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made between the two breathing traces to evaluate the phase shift in signal acquisition and the difference in breathing patterns. Two sets of 4DCT images with the same raw sinogram data for the same patient were reconstructed using the respiratory signals acquired by both systems. An amplitude-based sorting algorithm was applied to obtain the images of ten respiratory phases. The images reconstructed from the two different respiratory signals were compared for each individual phase. Image segmentation was performed in the treatment planning system to assess the differences in lung contours and the position of the diaphragm. Results: The phase shifts calculated by the time latency at the end inhalation between the two breathing traces were consistent for all ten patients and were measured as 0.2AE0.1 seconds. The breathing trace measured by the Anzai pressure sensor had a steeper falloff curve during exhalation than the RPM trace measured by the abdominal surface movement. In the 4DCT images reconstructed separately, changes in lung contouring and shifts in position of diaphragm were observed in each individual phase. Largest shifts of more than 5mm in the diaphragm location were found in phases between 40% exhalation and 20% inhalation. Conclusion: Phase shifts between breathing traces and differences in breathing patterns as measured by the abdominal pressure change and surface displacement were observed in this study. The internal thoracic motion during 4DCT scan can have different correlation relationships with different respiratory monitoring systems using external surrogates. This implicates that mixed use of different respiratory monitoring systems in 4DCT imaging for treatment planning and in respiratory gated treatment delivery may result in errors in the dose distribution received by the patient.

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The TARGIT E trial is an international single-arm trial (NCT01299987; Neumaier et al. BMC Cancer 2012) on risk-adapted therapy of elderly patients with low-risk breast cancer, consisting of a single dose of intraoperative radiotherapy (IORT), followed by whole breast radiotherapy (WBRT) in case risk factors are present. We here present the first per-protocol analysis of local recurrence rates and overall survival. Materials/Methods: Eligible patients (70 years, cT1/2 (< 3.5 cm), cN0, cM0, invasive carcinoma of no special type) were enrolled between February 2011 and September 2014. During breast-conserving surgery, a single dose of 20 Gy was applied using low-energy x-rays. In case risk factors (larger size, other histology, free margin < 1 cm, lymphatic vessel invasion, positive nodes, multifocal/-central lesions, extensive intraductal component) were present in the final pathology, patients received whole breast irradiation (46-50 Gy, 1.8-2.0 Gy per fraction). Systemic therapy was applied according to international standards and guidelines. The primary outcome was the local recurrence rate measured at 2.5,5 and 7.5 years using the Kaplan-Meier method. The secondary outcome was overall survival. Termination due to futility was deemed necessary in case local relapse rates exceeded 3/4/6% at 2.5/5/7.5 years. Results: A total of 541 patients were screened, 526 enrolled in the trial and 474 were included in this analysis (38 drop-outs, 13 withdrawals, 1 protocol violation). Of those, 347 (73%) received IORT only, 99 (21%) IORT plus WBRT, 22 (5 %) WBRT only and 7 (1%) surgery only with no subsequent adjuvant therapies. After a median follow-up of 3 years (range: 2-79 months), 4 ipsilateral in-breast recurrences after 11, 33, 42 and 43 months were observed, resulting in estimated local recurrence rates of 0.2 and 1.5% at 2.5 and 5 years. Overall, 20 patients died (3 breast-cancerrelated deaths, 17 non-breast-cancer-related deaths). Estimated overall survival rates at 2.5 and 5 years were 98.9% and 91.4%, respectively. Conclusion: The first per protocol analysis of the prospective TARGIT E trial shows that local relapse rates at 2.5 and 5 years are far below the predefined stopping rules. The current results therefore support the risk-adapted approach of accelerated partial breast radiotherapy (APBI) in selected patients.