57.nj, 87.57.N‐, 87.55.‐x

The efficacy of radiation therapy treatments for pancreatic cancer is compromised by abdominal motion which limits the spatial accuracy for dose delivery - especially for particles. In this work we investigate the potential of worst case optimization for interfractional offline motion mitigation in carbon ion treatments of pancreatic cancer. We implement a worst case optimization algorithm that explicitly models the relative biological effectiveness of carbon ions during inverse planning. We perform a comparative treatment planning study for seven pancreatic cancer patients. Treatment plans that have been generated using worst case optimization are compared against (1) conventional intensity-modulated carbon ion therapy, (2) single field uniform dose carbon ion therapy, and (3) an ideal yet impractical scenario relying on daily re-planning. The dosimetric quality and robustness of the resulting treatment plans is evaluated using reconstructions of the daily delivered dose distributions on fractional control CTs. Idealized daily re-planning consistently gives the best dosimetric results with regard to both target coverage and organ at risk sparing. The absolute reduction of D 95 within the gross tumor volume during fractional dose reconstruction is most pronounced for conventional intensity-modulated carbon ion therapy. Single field uniform dose optimization exhibits no substantial reduction for six of seven patients and values for D 95 for worst case optimization fall in between. The treated volume (D>95 % prescription dose) outside of the gross tumor volume is reduced by a factor of two by worst case optimization compared to conventional optimization and single field uniform dose optimization. Single field uniform dose optimization comes at an increased radiation exposure of normal tissues, e.g. ≈2 Gy (RBE) in the mean dose in the kidneys compared to conventional and worst case optimization and ≈4 Gy (RBE) in D 1 in the spinal cord compared to worst case optimization. Interfractional motion substantially deteriorates dose distributions for carbon ion treatments of pancreatic cancer patients. Single field uniform dose optimization mitigates the negative influence of motion on target coverage at an increased radiation exposure of normal tissue. Worst case optimization enables an exploration of the trade-off between robust target coverage and organ at risk sparing during inverse treatment planning beyond margin concepts.

Objectives The current literature on stereotactic body radiotherapy (SBRT) for oligometastatic disease is characterized by small patient cohorts with heterogeneous primary tumors, metastases location and dose regimes. Hence, this study established a multi-institutional database of 700 patients treated with SBRT for pulmonary metastases to identify prognostic factors influencing survival and local control. Materials and methods All German radiotherapy departments were contacted and invited to participate in this analysis. A total number of 700 patients with medically inoperable lung metastases treated with SBRT in 20 centers between 1997 and 2014 were included in a database. Primary and metastatic tumor characteristics, treatment characteristics and follow-up data including survival, local control, distant metastases, and toxicity were evaluated. Lung metastases were treated with median PTV-encompassing single doses of 12.5 Gy (range 3.0–33.0 Gy) in a median number of 3 fractions (range 1–13). Results After a median follow-up time of 14.3 months, 2-year local control (LC) and overall survival (OS) were 81.2% and 54.4%, respectively. In multivariate analysis, OS was most significantly influenced by pretreatment performance status, maximum metastasis diameter, primary tumor histology, time interval between primary tumor diagnosis and SBRT treatment and number of metastases. For LC, independent prognostic factors were pretreatment performance status, biological effective dose (BED) at PTV isocenter (BEDISO) and single fraction (PTV-encompassing) dose in multivariate analysis. Radiation-induced pneumonitis grade 2 or higher was observed in 6.5% of patients. The only factor significantly influencing toxicity was BEDISO (p = 0.006). Conclusion SBRT for medically inoperable patients with pulmonary metastases achieved excellent local control and promising overall survival. Important prognostic factors were identified for selecting patients who might benefit most from this therapy approach.

Purpose Most radiobiological models for prediction of tumor control probability (TCP) do not account for the fact that many events could remain unobserved because of censoring. We therefore evaluated a set of TCP models that take into account this censoring. Methods and Materials We applied 2 fundamental Bayesian cure rate models to a sample of 770 pulmonary metastasis treated with stereotactic body radiation therapy at German, Austrian, and Swiss institutions: ( 1 ) the model developed by Chen, Ibrahim and Sinha (the CIS99 model); and ( 2 ) a mixture model similar to the classic model of Berkson and Gage (the BG model). In the CIS99 model the number of clonogens surviving the radiation treatment follows a Poisson distribution, whereas in the BG model only 1 dominant recurrence-competent tissue mass may remain. The dose delivered to the isocenter, tumor size and location, sex, age, and pretreatment chemotherapy were used as covariates for regression. Results Mean follow-up time was 15.5 months (range: 0.1-125). Tumor recurrence occurred in 11.6% of the metastases. Delivered dose, female sex, peripheral tumor location and having received no chemotherapy before RT were associated with higher TCP in all models. Parameter estimates of the CIS99 were consistent with the classical Cox proportional hazards model. The dose required to achieve 90% tumor control after 15.5 months was 146 (range: 114-188) Gy 10 in the CIS99 and 133 (range: 101-164) Gy 10 in the BG model; however, the BG model predicted lower tumor control at long ( ≳ 20 months) follow-up times and gave a suboptimal fit to the data compared to the CIS99 model. Conclusions Biologically motivated cure rate models allow adding the time component into TCP modeling without being restricted to the follow-up period which is the case for the Cox model. In practice, application of such models to the clinical setting could allow for adaption of treatment doses depending on whether local control should be achieved in the short or longer term.

