During the past 4 decades, the treatment of Hodgkin lymphoma has changed dramatically, and combined modality treatment is now considered the standard of care for patients with early-stage disease. ...However, the risk of late effects has led to concerns regarding the use of radiation therapy, especially in young patients with a long life expectancy. In this study, we review the current evidence for modern radiation therapy planning and delivery techniques in the treatment of early-stage Hodgkin lymphoma with a focus on a reduced delivered dose, a reduced irradiated volume, and a more conformal dose distribution. Although studies are difficult to compare because of differences in field technique, prescribed dose, target volumes, patient population, and reported dosimetric and plan evaluation parameters, modern radiation therapy significantly reduces exposure to normal tissues and thereby the estimated risk of late effects. However, there is no such thing as a single best modern delivery technique when multiple organs at risk are considered simultaneously because of the heterogeneity in patient anatomy and disease location, and the choice of radiation therapy technique should be made individually for each patient.
Flattening filter-free (FFF) beams with higher dose rates and faster delivery are now clinically available. The purpose of this planning study was to compare optimized non-FFF and FFF RapidArc plans ...for stereotactic body radiotherapy (SBRT) and to validate the accuracy of fast arc delivery.
Ten patients with peripheral lung tumors and 10 with vertebral metastases were planned using RapidArc with a flattened 6-MV photon beam and a 10-MV FFF beam for fraction doses of 7.5-18 Gy. Dosimetry of the target and organs at risk (OAR), number of monitor units (MU), and beam delivery times were assessed. GafChromic EBT2 film measurements of FFF plans were performed to compare calculated and delivered dose distributions.
No major dosimetric differences were seen between the two delivery techniques. For lung SBRT plans, conformity indices and OAR doses were similar, although the average MU required were higher with FFF plans. For vertebral SBRT, FFF plans provided comparable PTV coverage, with no significant differences in OAR doses. Average beam delivery times were reduced by a factor of up to 2.5, with all FFF fractions deliverable within 4 min. Measured FFF plans showed high agreement with calculated plans, with more than 99% of the area within the region of interest fulfilling the acceptance criterion.
The higher dose rate of FFF RapidArc reduces delivery times significantly, without compromising plan quality or accuracy of dose delivery.
Purpose:
To investigate the stability of a water calorimetry system as a primary standard for absorbed dose to water using measurements performed in cobalt-60 and high-energy linac photon beams over ...a span of more than a decade.
Methods:
Calorimetry measures adsorbed dose directly by recording the amount of heat created when ionizing radiation passes through matter. The radiation-induced temperature rise was measured using two thermistors calibrated against the NRC temperature primary standard, using an AC bridge with lock-in amplifier for precise measurement. The calorimeter system was operated under thermal equilibrium at 4 °C (to eliminate convection) with drifts in water temperature less than 0.1 mK/min. Seven water vessels of various designs were used to make repeated measurements over the course of 17 years.
Results:
The standard uncertainty achieved for a set of ten calorimeter measurements (4 Gy delivered) was generally well below 0.15 % while the variation between multiple sets for a given vessel was consistent with this value. The long-term stability of the system combined with inter-vessel variations indicated that there was good control of the radiochemistry (chemical heat defect).
Conclusions:
The measurements performed over a period of several years showed that the combined water calorimeters showed stability at +/− 0.25 % level. Thus, rather than relying on a particular vessel as an artifact one can realize the Gray through the more generalized method of combining a glass vessel, high-purity water and thermistor probes. This provides increased robustness in the dissemination of absorbed dose to Canadian users.
To report tumor control and toxicity for patients treated with image-guided intensity-modulated radiotherapy (RT) for spinal metastases with high-dose single-fraction RT.
A total of 103 consecutive ...spinal metastases in 93 patients without high-grade epidural spinal cord compression were treated with image-guided intensity-modulated RT to doses of 18-24 Gy (median, 24 Gy) in a single fraction between 2003 and 2006. The spinal cord dose was limited to a 14-Gy maximal dose. The patients were prospectively examined every 3-4 months with clinical assessment and cross-sectional imaging.
