M. Hawkins

Improving image-guided target localization through deformable registration

Purpose. To quantify the improvements in online target localization using kV cone beam CT (CBCT) with deformable registration. Methods and material. Twelve patients treated under a 6 fraction liver cancer radiation therapy protocol were imaged in breath hold using kV CBCT at each treatment fraction. The images were imported into the treatment planning software and rigidly registered by fitting the liver, identified on the daily kV CBCT image, into the liver contours, previously drawn on the planning CT. The liver was then manually contoured on each CBCT image. Deformable registration was automatically performed, aligning the CT liver to the liver on each CBCT image using MORFEUS, a biomechanical model based deformable registration algorithm. The tumor, defined on planning CT, was mapped onto the CBCT, through MORFEUS. The center of mass (COM) displacement of the tumor was computed. Results. The mean (SD) displacement magnitude (absolute value) of the COM following deformable registration was 0.08 (0.07), 0.10 (0.11), and 0.10 (0.17) cm in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. The maximum displacement of the COM was 0.34, 0.65, and 0.97 cm in the LR, AP, and SI directions, respectively. Fifteen percent of the treatment fractions had a COM displacement of greater than 0.3 cm and 33% of patients had at least 1 fraction with a displacement of greater than 0.3 cm. The deformable registration, excluding the manual contouring of the liver, was performed in less than 1 minute, on average. Discussion. Rigid registration of the liver volume between planning CT and verification kV CBCT localizes the tumor to within 0.3 cm for the majority (66%) of patients; however, larger offsets in tumor position can be observed due to liver deformation.

Oesophagectomy after Definitive Chemoradiation in Patients with Locally Advanced Oesophageal Cancer

AIMS The clinical benefit of salvage oesophagectomy in patients who recur after radical chemoradiotherapy (CRT) is not clearly defined. This study retrospectively evaluated the outcome in patients who underwent salvage oesophagectomy having failed primary CRT. MATERIALS AND METHODS Between March 1999 and October 2005, 181 patients with oesophageal cancer were treated at the Royal Marsden Hospital with definitive CRT. Ten patients underwent salvage oesophagectomy. All of them had locally advanced cancer of the oesophagus at presentation (adenocarcinoma in three patients and squamous cell carcinoma in seven patients) and received combined CRT, consisting of 12 weeks of cisplatin and 5-fluorouracil-based chemotherapy followed by CRT. Radiotherapy was delivered with a computed tomography-planned technique to a dose of 54 Gy with daily 5-fluorouracil. RESULTS An Ivor-Lewis procedure was carried out in all cases. The median time between the end of CRT and surgery was 5 months (range 1-67). Curative resection was achieved in three patients, seven had microscopic positive circumferential margins. One patient died postoperatively and complications occurred in four cases: anastomotic leak in two patients, pneumonia in one patient, empyema and sepsis in one patient. The median critical care unit stay was 7 days (range 4-26) and hospitalisation was 21 days (range 15-84). With a median follow-up period of 45.5 months (range 5-89) the 1-, 2- and 3-year survival calculated from the completion of CRT was 70, 50 and 30%, respectively. Median survival was 21.5 months (range 8-90). CONCLUSIONS Salvage oesophagectomy may prolong survival in carefully selected patients with local relapse. Patients fit for surgery at presentation benefit from a more intensive follow-up protocol to detect early recurrence.

