K. DeWyngaert

THE AMERICAN BRACHYTHERAPY SOCIETY RECOMMENDATIONS FOR PERMANENT PROSTATE BRACHYTHERAPY POSTIMPLANT DOSIMETRIC ANALYSIS

PURPOSE The purpose of this report is to establish guidelines for postimplant dosimetric analysis of permanent prostate brachytherapy. METHODS Members of the American Brachytherapy Society (ABS) with expertise in prostate dosimetry evaluation performed a literature review and supplemented with their clinical experience formulated guidelines for performing and analyzing postimplant dosimetry of permanent prostate brachytherapy. RESULTS The ABS recommends that postimplant dosimetry should be performed on all patients undergoing permanent prostate brachytherapy for optimal patient care. At present, computed tomography (CT)-based dosimetry is recommended, based on availability cost and the ability to image the prostate as well as the seeds. Additional plane radiographs should be obtained to verify the seed count. Until the ideal postoperative interval for CT scanning has been determined, each center should perform dosimetric evaluation of prostate implants at a consistent postoperative interval. This interval should be reported. Isodose displays should be obtained at 50%, 80%, 90%, 100%, 150%, and 200% of the prescription dose and displayed on multiple cross-sectional images of the prostate. A dose-volume histogram (DVH) of the prostate should be performed and the D90 (dose to 90% of the prostate gland) reported by all centers. Additionally, the D80, D100, the fractional V80, V90, V100, V150 and V200 (i.e., the percentage of prostate volume receiving 80%, 90%, 100%, 150%, and 200% of the prescribed dose, respectively), the rectal, and urethral doses should be reported and ultimately correlated with clinical outcome in the research environment. On-line real-time dosimetry, the effects of dose heterogeneity, and the effects of tissue heterogeneity need further investigation. CONCLUSION It is essential that postimplant dosimetry should be performed on all patients undergoing permanent prostate brachytherapy. Guidelines were established for the performance and analysis of such dosimetry.

INTRAOPERATIVE PLANNING AND EVALUATION OF PERMANENT PROSTATE BRACHYTHERAPY: REPORT OF THE AMERICAN BRACHYTHERAPY SOCIETY

PURPOSE The preplanned technique used for permanent prostate brachytherapy has limitations that may be overcome by intraoperative planning. The goal of the American Brachytherapy Society (ABS) project was to assess the current intraoperative planning process and explore the potential for improvement in intraoperative treatment planning (ITP). METHODS AND MATERIALS Members of the ABS with expertise in ITP performed a literature review, reviewed their clinical experience with ITP, and explored the potential for improving the technique. RESULTS The ABS proposes the following terminology in regard to prostate planning process: *Preplanning--Creation of a plan a few days or weeks before the implant procedure. *Intraoperative planning--Treatment planning in the operating room (OR): the patient and transrectal ultrasound probe are not moved between the volume study and the seed insertion procedure. * Intraoperative preplanning--Creation of a plan in the OR just before the implant procedure, with immediate execution of the plan. *Interactive planning--Stepwise refinement of the treatment plan using computerized dose calculations derived from image-based needle position feedback. *Dynamic dose calculation--Constant updating of dose distribution calculations using continuous deposited seed position feedback. Both intraoperative preplanning and interactive planning are currently feasible and commercially available and may help to overcome many of the limitations of the preplanning technique. Dosimetric feedback based on imaged needle positions can be used to modify the ITP. However, the dynamic changes in prostate size and shape and in seed position that occur during the implant are not yet quantifiable with current technology, and ITP does not obviate the need for postimplant dosimetric analysis. The major current limitation of ITP is the inability to localize the seeds in relation to the prostate. Dynamic dose calculation can become a reality once these issues are solved. Future advances can be expected in methods of enhancing seed identification, in imaging techniques, and in the development of better source delivery systems. Additionally, ITP should be correlated with outcome studies, using dosimetric, toxicity, and efficacy endpoints. CONCLUSION ITP addresses many of the limitations of current permanent prostate brachytherapy and has some advantages over the preplanned technique. Further technologic advancement will be needed to achieve dynamic real-time calculation of dose distribution from implanted sources, with constant updating to allow modification of subsequent seed placement and consistent, ideal dose distribution within the target volume.

