A. Lundin

Pelvic Radiotherapy for Cancer of the Cervix: Is What You Plan Actually What You Deliver?

PURPOSE Whole pelvic intensity-modulated radiotherapy (IMRT) is increasingly being used to treat cervix cancer and other gynecologic tumors. However, tumor and normal organ movement during treatment can substantially detract from the benefits of this approach. This study explored the effect of internal anatomic changes on the dose delivered to the tumor and organs at risk using a strategy integrating deformable soft-tissue modeling with simulated dose accumulation. METHODS AND MATERIALS Twenty patients with cervix cancer underwent baseline and weekly pelvic magnetic resonance imaging during treatment. Interfraction organ motion and delivered (accumulated) dose was modeled for three treatment scenarios: four-field box, large-margin whole pelvic IMRT (20-mm planning target volume, but 10 mm inferiorly) and small-margin IMRT (5-mm planning target volume). RESULTS Individually, the planned dose was not the same as the simulated delivered dose; however, when taken as a group, this was not statistically significant for the four-field box and large-margin IMRT plans. The small-margin IMRT plans yielded adequate target coverage in most patients; however, significant target underdosing occurred in 1 patient who displayed excessive, unpredictable internal target movement. The delivered doses to the organs at risk were significantly reduced with the small-margin plan, although substantial variability was present among the patients. CONCLUSION Simulated dose accumulation might provide a more accurate depiction of the target and organ at risk coverage during fractionated whole pelvic IMRT for cervical cancer. The adequacy of primary tumor coverage using 5-mm planning target volume margins is contingent on the use of daily image-guided setup.

Automated Weekly Replanning for Intensity-Modulated Radiotherapy of Cervix Cancer

PURPOSE The adoption of intensity-modulated radiotherapy (IMRT) to treat cervical malignancies has been limited in part by complex organ and tumor motion during treatment. This study explores the limits of a highly adaptive, small-margin treatment scenario to accommodate this motion. In addition, the dosimetric consequences of organ and tumor motion are modeled using a combination of deformable registration and fractional dose accumulation techniques. METHODS AND MATERIALS Thirty-three cervix cancer patients had target volumes and organs-at-risk contoured on fused, pretreatment magnetic resonance-computed tomography images and weekly magnetic resonance scans taken during treatment. The dosimetric impact of interfraction organ and target motion was compared for two hypothetical treatment scenarios: a 3-mm margin plan with no replanning, and a 3-mm margin plan with an automated replan performed on the updated weekly patient geometry. RESULTS Of the 33 patients, 24 (73%) met clinically acceptable target coverage (98% of the clinical target volume receiving at least 95% of the prescription dose) using the 3-mm margin plan without replanning. The range in dose to 98% of the clinical target volume across all patients was 7.9% of the prescription dose if no replanning was performed. After weekly replanning, this range was tightened to 2.6% of the prescription dose and all patients met clinically acceptable target coverage while maintaining organ-at-risk dose sparing. CONCLUSIONS The dosimetric impact of anatomical motion underscores the challenges of applying IMRT to treat cervix cancer. An appropriate adaptive strategy can ensure target coverage for small-margin IMRT treatments and maintain favorable organ-at-risk dose sparing.