The effect of treatment position, prone or supine, on dose–volume histograms for pelvic radiotherapy in patients with rectal cancer

Patients undergoing radiotherapy for rectal cancer are generally treated in a prone position, with a full bladder, to reduce the volume of normal bowel in the high-dose volume. This position is difficult to maintain, and is not consistently reproducible. This study evaluates the volume of bowel and dose received in the prone and supine positions in patients undergoing pre-operative rectal cancer chemoradiation. Using CT planning, 19 consecutive patients with rectal cancer with a full bladder underwent CT scanning first in the prone position and then immediately afterwards in the supine position. The planning target volume was outlined for the prone position and transcribed to the supine scan using pre-set criteria. The bladder and small bowel were outlined in both positions. Radiotherapy was planned using three-dimensional conformal planning, and treatment was delivered using three fields with multileaf collimators in two phases: phase I, pelvis 45 Gy/25 fractions; and phase II, tumour 9 Gy/five fractions. For both positions, the volume of bowel receiving doses in 5 Gy increments from 5-45 Gy was calculated using dose-volume histograms. At 5 Gy and 10 Gy dose levels, a significantly higher volume of bowel was irradiated in the supine position (p<0.001). At 15 Gy, it was marginally significant (p = 0.018). From 20-45 Gy, there was no significant difference in the volume of bowel irradiated with each 5 Gy increment. This study demonstrates that the volume of bowel irradiated at doses associated with bowel toxicity in concurrent chemoradiation is not significantly higher in the supine position. This position could be adopted for patients undergoing pre-operative rectal cancer chemoradiation.

Cone Beam Computed Tomography-Derived Adaptive Radiotherapy for Radical Treatment of Esophageal Cancer

PURPOSE To investigate the potential for reduction in normal tissue irradiation by creating a patient specific planning target volume (PTV) using cone beam computed tomography (CBCT) imaging acquired in the first week of radiotherapy for patients receiving radical radiotherapy. METHODS AND MATERIALS Patients receiving radical RT for carcinoma of the esophagus were investigated. The PTV is defined as CTV(tumor, nodes) plus esophagus outlined 3 to 5 cm cranio-caudally and a 1.5-cm circumferential margin is added (clinical plan). Prefraction CBCT are acquired on Days 1 to 4, then weekly. No correction for setup error made. The images are imported into the planning system. The tumor and esophagus for the length of the PTV are contoured on each CBCT and 5 mm margin is added. A composite volume (PTV1) is created using Week 1 composite CBCT volumes. The same process is repeated using CBCT Week 2 to 6 (PTV2). A new plan is created using PTV1 (adaptive plan). The coverage of the 95% isodose of PTV1 is evaluated on PTV2. Dose-volume histograms (DVH) for lungs, heart, and cord for two plans are compared. RESULTS A total of 139 CBCT for 14 cases were analyzed. For the adaptive plan the coverage of the 95% prescription isodose for PTV1 = 95.6% +/- 4% and the PTV2 = 96.8% +/- 4.1% (t test, 0.19). Lungs V20 (15.6 Gy vs. 10.2 Gy) and heart mean dose (26.9 Gy vs. 20.7 Gy) were significantly smaller for the adaptive plan. CONCLUSIONS A reduced planning volume can be constructed within the first week of treatment using CBCT. A single plan modification can be performed within the second week of treatment with considerable reduction in organ at risk dose.

Quantification of organ motion during chemoradiotherapy of rectal cancer using cone-beam computed tomography.

PURPOSE There has been no previously published data related to the quantification of rectal motion using cone-beam computed tomography (CBCT) during standard conformal long-course chemoradiotherapy. The purpose of the present study was to quantify the interfractional changes in rectal movement and dimensions and rectal and bladder volume using CBCT and to quantify the bony anatomy displacements to calculate the margins required to account for systematic (Σ) and random (σ) setup errors. METHODS AND MATERIALS CBCT images were acquired from 16 patients on the first 3 days of treatment and weekly thereafter. The rectum and bladder were outlined on all CBCT images. The interfraction movement was measured using fixed bony landmarks as references to define the rectal location (upper, mid, and low), The maximal rectal diameter at the three rectal locations was also measured. The bony anatomy displacements were quantified, allowing the calculation of systematic (Σ) and random (σ) setup errors. RESULTS A total of 123 CBCT data sets were analyzed. Analysis of variance for standard deviation from planning scans showed that rectal anterior and lateral wall movement differed significantly by rectal location. Anterior and lateral rectal wall movements were larger in the mid and upper rectum compared with the low rectum. The posterior rectal wall movement did not change significantly with the rectal location. The rectal diameter changed more in the mid and upper than in the low rectum. No consistent relationship was found between the rectal and bladder volume and time, nor was a significant relationship found between the rectal volume and bladder volume. CONCLUSIONS In the present study, the anterior and lateral rectal movement and rectal diameter were found to change most in the upper rectum, followed by the mid rectum, with the smallest changes seen in the low rectum. Asymmetric margins are warranted to ensure phase 2 coverage.