Phase I-II Trial of Prone Accelerated Intensity Modulated Radiation Therapy to the Breast to Optimally Spare Normal Tissue

PURPOSE To report the clinical feasibility of a trial of accelerated whole-breast intensity modulated radiotherapy, with the patient in prone position, optimally to spare the heart and lung. PATIENTS AND METHODS Patients with stages I or II breast cancer, excised by breast conserving surgery with negative margins, were eligible for this institutional review board-approved prospective trial. Computed tomography simulation was performed with the patient prone on a dedicated breast board, in the exact position used for treatment. A dose of 40.5 Gy, delivered at 2.7 Gy in 15 fractions, was prescribed to the index breast with an additional concomitant boost of 0.5 Gy delivered to the tumor bed, for a total dose of 48 Gy to the lumpectomy site. Physics constraints consisted of limiting 5% of the heart volume to receive > or = 18 Gy and < or = 10% of the ipsilateral lung volume to receive > or = 20 Gy. RESULTS Between September 2003 and August 2005, 91 patients were enrolled on the study. Median length of follow-up was 12 months (range, 1 to 28 months). In all patients the technique was feasible and heart and lung sparing was achieved as prescribed by the protocol. Acute toxicities consisting mostly of reversible grades 1-2 skin dermatitis (67%) and fatigue (18%) occurred in 75 patients. One patient sustained a regional recurrence rapidly followed by distant metastases. CONCLUSION Accelerated whole breast intensity modulated radiotherapy in the prone position is feasible and it permits a drastic reduction in the volume of lung and heart tissue exposed to significant radiation.

Intensity modulated radiation therapy versus three- dimensional conformal radiation therapy for the treatment of high grade glioma: a dosimetric comparison

The present study compared the dosimetry of intensity‐modulated radiation therapy (IMRT) and three‐dimensional conformal radiation therapy (3D‐CRT) techniques in patients treated for high‐grade glioma. A total of 20 patients underwent computed tomography treatment planning in conjunction with magnetic resonance imaging fusion. Prescription dose and normal‐tissue constraints were identical for the 3D‐CRT and IMRT plans. The prescribed dose was 59.4 Gy delivered at 1.8 Gy per fraction using 4 – 10 MV photons. Normal‐tissue dose constraints were 50 – 54 Gy for the optic chiasm and nerves, and 55 – 60 Gy for the brainstem. The IMRT plan yielded superior target coverage as compared with the 3D‐CRT plan. Specifically, minimum and mean planning target volume cone down doses were 54.52 Gy and 61.74 Gy for IMRT and 50.56 Gy and 60.06 Gy for 3D‐CRT (p≤0.01). The IMRT plan reduced the percent volume of brainstem receiving a dose greater than 45 Gy by 31% (p=0.004) and the percent volume of brain receiving a dose greater than 18 Gy, 24 Gy, and 45 Gy by 10% (p=0.059), 14% (p=0.015), and 40% (p≤0.0001) respectively. With IMRT, the percent volume of optic chiasm receiving more than 45 Gy was also reduced by 30.40% (p=0.047). As compared with 3D‐CRT, IMRT significantly increased the tumor control probability (p≤0.005) and lowered the normal‐tissue complication probability for brain and brainstem (p<0.033). Intensity‐modulated radiation therapy improved target coverage and reduced radiation dose to the brain, brainstem, and optic chiasm. With the availability of new cancer imaging tools and more effective systemic agents, IMRT may be used to intensify tumor doses while minimizing toxicity, therefore potentially improving outcomes in patients with high‐grade glioma. PACs number: 87.53 Tf

Risk and Risk Reduction of Major Coronary Events Associated With Contemporary Breast Radiotherapy

Author Affiliations: Department of Emergency Medicine, University of California, San Francisco (Brownell, Hsia); medical student, School of Medicine, University of California, San Francisco (Wang); Division of Geriatrics, Department of Medicine, University of California, San Francisco (Smith); Geriatrics, Palliative and Extended Care, San Francisco Veterans Affairs Medical Center (Smith, Stephens); Department of Community Health Systems, University of California, San Francisco (Stephens).

