Q. Jackie Wu

A planning quality evaluation tool for prostate adaptive IMRT based on machine learning

PURPOSE To ensure plan quality for adaptive IMRT of the prostate, we developed a quantitative evaluation tool using a machine learning approach. This tool generates dose volume histograms (DVHs) of organs-at-risk (OARs) based on prior plans as a reference, to be compared with the adaptive plan derived from fluence map deformation. METHODS Under the same configuration using seven-field 15 MV photon beams, DVHs of OARs (bladder and rectum) were estimated based on anatomical information of the patient and a model learned from a database of high quality prior plans. In this study, the anatomical information was characterized by the organ volumes and distance-to-target histogram (DTH). The database consists of 198 high quality prostate plans and was validated with 14 cases outside the training pool. Principal component analysis (PCA) was applied to DVHs and DTHs to quantify their salient features. Then, support vector regression (SVR) was implemented to establish the correlation between the features of the DVH and the anatomical information. RESULTS DVH/DTH curves could be characterized sufficiently just using only two or three truncated principal components, thus, patient anatomical information was quantified with reduced numbers of variables. The evaluation of the model using the test data set demonstrated its accuracy approximately 80% in prediction and effectiveness in improving ART planning quality. CONCLUSIONS An adaptive IMRT plan quality evaluation tool based on machine learning has been developed, which estimates OAR sparing and provides reference in evaluating ART.

Radiotherapy treatment plans with RapidArc for prostate cancer involving seminal vesicles and lymph nodes.

PURPOSE Dosimetric results and treatment delivery efficiency of RapidArc plans to those of conventional intensity-modulated radiotherapy (IMRT) plans were compared using the Eclipse treatment planning system for high-risk prostate cancer. MATERIALS AND METHODS This study included 10 patients. The primary planning target volume (PTV(P)) contained prostate, seminal vesicles, and pelvic lymph nodes with a margin. The boost PTV (PTV(B)) contained prostate and seminal vesicles with a margin. The total prescription dose was 75.6 Gy (46.8 Gy to PTV(P) and an additional 28.8 Gy to PTV(B); 1.8 Gy/fraction). Three plans were generated for each PTV: Multiple-field IMRT, one-arc RapidArc (1ARC), and two-arc RapidArc (2ARC). RESULTS In the primary IMRT with PTV(P), average mean doses to bladder, rectum and small bowel were lower by 5.9%, 7.7% and 4.3%, respectively, than in the primary 1ARC and by 3.6%, 4.8% and 3.1%, respectively, than in the primary 2ARC. In the boost IMRT with PTV(B), average mean doses to bladder and rectum were lower by 2.6% and 4.8% than with the boost 1ARC and were higher by 0.6% and 0.2% than with the boost 2ARC. Integral doses were 7% to 9% higher with RapidArc than with IMRT for both primary and boost plans. Treatment delivery time was reduced by 2-7 minutes using RapidArc. CONCLUSION For PTVs including prostate, seminal vesicles, and lymph nodes, IMRT performed better in dose sparing for bladder, rectum, and small bowel than did RapidArc. For PTVs including prostate and seminal vesicles, RapidArc with two arcs provided plans comparable to those for IMRT. The treatment delivery is more efficient with RapidArc.

Volumetric Arc Intensity–Modulated Therapy for Spine Body Radiotherapy: Comparison With Static Intensity-Modulated Treatment