HER2 significance and treatment outcomes after radiotherapy for brain metastases in breast cancer patients

The aim of this retrospective study was to examine the influence of HER2 status on outcome in breast cancer patients following whole brain radiotherapy (WBRT) for cerebral metastases. One hundred and eighty one patients with recordable HER2 status, who received WBRT at single institution were identified and stratified according to HER2 status. Eighty eight were HER2 positive (HER2+) (49%) and 93 HER2 negative (HER2-) (51%). A total of 72 (82%) HER2+ group developed brain metastases whilst on chemotherapy compared with 45 (48%) in HER2- group. Median survival after WBRT was 8 months (1-38) for HER2+ patients and 4 (1-64) for HER2- patients p=0.01. On brain metastasis progression, 18 (20%) of HER2+ patients received further local therapy compared with 6 (6%) in HER2- group. This study shows superior survival in HER2+ group following WBRT as compared to HER2- group and more aggressive management on disease progression in HER2+ group.

Comparison of deliverable IMRT and VMAT for spine metastases using a simultaneous integrated boost

OBJECTIVE To effectively treat spine metastases, significant dose must be delivered to regions surrounding the spinal cord. We present a study comparing both step-and-shoot intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques to deliver a concomitant hypofractionated prescription dose to the diseased region and to the involved vertebrae. METHODS Seven-field IMRT and a single arc VMAT were inversely planned on five (two cervical and three thoracic) spinal metastatic patients. Planning target volumes PTVm (macroscopic) and PTVe (elective involved vertebrae) and associated organs at risk were localised. Mean doses of 35 Gy to PTVm and 20 Gy to PTVe were prescribed in five fractions. Dose statistics, estimated delivery time and results of verification using Delta(4) (ScandiDos, Uppsala, Sweden) were compared. RESULTS Deliverable plans were achieved with both IMRT and VMAT. The coverage to PTV was similar for both IMRT and VMAT (p=0.5) and the dose to the regions adjacent to the spinal cord was 1% higher with VMAT (p=0.04). The mean delivery time for VMAT was 3.5 min compared with 10.5 min for IMRT. Fewer monitor units were required to deliver IMRT than to deliver VMAT. The median (range) percentage of measured points with a γ-index <1 with 3%/3 mm was 100 (99.9-100)% for IMRT and 100 (88.5-100)% for VMAT. CONCLUSION Both VMAT and IMRT can deliver the concomitant hypofractionated regime proposed, and both offer different benefits in dose delivery. IMRT is currently preferred for its superior pre-treatment verification results and shorter planning times. ADVANCES IN KNOWLEDGE This study explores the feasibility of delivering tumouricidal doses of radiation to metastatic spine disease in the vicinity of the spinal cord.

Cone beam CT verification for oesophageal cancer - impact of volume selected for image registration.

