Gregory Kubicek

Quantifying Rigid and Nonrigid Motion of Liver Tumors During Stereotactic Body Radiation Therapy

PURPOSEnTo quantify rigid and nonrigid motion of liver tumors using reconstructed 3-dimensional (3D) fiducials from stereo imaging during CyberKnife-based stereotactic body radiation therapy (SBRT).nnnMETHODS AND MATERIALSnTwenty-three liver patients treated with 3 fractions of SBRT were used in this study. After 2 orthogonal kilovoltage images were taken during treatment, the 3D locations of the fiducials were generated by the CyberKnife system and validated using geometric derivations. A total of 4824 pairs of kilovoltage images from start to end of treatment were analyzed. For rigid motion, the rotational angles and translational shifts were reported by aligning 3D fiducial groups from different image pairs, using least-squares fitting. For nonrigid motion, we quantified interfractional tumor volume variations by using the proportional volume derived from the fiducials, which correlates to the sum of interfiducial distances. The individual fiducial displacements were also reported (1) after rigid corrections and (2) without angle corrections.nnnRESULTSnThe proportional volume derived by the fiducials demonstrated a volume-increasing trend in the second (101.9% ± 3.6%) and third (101.0 ± 5.9%) fractions among most patients, possibly due to radiation-induced edema. For all patients, the translational shifts in left-right, anteroposterior, and superoinferior directions were 2.1 ± 2.3 mm, 2.9 ± 2.8 mm, and 6.4 ± 5.5 mm, respectively. The greatest translational shifts occurred in the superoinferior direction, likely due to respiratory motion from the diaphragm. The rotational angles in roll, pitch, and yaw were 1.2° ± 1.8°, 1.8° ± 2.4°, and 1.7° ± 2.1°, respectively. The 3D individual fiducial displacements with rigid corrections were 0.2 ± 0.2 mm and increased to 0.5 ± 0.4 mm without rotational corrections.nnnCONCLUSIONSnAccurate 3D locations of internal fiducials can be reconstructed from stereo imaging during treatment. As an effective surrogate to tumor motion, fiducials provide a close estimation of both rigid and nonrigid motion of liver tumors. The reported displacements could be further utilized for tumor margin definition and motion management in conventional linear accelerator-based liver SBRT.

Stereotactic body radiotherapy as an alternative to brachytherapy in gynecologic cancer.

Introduction. Brachytherapy plays a key role in the treatment of many gynecologic cancers. However, some patients are unable to tolerate brachytherapy for medical or other reasons. For these patients, stereotactic body radiotherapy (SBRT) offers an alternative form of treatment. Methods. Retrospective review of patients prospectively collected on SBRT database is conducted. A total of 11 gynecologic patients who could not have brachytherapy received SBRT for treatment of their malignancies. Five patients have been candidates for interstitial brachytherapy, and six have required tandem and ovoid brachytherapy. Median SBRT dose was 25u2009Gy in five fractions. Results. At last followup, eight patients were alive, and three patients had died of progressive disease. One patient had a local recurrence. Median followup for surviving patients was 420 days (median followup for all patients was 120 days). Two patients had acute toxicity (G2 dysuria and G2 GI), and one patient had late toxicity (G3 GI, rectal bleeding requiring cauterization). Conclusions. Our data show acceptable toxicity and outcome for gynecologic patients treated with SBRT who were unable to receive a brachytherapy boost. This treatment modality should be further evaluated in a phase II study.

Biological implications of whole-brain radiotherapy versus stereotactic radiosurgery of multiple brain metastases