PURPOSE This clinical study evaluates the feasibility of using volumetric arc-modulated treatment (VMAT) for spine stereotactic body radiotherapy (SBRT) to achieve highly conformal dose distributions that spare adjacent organs at risk (OAR) with reduced treatment time. METHODS AND MATERIALS Ten spine SBRT patients were studied retrospectively. The intensity-modulated radiotherapy (IMRT) and VMAT plans were generated using either one or two arcs. Planning target volume (PTV) dose coverage, OAR dose sparing, and normal tissue integral dose were measured and compared. Differences in treatment delivery were also analyzed. RESULTS The PTV DVHs were comparable between VMAT and IMRT plans in the shoulder (D(99%)-D(90%)), slope (D(90%)-D(10%)), and tail (D(10%)-D(1%)) regions. Only VMAT(2arc) had a better conformity index than IMRT (1.09 vs. 1.15, p = 0.007). For cord sparing, IMRT was the best, and VMAT(1arc) was the worst. Use of IMRT achieved greater than 10% more D(1%) sparing for six of 10 cases and 7% to 15% more D(10%) sparing over the VAMT(1arc). The differences between IMRT and VAMT(2arc) were smaller and statistically nonsignificant at all dose levels. The differences were also small and statistically nonsignificant for other OAR sparing. The mean monitor units (MUs) were 8711, 7730, and 6317 for IMRT, VMAT(1arc), and VMAT(2arc) plans, respectively, with a 26% reduction from IMRT to VMAT(2arc). The mean treatment time was 15.86, 8.56, and 7.88 min for IMRT, VMAT(1arc,) and VMAT(2arc). The difference in integral dose was statistically nonsignificant. CONCLUSIONS Although VMAT provided comparable PTV coverage for spine SBRT, 1arc showed significantly worse spinal cord sparing compared with IMRT, whereas 2arc was comparable to IMRT. Treatment efficiency is substantially improved with the VMAT.

STEREOTACTIC BODY RADIOTHERAPY FOR LESIONS OF THE SPINE AND PARASPINAL REGIONS

PURPOSE To describe our experience and clinical strategy for stereotactic body radiotherapy (SBRT) of spinal lesions. METHODS AND MATERIALS Thirty-two patients with 33 spinal lesions underwent computed tomography-based simulation while free breathing. Gross/clinical target volumes included involved portions of the vertebral body and paravertebral/epidural tumor. Planning target volume (PTV) expansion was 6 mm axially and 3 mm radially; the cord was excluded from the PTV. Biologic equivalent dose was calculated using the linear quadratic model with alpha/beta = 3 Gy. Treatment was linear accelerator based with on-board imaging; dose was adjusted to maintain cord dose within tolerance. Survival, local control, pain, and neurologic status were monitored. RESULTS Twenty-one patients are alive at 1 year (median survival, 14 months). Median follow-up is 6 months for all patients (7 months for survivors). Mean previous radiotherapy dose to 22 patients was 35 Gy, and median interval was 17 months. Renal (31%), breast, and lung (19% each) were the most common histologic sites. Three SBRT fractions (range, one to four fractions) of 7 Gy (range, 5-16 Gy) were delivered. Median cord and target biologic equivalent doses were 70 Gy(3) and 34.3 Gy(10), respectively. Thirteen patients reported complete and 17 patients reported partial pain relief at 1 month. There were four failures (mean, 5.8 months) with magnetic resonance imaging evidence of in-field progression. No dosimetric parameters predictive of failure were identified. No treatment-related toxicity was seen. CONCLUSIONS Spinal SBRT is effective in the palliative/re-treatment setting. Volume expansion must ensure optimal PTV coverage while avoiding spinal cord toxicity. The long-term safety of spinal SBRT and the applicability of the linear-quadratic model in this setting remain to be determined, particularly the time-adjusted impact of prior radiotherapy.

Quantitative analysis of the factors which affect the interpatient organ-at-risk dose sparing variation in IMRT plans

