Observing early metabolic changes in positron emission tomography (PET) is an essential tool to assess treatment efficiency in radiotherapy. However, for thoracic regions, the use of three-dimensional (3D) PET imaging is unfeasible because the radiotracer activity is smeared by the respiratory motion and averaged during the imaging acquisition process. This motion-induced degradation is similar in magnitude with the treatment-induced changes, and the two occurrences become indiscernible. We present a customized temporal-spatial deformable registration method for quantifying respiratory motion in a four-dimensional (4D) PET dataset. Once the motion is quantified, a motion-corrected (MC) dataset is created by tracking voxels to eliminate breathing-induced changes in the 4D imaging scan. The 4D voxel-tracking data is then summed to yield a 3D MC-PET scan containing only treatment-induced changes. This proof of concept is exemplified on both phantom and clinical data, where the proposed algorithm tracked the trajectories of individual points through the 4D datasets reducing motion to less than 4 mm in all phases. This correction approach using deformable registration can discern motion blurring from treatment-induced changes in treatment response assessment using PET imaging.
Background: The purpose of this study was to evaluate predictors of early distant brain failure (DBF) and salvage whole brain radiotherapy (WBRT) after treatment with stereotactic radiosurgery (SRS) for brain metastases and create a clinically relevant risk score in order to stratify patients’ risk of these events.
Methods: We reviewed records of 270 patients with brain metastases treated with SRS between 2003-2012. Pre-treatment patient and tumor characteristics were analyzed by univariate and multivariable analyses. Cumulative incidence (CI) of first DBF and salvage WBRT were calculated. Significant factors were used to create a score for stratifying early (6-month) DBF risk.
Results: No prior WBRT, total lesion volume <1.3 cm3, primary breast cancer or malignant melanoma histology, and multiple metastases (≥2) were found to be significant predictors for early DBF. Each factor was ascribed one point due to similar hazard ratios. Scores of 0-1, 2, and 3-4 were considered low, intermediate, and high risk, respectively. This correlated with 6-month CI of DBF of 16.6%, 28.8%, and 54.4%, respectively (p<0.001). For patients without prior WBRT, the 6-month CI of salvage WBRT by 6-months was 2%, 17.7%, and 25.7%, respectively (p<0.001).
Conclusion: Early DBF after SRS requiring salvage WBRT remains a significant clinical problem. Patient stratification for early DBF can better inform the decision for initial treatment strategy for brain metastases. The provided risk score may help predict for early DBF and subsequent salvage WBRT if initial SRS is used. External validation is needed prior to clinical implementation.
For the treatment of choroidal melanoma, palladium-103 ( 103 Pd) and ruthenium-106 ( 106 Ru) plaque brachytherapy shows reduced toxicity compared with the historical standard iodine-125. No report has directly compared the clinical outcomes between 103 Pd and 106 Ru, and the reasons for the selection of one over the other remain purely theoretical. Patients with choroidal melanoma with apical tumor height up to 5 mm were included. Patients from Emory University were treated with 103 Pd between 1993 and 2012. Patients from Cleveland Clinic were treated with 106 Ru between 2005 and 2010. Medical records were retrospectively reviewed. We compared post-treatment visual acuity (VA), toxicity, and oncologic outcomes. 103 Pd patients (n = 124) and 106 Ru patients (n = 42) had a median follow-up of 4.2 and 5.0 years, respectively. Radiation retinopathy-free survival was similar for both radioisotopes, but 106 Ru had lower grades of retinopathy (P = 0.006). 103 Pd was associated with worse VA preservation (≥20/40) by year 3 (odds ratio: 3.8; 95% confidence interval: 1.01-14.31, P = 0.048). 103 Pd was associated with higher distant metastases-free survival (DMFS) in multivariate analysis (hazard ratio: 0.10; 95% confidence interval: 0.02-0.38; P < 0.001). 106 Ru had lower grades of radiation retinopathy and improved long-term VA preservation, but also inferior DMFS, compared with 103 Pd. Because of the inherent limitations of a retrospective analysis, the significance of the inferior DMFS for 106 Ru remains unclear, although the suggestion of a slight inferiority in terms of DMFS for 106 Ru is consistent with the other limited literature. On the basis of this study, we believe that both radioisotopes remain appropriate for the treatment of small choroidal melanomas up to 5 mm in apical height.