The overall actuarial local control rate was 90% (local failure developed in 7 patients) at a median follow-up of 15 months (range, 2-45 months). The median time to local failure was 9 months (range, 2-15 months) from the time of treatment. Of the 93 patients, 37 died. The median overall survival was 15 months. In all cases, death was from progression of systemic disease and not local failure. The histologic type was not a statistically significant predictor of survival or local control. The radiation dose was a significant predictor of local control (p = 0.03). All patients without local failure also reported durable symptom palliation. Acute toxicity was mild (Grade 1-2). No case of radiculopathy or myelopathy has developed.
High-dose, single-fraction image-guided intensity-modulated RT is a noninvasive intervention that appears to be safe and very effective palliation for patients with spinal metastases, with minimal negative effects on quality of life and a high probability of tumor control.
Purpose:
To evaluate the main characteristics of the Exradin W1 scintillator as a dosimeter and to estimate measurement uncertainties when used in radiotherapy.
Methods:
We studied the calibration ...procedure, energy and modality dependence, short‐term repeatability, dose‐response linearity, angular dependence, temperature dependence, time to reach thermal equilibrium, dose‐rate dependence, water‐equivalent depth of the effective measurement point, and long‐term stability. An uncertainty budget was derived for relative and absolute dose measurements in photon and electron beams.
Results:
Exradin W1 showed a temperature dependence of −0.225% °C−1. The loss of sensitivity with accumulated dose decreased with use. The sensitivity of Exradin W1 was energy independent for high‐energy photon and electron beams. All remaining dependencies of Exradin W1 were around or below 0.5%, leading to an uncertainty budget of about 1%. When a dual channel electrometer with automatic trigger was not used, timing effects became significant, increasing uncertainties by one order of magnitude.
Conclusions:
The Exradin W1 response is energy independent for high energy x‐rays and electron beams, and only one calibration coefficient is needed. A temperature correction factor should be applied to keep uncertainties around 2% for absolute dose measurements and around 1% for relative measurements in high‐energy photon and electron beams. The Exradin W1 scintillator is an excellent alternative to detectors such as diodes for relative dose measurements.
To prospectively evaluate cognitive function and intracranial failure patterns after hippocampal-sparing prophylactic cranial irradiation (PCI) for limited-stage small cell lung cancer (SCLC).
Adults ...with limited-stage SCLC, achieving a complete response to chemoradiotherapy and no brain metastases, were eligible. Patients received PCI 25 Gy/10 fractions, with a mean hippocampal dose limited to <8 Gy and ≥90% of the brain receiving 90% of the prescription. A diverse battery of neuropsychological testing was performed at baseline and 6 and 12 months after PCI. Brain MRI scans were performed at baseline and 6, 12, 18, and 24 months. The primary endpoint was memory measured by the Hopkins Verbal Learning Test-Revised Delayed Recall at 6 months after PCI. The 25-Gy arm of Radiation Therapy Oncology Group protocol 0212 was used as a reference of potential efficacy. Development of intracranial metastases was recorded. Overall survival and progression-free survival were estimated using the Kaplan-Meier method.
Eight men and 12 women with a median age of 61 years enrolled. Two-year overall survival was 88% (95% confidence interval 68%-100%). There was no significant decline in performance between baseline and 6 or 12 months for any of the tests. The association between baseline intelligence quotient and change in performance on testing was not significant. Magnetic resonance imaging revealed asymptomatic brain metastases at a cumulative rate of 20%, with no concurrent extracranial progression. Two patients developed a metastasis in the under-dosed region. Neither involved the dentate gyrus, but 1 involved the avoidance region. Both patients concurrently developed additional metastasis in fully treated brain regions. There were 2 neurologic deaths.
