Katharina E. Sixel

A Multicenter Randomized Trial of Breast Intensity-Modulated Radiation Therapy to Reduce Acute Radiation Dermatitis

PURPOSE Dermatitis is a frequent adverse effect of adjuvant breast radiotherapy. It is more likely in full-breasted women and when the radiation is distributed nonhomogeneously in the breast. Breast intensity-modulated radiation therapy (IMRT) is a technique that ensures a more homogeneous dose distribution. PATIENTS AND METHODS A multicenter, double-blind, randomized clinical trial was performed to test if breast IMRT would reduce the rate of acute skin reaction (notably moist desquamation), decrease pain, and improve quality of life compared with standard radiotherapy using wedges. Patients were assessed each week during and up to 6 weeks after radiotherapy. RESULTS A total of 358 patients were randomly assigned between July 2003 and March 2005 in two Canadian centers, and 331 were included in the analysis. Breast IMRT significantly improved the dose distribution compared with standard radiation. This translated into a lower proportion of patients experiencing moist desquamation during or up to 6 weeks after their radiation treatment; 31.2% with IMRT compared with 47.8% with standard treatment (P = .002). A multivariate analysis found the use of breast IMRT (P = .003) and smaller breast size (P < .001) were significantly associated with a decreased risk of moist desquamation. The use of IMRT did not correlate with pain and quality of life, but the presence of moist desquamation did significantly correlate with pain (P = .002) and a reduced quality of life (P = .003). CONCLUSION Breast IMRT significantly reduced the occurrence of moist desquamation compared with a standard wedged technique. Moist desquamation was correlated with increased pain and reduction in the quality of life.

Deep inspiration breath hold to reduce irradiated heart volume in breast cancer patients.

Abstract Purpose: To evaluate the use of deep inspiration breath hold (DIBH) during tangential breast radiation therapy as a means of reducing irradiated cardiac volume. Methods and Materials: The Active Breathing Control (ABC) device designed at William Beaumont Hospital, Michigan was used to quantify the potential benefit of radiation delivery during DIBH for five left-sided breast cancer patients. This device initiates a breath hold at a predefined, reproducible lung volume. For each patient, two CT scans were acquired with and without breath hold, and virtual simulation was performed for regular tangent and wide-tangent techniques. The resulting dose–volume histograms were calculated, and the volume of heart irradiated to 25 Gy or more was assessed. Results: The influence of ABC on irradiated heart volumes varied considerably among the five patients. Three patients with substantial cardiac volume in the treatment field during normal respiration showed a significant dose–volume histogram reduction when deep inspiration was applied, with decreases in the heart volume receiving 25 Gy of more than 40 cc observed. For one patient, deep inspiration reduced irradiated cardiac volumes only with the wide-tangent technique, while one patient showed no substantial irradiated volume decrease. Conclusion: A DIBH technique during tangential breast irradiation has the potential to significantly decrease irradiated cardiac volume for suitably selected patients. The magnitude of the impact of the breath hold application depends on patient anatomy, lung capacity, and pulmonary function.

Digital fluoroscopy to quantify lung tumor motion: potential for patient-specific planning target volumes ☆

PURPOSE To apply digital fluoroscopy integrated with CT simulation to measure lung tumor motion and aid in the quantification of individualized planning target volumes. METHODS AND MATERIALS A flat panel digital fluoroscopy unit was modified and integrated with a CT simulator. The stored fluoroscopy images were overlaid with digitally reconstructed radiographs, allowing measurement of the observed lung tumor motion in relation to the corresponding contours on the static digitally reconstructed radiographs. CT simulation and digital fluoroscopy was performed on 10 patients with non-small-cell lung cancer. Actual tumor motion was measured in three dimensions using the overlaid images. RESULTS Combining the dynamic data with digitally reconstructed radiographs allowed the tumor shadow from the fluoroscopy to be tracked in relation to the CT lung tumor contour. For all patients, the extent of tumor motion in three dimensions was unique. The motion was greatest in the superoinferior direction and minimal in the AP and lateral directions. CONCLUSION We have developed a tool that allows CT simulation to be combined with digital fluoroscopy. Quantitative evaluation of the tumor motion in relation to the CT plan allows for customization of the planning target volume. The variability observed clearly demonstrates the need to generate patient-specific internal motion margins.