OBJECTnThe efficacy and safety of treatment with whole-brain radiotherapy (WBRT) or with stereotactic radiosurgery (SRS) for multiple brain metastases (> 10) are topics of ongoing debate. This study presents detailed dosimetric and biological information to investigate the possible clinical outcomes of these 2 modalities.nnnMETHODSnFive patients with multiple brain metastases (n = 11-23) underwent SRS. Whole-brain radiotherapy plans were retrospectively designed with the same MR image set and the same structure set for each patient, using the standard opposing lateral beams and fractionation (3 Gy × 10). Physical radiation doses and biologically effective doses (BEDs) in WBRT and SRS were calculated for each lesion target and for the normal brain tissues for comparison of the 2 modalities in the context of clinical efficacy and published toxicities.nnnRESULTSnThe BEDs targeted to the tumor were higher in SRS than in WBRT by factors ranging from 2.4- to 3.0- fold for the mean dose and from 3.2- to 5.3-fold for the maximum dose. In the 5 patients, mean BEDs in SRS (calculated as percentages of BEDs in WBRT) were 1.3%-34.3% for normal brain tissue, 0.7%-31.6% for the brainstem, 0.5%-5.7% for the chiasm, 0.2%-5.7% for optic nerves, and 0.6%-18.1% for the hippocampus.nnnCONCLUSIONSnThe dose-volume metrics presented in this study were essential to understanding the safety and efficacy of WBRT and SRS for multiple brain metastases. Whole-brain radiotherapy results in a higher incidence of radiation-related toxicities than SRS. Even in patients with > 10 brain metastases, the normal CNS tissues receive significantly lower doses in SRS. The mean normal brain dose in SRS correlated with the total volume of the lesions rather than with the number of lesions treated.

Validity of Current Stereotactic Body Radiation Therapy Dose Constraints for Aorta and Major Vessels

Understanding dose constraints for critical structures in stereotactic body radiation therapy (SBRT) is essential to generate a plan for optimal efficacy and safety. Published dose constraints are derived by a variety of methods, including crude statistics, actuarial analysis, modeling, and simple biologically effective dose (BED) conversion. Many dose constraints reported in the literature are not consistent with each other, secondary to differences in clinical and dosimetric parameters. Application of a dose constraint without discriminating the variation of all the factors involved may result in suboptimal treatment. This issue of Seminars in Radiation Oncology validates dose tolerance limits for 10 critical anatomic structures based on dose response modeling of clinical outcomes data to include detailed dose-volume metrics. This article presents a logistic dose-response model for aorta and major vessels based on 238 cases from the literature in addition to 387 cases from MD Anderson Cancer Center at Cooper University Hospital, for a total of 625 cases. The Radiation Therapy Oncology Group (RTOG) 0813 dose-tolerance limit of Dmax = 52.5Gy in 5 fractions was found to have a 1.2% risk of grade 3-5 toxicity, and the Timmerman 2008 limit of Dmax = 45Gy in 3 fractions had 2.3% risk. From the model, the 1% and 2% risk levels for D4cc, D1cc, and D0.5cc are also provided in 1-5 fractions, in the form of a dose-volume histogram (DVH) Risk Map.

Chemotherapy advances in locally advanced head and neck cancer

The management of locally advanced unresectable head and neck squamous cell cancer (HNSCC) continues to improve. One of the major advances in the treatment of HNSCC was the addition of chemotherapy to radiation in the treatment of non-surgical patients. The majority of the data regarding chemotherapy in HNSCC involve cisplatin chemotherapy with concurrent radiation. However, several new approaches have included targeted therapy against epidermal growth factor receptor and several recent studies have explored the role of induction chemotherapy in the treatment of HNSCC. The purpose of this article is to provide an overview of the role of chemotherapy in the treatment of locally advanced HNSCC.

Stereotactic Body Radiotherapy Treatment for Recurrent, Previously Irradiated Head and Neck Cancer

Purpose: Locally recurrent, previously irradiated primary head and neck tumors have historically been associated with poor outcomes. Stereotactic body radiation therapy has emerged as a feasible and promising treatment option for tumor recurrence, particularly in nonsurgical candidates. This study aimed to assess the associated outcomes of stereotactic body radiation therapy used in this setting. Methods: Retrospective analysis of a prospectively collected database of 25 patients treated with CyberKnife for unresectable, recurrent head and neck cancer in a previously irradiated field. The primary end points evaluated were rates of survival, tumor control, and treatment-related toxicities. Results: Median survival of the study population was 7.5 months (range, 1.5-47.0 months). Median survival of the 20 (80%) patients who were treated with curative purpose was 8.3 months. One-year overall survival rate for the entire population was 32%. The respective 1-year and 2-year survival rates for the curative subcohort were 40% and 20%, respectively. Local and locoregional failure occurred in 8 (32%) and 7 (28%) patients, respectively. Low severe acute (4%) and late (6%) treatment-related toxicity rates were observed. No grade 4 or 5 toxicities were observed. Conclusion: Stereotactic body radiation therapy is a viable treatment option for patients with unresectable, recurrent head and neck cancer. Significant tumor control rates are achievable with minimal severe toxicity. Although perhaps associated with patient selection and a heterogeneous sample, overall survival of stereotactic body radiation therapy outcomes appears unfavorable.