This prospective study suggests a potential benefit of hippocampal sparing in limiting the neuropsychological sequelae of brain radiation, but with a risk of failures in the spared region. These data strongly support continued enrollment on ongoing cooperative group randomized trials. Clinical Trials registration number: NCT01797159.
Women with biologically favorable early-stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the ...large postoperative treatment volumes required for external beam PBI. Relative to external beam delivery, alternative PBI techniques require equipment that is not universally available. To address these issues, we designed a phase 1 trial utilizing widely available technology to 1) evaluate the safety of a single radiation treatment delivered preoperatively to the small-volume, intact breast tumor and 2) identify imaging and genomic markers of radiation response.
Women aged ≥55 years with clinically node-negative, estrogen receptor-positive, and/or progesterone receptor-positive HER2-, T1 invasive carcinomas, or low- to intermediate-grade in situ disease ≤2 cm were enrolled (n=32). Intensity modulated radiation therapy was used to deliver 15 Gy (n=8), 18 Gy (n=8), or 21 Gy (n=16) to the tumor with a 1.5-cm margin. Lumpectomy was performed within 10 days. Paired pre- and postradiation magnetic resonance images and patient tumor samples were analyzed.
No dose-limiting toxicity was observed. At a median follow-up of 23 months, there have been no recurrences. Physician-rated cosmetic outcomes were good/excellent, and chronic toxicities were grade 1 to 2 (fibrosis, hyperpigmentation) in patients receiving preoperative radiation only. Evidence of dose-dependent changes in vascular permeability, cell density, and expression of genes regulating immunity and cell death were seen in response to radiation.
Preoperative single-dose radiation therapy to intact breast tumors is well tolerated. Radiation response is marked by early indicators of cell death in this biologically favorable patient cohort. This study represents a first step toward a novel partial breast radiation approach. Preoperative radiation should be tested in future clinical trials because it has the potential to challenge the current treatment paradigm and provide a path forward to identify radiation response biomarkers.
The optimum dose and fractionation in radiation therapy of curative intent for non-small cell lung cancer remains uncertain. We undertook a published data meta-analysis of randomized trials to ...examine whether radiation therapy regimens with higher time-corrected biologically equivalent doses resulted in longer survival, either when given alone or when given with chemotherapy.
Eligible studies were randomized comparisons of 2 or more radiation therapy regimens, with other treatments identical. Median survival ratios were calculated for each comparison and pooled.
3795 patients in 25 randomized comparisons of radiation therapy dose were studied. The median survival ratio, higher versus lower corrected dose, was 1.13 (95% confidence interval CI 1.04-1.22) when radiation therapy was given alone and 0.83 (95% CI 0.71-0.97) when it was given with concurrent chemotherapy (P for difference=.001). In comparisons of radiation therapy given alone, the survival benefit increased with increasing dose difference between randomized treatment arms (P for trend=.004). The benefit increased with increasing dose in the lower-dose arm (P for trend=.01) without reaching a level beyond which no further survival benefit was achieved. The survival benefit did not differ significantly between randomized comparisons where the higher-dose arm was hyperfractionated and those where it was not. There was heterogeneity in the median survival ratio by geographic region (P<.001), average age at randomization (P<.001), and year trial started (P for trend=.004), but not for proportion of patients with squamous cell carcinoma (P=.2).
In trials with concurrent chemotherapy, higher radiation therapy doses resulted in poorer survival, possibly caused, at least in part, by high levels of toxicity. Where radiation therapy was given without chemotherapy, progressively higher radiation therapy doses resulted in progressively longer survival, and no upper dose level was found above which there was no further benefit. These findings support the consideration of further radiation therapy dose escalation trials, making use of modern treatment methods to reduce toxicity.
Neurologic deficits after brain radiation therapy (RT) typically involve decline in higher-order cognitive functions such as attention and memory rather than sensory defects or paralysis. We sought ...to determine whether areas of the cortex critical to cognition are selectively vulnerable to radiation dose-dependent atrophy.
