Qianyi Xu

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.

Dosimetric investigation of accelerated partial breast irradiation (APBI) using CyberKnife

PURPOSEnTo investigate the dosimetric feasibility of accelerated partial breast irradiation (APBI) using CyberKnife.nnnMETHODSnFourteen previously treated patients with early-stage breast cancer were selected for a retrospective study. Six of these patients had been treated to 38.5 Gy in 10 fractions in a phase III accelerated partial breast trial and the rest of the patients were treated to 50.4 Gy in 28 fractions. In this planning study, the guidelines in the protocol for the phase III partial breast trial were followed for organ delineation and CyberKnife planning. The achievable dosimetric parameters from all CyberKnife plans were compared to Intensity-modulated radiation therapy (IMRT) and 3D-CRT methods. The reproducibility of the dose delivery with and without respiratory motion was assessed through delivering a patient plan to a breast phantom. Different dose calculation algorithms were also compared between ray tracing and Monte Carlo.nnnRESULTSnFor all the patients in the study, the dosimetric parameters met the guidelines from the NSABP B39∕RTOG 0413 protocol strictly. The mean PTV volume covered by 100% of the prescription dose was 95.7 ± 0.7% (94.7%-97.1%). The mean maximal dose was 104 ± 2% of the prescription dose. The mean V(50%) and mean V(100%) to the ipsilateral normal breast were 23.1 ± 11.6% and 9.0 ± 5.8%, respectively. The conformity index of all plans was 1.14 ± 0.04. The maximum dose to the contralateral breast varied from 1.3 cGy to 111 cGy. The mean V(5%) and mean V(30%) to the contralateral and ipsilateral lungs were 1.0 ± 1.6% and 1.3 ± 1.2%, respectively. In our study, the mean V(5%) to the heart was 0.2 ± 0.5% for right-sided tumors and 9.4 ± 10.1% for left-sided tumors. Compared with IMRT and 3D-CRT planning, the PTV coverage from CyberKnife planning was the highest, and the ratio of V(20%) to V(100%) of the breast from CyberKnife planning was the smallest. The heart and lung doses were similar in all the techniques except that the V(5%) for the lung and heart in CyberKnife planning was slightly higher.nnnCONCLUSIONSnThe dosimetric feasibility of APBI using CyberKnife was investigated in this retrospective study. All the dosimetric parameters strictly met the guidelines from the NSABP B39∕RTOG 0413 protocol. With advanced real-time tracking capability, CyberKnife should provide better target coverage and spare nearby critical organs for APBI treatment.

Small Bowel Dose Tolerance for Stereotactic Body Radiation Therapy

Inconsistencies permeate the literature regarding small bowel dose tolerance limits for stereotactic body radiation therapy (SBRT) treatments. In this review, we organized these diverse published limits with MD Anderson at Cooper data into a unified framework, constructing the dose-volume histogram (DVH) Risk Map, demonstrating low-risk and high-risk SBRT dose tolerance limits for small bowel. Statistical models of clinical data from 2 institutions were used to assess the safety spectrum of doses used in the exposure of the gastrointestinal tract in SBRT; 30% of the analyzed cases had vascular endothelial growth factor inhibitors (VEGFI) or other biological agents within 2 years before or after SBRT. For every dose tolerance limit in the DVH Risk Map, the probit dose-response model was used to estimate the risk level from our clinical data. Using the current literature, 21Gy to 5cc of small bowel in 3 fractions has low toxicity and is reasonably safe, with 6.5% estimated risk of grade 3 or higher complications, per Common Terminology Criteria for Adverse Events version 4.0. In the same fractionation for the same volume, if lower risk is required, 16.2Gy has an estimated risk of only 2.5%. Other volumes and fractionations are also reviewed; for all analyzed high-risk small bowel limits, the risk is 8.2% or less, and the low-risk limits have 4% or lower estimated risk. The results support current clinical practice, with some possibility for dose escalation.

Stereotactic Body Radiotherapy for Large (> 5 cm) Non-Small-Cell Lung Cancer.