Abstract Purpose. Oesophageal cancers are difficult to visualise on volumetric imaging and reliable surrogate are needed for accurate tumour registration. The aim of this investigation is to evaluate the effect of a user defined volume with automated registration techniques using commercially available software with the on-board volumetric imaging for treatment verification of oesophageal cancer and determine the optimum location of this volume. Material and methods. In 20 patients four ‘clipbox’(C) volumes were defined: C-planning target volume (PTV), C-carina, C-vertebrae, C-thorax. The set-up corrections (translational and rotational) for C-PTV were compared to the corrections using C-carina, C-vertebrae and C-thorax. Results. Six hundred and eight registrations were performed. The best concordance in set-up corrections was found in the superior/inferior direction between C-PTV and C-carina (76%). In the right/left and anterior/posterior direction, better agreement was found between C-PTV and C-thorax with 80% and 76% agreement, respectively. Automatic ‘bone’ registration using C-vertebrae failed in 28% of scans. The correlation ratio between C-PTV and C-carina (n = 4) for mid-oesophageal tumours was 0.88, 0.79, and 0.95 in the right/left, superior/inferior and anterior/posterior directions, respectively. Conclusion. The defined volume for matching is important for oesophageal tumours. The alignment ‘clipbox’ and registration method selected can affect the displacements obtained. This may best be determined by tumour location and highlights the need to diversify protocols within one tumour treatment site. Further analysis is required to validate carina as a tumour surrogate for mid-oesophageal tumours.

Dynamic shape instantiation for intra-operative guidance

Primary liver cancer and oligometastatic liver disease are one of the major causes of mortality worldwide and its treatment ranges from surgery to more minimally invasive ablative procedures. With the increasing availability of minimally invasive hepatic approaches, a real-time method of determining the 3D structure of the liver and its location during the respiratory cycle is clinically important. However, during treatment, it is difficult to acquire images spanning the entire 3D volume rapidly. In this paper, a dynamic 3D shape instantiation scheme is developed for providing subject-specific optimal scan planning. Using only limited planar information, it is possible to instantiate the entire 3D geometry of the organ of interest. The efficacy of the proposed method is demonstrated with both detailed numerical simulation and a liver phantom with known ground-truth data. Preliminary clinical application of the technique is evaluated on a patient group with metastatic liver tumours.

Fractionated radiosurgery for painful spinal metastases: DOSIS - a phase II trial

BackgroundOne third of all cancer patients will develop bone metastases and the vertebral column is involved in approximately 70% of these patients. Conventional radiotherapy with of 1–10 fractions and total doses of 8-30 Gy is the current standard for painful vertebral metastases; however, the median pain response is short with 3–6 months and local tumor control is limited with these rather low irradiation doses. Recent advances in radiotherapy technology – intensity modulated radiotherapy for generation of highly conformal dose distributions and image-guidance for precise treatment delivery – have made dose-escalated radiosurgery of spinal metastases possible and early results of pain and local tumor control are promising. The current study will investigate efficacy and safety of radiosurgery for painful vertebral metastases and three characteristics will distinguish this study. 1) A prognostic score for overall survival will be used for selection of patients with longer life expectancy to allow for analysis of long-term efficacy and safety. 2) Fractionated radiosurgery will be performed with the number of treatment fractions adjusted to either good (10 fractions) or intermediate (5 fractions) life expectancy. Fractionation will allow inclusion of tumors immediately abutting the spinal cord due to higher biological effective doses at the tumor - spinal cord interface compared to single fraction treatment. 3) Dose intensification will be performed in the involved parts of the vertebrae only, while uninvolved parts are treated with conventional doses using the simultaneous integrated boost concept.Methods / DesignIt is the study hypothesis that hypo-fractionated image-guided radiosurgery significantly improves pain relief compared to historic data of conventionally fractionated radiotherapy. Primary endpoint is pain response 3 months after radiosurgery, which is defined as pain reduction of ≥ 2 points at the treated vertebral site on the 0 to 10 Visual Analogue Scale. 60 patients will be included into this two-centre phase II trial.ConclusionsResults of this study will refine the methods of patient selection, target volume definition, treatment planning and delivery as well as quality assurance for radiosurgery. It is the intention of this study to form the basis for a future randomized controlled trial comparing conventional radiotherapy with fractionated radiosurgery for palliation of painful vertebral metastases.Trial registrationClinicalTrials.gov Identifier: NCT01594892