We measured change in cortical thickness in 54 primary brain tumor patients who underwent fractionated, partial brain RT. The study patients underwent high-resolution, volumetric magnetic resonance imaging (T1-weighted; T2 fluid-attenuated inversion recovery, FLAIR) before RT and 1 year afterward. Semiautomated software was used to segment anatomic regions of the cerebral cortex for each patient. Cortical thickness was measured for each region before RT and 1 year afterward. Two higher-order cortical regions of interest (ROIs) were tested for association between radiation dose and cortical thinning: entorhinal (memory) and inferior parietal (attention/memory). For comparison, 2 primary cortex ROIs were also tested: pericalcarine (vision) and paracentral lobule (somatosensory/motor). Linear mixed-effects analyses were used to test all other cortical regions for significant radiation dose-dependent thickness change. Statistical significance was set at α = 0.05 using 2-tailed tests.
Cortical atrophy was significantly associated with radiation dose in the entorhinal (P=.01) and inferior parietal ROIs (P=.02). By contrast, no significant radiation dose-dependent effect was found in the primary cortex ROIs (pericalcarine and paracentral lobule). In the whole-cortex analysis, 9 regions showed significant radiation dose-dependent atrophy, including areas responsible for memory, attention, and executive function (P≤.002).
Areas of cerebral cortex important for higher-order cognition may be most vulnerable to radiation-related atrophy. This is consistent with clinical observations that brain radiation patients experience deficits in domains of memory, executive function, and attention. Correlations of regional cortical atrophy with domain-specific cognitive functioning in prospective trials are warranted.
Purpose:
In this study, the authors are evaluating a new, commercially available 2D array that offers 3D dose reconstruction for patient specific intensity modulated radiation therapy quality ...assurance (IMRT QA).
Methods:
The OCTAVIUS 4D system and its accompanying software (VERISOFT) by PTW were evaluated for the accuracy of the dose reconstruction for patient specific pretreatment IMRT QA. OCTAVIUS 4D measures the dose plane at the linac isocenter as the phantom rotates synchronously with the gantry, maintaining perpendicularity with the beam, by means of an inclinometer and a motor. The measurements collected during a volumetric modulated arc therapy delivery (VMAT) are reconstructed into a 3D dose volume. The VERISOFT application is used to perform the analysis, by comparing the reconstructed dose against the 3D dose matrix from the treatment planning system (TPS) that is computed for the same geometry and beam arrangement as that of the measurement. In this study, the authors evaluated the 3D dose reconstruction algorithm of this new system using a series of tests. Using the Octavius 4D phantom as the patient, dose distributions for various field sizes, beam orientations, shapes, and combination of fields were calculated using the Pinnacle3, TPS, and the respective DICOMRT dose was exported to the VERISOFT analysis software. Measurements were obtained by delivering the test treatment plans and comparisons were made based on gamma index, dose profiles, and isodose distribution analysis. In addition, output factors were measured and the dose linearity of the array was assessed. Those measurements were compared against measurements in water using a single, calibrated ionization chamber as well as calculations from Pinnacle for the same delivery geometries.
Results:
The number of voxels that met the 3%/3 mm criteria for the volumetric 3D gamma index analysis ranged from 92.3% to 98.9% for all the patient plans that the authors evaluated. 2D gamma analysis in the axial, sagittal, and coronal planes produced similar results to those in the 3D gamma analysis. The new detector system does not require an angular dependence correction because it rotates in synchrony with the gantry and the detector array maintains a constant SAD while always perpendicular to the beam axis. Output factors were within 2% when compared to ionization chamber measurements and Pinnacle calculations. Similar agreement was observed when testing the MU linearity (for MU values above 2) as well as dose rate effect.
Conclusions:
The OCTAVIUS 4D system has some unique characteristics that can potentially improve the patient specific pretreatment IMRT QA data collection and analysis. The ability of the software to reconstruct from the measurements the true 3D dose distribution in the phantom, provides a unique perspective for the medical physicist that evaluates a patient's QA plan.
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