PURPOSE The authors present an evidence-based approach to quantify the effects of an array of patient anatomical features of the planning target volumes (PTVs) and organs-at-risk (OARs) and their spatial relationships on the interpatient OAR dose sparing variation in intensity modulated radiation therapy (IMRT) plans by learning from a database of high-quality prior plans. METHODS The authors formulized the dependence of OAR dose volume histograms (DVHs) on patient anatomical factors into feature models which were learned from prior plans by a stepwise multiple regression method. IMRT plans for 64 prostate, 82 head-and-neck (HN) treatments were used to train the models. Two major groups of anatomical features were considered in this study: the volumetric information and the spatial information. The geometry of OARs relative to PTV is represented by the distance-to-target histogram, DTH. Important anatomical and dosimetric features were extracted from DTH and DVH by principal component analysis. The final models were tested by additional 24 prostate and 24 HN plans. RESULTS Significant patient anatomical factors contributing to OAR dose sparing in prostate and HN IMRT plans have been analyzed and identified. They are: the median distance between OAR and PTV, the portion of OAR volume within an OAR specific distance range, and the volumetric factors: the fraction of OAR volume which overlaps with PTV and the portion of OAR volume outside the primary treatment field. Overall, the determination coefficients R(2) for predicting the first principal component score (PCS1) of the OAR DVH by the above factors are above 0.68 for all the OARs and they are more than 0.53 for predicting the second principal component score (PCS2) of the OAR DVHs except brainstem and spinal cord. Thus, the above set of anatomical features combined has captured significant portions of the DVH variations for the OARs in prostate and HN plans. To test how well these features capture the interpatient organ dose sparing variations in general, the DVHs and specific dose-volume indices calculated from the regression models were compared with the actual DVHs and dose-volume indices from each patients plan in the validation dataset. The dose-volume indices compared were V99%, V85%, and V50% for bladder and rectum in prostate plans and parotids median dose in HN plans. The authors found that for the bladder and rectum models, 17 out of 24 plans (71%) were within 6% OAR volume error and 21 plans (85%) were within 10% error; For the parotids model, the median dose values for 30 parotids out of 48 (63%) were within 6% prescription dose error and the values in 40 parotids (83%) were within 10% error. CONCLUSIONS Quantitative analysis of patient anatomical features and their correlation with OAR dose sparing has identified a number of important factors that explain significant amount of interpatient DVH variations in OARs. These factors can be incorporated into evidence-based learning models as effective features to provide patient-specific OAR dose sparing goals.

INTENSITY-MODULATED RADIATION THERAPY FOR ANAL MALIGNANCIES: A PRELIMINARY TOXICITY AND DISEASE OUTCOMES ANALYSIS

PURPOSE Intensity-modulated radiation therapy (IMRT) has the potential to reduce toxicities associated with chemoradiotherapy in the treatment of anal cancer. This study reports the results of using IMRT in the treatment of anal cancer. METHODS AND MATERIALS Records of patients with anal malignancies treated with IMRT at Duke University were reviewed. Acute toxicity was graded using the NCI CTCAEv3.0 scale. Overall survival (OS), metastasis-free survival (MFS), local-regional control (LRC) and colostomy-free survival (CFS) were calculated using the Kaplan-Meier method. RESULTS Forty-seven patients with anal malignancy (89% canal, 11% perianal skin) were treated with IMRT between August 2006 and September 2008. Median follow-up was 14 months (19 months for SCC patients). Median radiation dose was 54 Gy. Eight patients (18%) required treatment breaks lasting a median of 5 days (range, 2-7 days). Toxicity rates were as follows: Grade 4: leukopenia (7%), thrombocytopenia (2%); Grade 3: leukopenia (18%), diarrhea (9%), and anemia (4%); Grade 2: skin (93%), diarrhea (24%), and leukopenia (24%). The 2-year actuarial overall OS, MFS, LRC, and CFS rates were 85%, 78%, 90% and 82%, respectively. For SCC patients, the 2-year OS, MFS, LRC, and CFS rates were 100%, 100%, 95%, and 91%, respectively. CONCLUSIONS IMRT-based chemoradiotherapy for anal cancer results in significant reductions in normal tissue dose and acute toxicities versus historic controls treated without IMRT, leading to reduced rates of toxicity-related treatment interruption. Early disease-related outcomes seem encouraging. IMRT is emerging as a standard therapy for anal cancer.