To evaluate whether local tumor control probability (TCP) in stereotactic body radiotherapy (SBRT) varies between lung metastases of different primary cancer sites and between primary non-small cell lung cancer (NSCLC) and secondary lung tumors.A retrospective multi-institutional (n=22) database of 399 patients with stage I NSCLC and 397 patients with 525 lung metastases was analyzed. Irradiation doses were converted to biologically effective doses (BED). Logistic regression was used for local tumor control probability (TCP) modeling and the second-order bias corrected Akaike Information Criterion was used for model comparison.After median follow-up of 19 months and 16 months (n.s.), local tumor control was observed in 87.7% and 86.7% of the primary and secondary lung tumors (n.s.), respectively. A strong dose-response relationship was observed in the primary NSCLC and metastatic cohort but dose-response relationships were not significantly different: the TCD90 (dose to achieve 90% TCP; BED of maximum planning target volume dose) estimates were 176 Gy (151-223) and 160 Gy (123-237) (n.s.), respectively. The dose-response relationship was not influenced by the primary cancer site within the metastatic cohort.Dose-response relationships for local tumor control in SBRT were not different between lung metastases of various primary cancer sites and between primary NSCLC and lung metastases.

Several prognostic factors for local tumor control probability (TCP) after stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) have been described, but no attempts have been undertaken to explore whether a nonlinear combination of potential factors might synergistically improve the prediction of local control.We investigated a support vector machine (SVM) for predicting TCP in a cohort of 399 patients treated at 13 German and Austrian institutions. Among 7 potential input features for the SVM we selected those most important on the basis of forward feature selection, thereby evaluating classifier performance by using 10-fold cross-validation and computing the area under the ROC curve (AUC). The final SVM classifier was built by repeating the feature selection 10 times with different splitting of the data for cross-validation and finally choosing only those features that were selected at least 5 out of 10 times. It was compared with a multivariate logistic model that was built by forward feature selection.Local failure occurred in 12% of patients. Biologically effective dose (BED) at the isocenter (BED(ISO)) was the strongest predictor of TCP in the logistic model and also the most frequently selected input feature for the SVM. A bivariate logistic function of BED(ISO) and the pulmonary function indicator forced expiratory volume in 1 second (FEV1) yielded the best description of the data but resulted in a significantly smaller AUC than the final SVM classifier with the input features BED(ISO), age, baseline Karnofsky index, and FEV1 (0.696 ± 0.040 vs 0.789 ± 0.001, P.03). The final SVM resulted in sensitivity and specificity of 67.0% ± 0.5% and 78.7% ± 0.3%, respectively.These results confirm that machine learning techniques like SVMs can be successfully applied to predict treatment outcome after SBRT. Improvements over traditional TCP modeling are expected through a nonlinear combination of multiple features, eventually helping in the task of personalized treatment planning.

Background: The aim of this trial was to investigate neurological outcome after emergency RT in MSCC of NSCLC patients with acute neurological deficit. Methods This pilot trial was prospective, non-randomized, and monocentre, ten patients were treated from July 2012 until June 2013. After onset of neurological symptoms RT was started within 12 hours. The neurological outcome was assessed at baseline, and six weeks after RT using the ASIA Impairment Scale (AIS). Results: The results showed an improved neurological outcome in one patient (10%), one patient (10%) had a decreased, and five patients (50%) a constant outcome after six weeks. Three patients (30%) died within the first six weeks following RT, additional 4 patients (40%) died within 4 month due to tumor progression. Conclusion: In this group of NSCLC patients we were able to show that emergency RT in MSCC with acute neurological deficit had no considerable benefit in neurological outcome. Therefore, short-course regime or best supportive care due to poor survival should be considered for these patients with additional distant metastases. Patients with favorable prognosis may be candidates for long-course RT. Trial Registration: Clinical trial identifier http://www.clinicaltrials.gov/