Phase II study assessing the effectiveness of Biafine cream as a prophylactic agent for radiation-induced acute skin toxicity to the breast in women undergoing radiotherapy with concomitant CMF chemotherapy

PURPOSE To assess the efficacy of Biafine cream in preventing Grade 2 acute radiation dermatitis, according to the National Cancer Institute of Canada skin radiation toxicity criteria in patients undergoing concomitant adjuvant chemotherapy and radiotherapy to the breast. METHODS AND MATERIALS Sixty patients participated in this study. Patients were treated with a lumpectomy followed by concomitant chemotherapy and radiotherapy to the breast. Biafine cream was applied daily, starting on the first day and ending 2 weeks post-radiotherapy. Patients underwent weekly skin assessments throughout radiotherapy and at 2 and 4 weeks after treatment. Outcome measures were assessed using a Skin Assessment Questionnaire that was scored according to the National Cancer Institute of Canada skin radiation toxicity criteria and a self-administered questionnaire that evaluated skin symptoms. RESULTS The maximum skin toxicity observed during the course of treatment was as follows: less than Grade 2 toxicity, 15% (9 patients); Grade 2, 83% (50 patients); Grade 3, 2% (1 patient); Grade 4, 0% (0 patients). The majority of the radiation dermatitis was observed after 3 weeks of radiotherapy. CONCLUSION The majority of patients who underwent concomitant chemo- and radiotherapy for breast cancer developed Grade 2 radiation dermatitis with the use of Biafine cream. However, no treatment delays or interruptions were observed because of skin toxicity.

Calculation of x‐ray spectra for radiosurgical beams

As conformal radiosurgery using micromultileaf collimators gains feasibility, dose calculation algorithms based on Monte Carlo or convolution techniques may become necessary. These require radiosurgical x-ray spectra. The most accurate method currently available to estimate clinical radiosurgery spectra is the Monte Carlo method. In this study the EGS4 Monte Carlo system was used to simulate the thick target of a 6 MV linear accelerator used for radiosurgery in our center. The calculated spectrum was attenuated through any significant mass thickness of material downstream from the target. The attenuated thick-target spectral distributions calculated both with and without the flattening filter were compared to the attenuated, thin target spectrum based on the small angle Schiff analytical spectrum calculated for the same target and attenuator material, as well as with a published spectrum from a full Monte Carlo simulation of a treatment head with a flattener in place. The Schiff spectrum neglects contributions from lower-energy scattered electrons that significantly degrade the quality of the beam. The flattener is removed from our accelerator during radiosurgery to increase the dose rate to approximately 750 cGy/min for a 10 x 10 cm2 field at the depth of dose maximum. This leaves a substantial fluence of photons below 1 MeV that are not observed in published spectra calculated for accelerators with flattening filters. Removal of the flattening filter has a measurable effect on the central axis depth dose, reducing the percentage dose at 10 cm depth from 59.2% to 54.3% for a 10 mm diam field. Radiosurgical off-axis ratios and percentage depth dose distributions calculated from these spectra with the EGS4 Monte Carlo code were compared to measured data. Measured and calculated dose distributions both with and without flattener were in good agreement. The dose distributions were found to be insensitive to the differences in the various calculated spectral distributions. Thus, although the attenuated Schiff spectrum is significantly harder than the clinical beam, it is adequate for dose calculations of radiosurgical beams.

Prediction of obliteration of arteriovenous malformations after radiosurgery: the obliteration prediction index.