Background Stereotactic body radiotherapy (SBRT) is a well‐established treatment option for early stage non–small‐cell lung cancer (NSCLC) tumors < 5 cm. There is limited information on tumors > 5 cm. Patients and Methods We performed retrospective data collection of patients enrolled onto a prospective SBRT registry study. Eligible patients for this study had node‐negative NSCLC measuring > 5 cm in any dimension. Data from 41 patients were analyzed. Median patient age was 75 years, and median tumor size was 5.6 cm (range, 5.0‐12.2 cm). Sixteen patients had squamous disease, 20 patients adenocarcinoma, and 1 mixed tumor; 4 patients had no biopsy. Median radiation dose per fraction was 50 Gy in 5 fractions. Radiation was prescribed to isodose line, median 66% (range, 50%‐84%). Results Before SBRT, 6 patients had previous chemotherapy and 7 patients had previous radiation. Median follow‐up for all patients was 15.2 months (range, 0.56‐48.1 months). At last follow‐up, 16 patients were still alive, with a median follow‐up of 16.1 months for surviving patients. The median survival was 17.5 months with 1‐ and 2‐year survivals of 65% and 34%. Two patients (4.8%) had local failure, and 13 patients (31%) had distant failure. Four patients (9.8%) had acute toxicity, and 7 patients (17.1%) had late toxicity, including 2 (4.8%) grade 3 late toxicities. Conclusion SBRT for tumors > 5 cm is effective, with good local control rates and acceptable toxicity. The main pattern of failure is distant, suggesting a possible role for systemic chemotherapy in these patients. Micro‐Abstract This study was undertaken to provide a better understanding of stereotactic body radiotherapy (SBRT) in nonoperable non–small‐cell lung cancer with a largest tumor dimension of > 5 cm. A retrospective analysis was conducted on a prospective SBRT registry, with analysis of 41 patients. SBRT results in good local control and acceptable rates of distant control and treatment‐induced toxicities in larger lung tumors.

Preoperative Radiosurgery for Soft Tissue Sarcoma.

Objectives: Preoperative radiation followed by surgical resection is a standard treatment for soft tissue sarcomas (STSs). The conventional method of radiation is 5 weeks to approximately 50 Gy. We report on our initial experience and phase II single-arm study assessing 5 fractions of stereotactic body radiotherapy (SBRT), followed by surgical resection for STS. Methods: Thirteen patients and 14 tumors were treated with preoperative SBRT; tumors were mostly poorly differentiated (5) or myxoid (5) and were located on the leg (10), arm (2) or groin (2). The median tumor size in greatest dimension was 7.6 cm (maximum 16 cm). Twelve patients received 35 Gy in 5 fractions; for 2 deeper tumors the dose was 40 Gy in 5 fractions. Ten patients were administered 0.5 cm bolus to improve the dose. Gross tumor volume was expanded 0.5 cm radially and 3 cm along the tissue plane. Treatment was to an isodose line (median 81%) and was delivered every other day. Maximum dose to the skin was 46 Gy (median 41 Gy). Results: The median follow-up period was 279 days. Surgical resection occurred a median of 37 days after completion of SBRT. Four patients had acute toxicity consisting of 2 grade 2 and 2 grade 3 skin reactions; all cases of skin toxicity resolved by the time of surgery. Percent tumor necrosis ranged from 10% to 95% (median 60%). All patients had negative margins. Planned vacuum-assisted wound closure was used in 4 patients; there were no other major wound complications. There was 1 local recurrence and 7 distant recurrences. Conclusion: This is the initial experience of radiosurgery for preoperative treatment of STSs. We have found this to be well tolerated, convenient for the patients, and a much shorter treatment course, allowing patients to undergo surgery and subsequent chemotherapy quicker. Surgical complications and control rates are satisfactory. The initial results are encouraging for further investigation.

Improved Dose Conformity for Adjacent Targets: A Novel Planning Technique for Gamma Knife Stereotactic Radiosurgery

Purpose In the current Gamma Knife (GK) planning system (GammaPlan, version 10.2, Elekta AB, Stockholm, Sweden), multiple adjacent brain metastasis (BMs) had to be planned sequentially if BMs were drawn separately, leading to less conformal target dose in the composite plan due to inter-target dose contribution and fine-tuning of the shots being quite tedious. We proposed a method to improve target dose conformality and planning efficiency for such cases. Methods and Materials Fifteen patients with multiple BMs treated on the Leksell GK Perfexion system were retrospectively replanned in the Institutional Review Board (IRB) approved study. The recruitment criterion was all the BMs should be entirely encompassed within the maximum dose grid allowed in the GammaPlan. The BMs were first planned sequentially as routine clinic cases. The contours of the BMs were then exported to the VelocityAI (Varian, CA, USA) to generate a composite contour after a union operation, and all the BMs were planned again simultaneously using this composite contour in the GammaPlan. The inverse planning (IP) was employed in both methods with the same treatment time allowed for a fair plan comparison. Dose evaluation was performed in the VelocityAI with all planning magnetic resonance (MR) images, structure set and dose were exported to the VelocityAI. The dosimetery parameters, including conformality index (CI), V20Gy, V16Gy, V12Gy, and V5Gy, were compared between the two methods. Results The planning results from both methods were reviewed qualitatively and quantitatively. The proposed method exhibited superior CI, except for an outlier case with very tiny BMs. The mean and standard deviation (std.) of the Paddick CI for all patients were 0.76±0.11 for the proposed method, comparing to 0.69±0.13 for the sequential method. The V20Gy, V16Gy, V12Gy, and V5Gy for the proposed method were 10.9±0.9%, 9.5±10.2%, 6.2±16.4% and 3.3±21.8%, all lower than those from the sequential method. Conclusions The proposed method showed improved target dose conformality for all cases except for very tiny BMs. Planning efficiency is considerably better with the combined target technique. The improved dose conformality will be beneficial to patients in long term with lowered risk of radiation necrosis after GK stereotactic radiosurgery (SRS).