Hybrid adaptive radiotherapy with on-line MRI in cervix cancer IMRT

PURPOSE Substantial organ motion and tumor shrinkage occur during radiotherapy for cervix cancer. IMRT planning studies have shown that the quality of radiation delivery is influenced by these anatomical changes, therefore the adaptation of treatment plans may be warranted. Image guidance with off-line replanning, i.e. hybrid-adaptation, is recognized as one of the most practical adaptation strategies. In this study, we investigated the effects of soft tissue image guidance using on-line MR while varying the frequency of off-line replanning on the adaptation of cervix IMRT. MATERIALS AND METHOD 33 cervical cancer patients underwent planning and weekly pelvic MRI scans during radiotherapy. 5 patients of 33 were identified in a previous retrospective adaptive planning study, in which the coverage of gross tumor volume/clinical target volume (GTV/CTV) was not acceptable given single off-line IMRT replan using a 3mm PTV margin with bone matching. These 5 patients and a randomly selected 10 patients from the remaining 28 patients, a total of 15 patients of 33, were considered in this study. Two matching methods for image guidance (bone to bone and soft tissue to dose matrix) and three frequencies of off-line replanning (none, single, and weekly) were simulated and compared with respect to target coverage (cervix, GTV, lower uterus, parametrium, upper vagina, tumor related CTV and elective lymph node CTV) and OAR sparing (bladder, bowel, rectum, and sigmoid). Cost (total process time) and benefit (target coverage) were analyzed for comparison. RESULTS Hybrid adaptation (image guidance with off-line replanning) significantly enhanced target coverage for both 5 difficult and 10 standard cases. Concerning image guidance, bone matching was short of delivering enough doses for 5 difficult cases even with a weekly off-line replan. Soft tissue image guidance proved successful for all cases except one when single or more frequent replans were utilized in the difficult cases. Cost and benefit analysis preferred (soft tissue) image guidance over (frequent) off-line replanning. CONCLUSIONS On-line MRI based image guidance (with combination of dose distribution) is a crucial element for a successful hybrid adaptive radiotherapy. Frequent off-line replanning adjuvantly enhances adaptation quality.

Dosimetrically triggered adaptive intensity modulated radiation therapy for cervical cancer.

PURPOSE The widespread use of intensity modulated radiation therapy (IMRT) for cervical cancer has been limited by internal target and normal tissue motion. Such motion increases the risk of underdosing the target, especially as planning margins are reduced in an effort to reduce toxicity. This study explored 2 adaptive strategies to mitigate this risk and proposes a new, automated method that minimizes replanning workload. METHODS AND MATERIALS Thirty patients with cervical cancer participated in a prospective clinical study and underwent pretreatment and weekly magnetic resonance (MR) scans over a 5-week course of daily external beam radiation therapy. Target volumes and organs at risk (OARs) were contoured on each of the scans. Deformable image registration was used to model the accumulated dose (the real dose delivered to the target and OARs) for 2 adaptive replanning scenarios that assumed a very small PTV margin of only 3 mm to account for setup and internal interfractional motion: (1) a preprogrammed, anatomy-driven midtreatment replan (A-IMRT); and (2) a dosimetry-triggered replan driven by target dose accumulation over time (D-IMRT). RESULTS Across all 30 patients, clinically relevant target dose thresholds failed for 8 patients (27%) if 3-mm margins were used without replanning. A-IMRT failed in only 3 patients and also yielded an additional small reduction in OAR doses at the cost of 30 replans. D-IMRT assured adequate target coverage in all patients, with only 23 replans in 16 patients. CONCLUSIONS A novel, dosimetry-triggered adaptive IMRT strategy for patients with cervical cancer can minimize the risk of target underdosing in the setting of very small margins and substantial interfractional motion while minimizing programmatic workload and cost.

TH‐E‐BRA‐08: MR Guided Radiotherapy for Cervix Cancer Treatment; Retrospective Feasibility Study