OBJECTIVE To describe the response to single dose photon stereotactic radiosurgery of arteriovenous malformations (AVMs) so that the probability of success or failure of treatment may be predicted for the individual patient. METHOD The obliteration prediction index (OPI) was calculated for AVMs by dividing the marginal dose of radiation in Gray (Gy) by the lesion diameter in centimetres in cohorts of 42 patients treated with the modified linear accelerator at Toronto-Sunnybrook Regional Cancer Centre and 394 patients treated with the gamma unit at the Royal Hallamshire Hospital, Sheffield, United Kingdom. Patients were grouped into ranges by OPI and the proportion of success and failure was calculated for each group. An exponential function [P = 1-A.e(-B.OPI)] was fitted to the data by the least squares method. RESULTS Despite systematic differences in radiation treatment, that is, marginal doses of 15 and 20 Gy in Toronto and most Sheffield patients with a marginal dose of 25 Gy, the resultant data points exhibited similar behaviour. CONCLUSION The function [P = 1-A.e(-B.OPI)] partly describes the biological effect of radiation and is independent of the radiation device used. Radiosurgery centres can use this model to facilitate predictions of successful treatment for individual patients.

COMPUTED TOMOGRAPHIC SIMULATION OF CRANIOSPINAL FIELDS IN PEDIATRIC PATIENTS: IMPROVED TREATMENT ACCURACY AND PATIENT COMFORT

PURPOSE To reduce the time required for planning and simulating craniospinal fields through the use of a computed tomography (CT) simulator and virtual simulation, and to improve the accuracy of field and shielding placement. METHODS AND MATERIALS A CT simulation planning technique was developed. Localization of critical anatomic features such as the eyes, cribriform plate region, and caudal extent of the thecal sac are enhanced by this technique. Over a 2-month period, nine consecutive pediatric patients were simulated and planned for craniospinal irradiation. Four patients underwent both conventional simulation and CT simulation. Five were planned using CT simulation only. The accuracy of CT simulation was assessed by comparing digitally reconstructed radiographs (DRRs) to portal films for all patients and to conventional simulation films as well in the first four patients. RESULTS Time spent by patients in the CT simulation suite was 20 min on average and 40 min maximally for those who were noncompliant. Image acquisition time was <10 min in all cases. In the absence of the patient, virtual simulation of all fields took 20 min. The DRRs were in agreement with portal and/or simulation films to within 5 mm in five of the eight cases. Discrepancies of > or =5 mm in the positioning of the inferior border of the cranial fields in the first three patients were due to a systematic error in CT scan acquisition and marker contouring which was corrected by modifying the technique after the fourth patient. In one patient, the facial shield had to be moved 0.75 cm inferiorly owing to an error in shield construction. CONCLUSIONS Our analysis showed that CT simulation of craniospinal fields was accurate. It resulted in a significant reduction in the time the patient must be immobilized during the planning process. This technique can improve accuracy in field placement and shielding by using three-dimensional CT-aided localization of critical and target structures. Overall, it has improved staff efficiency and resource utilization.

Hypofractionated Accelerated Radiotherapy Using Concomitant Intensity-Modulated Radiotherapy Boost Technique for Localized High-Risk Prostate Cancer: Acute Toxicity Results

PURPOSE To evaluate the acute toxicities of hypofractionated accelerated radiotherapy (RT) using a concomitant intensity-modulated RT boost in conjunction with elective pelvic nodal irradiation for high-risk prostate cancer. METHODS AND MATERIALS This report focused on 66 patients entered into this prospective Phase I study. The eligible patients had clinically localized prostate cancer with at least one of the following high-risk features (Stage T3, Gleason score >or=8, or prostate-specific antigen level >20 ng/mL). Patients were treated with 45 Gy in 25 fractions to the pelvic lymph nodes using a conventional four-field technique. A concomitant intensity-modulated radiotherapy boost of 22.5 Gy in 25 fractions was delivered to the prostate. Thus, the prostate received 67.5 Gy in 25 fractions within 5 weeks. Next, the patients underwent 3 years of adjuvant androgen ablative therapy. Acute toxicities were assessed using the Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment and at 3 months after RT. RESULTS The median patient age was 71 years. The median pretreatment prostate-specific antigen level and Gleason score was 18.7 ng/L and 8, respectively. Grade 1-2 genitourinary and gastrointestinal toxicities were common during RT but most had settled at 3 months after treatment. Only 5 patients had acute Grade 3 genitourinary toxicity, in the form of urinary incontinence (n = 1), urinary frequency/urgency (n = 3), and urinary retention (n = 1). None of the patients developed Grade 3 or greater gastrointestinal or Grade 4 or greater genitourinary toxicity. CONCLUSION The results of the present study have indicated that hypofractionated accelerated RT with a concomitant intensity-modulated RT boost and pelvic nodal irradiation is feasible with acceptable acute toxicity.