Objective: Both stereotactic radiosurgery (SRS) and fractionated radiation therapy (FRT) techniques are used for treatment of intracranial meningiomas with excellent local control (LC) rates. Although SRS techniques are convenient, toxicity including treatment-related edema can significantly impact patient quality of life. The long-term clinical outcomes of patients with magnetic resonance imaging (MRI)–defined meningiomas treated with radiation therapy (RT) alone are reported. Methods: The charts of 211 patients with meningiomas diagnosed by contrast-enhanced MRI treated with either SRS or FRT between 1991 and 2012 at a single institution were reviewed. Actuarial rates for LC and development of treatment-related radiographic edema (TRE) were determined by the Kaplan-Meier method. Results: There were 211 patients who received radiation therapy for 223 lesions. Median follow-up was 5.7 years. Eleven patients experienced a local failure; of these, 2 were ultimately found to have pathologically proven metastatic carcinoma. Two- and 5-year LC was 97.8% and 94.6%, respectively, with no significant difference based on modality of therapy. Actuarial rate for development of TRE at 1 and 2 years was 30.1% and 34.6% for the SRS group and 1.6% and 2.5% for the FRT group, respectively (P < 0.001). Conclusions: RT alone using a limited margin is an effective treatment option for MRI-defined meningiomas and should be considered even without biopsy if surgery will present significant morbidity. Although LC with SRS versus FRT was comparable, FRT was associated with a significantly decreased risk of TRE.
Purpose: Stereotactic radiosurgery (SRS) is increasingly used in the management of patients with resected brain metastases (rBMs). A significant complication of this therapy can be radiation necrosis (RN). Despite radiation therapy dose de-escalation and the delivery of several rather than a single dose fraction, rates of RN after SRS for rBMs remain high. We evaluated the dosimetric parameters associated with radiographic RN for rBMs.
Methods and Materials: From 2008 to 2016, 55 rBMs at a single institution that were treated postoperatively with 5-fraction linear accelerator–based SRS (25-35 Gy) with minimum 3 months follow-up were evaluated. For each lesion, variables recorded included radiation therapy dose to normal brain, location and magnitude of hotspots, clinical target volume (CTV), and margin size. Hotspot location was stratified as within the tumor bed alone (CTV) or within the planning target volume (PTV) expansion margin volume (PTV minus CTV). Cumulative incidence with competing risks was used to estimate rates of RN and local recurrence. Optimal cut-points predicting for RN for hotspot magnitude based on location were identified via maximization of the log-rank test statistic.
Results: Median age for all patients was 58.5 years. For all targets, the median CTV was 17.53 cm3, the median expansion margin to PTV was 2 mm, and the median max hotspot was 111%. At 1 year, cumulative incidence of radiographic RN was 18.2%. Univariate analysis showed that max hotspots with a hazard ratio of 3.28 (P = .045), hotspots within the PTV expansion margin with relative magnitudes of 105%, 110%, and 111%, and an absolute dose of 33.5 Gy predicted for RN (P = .029, P = .04, P = .038, and P = .0488, respectively), but hotspots within the CTV did not.
Conclusions: To our knowledge, this is the first study that investigated dosimetric factors that predict for RN after 5-fraction hypofractionated SRS for rBM. Hotspot location and magnitude appear important for predicting RN risk, thus these parameters should be carefully considered during treatment planning.
