TN-RS: a novel scoring system predicts Gamma Knife Radiosurgery outcome for trigeminal neuralgia patients.

BACKGROUND: Gamma Knife Radiosurgery (GKRS) is an effective treatment option for medically refractory trigeminal neuralgia (TN). This study examines GKRS outcome in a large cohort of TN patients and highlights pretreatment factors associated with pain relief. METHODS: This is a single-center retrospective analysis of patients treated with GKRS for TN between 2011 and 2019. Pain relief was assessed at 1 year, and 2-3 years following GKRS. Multivariable analysis identified several factors that predicted pain relief. These predicting factors were applied to establish a pain relief scoring system. RESULTS: A total of 162 patients met inclusion criteria. At 1 year post-GKRS, the breakdown of Barrow Neurological Institute (BNI) score for pain relief was as follows: 77 (48%) score of I, 13 (8%) score of II, 37 (23%) score of III, 22 (14%) score of IV, and 13 (8%) score of V. Factors that were significantly associated with pain-free outcome at 1 year were: Typical form of TN (OR = 2.2 [1.1, 4.9], p = 0.049), No previous microvascular decompression (OR = 4.4 [1.6, 12.5], p = 0.005), Response to medical therapy (OR = 2.7 [1.1, 6.1], p = 0.018), and Seniority > 60 years (OR = 2.8 [1.4, 5.5], p = 0.003). The term "Trigeminal Neuralgia-RadioSurgery" was used to create the TN-RS acronym representing the significant factors. A stepwise increase in the median predicted probability of pain-free outcome at 1 year from 3% for patients with a score of 0 to 69% for patients with a maximum score of 4. CONCLUSION: The TN-RS scoring system can assist clinicians in identifying patients that may benefit from GNRS for TN by predicting 1-year pain-free outcomes.

Multicenter Trial of Stereotactic Body Radiation Therapy for Low- and Intermediate-Risk Prostate Cancer: Survival and Toxicity Endpoints.

PURPOSE: The radiobiology of prostate cancer may favor the extreme hypofractionation inherent in stereotactic body radiation therapy (SBRT); however, data from a large multicenter study are lacking. We therefore examined the hypothesis that dose-escalated SBRT can be safely administered across multiple institutions, with favorable 5-year disease-free survival (DFS) rates compared with historical controls. METHODS AND MATERIALS: Twenty-one centers enrolled 309 patients with prostate adenocarcinoma: 172 with low-risk (LR) and 137 with intermediate-risk (IR) disease. All were treated with a non-coplanar robotic SBRT platform using real-time tracking of implanted fiducials. The prostate was prescribed 40 Gy in 5 fractions of 8 Gy. We assessed toxicities using Common Terminology Criteria for Adverse Events (CTCAE) version 3 and biochemical failure using the "nadir + 2" definition. The study population yielded 90% power to identify excessive (>10%) rates of grade ≥3 genitourinary (GU) or gastrointestinal toxicities and, in the LR group, 80% power to show superiority in DFS over a 93% historical comparison rate. RESULTS: At a median follow-up of 61 months, 2 LR patients (1.2%) and 2 IR patients (1.5%) experienced grade 3 GU toxicities, far below the 10% toxicity rate deemed excessive (upper limits of 95% confidence interval, 3.5% and 4.3%, respectively). No grade 4 or 5 toxicities occurred. All grade 3 toxicities were GU, occurring 11 to 51 months after treatment. For the entire group, the actuarial 5-year overall survival rate was 95.6% and the DFS rate was 97.1%. The 5-year DFS rate was 97.3% for LR patients (superior to the 93% DFS rate for historical controls; P = .0008; lower limit of 95% confidence interval, 94.6%) and 97.1% for IR patients. CONCLUSIONS: Dose-escalated prostate SBRT was administered with minimal toxicity in this multi-institutional study. Relapse rates compared favorably with historical controls. SBRT is a suitable option for LR and IR prostate cancer.

Accelerated Partial Breast Irradiation: Using the CyberKnife as the Radiation Delivery Platform in the Treatment of Early Breast Cancer.