Purpose: To evaluate the efficacy of on‐line MR guided radiotherapy for cervix cancer patients. MR guidance was simulated in order to optimize the fractional dose to the on‐line targets. Methods: 33 cervical cancer patients underwent planning and weekly pelvic MRI scans during radiotherapy. In the previous retrospective adaptive planning study using 3 mm PTV margin, 5 over 33 patient cases were identified and enrolled in this study in which the coverage of GTV/CTVs was not acceptable with single IMRT adaptation with bone matching. MR guidance was simulated in order to maximize online high risk CTV (HRCTV) volume to be within 95% of the prescription dose (95p). Fractional dose after the image guidance was calculated, and was deformed back to the reference (planning) image for dose accumulation. Accumulated dose of the proposed technique was compared with that of current standard image guidance technique, bone matching in terms of the target coverage (cervix, GTV, HRCTV, lower uterus, parametria, and upper vagina) and OAR sparing (bladder, bowl, rectum, and sigmoid). Target coverage was considered acceptable if 95p dose or more was delivered to 98% of the target volume. OAR sparing was evaluated with accumulated V45 and D2cc. Results: On line MR based soft tissue guidance proposed in this study achieved the acceptance of target coverage to 97% from 53% (bone matching). Dose delivery to HRCTV and lower uterus was significantly improved (p<0.001, paired t‐test). The mean D2cc and V45 were reduced in bladder, rectum and sigmoid compared to bone matching. Conclusions: The retrospective study revealed that the on‐line MR based soft‐tissue image guidance is very effective for cervix cancer treatment. The technique significantly and successfully improved target coverage for the most difficult patient group identified from the previous study. Statistically significant improvement in OAR sparing was also noted. Anna Lundin and Henrik Rehbinder are both employees and shareholders of RaySearch Laboratories AB. All other authors have no conflicts to report.

56 DOSIMETRIC TREATMENT EVALUATION AND OPTIMIZED REPLANNING FOR IMRT OF CERVIX CANCER

Purpose: Palliative Radiotherapy (PRT) plays an important role in the relief of neurologic symptoms in patients with brain metastases; however, little is known about the use of PRT on a population level. The purpose of this study was to describe temporal trends in the use of PRT for brain metastases in Ontario. Methods: The Ontario Cancer Registry was used to gather information on all cancer deaths in Ontario between the years 1984-2004. The proportion of these cases receiving at least one course of PRT for bone metastases within the last two years of life was described over time and by disease site. Results: There were 435,055 cancer deaths in Ontario during the study period. Of these cases, 4.0% received at least one course of PRT for brain mets within the last two years of life. The rate of PRT varied significantly by primary site (e.g. lung8.7%, breast-6.4%, kidney-5.0%, prostate-0.6%) (p<0.001). Over time, the proportion of cases receiving PRT for brain mets increased from 2.1% to 5.0% (p<0.001). This increasing trend remained significant after taking into account primary site, age, sex, and time from diagnosis till death (p<0.001). The rate over time also varied by primary site (e.g. lung5.3% to 11.2%, breast3.7% to 8.8%, kidney2.2% to 6.0%, prostate0 to 0.9%) (p<0.001). Conclusion: The rate of PRT for brain metastases in Ontario has significantly increased over time. Explanations for these trends will be discussed.

SU‐GG‐J‐102: Image Guided Radiotherapy of the Cervix with Biomechanical Model‐Based Deformable Registration

Purpose: Evaluate the potential geometric and dosimetric improvements in image‐guidedradiotherapy of the cervix using deformable registration. Method and Materials: Weekly MR images obtained prior to and during radiotherapy for 29 women with cervix cancer were selected. The bladder, rectum, and GTV were contoured on each image following rigid, bony anatomy based registration. Deformable registration was performed using MORFEUS, a multi‐organ finite element model‐based deformable registration algorithm. The bladder and rectum were explicitly registered between planning and each week. The GTV displacement was estimated by the biomechanical model and the bladder and rectum displacement. The improvements using couch shifts based on deformable registration were assessed using 3 metrics: 1) improvement in localization of tumor COM, 2) improvements in GTV coverage by the PTV, and 3) improvements in the dosimetric coverage of the GTV and CTV accumulated over the treatment using deformable dose accumulation in ORBIT Workstation. Results: The average error in COM alignment of the tumor improved by 0.3, 2.1, and 1.1 mm in the LR, AP, and SI directions, respectively with deformable registration. Following bony registration, 69% of GTVs were at least 95% covered by the PTV, improving to 86% following deformable registration. Dosimetric coverage of the GTV improved from 93% of patients achieving 98% volume coverage by 4900 cGy to 100% following deformable registration‐based couch shift for tumor COM correction. CTV coverage improved from 83% of patients achieving 98% volume coverage by 4750 cGy to 93% following deformable registration‐based couch shift for tumor COM correction. Conclusion: A method has been developed to perform deformable registration of surrounding anatomy to calculate the COM of the tumor for application in volumetric image guidance where the tumor is not visible. Both geometric and dosimetric improvements were demonstrated. Supported by RaySearch Laboratories and National Cancer Institute of Canada — Terry Fox Foundation.