Background: To investigate the impact of proton radiotherapy (PBT) on overall survival (OS) and evaluate PBT usage trends for patients with gliomas in the National Cancer Data Base (NCDB). Methods: Patients with a diagnosis of World Health Organization (WHO) Grade I-IV glioma treated with definitive radiation therapy (RT) between the years of 2004-13 were identified. Patients were stratified based on WHO Grade and photon radiotherapy (XRT) vs. PBT. Univariate (UVA) and multivariable analysis (MVA) with OS were performed by Cox proportional hazards model and log-rank tests. Propensity score (PS) weighting was utilized to account for differences in patient characteristics and to minimize selection bias. Results: There were a total of 49,405 patients treated with XRT and 170 patients treated with PBT. Median follow-up time was 62.1 months. On MVA, the following factors were associated with receipt of PBT (all p < 0.05): WHO Grade I-II gliomas, treatment at an academic/research program, west geographic facility location, and surgical resection. After PS weighting, all patients treated with PBT were found to have superior median and 5 year survival than patients treated with XRT: 45.9 vs. 29.7 months (p = 0.009) and 46.1 vs. 35.5% (p = 0.0160), respectively. Conclusions: PBT is associated with improved OS compared to XRT for patients with gliomas. This finding warrants verification in the randomized trial setting in order to account for potential patient imbalances not adequately captured by the NCDB, such as tumor molecular characteristics and patient performance status. Importance of the Study: This is the first study that compares the outcomes of patients treated with photon based radiotherapy vs. proton based radiotherapy for patients with gliomas. In this retrospective analysis, the results demonstrate that proton therapy is associated with improved outcomes which support ongoing prospective, randomized clinical trials comparing the two modalities in patients with gliomas.
Purpose: To evaluate outcomes of choroidal melanoma patients treated with 125 I or 103 Pd plaque brachytherapy.
Methods and Materials: From 1993 to 2012, our institution treated 160 patients with 103 Pd (56.1%) and 125 patients with 125 I (43.9%) plaque brachytherapy. Tumor outcomes, visual acuity (VA), and toxicity were compared. Multivariate analyses (MVAs) and propensity score analysis were used to help address differences in baseline characteristics.
Results: Median followup was longer for 125 I patients, 52.7 vs. 43.5 months (p < 0.01). At baseline, 103 Pd patients had lower rates of VA worse than 20/200 (4.4% vs. 16%, p = 0.002), T3–T4 tumors (17.5% vs. 32.8%, p = 0.03), and transpupillary thermotherapy use (3.1% vs. 9.6%, p = 0.001). Both 103 Pd and 125 I provided > 90% 3-year overall survival and > 93% 5-year secondary enucleation-free survival. On MVA, radionuclide was not predictive for tumor outcomes. A higher percentage maintained vision better than 20/40 with 103 Pd (63% vs. 35%, p = 0.007) at 3 years. MVA demonstrated 103 Pd radionuclide (odds ratio [OR]: 2.12, p = 0.028) and tumor height ≤5 mm (OR: 2.78, p = 0.017) were associated with VA better than 20/40. Propensity score analysis matched 23 125 I with 107 103 Pd patients. 103 Pd continued to predict better VA at 3 years (OR: 8.10, p = 0.014). On MVA for the development of VA worse than 20/200 or degree of vision loss, radionuclide was not significant. Lower rates of radiation retinopathy were seen with 103 Pd than 125 I (3 years: 47.3% vs. 63.9%, p = 0.016), with radionuclide significant in MVA.
Conclusions: Both 125 I and 103 Pd achieve excellent tumor control. An increased probability of long-term VA better than 20/40 and reduced risk of radiation retinopathy is associated with 103 Pd.
Although historical trials have established the role of surgical resection followed by whole brain irradiation (WBRT) for brain metastases, WBRT has recently been shown to cause significant neurocognitive decline. Many practitioners have employed postoperative stereotactic radiosurgery (SRS) to tumor resection cavities to increase local control without causing significant neurocognitive sequelae. However, studies analyzing outcomes of large brain metastases treated with resection and postoperative SRS are lacking. Here we compare outcomes in patients with large brain metastases > 4 cm to those with smaller metastases ≤4 cm treated with surgical resection followed by SRS to the resection cavity. Methods and materials Consecutive patients with brain metastases treated at our institution with surgical resection and postoperative SRS were retrospectively reviewed. Patients were stratified into ≤4 cm and > 4 cm cohorts based on preoperative maximal tumor dimension. Cumulative incidence of local failure, radiation necrosis, and death were analyzed for the 2 cohorts using a competing-risk model, defined as the time from SRS treatment date to the measured event, death, or last follow-up. Results A total of 117 consecutive cases were identified. Of these patients, 90 (77%) had preoperative tumors ≤4 cm, and 27 (23%) > 4 cm in greatest dimension. The only significant baseline difference between the 2 groups was a higher proportion of patients who underwent gross total resection in the ≤4 cm compared with the > 4 cm cohort, 76% versus 48%, respectively (P < .01). The 1-year rates of local failure, radiation necrosis, and overall survival for the ≤4 cm and > 4 cm cohorts were 12.3% and 16.0%, 26.9% and 28.4%, and 80.6% and 67.6%, respectively (all P > .05). The rates of local failure and radiation necrosis were not statistically different on multivariable analysis based on tumor size. Conclusions Brain metastases > 4 cm in largest dimension managed by resection and radiosurgery to the tumor cavity have promising local control rates without a significant increase in radiation necrosis on our retrospective review.