Integration of digital fluoroscopy with CT-based radiation therapy planning of lung tumors

Radiation dose escalation may be a means to increase the local control rate of inoperable lung tumors. Treatment plans involve the creation of a uniform planning target volume (PTV) to ensure proper coverage despite patient breathing and setup error. This may lead to unnecessary radiation of normal tissue in shallow breathers or target underdosing for patients with excess internal motion. Therefore, the nature of tumor motion for each patient should be measured in 3D, something that cannot be done with CT alone. We have developed a method that acquires 2D real-time fluoroscopic images (loops) and coregisters them with 2D digitally reconstructed radiographs (DRR) formed from the CT scan. The limitations of CT to encompass motion can be overcome by merging the two modalities together. The accuracy of the coregistration method is tested with a stationary grid of radio-opaque markers at various spatial positions. The in-plane (at-depth) displacement between markers on the fluoroscopic image versus the DRR varies with position across the image due to slight misalignments between the x-ray source used in fluoroscopy and the virtual source used for the DRR relative to the test object. At clinically relevant positions, the maximum, measured in-plane displacement, is 1.1 mm. The method is applied to the thorax of an anthropomorphic phantom and a good fit is observed between the appearances of the bony anatomical structures on the coregistered image. Finally, a series of motion measurements are carried out on two oscillating cylindrical objects. The degree of motion as measured by fluoroscopy is accurate to within 1.0 mm, whereas the DRR is inconsistent in predicting motion. The coregistration of fluoroscopic loops with the DRR shows at what point within the oscillation the DRR fails to encompass motion. For any treatment site involving target motion, this real-time imaging is a useful asset in the planning stage.

The influence of patient geometry on the selection of chest wall irradiation techniques in post-mastectomy breast cancer patients

BACKGROUND AND PURPOSE To evaluate three chest wall (CW) irradiation techniques: wide tangential photon beams, direct appositional electron field and electron arc therapy with regards to target coverage and normal tissue tolerance. MATERIALS AND METHODS Thirty-two post-mastectomy breast cancer patients were planned using three CW irradiation techniques. Computed tomography (CT) simulation was done on all patients and clinical target, heart and lung volumes were contoured. For each technique, dose distributions and dose-volume histograms (DVH) were calculated. Pass/fail criteria were applied based on volumetric target and critical structure dose coverage. Passing criteria for target was 95% of target receiving 95% of dose using a standard dose of 50 Gy/25 fractions, for heart </=10% volume receiving 50% dose (i.e. 25 Gy) and for lung </=25% volume ipsilateral lung receiving 50% dose (i.e. 25 Gy). RESULTS The number of patients optimally treated by each technique were as follows: wide tangential photon beams 23/32 (72%), direct appositional electron field 1/32 (3%), electron arc 4/32 (12.5%) and in 4/32 (12.5%) no technique was optimal. Geometric predictors for technique suitability include CW thickness, medial to lateral CW curvature, uniformity of superior to inferior CW curvature and length of mastectomy scar. CONCLUSIONS This study confirms the utility of CT planning and DVH analysis for treatment planning of breast cancer. Patient factors that predict for treatment technique suitability and aid in technique selection can be identified. In a small subset of patients, none of the currently studied techniques were optimal and more novel methods of chest wall irradiation are required.