Background To retrospectively access outcome and toxicity of whole brain radiotherapy (WBRT) in patients with multiple brain metastases (BM) from malignant melanoma (MM). Patients and methods Results of 87 patients (median age 58 years; 35 female, 52 male) treated by WBRT for BM of MM between 2000 and 2011 were reviewed. Total dose applied was either 30 Gy in 10 fractions (n = 56) or 40 Gy in 20 fractions (n = 31). All but 9 patients suffered from extra-cerebral metastases. Prior surgical resection of BM was performed in 18 patients, salvage stereotactic radiosurgery in 13 patients. Results Mean follow-up was 8 months (range, 0–57 months), the 6- and 12-months overall-(OS) survival rates were 29.2% and 16.5%, respectively. The median OS was 3.5 months. In cerebral follow-up imaging 6 (11) patients showed a complete (partial) remission, while 11 (17) patients had stable disease (intra-cerebral tumor progression). In comparison of total dose, the group treated with 40 Gy in 20 fractions achieved a significant longer OS (p = 0.003, median 3.1 vs. 5.6 months). Furthermore, DS-GPA score (p Conclusion Treatment of BM from MM with WBRT is tolerated well and some remissions of BM could be achieved. An advantage for higher treatment total doses was seen. However, outcome is non-satisfying, and further improvements in treatment of BM from MM are warranted.

Background The prognosis for patients with advanced FIGO stage III epithelial ovarian cancer remains poor despite the aggressive standard treatment, consisting of maximal cytoreductive surgery and platinum-based chemotherapy. The median time to recurrence is less than 2 years, with a 5-years survival rate of -20-25%. Recurrences of the disease occur mostly intraperitoneally. Ovarian cancer is a radiosensitive tumor, so that the use of whole abdominal radiotherapy (WAR) as a consolidation therapy would appear to be a logical strategy. WAR used to be the standard treatment after surgery before the chemotherapy era; however, it has been almost totally excluded from the treatment of ovarian cancer during the past decade because of its high toxicity. Modern intensity-modulated radiation therapy (IMRT) has the potential of sparing organs at risk like kidneys, liver, and bone marrow while still adequately covering the peritoneal cavity with a homogenous dose. Our previous phase I study showed for the first time the clinical feasibility of intensity-modulated WAR and pointed out promising results concerning treatment tolerance. The current phase-II study succeeds to the phase-I study to further evaluate the toxicity of this new treatment. Methods/design The OVAR-IMRT-02 study is a single-center one arm phase-II trial. Thirty seven patients with optimally debulked ovarian cancer stage FIGO III having a complete remission after chemotherapy will be treated with intensity-modulated WAR as a consolidation therapy. A total dose of 30 Gy in 20 fractions of 1.5 Gy will be applied to the entire peritoneal cavity including the liver surface and the pelvic and para-aortic node regions. Organ at risk are kidneys, liver (except the 1 cm-outer border), heart, vertebral bodies and pelvic bones. Primary endpoint is tolerability; secondary objectives are toxicity, quality of life, progression-free and overall survival. Discussion Intensity-modulated WAR provides a new promising option in the consolidation treatment of ovarian carcinoma in patients with a complete pathologic remission after adjuvant chemotherapy. Further consequent studies will be needed to enable firm conclusions regarding the value of consolidation radiotherapy within the multimodal treatment of advanced ovarian cancer. Trial registration Clinicaltrials.gov: NCT01180504

Adjuvant and salvage radiotherapy of the prostate bed are established treatment options for prostate cancer. While the benefit of an additional radiotherapy of the pelvic lymph nodes is still under debate, the PLATIN 3 prospective phase II clinical trial was initiated to substantiate toxicity data on postoperative IMRT of the pelvic lymph nodes and the prostate bed. From 2009 to 2011, 40 patients with high-risk prostate cancer after prostatectomy with pT3 R0/1 M0 or pT2 R1 M0 or a PSA recurrence and either > 20% risk of lymph node involvement and inadequate lymphadenectomy or pN + were enrolled. Patients received two months of antihormonal treatment (AT) before radiotherapy. AT continuation was mandatory during radiotherapy and was recommended for another two years. IMRT of the pelvic lymph nodes (51.0 Gy) with a simultaneous integrated boost to the prostate bed (68.0 Gy) was performed in 34 fractions. PSA level, prostate-related symptoms and quality of life were assessed at regular intervals for 24 months. Of the 40 patients enrolled, 39 finished treatment as planned. Overall acute toxicity rates were low and no acute grade 3/4 toxicity occurred. Only 22.5% of patients experienced acute grade 2 gastrointestinal (GI) and genitourinary (GU) toxicity. During follow-up, 10.0% late grade 2 GI and 5.0% late grade 2 GU toxicity occurred, and one patient developed late grade 3 proctitis and enteritis. After a median observation time of 24 months the PLATIN 3 trial has shown in 97.5% of all patients sufficient safety and thus met its prospectively defined aims. After a median of 24 months, 34/38 patients were free of a PSA recurrence. Postoperative whole-pelvis IMRT with an integrated boost to the prostate bed can be performed safely and without excessive toxicity. Trial Numbers: ARO 2009–05, ClinicalTrials.gov: NCT01903408 .