Background
To dosimetrically evaluate the effect of reduced margin radiotherapy on hippocampal dose for glioblastoma multiforme (GBM) patients.
Methods
GBM patients enrolled on the Radiation Therapy Oncology Group (RTOG) 0825 trial at our institution were identified. Standard RTOG 0825 expansions were 2 cm + 3-5 mm from the gross tumor volume (GTV) to the clinical tumor volume (CTV) and from the CTV to the planning tumor volume (PTV), respectively. These same patients also had reduced margin tumor volumes generated with 8 mm (GTV to CTV) + 3 mm (CTV to PTV) expansions. Individual plans were created for both standard and reduced margin structures. The dose-volume histograms were statistically compared with a paired, two-tailed Student’s t-test with a significance level of p < 0.05.
Results
A total of 16 patients were enrolled on RTOG 0825. The reduced margins resulted in statistically significant reductions in hippocampal dose at all evaluated endpoints. The hippocampal Dmax was reduced from a mean of 61.4 Gy to 56.1 Gy (8.7%), D40% was reduced from 49.9 Gy to 36.5 Gy (26.9%), D60% was reduced from 32.7 Gy to 18.7 Gy (42.9%) and the D80% was reduced from 27.3 Gy to 15.3 Gy (44%).
Conclusions
The use of reduced margin PTV expansions in the treatment of GBM patients results in significant reductions in hippocampal dose. Though the exact clinical benefit of this reduction is currently unclear, this study does provide support for a future prospective trial evaluating the neurocognitive benefits of reduced margin tumor volumes in the treatment of GBM patients.
Keywords: Glioblastoma multiforme; GBM; Hippocampus
Background
Hypofractionated Radiosurgery (HR) is a therapeutic option for delivering partial brain radiotherapy (RT) to large brain metastases or resection cavities otherwise not amenable to single fraction radiosurgery (SRS). The use, safety and efficacy of HR for brain metastases is not well characterized and the optimal RT dose-fractionation schedule is undefined.
Methods
Forty-two patients treated with HR in 3-5 fractions for 20 (48%) intact and 22 (52%) resected brain metastases with a median maximum dimension of 3.9 cm (0.8-6.4 cm) between May 2008 and August 2011 were reviewed. Twenty-two patients (52%) had received prior radiation therapy. Local (LC), intracranial progression free survival (PFS) and overall survival (OS) are reported and analyzed for relationship to multiple RT variables through Cox-regression analysis.
Results
The most common dose-fractionation schedules were 21 Gy in 3 fractions (67%), 24 Gy in 4 fractions (14%) and 30 Gy in 5 fractions (12%). After a median follow-up time of 15 months (range 2-41), local failure occurred in 13 patients (29%) and was a first site of failure in 6 patients (14%). Kaplan-Meier estimates of 1 year LC, intracranial PFS, and OS are: 61% (95% CI 0.53 – 0.70), 55% (95% CI 0.47 – 0.63), and 73% (95% CI 0.65 – 0.79), respectively. Local tumor control was negatively associated with PTV volume (p = 0.007) and was a significant predictor of OS (HR 0.57, 95% CI 0.33 - 0.98, p = 0.04). Symptomatic radiation necrosis occurred in 3 patients (7%).
Conclusions
HR is well tolerated in both new and recurrent, previously irradiated intact or resected brain metastases. Local control is negatively associated with PTV volume and a significant predictor of overall survival, suggesting a need for dose escalation when using HR for large intracranial lesions.
Keywords: Hypofractionated; Radiosurgery; Brain; Metastases