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‐C‐BRB‐02: A Phase Resolved Fiducial Setup Scheme for Stereotactic Body Radiation Therapy (SBRT)

Purpose: For CyberKnife based SBRT,CT scan of a single breathing phase is utilized for real‐time tumor tracking. However, x‐ray images for tracking are more often not in phase with the reference CT. Non‐rigid fiducial movement due to tumor deformation can induce significant uncertainties when matching images from different phases and this poses great difficulties for patient setup. A phase resolved fiducial setup scheme is developed that finds the best rigid transformation with tumor deformation corrected. Methods: Five cases (2 liver and 3 lung patients) were retrospectively analyzed in this study. For each patient, two sets of fiducials (at the ends of exhale (EOE) and inhale (EOI)) were first aligned by their centroids and linearly interpolated to generate fiducial sets for the phases in between. The fiducial set in 3D at each phase is iteratively registered to the fiducial set in x‐ray image until minimal residual error (RE) or mean distance between the projected fiducials and fiducials in the x‐ray image is reached. The phase with the smallest RE after registration of fiducial sets in 5 phases is determined as the phase of the x‐ray image. Results: For a liver case, 30 pairs of x‐ray images were registered to all 5 phases. The RE for registration with different phases was a smooth function with a distinct minimum. Fiducial matching for all the x‐ray images was also performed to the EOE phase. The REs resulted by our method were 4.2±0.58 mm, versus 5.3±1.48 mm with only EOE phase used for registration. The latter represented the RE currently achievable in current system. Similar results were also observed for the other 4 patients. Conclusions: In this study, a phase resolved fiducial setup scheme was developed and tested for 5 patients. It facilitates patient setup and tracking accuracy with reduced REs.

SU‐E‐T‐509: Automatic Detection of Non‐Rigid Fiducial Motion for Stereotactic Body Radiation Therapy (SBRT) of Moving Tumors

Purpose: CyberKnife based SBRT is capable of tracking a moving target in real‐time assuming a rigid‐body motion. However, Oberseved non‐rigid fiducial movements due to respiratory tumor deformation can induce uncertianites in tracking. Handling fiducial mismatch by trial‐and‐error is time‐consuming and incurring extra imagingdose. A novel method is developed to automatically detect non‐rigid fiducial movements and to evaluate the confidence in individual fiducials for tumor tracking. Methods: The respiratory phase was first identified for registration of x‐ray images and numerous sets of DRRs in correct phase were generated for fiducial matching. In an iterative process one fiducial was evaluated at a time. The fiducial set excluding the one under evaluation was registered to derive the optimal rigid transformation. The transformation was then applied to calculate the matching error for the evaluated fiducial only. The fiducials with dominating contribution to a large non‐rigid movement would be identified when the matching error under evaluation was greater than the residual error from the registration. Following evaluation of all fiducials a confidence factor was assigned to each fiducial to be weighted, or even eliminated, for tracking. Results: Our method was validated using data of 5 CyberKnife cases. Multiple x‐ray images up to 25 pairs were studied for each case. In a lung case a single fiducial had 14.6 mm and 3 mm matching errors in two views, while all others errors were less than 2 mm. There was evident that the large fiducial error was due non‐rigid respiratory motion. For other cases more stable matching errors less than 2.3 mm were obtained and confidence factors were evaluated. Conclusions: An automatic detection of non‐rigid fiducial motion will reduce fiducial tracking errors and thus treatment interruptions. Differentiating confidence level in individual fiducial will help to achieve accurate setup and tumor tracking for CyberKnife based SBRT, as well as conventional radiotherapy.