The dosimetric impact of the prescription isodose line (IDL) on the quality of robotic stereotactic radiosurgery (SRS) plans

Purpose: There is no consensus on the optimal prescription isodose line (IDL) in CyberKnife (CK) SRS. We designed a strategy to search for optimal CK plans at different levels of IDLs and investigated the dosimetric impact on the quality of CK plans. Methods and materials: The retrospective study consisted of 13 CK patients with 16 brain tumors. The mean volume and size of the tumors was 9.7 ± 10.4 cc and 30.3 ± 10.9 mm, respectively. Four shells were created at distances of 2–3 mm to 60 mm from the target. The constraint dose of the innermost shell (D1) was the primary optimization parameter. For isolated brain tumors, D1 started from the prescription dose and gradually reduced after optimization started over. The optimal plans were reached when the coverage started to degrade and the desired IDL was achieved. For eight tumors abutting an OAR, both the D1 and constraint dose to the OAR were gradually pushed until an optimal plan was reached for the desired IDL. Results: For the isolated tumors, the V5 Gy, V10 Gy, V15 Gy, V20 Gy, and V25 Gy of low IDL (49.6 ± 2.1%) plans were on average 23.6%, 28.6%, 33.8%, 26.2%, and 10.6% lower, respectively, comparing to the high IDL (88.6 ± 1.3%) plans. The Conformality Index (CI) of the low IDL plans outperformed the high IDL plans (mean: 1.15 vs. 1.24), except for a lesion under 0.5 cc. The quality of the middle IDL plans (69.6 ± 1.5%) was close to the low IDL plans. Similar results were observed for tumors abutting an OAR. Conclusions: Low IDL plans outperformed high IDL plans for all metrics in tumors > 0.5 cc. The lower dose exposure of normal brain tissue and better CI could potentially reduce radiation necrosis while the higher maximum dose could improve local control.

Assessment of Brain Tumor Displacements after Skull-based Registration: A CT/MRI Fusion Study

Purpose: To assess brain tumor displacements between skull based and soft-tissue based matching during CTMRI fusion for a total of 35 brain lesions. nMethods: Twenty-five patients who underwent CT and MRI scans in the same day were retrospectively recruited into the study. Semi-automatic skull based fusion was first performed and reviewed on a Treatment Planning System (TPS). A secondary fine-tuning of the fusion was then performed, if mismatch was observed in the tumor or neighboring soft-tissue, using nearby visible soft-tissue, such as gyri, sulci, and fissures. Two physicists fine-tuned the secondary fusion until the best match could be agreed upon. The resulting rotations and translations between the two fusions were recorded, which indicated local displacements between skull based and soft-tissue based matching. We further created a PTV by expanding a 2 mm margin around the GTV after skull-based fusion, and then evaluated the coverage of the GTV within the PTV after fine tuning with soft-tissue based fusion. nResults: In 29 of the 35 lesions, minor to no mismatch was found between the soft-tissue and skull based fusions. The corresponding translational and rotational shifts were 0.05 ± 0.63 mm (LR), 0.01 ± 0.79 mm (AP), 0.37 ± 1.01 mm (SI); -0.15 ± 0.67° (pitch), -0.19 ± 0.34° (yaw), and -0.12 ± 0.49° (roll). Thus the GTV, after soft-tissue based fusion, was 100% covered by the PTV. However, in the remaining 6 lesions in the study, noticeable displacements were observed between the skull and soft-tissue based fusions. Excluding an outlier lesion, the mean translational and rotational shifts for 5 of the 6 remaining lesions were 0.90 ± 2.15 mm (LR), 1.50 ± 2.27 mm (AP), -1.01 ± 1.83 mm (SI); -1.42 ± 3.12°(pitch), 0.02 ± 0.83°(yaw), and -0.17 ± 0.68°(roll). For the outlier lesion, the GTV was nearly missed by the PTV, and for the rest of the 5 lesions, the mean coverage of the GTV was 98.9% within the PTV. nConclusion: In a small portion of lesions, our study showed noticeable brain tumor displacement with typical patient setup in CT and MRI scans when using skull based fusion in comparison with soft-tissue fusion. Careful review of the skull based fusion is recommended by examining the match with nearby soft-tissue and/or tumors. If fusion deviations are found, it is also recommended to consider adding a margin to the GTV to account for such variations, since such variations could potentially affect target localization accuracy at the time of treatment.