We evaluate the CyberKnife (Accuray Incorporated, Sunnyvale, CA, USA) for non-invasive delivery of accelerated partial breast irradiation (APBI) in early breast cancer patients. Between 6/2009 and 5/2011, nine patients were treated with CyberKnife APBI. Normal tissue constraints were imposed as outlined in the National Surgical Adjuvant Breast and Bowel Project B-39/Radiation Therapy Oncology Group 0413 (NSABP/RTOG) Protocol (Vicini and White, 2007). Patients received a total dose of 30 Gy in five fractions (group 1, n = 2) or 34 Gy in 10 fractions (group 2, n = 7) delivered to the planning treatment volume (PTV) defined as the clinical target volume (CTV) +2 mm. The CTV was defined as either the lumpectomy cavity plus 10 mm (n = 2) or 15 mm (n = 7). The cavity was defined by a T2-weighted non-contrast breast MRI fused to a planning non-contrast thoracic CT. The CyberKnife Synchrony system tracked gold fiducials sutured into the cavity wall during lumpectomy. Treatments started 4-5 weeks after lumpectomy. The mean PTV was 100 cm(3) (range, 92-108 cm(3)) and 105 cm(3) (range, 49-241 cm(3)) and the mean PTV isodose prescription line was 70% for groups 1 and 2, respectively. The mean percent of whole breast reference volume receiving 100 and 50% of the dose (V(100) and V(50)) for group 1 was 11% (range, 8-13%) and 23% (range, 16-30%) and for group 2 was 11% (range, 7-14%) and 26% (range, 21-35.0%), respectively. At a median 7 months follow-up (range, 4-26 months), no acute toxicities were seen. Acute cosmetic outcomes were excellent or good in all patients; for those patients with more than 12 months follow-up the late cosmesis outcomes were excellent or good. In conclusion, the lack of observable acute side effects and current excellent/good cosmetic outcomes is promising. We believe this suggests the CyberKnife is a suitable non-invasive radiation platform for delivering APBI with achievable normal tissue constraints.

Stereotactic body radiotherapy for localized prostate cancer: interim results of a prospective phase II clinical trial.

PURPOSE: The radiobiology of prostate cancer favors a hypofractionated dose regimen. We report results of a prospective Phase II clinical trial of stereotactic body radiotherapy (SBRT) for localized prostate cancer. METHODS AND MATERIALS: Forty-one low-risk prostate cancer patients with 6 months' minimum follow-up received 36.25 Gy in five fractions of 7.25 Gy with image-guided SBRT alone using the CyberKnife. The early (<3 months) and late (>6 months) urinary and rectal toxicities were assessed using validated quality of life questionnaires (International Prostate Symptom Score, Expanded Prostate Cancer Index Composite) and the Radiation Therapy Oncology Group (RTOG) toxicity criteria. Patterns of prostate-specific antigen (PSA) response are analyzed. RESULTS: The median follow-up was 33 months. There were no RTOG Grade 4 acute or late rectal/urinary complications. There were 2 patients with RTOG Grade 3 late urinary toxicity and none with RTOG Grade 3 rectal complications. A reduced rate of severe rectal toxicities was observed with every-other-day vs. 5 consecutive days treatment regimen (0% vs. 38%, p = 0.0035). A benign PSA bounce (median, 0.4 ng/mL) was observed in 12 patients (29%) occurring at 18 months (median) after treatment. At last follow-up, no patient has had a PSA failure regardless of biochemical failure definition. Of 32 patients with 12 months minimum follow-up, 25 patients (78%) achieved a PSA nadir

Prostate cancer therapy with stereotactic body radiation therapy.

The purpose of this work is to provide background and current directions of image guidance for localized prostate cancer treatments. We will describe the external beam hypofractionation protocol for localized prostate cancer currently in progress at Stanford University and the biological bases for large fractions in an abbreviated treatment course for prostate cancer. The need for image guidance in external beam prostate cancer treatments will be discussed. Our experience with two imageguided implementations of hypofractionated radiotherapy for localized prostate cancer will be presented. These are the Cyberknife System (Accuray, Inc.) and the Trilogy System (Varian Medical Systems, Inc.).

Investigation of linac-based image-guided hypofractionated prostate radiotherapy.

A hypofractionation treatment protocol for prostate cancer was initiated in our department in December 2003. The treatment regimen consists of a total dose of 36.25 Gy delivered at 7.25 Gy per fraction over 10 days. We discuss the rationale for such a prostate hypofractionation protocol and the need for frequent prostate imaging during treatment. The CyberKnife (Accuray Inc., Sunnyvale, CA), a linear accelerator mounted on a robotic arm, is currently being used as the radiation delivery device for this protocol, due to its incorporation of near real-time kV imaging of the prostate via 3 gold fiducial seeds. Recently introduced conventional linac kV imaging with intensity modulated planning and delivery may add a new option for these hypofractionated treatments. The purpose of this work is to investigate the use of intensity modulated radiotherapy (IMRT) and the Varian Trilogy Accelerator with on-board kV imaging (Varian Medical Systems Inc., Palo Alto, CA) for treatment of our hypofractionated prostate patients. The dose-volume histograms and dose statistics of 2 patients previously treated on the CyberKnife were compared to 7-field IMRT plans. A process of acquiring images to observe intrafraction prostate motion was achieved in an average time of about 1 minute and 40 seconds, and IMRT beam delivery takes about 40 seconds per field. A complete 7-field IMRT plan can therefore be imaged and delivered in 10 to 17 minutes. The Varian Trilogy Accelerator with on-board imaging and IMRT is well suited for image-guided hypofractionated prostate treatments. During this study, we have also uncovered opportunities for improvement of the on-board imaging hardware/software implementation that would further enhance performance in this regard.

