Karen Lim

Consensus Guidelines for Delineation of Clinical Target Volume for Intensity-Modulated Pelvic Radiotherapy for the Definitive Treatment of Cervix Cancer

PURPOSE Accurate target definition is vitally important for definitive treatment of cervix cancer with intensity-modulated radiotherapy (IMRT), yet a definition of clinical target volume (CTV) remains variable within the literature. The aim of this study was to develop a consensus CTV definition in preparation for a Phase 2 clinical trial being planned by the Radiation Therapy Oncology Group. METHODS AND MATERIALS A guidelines consensus working group meeting was convened in June 2008 for the purposes of developing target definition guidelines for IMRT for the intact cervix. A draft document of recommendations for CTV definition was created and used to aid in contouring a clinical case. The clinical case was then analyzed for consistency and clarity of target delineation using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE), with kappa statistics as a measure of agreement between participants. RESULTS Nineteen experts in gynecological radiation oncology generated contours on axial magnetic resonance images of the pelvis. Substantial STAPLE agreement sensitivity and specificity values were seen for gross tumor volume (GTV) delineation (0.84 and 0.96, respectively) with a kappa statistic of 0.68 (p < 0.0001). Agreement for delineation of cervix, uterus, vagina, and parametria was moderate. CONCLUSIONS This report provides guidelines for CTV definition in the definitive cervix cancer setting for the purposes of IMRT, building on previously published guidelines for IMRT in the postoperative setting.

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.

A review of segmentation and deformable registration methods applied to adaptive cervical cancer radiation therapy treatment planning

OBJECTIVE Manual contouring and registration for radiotherapy treatment planning and online adaptation for cervical cancer radiation therapy in computed tomography (CT) and magnetic resonance images (MRI) are often necessary. However manual intervention is time consuming and may suffer from inter or intra-rater variability. In recent years a number of computer-guided automatic or semi-automatic segmentation and registration methods have been proposed. Segmentation and registration in CT and MRI for this purpose is a challenging task due to soft tissue deformation, inter-patient shape and appearance variation and anatomical changes over the course of treatment. The objective of this work is to provide a state-of-the-art review of computer-aided methods developed for adaptive treatment planning and radiation therapy planning for cervical cancer radiation therapy. METHODS Segmentation and registration methods published with the goal of cervical cancer treatment planning and adaptation have been identified from the literature (PubMed and Google Scholar). A comprehensive description of each method is provided. Similarities and differences of these methods are highlighted and the strengths and weaknesses of these methods are discussed. A discussion about choice of an appropriate method for a given modality is provided. RESULTS In the reviewed papers a Dice similarity coefficient of around 0.85 along with mean absolute surface distance of 2-4mm for the clinically treated volume were reported for transfer of contours from planning day to the treatment day. CONCLUSIONS Most segmentation and non-rigid registration methods have been primarily designed for adaptive re-planning for the transfer of contours from planning day to the treatment day. The use of shape priors significantly improved segmentation and registration accuracy compared to other models.

Consensus recommendations for radiation therapy contouring and treatment of vulvar carcinoma

PURPOSE The purpose of this study was to develop a radiation therapy (RT) contouring atlas and recommendations for women with postoperative and locally advanced vulvar carcinoma. METHODS AND MATERIALS An international committee of 35 expert gynecologic radiation oncologists completed a survey of the treatment of vulvar carcinoma. An initial set of recommendations for contouring was discussed and generated by consensus. Two cases, 1 locally advanced and 1 postoperative, were contoured by 14 physicians. Contours were compared and analyzed using an expectation-maximization algorithm for simultaneous truth and performance level estimation (STAPLE), and a 95% confidence interval contour was developed. The level of agreement among contours was assessed using a kappa statistic. STAPLE contours underwent full committee editing to generate the final atlas consensus contours. RESULTS Analysis of the 14 contours showed substantial agreement, with kappa statistics of 0.69 and 0.64 for cases 1 and 2, respectively. There was high specificity for both cases (≥99%) and only moderate sensitivity of 71.3% and 64.9% for cases 1 and 2, respectively. Expert review and discussion generated consensus recommendations for contouring target volumes and treatment for postoperative and locally advanced vulvar cancer. CONCLUSIONS These consensus recommendations for contouring and treatment of vulvar cancer identified areas of complexity and controversy. Given the lack of clinical research evidence in vulvar cancer radiation therapy, the committee advocates a conservative and consistent approach using standardized recommendations.

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.

High-risk CTV delineation for cervix brachytherapy: application of GEC-ESTRO guidelines in Australia and New Zealand

Image‐based brachytherapy for cervical cancer using MRI has been implemented in Australia and New Zealand. The aims of this study were to measure variability in High‐risk CTV (HR‐CTV) delineation and evaluate dosimetric consequences of this.

The impact of imaging modality (CT vs MRI) and patient position (supine vs prone) on tangential whole breast radiation therapy planning

PURPOSE The purpose of this study was to evaluate the impact of magnetic resonance imaging (MRI) versus computed tomography (CT)-derived planning target volumes (PTVs), in both supine and prone positions, for whole breast (WB) radiation therapy. METHODS AND MATERIALS Four WB radiation therapy plans were generated for 28 patients in which PTVs were generated based on CT or MRI data alone in both supine and prone positions. A 6-MV tangential intensity modulated radiation therapy technique was used, with plans designated as ideal, acceptable, or noncompliant. Dose metrics for PTVs and organs at risk were compared to analyze any differences based on imaging modality (CT vs MRI) or patient position (supine vs prone). RESULTS With respect to imaging modality 2/11 whole breast planning target volume (WB_PTV) dose metrics (percentage of PTV receiving 90% and 110% of prescribed dose) displayed statistically significant differences; however, these differences did not alter the average plan compliance rank. With respect to patient positioning, the odds of having an ideal plan versus a noncompliant plan were higher for the supine position compared with the prone position (P = .026). The minimum distance between the seroma cavity planning target volume (SC_PTV) and the chest wall was increased with prone positioning (P < .001, supine and prone values 1.1 mm and 8.7 mm, respectively). Heart volume was greater in the supine position (P = .005). Heart doses were lower in the supine position than prone (P < .01, mean doses 3.4 ± 1.55 Gy vs 4.4 ± 1.13 Gy for supine vs prone, respectively). Mean lung doses met ideal dose constraints in both positions, but were best spared in the prone position. The contralateral breast maximum dose to 1cc (D1cc) showed significantly lower doses in the supine position (P < .001, 4.64 Gy vs 9.51 Gy). CONCLUSIONS Planning with PTVs generated from MRI data showed no clinically significant differences from planning with PTVs generated from CT with respect to PTV and doses to organs at risk. Prone positioning within this study reduced mean lung dose and whole heart volumes but increased mean heart and contralateral breast doses compared with supine.

Image-Guidance in External Beam Planning for Locally Advanced Cervical Cancer

The use of highly conformal external beam radiotherapy may decrease toxicity and enhance tumor control. However, the marked tumor regression seen in cervix cancer during radiotherapy, combined with the complex organ motion of surrounding normal tissues, could also result in geographical target miss without appropriate imaging, contouring and planning expertise. As such, image guidance plays a vital role in the planning and treatment aspects of cervix cancer when highly conformal treatment is being considered. This chapter highlights the current data on tumor motion and regression as well as the emerging importance of the impact of normal tissue motion and deformation on radiotherapy planning and treatment. As emergent technologies advance, the feasibility of adaptive strategies will undoubtedly result in improvements in the outcomes of these patients.