Dosimetric characteristics of Novalis Tx system with high definition multileaf collimator

A new Novalis Tx system equipped with a high definition multileaf collimator (HDMLC) recently became available to perform both image-guided radiosurgery and conventional radiotherapy. It is capable of delivering a highly conformal radiation dose with three energy modes: 6 MV photon energy, 15 MV photon energy, and 6 MV photon energy in a stereotactic radiosurgery mode with 1000 MU/min dose rate. Dosimetric characteristics of the new Novalis Tx treatment unit with the HDMLC are systematically measured for commissioning. A high resolution diode detector and miniion-chamber detector are used to measure dosimetric data for a range of field sizes from 4 x 4 mm to 400 x 400 mm. The commissioned Novalis Tx system has passed the RPC stereotactic radiosurgery head phantom irradiation test. The Novalis Tx system not only expands its capabilities with three energy modes, but also achieves better beam conformity and sharer beam penumbra with HDMLC. Since there is little beam data information available for the new Novalis Tx system, we present in this work the dosimetric data of the new modality for reference and comparison.

ExacTrac X-ray 6 degree-of-freedom image-guidance for intracranial non-invasive stereotactic radiotherapy: Comparison with kilo-voltage cone-beam CT

BACKGROUND AND PURPOSE To compare the residual setup errors measured with ExacTrac X-ray 6 degree-of-freedom (6D) and cone-beam computed tomography (CBCT) for a head phantom and patients receiving intracranial non-invasive fractionated stereotactic radiotherapy (SRT). MATERIALS AND METHODS Setup data were collected on a Novalis Tx treatment unit for an anthropomorphic head phantom and 18 patients with intracranial tumors. Initial corrections were determined and corrected with the ExacTrac system only, and then the residual setup error was determined by means of three different procedures. These procedures included registrations of ExacTrac X-ray images with the corresponding digitally reconstructed radiographs (DRRs) using the ExacTrac 6D fusion, and registrations of CBCT images with the planning CT using both online 3D fusion and offline 6D fusion. The difference in residual setup errors between ExacTrac system and CBCT was computed. The impact of rotations on the difference was evaluated. RESULTS A modest difference in residual setup errors was found between ExacTrac system and CBCT. The root-mean-square (RMS) of the differences observed for translations was typically <0.5mm for phantom, and <1.5mm for patients, respectively. The RMS of the differences for rotation(s) was however <0.2 degree for phantom, and <1.0 degree for patients, respectively. The impact of rotation on the setup difference was minor but not negligible. CONCLUSIONS This study indicates that there is a general agreement between ExacTrac system and CBCT.

Impact of collimator leaf width and treatment technique on stereotactic radiosurgery and radiotherapy plans for intra- and extracranial lesions

BackgroundThis study evaluated the dosimetric impact of various treatment techniques as well as collimator leaf width (2.5 vs 5 mm) for three groups of tumors – spine tumors, brain tumors abutting the brainstem, and liver tumors. These lesions often present challenges in maximizing dose to target volumes without exceeding critical organ tolerance. Specifically, this study evaluated the dosimetric benefits of various techniques and collimator leaf sizes as a function of lesion size and shape.MethodsFifteen cases (5 for each site) were studied retrospectively. All lesions either abutted or were an integral part of critical structures (brainstem, liver or spinal cord). For brain and liver lesions, treatment plans using a 3D-conformal static technique (3D), dynamic conformal arcs (DARC) or intensity modulation (IMRT) were designed with a conventional linear accelerator with standard 5 mm leaf width multi-leaf collimator, and a linear accelerator dedicated for radiosurgery and hypofractionated therapy with a 2.5 mm leaf width collimator. For the concave spine lesions, intensity modulation was required to provide adequate conformality; hence, only IMRT plans were evaluated using either the standard or small leaf-width collimators.A total of 70 treatment plans were generated and each plan was individually optimized according to the technique employed. The Generalized Estimating Equation (GEE) was used to separate the impact of treatment technique from the MLC system on plan outcome, and t-tests were performed to evaluate statistical differences in target coverage and organ sparing between plans.ResultsThe lesions ranged in size from 2.6 to 12.5 cc, 17.5 to 153 cc, and 20.9 to 87.7 cc for the brain, liver, and spine groups, respectively. As a group, brain lesions were smaller than spine and liver lesions. While brain and liver lesions were primarily ellipsoidal, spine lesions were more complex in shape, as they were all concave. Therefore, the brain and the liver groups were compared for volume effect, and the liver and spine groups were compared for shape. For the brain and liver groups, both the radiosurgery MLC and the IMRT technique contributed to the dose sparing of organs-at-risk(OARs), as dose in the high-dose regions of these OARs was reduced up to 15%, compared to the non-IMRT techniques employing a 5 mm leaf-width collimator. Also, the dose reduction contributed by the fine leaf-width MLC decreased, as dose savings at all levels diminished from 4 – 11% for the brain group to 1 – 5% for the liver group, as the target structures decreased in volume. The fine leaf-width collimator significantly improved spinal cord sparing, with dose reductions of 14 – 19% in high to middle dose regions, compared to the 5 mm leaf width collimator.ConclusionThe fine leaf-width MLC in combination with the IMRT technique can yield dosimetric benefits in radiosurgery and hypofractionated radiotherapy. Treatment of small lesions in cases involving complex target/OAR geometry will especially benefit from use of a fine leaf-width MLC and the use of IMRT.