A study of the accuracy of cyberknife spinal radiosurgery using skeletal structure tracking.

OBJECTIVE: New technology has enabled the increasing use of radiosurgery to ablate spinal lesions. The first generation of the CyberKnife (Accuray, Inc., Sunnyvale, CA) image-guided radiosurgery system required implanted radiopaque markers (fiducials) to localize spinal targets. A recently developed and now commercially available spine tracking technology called Xsight (Accuray, Inc.) tracks skeletal structures and eliminates the need for implanted fiducials. The Xsight system localizes spinal targets by direct reference to the adjacent vertebral elements. This study sought to measure the accuracy of Xsight spine tracking and provide a qualitative assessment of overall system performance. METHODS: Total system error, which is defined as the distance between the centroids of the planned and delivered dose distributions and represents all possible treatment planning and delivery errors, was measured using a realistic, anthropomorphic head-and-neck phantom. The Xsight tracking system error component of total system error was also computed by retrospectively analyzing image data obtained from eleven patients with a total of 44 implanted fiducials who underwent CyberKnife spinal radiosurgery. RESULTS: The total system error of the Xsight targeting technology was measured to be 0.61 mm. The tracking system error component was found to be 0.49 mm. CONCLUSION: The Xsight spine tracking system is practically important because it is accurate and eliminates the use of implanted fiducials. Experience has shown this technology to be robust under a wide range of clinical circumstances.

Segment-based dose optimization using a genetic algorithm.

Intensity modulated radiation therapy (IMRT) inverse planning is conventionally done in two steps. Firstly, the intensity maps of the treatment beams are optimized using a dose optimization algorithm. Each of them is then decomposed into a number of segments using a leaf-sequencing algorithm for delivery. An alternative approach is to pre-assign a fixed number of field apertures and optimize directly the shapes and weights of the apertures. While the latter approach has the advantage of eliminating the leaf-sequencing step, the optimization of aperture shapes is less straightforward than that of beamlet-based optimization because of the complex dependence of the dose on the field shapes, and their weights. In this work we report a genetic algorithm for segment-based optimization. Different from a gradient iterative approach or simulated annealing, the algorithm finds the optimum solution from a population of candidate plans. In this technique, each solution is encoded using three chromosomes: one for the position of the left-bank leaves of each segment, the second for the position of the right-bank and the third for the weights of the segments defined by the first two chromosomes. The convergence towards the optimum is realized by crossover and mutation operators that ensure proper exchange of information between the three chromosomes of all the solutions in the population. The algorithm is applied to a phantom and a prostate case and the results are compared with those obtained using beamlet-based optimization. The main conclusion drawn from this study is that the genetic optimization of segment shapes and weights can produce highly conformal dose distribution. In addition, our study also confirms previous findings that fewer segments are generally needed to generate plans that are comparable with the plans obtained using beamlet-based optimization. Thus the technique may have useful applications in facilitating IMRT treatment planning.

IMRT dose shaping with regionally variable penalty scheme.

A commonly known deficiency of currently available inverse planning systems is the difficulty in fine-tuning the final dose distribution. In practice, it is not uncommon that just a few unsatisfactory regions in the planning target volume or an organ at risk prevent an intensity modulated radiation therapy (IMRT) plan from being clinically acceptable. The purpose of this work is to introduce a mechanism for controlling the regional doses after a conventional IMRT plan is obtained and to demonstrate its clinical utility. Two types of importance factors are introduced in the objective function to model the tradeoffs of different clinical objectives. The first is the conventional structure-dependent importance factor, which quantifies the interstructure tradeoff. The second type is the voxel-dependent importance factor which "modulates" the importance of different voxels within a structure. The planning proceeds in two major steps. First a conventional inverse planning is performed, where the structure-dependent importance factors are determined in a trial-and-error fashion. The next level of planning involves fine-tuning the regional doses to meet specific clinical requirements. To achieve this, the voxels where doses need to be modified are identified either graphically on the isodose layouts, or on the corresponding dose-volume histogram (DVH) curves. The importance value of these voxels is then adjusted to increase/decrease the penalty at the corresponding regions. The technique is applied to two clinical cases. It was found that both tumor hot spots and critical structure maximal doses can be easily controlled by varying the regional penalty. One to three trials were sufficient for the conventionally optimized dose distributions to be adjusted to meet clinical expectation. Thus introducing the voxel-dependent penalty scheme provides an effective means for IMRT dose distributions painting and sculpting.

Therapeutic treatment plan optimization with probability density-based dose prescription.