SU‐E‐J‐225: Quantitative Evaluation of Rigid and Non‐Rigid Motion of Liver Tumors Using Stereo Imaging During SBRT

PURPOSEnTo quantitatively evaluate rigid and nonrigid motion of liver tumors based on fiducial tracking in 3D by stereo imaging during CyberKnife SBRT.nnnMETHODSnTwenty-five liver patients previously treated with three-fractions of SBRT were retrospectively recruited in this study. During treatment, the 3D locations of fiducials were reported by the CyberKnife system after two orthogonal kV X-ray images were taken and further validated by geometry derivations. A total of 5004 pairs of X-ray images acquired during the course of treatment for all the patients, were analyzed. For rigid motion, the rotational angles and translational shifts by aligning 3D fiducial groups in different image pairs after least-square fitting were reported. For nonrigid motion, the relative interfractional tumor shape variations were reported and correlated to the sum of inter-fiducial distances. The individual fiducial displacements were also reported after rigid corrections and without angle corrections.nnnRESULTSnThe relative tumor volume variation indicated by the inter-fiducial distances demonstrated an increasing trend in the second (101.6±3.4%) and third fraction (101.2±5.6%) among most patients. The cause could be possibly due to radiation-induced edema. For all the patients, the translational shift was 8.1±5.7 mm, with shifts in LR, AP and SI were 2.1±2.4 mm, 2.8±2.9 mm and 6.7±5.1 mm, respectively. The greatest translation shift occurred in SI, mainly due the breathing motion of diaphragm The rotational angles were 1.1±1.7°, 1.9±2.6° and 1.6±2.2°, in roll, pitch, and yaw, respectively. The 3D fiducial displacement with rigid corrections were 0.2±0.2 mm and increased to 0.6±0.3 mm without rotational corrections.nnnCONCLUSIONnThe fiducial locations in 3D can be precisely reconstructed from CyberKnife stereo imaging system during treatment. The fiducials provide close estimation of both rigid and nonrigid motion of .liver tumors. The reported data could be further utilized for tumor margin design and motion management in in conventional linac-based treatments.

SU‐E‐J‐147: Internal Brain Motion Between CT and MR Scanning

Purpose: To evaluate the internal brain motion between two imaging studies of CT and MRI. A study with 30 healthy volunteers with MRI scans in 4 different positions showed significant brain to skull motion up to 1 cm. Such motion among patients for radiotherapy to the brain is evaluated in this study. Methods: Twenty‐five patients underwent MRI and CT scans in the same day for radiotherapy planning were recruited. A whole brain fusion was first performed. Three to five pairs of control points were selected on both CT and MRI for starting an automated intensity based registration. The fusion was reviewed and fine‐tuned for the best skull‐to‐skull matching. To study potential internal brain motion, a subsequent fine‐tuning of the fusion was performed by matching the visible features, such as gyri, sulci and fissures, near the tumor site. The second fusion was reviewed and fine‐tuned by two physicists until the best visible feature matching could be agreed upon. The resulting rotation and translation between the whole brain and feature‐based fusions indicated potential internal brain motion between the two scans. Results: Between two fusions the mean internal shifts in x (LR), y (AP) and z (SI) were 0.34±0.95 mm, 0.21±1.18 mm and −0.34±0.8 mm, respectively. The mean overall shift was 1.4±1.1 mm, and the largest shift was 3.5 mm. The mean rotation angles were 0.22±1.32° (pitch), 0.14±0.4° (yaw) and 0.08±0.53° (roll), respectively. The pitch motion was predominant (head up and down) due to difference of couch tops of CT and MRI scanners. Conclusion: Our study showed small but measurable internal brain motion among radiotherapy patients with typical clinical setting for CT and MRI imaging. Therefore the CT‐MRI fusion should be carefully checked for internal structure matching. An additional treatment margin may be needed if an internal motion is observed.