SU‐GG‐T‐56: Planning Target Volume Adaptation Using Convex Hull of CTVs for Cervix Cancer Patients

Purpose: Adaptive IMRT planning studies have shown that intra‐ and inter‐fractional organ motion can significantly decrease the coverage of the clinical target volume (CTV) for cervix cancer patients. Adaptive mid‐treatment re‐planning was effective in minimizing CTV underdosage, but this strategy only worked for patients with consistent bladder filling. This study investigated planning target volume (PTV) adaptation using a convex hull (CH) technique for patients whose bladder filling is variable over the course of radiation treatment.Method and Materials: Nine cervix cancer patients with variable bladder filling during the treatment were selected from 35 patients enrolled in an adaptive IMRT planning study. All patients were MR‐scanned once for planning and weekly during treatment. CTV and organs at risk (OAR) were contoured on each MR scan fused to planning CT with bony alignment. Contours were converted to 3D surface meshes for deformation analysis considering tissuebiomechanics. Two MR scans with full/empty bladder were identified and an adaptive PTV was found using a convex hull algorithm in the research planning software. IMRT plans were generated on the CH PTV and accumulated dose on deformed organs were simulated. Results: The average volume of CH PTV was 16% larger than that of small margin (3mm) PTV (477vs411cc). Most of the volume increase was found in the area of rectum where the concavity of the CTV was largest. The CH PTV had a non‐uniform margin around CTV representing patient‐specific CTV motion and deformation. The CH plan maintained target coverage but increased dose at OARs compared to adaptive mid‐treatment re‐planning. Discussion: Adaptive planning strategy using convex hull of CTVs demonstrates good target coverage for cervix cancer patients with variable bladder filling. Refindment of the CH to spare OARs might allow a reduction in critical organdose while still maintaining target coverage.

TH‐E‐M100F‐01: Impact of Organ Motion On IMRT Dose Distributions for Patients with Cancer of the Cervix

Purpose: To investigate IMRT for treatment of cervical cancer and the need for adaptive treatment strategies. To use deformable dose registration to assess the effect of organ motion on dose.Method and Materials: Eight women with IB‐IVA cervix cancer were retrospectively selected. All patients had initial CT and MRI prior to treatment, and weekly MRI during external beam radiotherapy. Gross tumor volume, bladder, rectum, sigmoid, cervix, upper vagina, uterus and bilateral parametria regions were contoured on all MR. Clinical target volumes for tumor (HRCTV), pelvic nodes (nodeCTV) and vessels were contoured on the baseline MR. For each patient two IMRTtreatments were planned; Large Margin (LM) using 20mm margin for HRCTV (except inferiorly) and Small Margin (SM) using 5mm. For nodeCTV, 5mm margin was used. Surface‐mesh representations of the ROIs were propagated and conformed to corresponding contours from the weekly datasets. Meshes were exported to a research software, where the effect of organ motion was assessed by deformable dose registration. Results: Simulated treatment delivery, with deformable dose accumulation, showed that five out of eight patients would have achieved clinically approved target coverage from both LM and SM. For three patients, target coverage was unacceptable with SM. For one of those three, LM managed to fulfill target coverage. For all patients, SM showed better OAR protection than LM. Conclusion: The effect of organ motion on delivered dose has been studied by numerical simulation, showing that a large margin of 20mm cannot guarantee target coverage. For a majority of the patients, the smaller margin was enough to achieve full target coverage, this with enhanced OAR protection. This suggests large gain from more advanced patient specific margin recipes and adaptive treatment delivery. Conflict of Interest: This research was sponsored by RaySearch Laboratories, where some of the authors are employees and stock owners.