Clinical evaluation of synthetic computed tomography methods in adaptive proton therapy of lung cancer patients.

Background and purpose: Efficient workflows for adaptive proton therapy are of high importance. This study evaluated the possibility to replace repeat-CTs (reCTs) with synthetic CTs (sCTs), created based on cone-beam CTs (CBCTs), for flagging the need of plan adaptations in intensity-modulated proton therapy (IMPT) treatment of lung cancer patients. Materials and methods: Forty-two IMPT patients were retrospectively included. For each patient, one CBCT and a same-day reCT were included. Two commercial sCT methods were applied; one based on CBCT number correction (Cor-sCT), and one based on deformable image registration (DIR-sCT). The clinical reCT workflow (deformable contour propagation and robust dose re-computation) was performed on the reCT as well as the two sCTs. The deformed target contours on the reCT/sCTs were checked by radiation oncologists and edited if needed. A dose-volume-histogram triggered plan adaptation method was compared between the reCT and the sCTs; patients needing a plan adaptation on the reCT but not on the sCT were denoted false negatives. As secondary evaluation, dose-volume-histogram comparison and gamma analysis (2%/2mm) were performed between the reCT and sCTs. Results: There were five false negatives, two for Cor-sCT and three for DIR-sCT. However, three of these were only minor, and one was caused by tumour position differences between the reCT and CBCT and not by sCT quality issues. An average gamma pass rate of 93% was obtained for both sCT methods. Conclusion: Both sCT methods were judged to be of clinical quality and valuable for reducing the amount of reCT acquisitions.

Actual target coverage after setup verification using surgical clips compared with external skin markers in postoperative breast cancer radiation therapy.

PURPOSE: After changing from offline setup verification to online setup verification using external skin markers in breast cancer patients, we noticed an increase in localized acute skin toxicity beneath the markers. Also, in vivo 3-dimensional dose measurements showed deviations between the delivered and the planned dose distributions; therefore, we investigated the accuracy of setup verification using surgical clips in the tumor bed, with a focus on target coverage of whole breast and tumor bed. METHODS AND MATERIALS: Orthogonal kilovoltage images were acquired before every fraction in 35 breast cancer patients, deriving an online 3-dimensional setup error by matching on external skin markers. In retrospect, a rematch was performed using surgical clips. For 155 fractions (ie, 5-6 fractions/patient), a cone beam computed tomography (CT) scan was available. Analysis concerned: (1) visibility of the clips, (2) migration of the clips, (3) comparison of setup errors according to both match methods, and (4) comparison of target coverage by recalculating the dose on the online setup-corrected cone beam CT scan with the patient setup according to both match methods. External validation of the surgical clip-based online setup verification was performed in 23 patients by analyzing kilovoltage images of 100 fractions, obtained after treatment. RESULTS: All types of surgical clips could be visualized. The clip to center-of-mass distance decreased on average by 2 mm (standard deviation, 1) over the course of treatment. Setup differences between match methods were on average <0.5 mm in all directions. The reconstructed dose distributions showed standard deviations of volumes receiving 95% or 107% of prescribed dose and mean dose of the breast and boost planning target volume were similar for the planning CT and the cone beam CTs, for both match procedures. An external validation in 23 patients showed reassuring setup errors <2 mm. CONCLUSIONS: Online setup verification using surgical clips results in comparable setup corrections and target volume coverage as verification using skin markers. By omitting skin markers acute skin toxicity beneath the markers is prevented.

The PET-boost randomised phase II dose-escalation trial in non-small cell lung cancer.

PURPOSE: The local site of relapse in non-small cell lung cancer (NSCLC) is primarily located in the high FDG uptake region of the primary tumour prior to treatment. A phase II PET-boost trial (NCT01024829) randomises patients between dose-escalation of the entire primary tumour (arm A) or to the high FDG uptake region inside the primary tumour (>50% SUV(max)) (arm B), whilst giving 66 Gy in 24 fractions to involved lymph nodes. We analysed the planning results of the first 20 patients for which both arms A and B were planned. METHODS: Boost dose levels were escalated up to predefined normal tissue constraints with an equal mean lung dose in both arms. This also forces an equal mean PTV dose in both arms, hence testing pure dose-redistribution. Actual delivered treatment plans from the ongoing clinical trial were analysed. Patients were randomised between arms A and B if dose-escalation to the primary tumour in arm A of at least 72 Gy in 24 fractions could be safely planned. RESULTS: 15/20 patients could be escalated to at least 72 Gy. Average prescribed fraction dose was 3.27±0.31 Gy [3.01-4.28 Gy] and 3.63±0.54 Gy [3.20-5.40 Gy] for arms A and B, respectively. Average mean total dose inside the PTV of the primary tumour was comparable: 77.3±7.9 Gy vs. 77.5±10.1 Gy. For the boost region dose levels of on average 86.9±14.9 Gy were reached. No significant dose differences between both arms were observed for the organs at risk. Most frequent observed dose-limiting constraints were the mediastinal structures (13/15 and 14/15 for arms A and B, respectively), and the brachial plexus (3/15 for both arms). CONCLUSION: Dose-escalation using an integrated boost could be achieved to the primary tumour or high FDG uptake regions whilst keeping the pre-defined dose constraints.