Modeling the dosimetry of organ-at-risk in head and neck IMRT planning: An intertechnique and interinstitutional study

PURPOSE To build a statistical model to quantitatively correlate the anatomic features of structures and the corresponding dose-volume histogram (DVH) of head and neck (HN) Tomotherapy (Tomo) plans. To study if the model built upon one intensity modulated radiation therapy (IMRT) technique (such as conventional Linac) can be used to predict anticipated organs-at-risk (OAR) DVH of patients treated with a different IMRT technique (such as Tomo). To study if the model built upon the clinical experience of one institution can be used to aid IMRT planning for another institution. METHODS Forty-four Tomotherapy intensity modulate radiotherapy plans of HN cases (Tomo-IMRT) from Institution A were included in the study. A different patient group of 53 HN fixed gantry IMRT (FG-IMRT) plans was selected from Institution B. The analyzed OARs included the parotid, larynx, spinal cord, brainstem, and submandibular gland. Two major groups of anatomical features were considered: the volumetric information and the spatial information. The volume information includes the volume of target, OAR, and overlapped volume between target and OAR. The spatial information of OARs relative to PTVs was represented by the distance-to-target histogram (DTH). Important anatomical and dosimetric features were extracted from DTH and DVH by principal component analysis. Two regression models, one for Tomotherapy plan and one for IMRT plan, were built independently. The accuracy of intratreatment-modality model prediction was validated by a leave one out cross-validation method. The intertechnique and interinstitution validations were performed by using the FG-IMRT model to predict the OAR dosimetry of Tomo-IMRT plans. The dosimetry of OARs, under the same and different institutional preferences, was analyzed to examine the correlation between the model prediction and planning protocol. RESULTS Significant patient anatomical factors contributing to OAR dose sparing in HN Tomotherapy plans have been analyzed and identified. For all the OARs, the discrepancies of dose indices between the model predicted values and the actual plan values were within 2.1%. Similar results were obtained from the modeling of FG-IMRT plans. The parotid gland was spared in a comparable fashion during the treatment planning of two institutions. The model based on FG-IMRT plans was found to predict the median dose of the parotid of Tomotherapy plans quite well, with a mean error of 2.6%. Predictions from the FG-IMRT model suggested the median dose of the larynx, median dose of the brainstem and D2 of the brainstem could be reduced by 10.5%, 12.8%, and 20.4%, respectively, in the Tomo-IMRT plans. This was found to be correlated to the institutional differences in OAR constraint settings. Re-planning of six Tomotherapy patients confirmed the potential of optimization improvement predicted by the FG-IMRT model was correct. CONCLUSIONS The authors established a mathematical model to correlate the anatomical features and dosimetric indexes of OARs of HN patients in Tomotherapy plans. The model can be used for the setup of patient-specific OAR dose sparing goals and quality control of planning results.The institutional clinical experience was incorporated into the model which allows the model from one institution to generate a reference plan for another institution, or another IMRT technique.