Background Radiation therapy is an essential modality in the treatment of breast cancer. Addition of radiotherapy to surgery has significantly increased local control and survival rates of the disease. However, radiotherapy is also associated with side effects, such as tissue fibrosis or enhanced vascular morbidity. Modern radiotherapy strategies, such as intensity modulated radiotherapy (IMRT), can shorten the overall treatment time by integration of the additional tumor bed boost significantly. To what extent this might be possible without impairing treatment outcome and cosmetic results remains to be clarified. Methods/Design The IMRT-MC2 study is a prospective, two armed, multicenter, randomized phase-III-trial comparing intensity modulated radiotherapy with integrated boost to conventional radiotherapy with consecutive boost in patients with breast cancer after breast conserving surgery. 502 patients will be recruited and randomized into two arms: patients in arm A will receive IMRT in 28 fractions delivering 50.4 Gy to the breast and 64.4 Gy to the tumor bed by integrated boost, while patients in arm B will receive conventional radiotherapy of the breast in 28 fractions to a dose of 50.4 Gy and consecutive boost in 8 fractions to a total dose of 66.4 Gy. Discussion Primary objectives of the study are the evaluation of the cosmetic results 6 weeks and 2 years post treatment and the 2- and 5-year local recurrence rates for the two different radiotherapy strategies. Secondary objectives are long term overall survival, disease free survival and quality of life. Trial Registration ClinicalTrials.gov Protocol ID: NCT01322854.

Purpose Multi-parametric magnetic resonance imaging (MP-MRI) is currently the most comprehensive work up for non-invasive primary tumor staging of prostate cancer (PCa). Prostate-specific membrane antigen (PSMA)-Positron emission tomography–computed tomography (PET/CT) is presented to be a highly promising new technique for N- and M-staging in recurrent PCa-patients. The actual investigation analyses the potential of 68Ga-PSMA11-PET/CT to assess the extent of primary prostate cancer by intra-individual comparison to MP-MRI. Methods In a retrospective study, ten patients with primary PCa underwent MP-MRI and PSMA-PET/CT for initial staging. All tumors were proven histopathological by biopsy. Image analysis was done in a quantitative (SUVmax) and qualitative (blinded read) fashion based on PI-RADS. The PI-RADS schema was then translated into a 3D-matrix and the euclidian distance of this coordinate system was used to quantify the extend of agreement. Results Both MP-MRI and PSMA-PET/CT presented a good allocation of the PCa, which was also in concordance to the tumor location validated in eight-segment resolution by biopsy. An Isocontour of 50 % SUVmax in PSMA-PET resulted in visually concordant tumor extension in comparison to MP-MRI (T2w and DWI). For 89.4 % of sections containing a tumor according to MP-MRI, the tumor was also identified in total or near-total agreement (euclidian distance ≤1) by PSMA-PET. Vice versa for 96.8 % of the sections identified as tumor bearing by PSMA-PET the tumor was also found in total or near-total agreement by MP-MRI. Conclusions PSMA-PET/CT and MP-MRI correlated well with regard to tumor allocation in patients with a high pre-test probability for large tumors. Further research will be needed to evaluate its value in challenging situation such as prostatitis or after repeated negative biopsies.

Background Even today, treatment of Stage III NSCLC still poses a serious challenge. So far, surgical resection is the treatment of choice. Patients whose tumour is not resectable or who are unfit to undergo surgery are usually referred to a combined radio-chemotherapy. However, combined radio-chemotherapeutic treatment is also associated with sometimes marked side effects but has been shown to be more efficient than radiation therapy alone. Nevertheless, there is a significant subset of patients whose overall condition does not permit administration of chemotherapy in a combined-modality treatment. It could be demonstrated though, that NSCLCs often exhibit over-expression of EGF-receptors hence providing an excellent target for the monoclonal EGFR-antagonist cetuximab (Erbitux®) which has already been shown to be effective in colorectal as well as head-and-neck tumours with comparatively mild side-effects. Methods/design The NEAR trial is a prospective phase II feasibility study combining a monoclonal EGF-receptor antibody with loco-regional irradiation in patients with stage III NSCLC. This trial aims at testing the combination's efficacy and rate of development of distant metastases with an accrual of 30 patients. Patients receive weekly infusions of cetuximab (Erbitux®) plus loco-regional radiation therapy as intensity-modulated radiation therapy. After conclusion of radiation treatment patients continue to receive weekly cetuximab for 13 more cycles. Discussion The primary objective of the NEAR trial is to evaluate toxicities and feasibility of the combined treatment with cetuximab (Erbitux®) and IMRT loco-regional irradiation. Secondary objectives are remission rates, 3-year-survival and local/systemic progression-free survival.