The dose optimization in inverse planning is realized under the guidance of an objective function. The prescription doses in a conventional approach are usually rigid values, defining in most instances an ill-conditioned optimization problem. In this work, we propose a more general dose optimization scheme based on a statistical formalism [Xing et al., Med. Phys. 21, 2348-2358 (1999)]. Instead of a rigid dose, the prescription to a structure is specified by a preference function, which describes the user's preference over other doses in case the most desired dose is not attainable. The variation range of the prescription dose and the shape of the preference function are predesigned by the user based on prior clinical experience. Consequently, during the iterative optimization process, the prescription dose is allowed to deviate, with a certain preference level, from the most desired dose. By not restricting the prescription dose to a fixed value, the optimization problem becomes less ill-defined. The conventional inverse planning algorithm represents a special case of the new formalism. An iterative dose optimization algorithm is used to optimize the system. The performance of the proposed technique is systematically studied using a hypothetical C-shaped tumor with an abutting circular critical structure and a prostate case. It is shown that the final dose distribution can be manipulated flexibly by tuning the shape of the preference function and that using a preference function can lead to optimized dose distributions in accordance with the planner's specification. The proposed framework offers an effective mechanism to formalize the planner's priorities over different possible clinical scenarios and incorporate them into dose optimization. The enhanced control over the final plan may greatly facilitate the IMRT treatment planning process.

Inverse planning for functional image-guided intensity-modulated radiation therapy.

Radiation therapy is an image-guided process whose success critically depends on the imaging modality used for treatment planning and the level of integration of the available imaging information. In this work, we establish a dose optimization framework for incorporating metabolic information from functional imaging modalities into the intensity-modulated radiation therapy (IMRT) inverse planning process and to demonstrate the technical feasibility of planning deliberately non-uniform dose distributions in accordance with functional imaging data. For this purpose, a metabolic map from functional images is discretized into a number of abnormality levels (ALs) and then fused with CT images. To escalate dose to the metabolically abnormal regions, we assume, for a given spatial point, a linear relation between the AL and the prescribed dose. But the formalism developed here is independent of the assumption and any other relation between AL and prescription is applicable. For a given AL and prescription relation, it is only necessary to prescribe the dose to the lowest AL in the target and the desired doses to other regions with higher AL values are scaled accordingly. To accomplish differential sparing of a sensitive structure when its functional importance (FI) distribution is known, we individualize the tolerance doses of the voxels within the structure according to their Fl levels. An iterative inverse planning algorithm in voxel domain is used to optimize the system with in homogeneous dose prescription. To model intra-structural trade-off, a mechanism is introduced through the use of voxel-dependent weighting factors, in addition to the conventional structure specific weighting factors which model the inter-structural trade-off. The system is used to plan a phantom case with a few hypothetical functional distributions and a brain tumour treatment with incorporation of magnetic resonance spectroscopic imaging data. The results indicated that it is technically feasible to produce deliberately non-uniform dose distributions according to the functional imaging requirements. Integration of functional imaging information into radiation therapy dose optimization allows for consideration of patient-specific biologic information and provides a significant opportunity to truly individualize radiation treatment. This should enhance our capability to safely and intelligently escalate dose and lays the technical foundation for future clinical studies of the efficacy of functional imaging-guided IMRT.

Using voxel-dependent importance factors for interactive DVH-based dose optimization.

Intensity modulated radiation therapy (IMRT) inverse planning is usually performed by pre-selecting parameters such as beam modality, beam configuration and importance factors and then optimizing the fluence profiles or beamlet weights. In reality, the IMRT dose optimization problem may be ill-conditioned and there may not be a physical solution to account for the chosen parameters and constraints. Planner intervention is often required to conduct a multiple trial-and-error process where several parameters are sequentially varied until an acceptable compromise is achieved. The resulting solution reflects a balance between the conflicting requirements of the target and the sensitive structures. A major problem of the conventional inverse planning formalism is that there exists no effective mechanism for a planner to fine-tune the dose distribution on a local level or to differentially modify the dose-volume histograms (DVHs) of the involved structures. In this paper we introduce a new inverse planning scheme with voxel-dependent importance factors and demonstrate that it provides us with an effective link between the system parameters and the dosimetric behaviour at a local level. The planning proceeds in two steps. After a conventional trial-and-error inverse planning procedure is completed, we identify the dose interval at which the fractional volume on the DVH curve needs to be changed. The voxels that receive dose in the selected range are then located and their voxel-dependent importance factors are adjusted accordingly. The fine-tuning of the DVHs is iterative in nature and, using widely available computer graphic software tools, the process can be made graphically interactive. The new IMRT planning scheme is applied to two test cases and the results indicate that our control over the differential shapes of the DVHs of the involved structures is,greatly enhanced. Thus the technique may have significant practical implications in facilitating the IMRT treatment planning process.