The Role of a Prone Setup in Breast Radiation Therapy

Most patients undergoing breast conservation therapy receive radiotherapy in the supine position. Historically, prone breast irradiation has been advocated for women with large pendulous breasts in order to decrease acute and late toxicities. With the advent of CT planning, the prone technique has become both feasible and reproducible. It was shown to be advantageous not only for women with larger breasts but in most patients since it consistently reduces, if not eliminates, the inclusion of heart and lung within the field. The prone setup has been accepted as the best localizing position for both MRI and stereotactic biopsy, but its adoption has been delayed in radiotherapy. New technological advances including image-modulated radiation therapy and image-guided radiation therapy have made possible the exploration of accelerated fractionation schemes with a concomitant boost to the tumor bed in the prone position, along with better imaging and verification of reproducibility of patient setup. This review describes some of the available techniques for prone breast radiotherapy and the available experience in their application. The NYU prone breast radiotherapy approach is discussed, including a summary of the results from several prospective trials.

Ionizing radiation modulates the exposure of the HUIV26 cryptic epitope within collagen type IV during angiogenesis

PURPOSE The majority of the research on the biologic effects of ionizing radiation has focused on the impact of radiation on cells in terms of gene expression, DNA damage, and cytotoxicity. In comparison, little information is available concerning the direct effects of radiation on the extracellular microenvironment, specifically the extracellular matrix and its main component, collagen. We have developed a series of monoclonal antibodies that bind to cryptic epitopes of collagen Type IV that are differentially exposed during matrix remodeling and are key mediators of angiogenesis. We have hypothesized that ionizing radiation might affect the process of angiogenesis through a direct effect on the extracellular matrix and specifically on collagen Type IV. METHODS AND MATERIALS Angiogenesis was induced in a chick chorioallantoic membrane (CAM) model; 24 h later, a single-dose treatment with ionizing radiation (0.5, 5, and 20 cGy) was administered. Angiogenesis was assessed, and the exposure of two cryptic regulatory epitopes within collagen Type IV (HUI77 and HUIV26) was studied in vitro by solid-phase ELISA and in vivo by immunofluorescence staining. RESULTS A dose-dependent reduction of angiogenesis with maximum inhibition (85%-90%) occurring at 20 cGy was demonstrated in the CAM model. Exposure of the cryptic HUIV26 site, an angiogenesis control element, was inhibited both in vitro and in vivo by the same radiation dose, whereas little if any change was observed for the HUI77 cryptic epitope. CONCLUSIONS A dose-dependent alteration of the functional exposure of the HUIV26 cryptic epitope is induced by radiation in vitro and in the CAM model in vivo. This radiation-induced change in protein structure and function may contribute to the inhibitory effects of ionizing radiation on new blood vessel growth and warrants further studies in other models.

Prone Breast Intensity Modulated Radiation Therapy: 5-Year Results

PURPOSE To report the 5-year results of a technique of prone breast radiation therapy delivered by a regimen of accelerated intensity modulated radiation therapy with a concurrent boost to the tumor bed. METHODS AND MATERIALS Between 2003 and 2006, 404 patients with stage I-II breast cancer were prospectively enrolled into 2 consecutive protocols, institutional trials 03-30 and 05-181, that used the same regimen of 40.5 Gy/15 fractions delivered to the index breast over 3 weeks, with a concomitant daily boost to the tumor bed of 0.5 Gy (total dose 48 Gy). All patients were treated after segmental mastectomy and had negative margins and nodal assessment. Patients were set up prone: only if lung or heart volumes were in the field was a supine setup attempted and chosen if found to better spare these organs. RESULTS Ninety-two percent of patients were treated prone, 8% supine. Seventy-two percent had stage I, 28% stage II invasive breast cancer. In-field lung volume ranged from 0 to 228.27 cm(3), mean 19.65 cm(3). In-field heart volume for left breast cancer patients ranged from 0 to 21.24 cm(3), mean 1.59 cm(3). There was no heart in the field for right breast cancer patients. At a median follow-up of 5 years, the 5-year cumulative incidence of isolated ipsilateral breast tumor recurrence was 0.82% (95% confidence interval [CI] 0.65%-1.04%). The 5-year cumulative incidence of regional recurrence was 0.53% (95% CI 0.41%-0.69%), and the 5-year overall cumulative death rate was 1.28% (95% CI 0.48%-3.38%). Eighty-two percent (95% CI 77%-85%) of patients judged their final cosmetic result as excellent/good. CONCLUSIONS Prone accelerated intensity modulated radiation therapy with a concomitant boost results in excellent local control and optimal sparing of heart and lung, with good cosmesis. Radiation Therapy Oncology Group protocol 1005, a phase 3, multi-institutional, randomized trial is ongoing and is evaluating the equivalence of a similar dose and fractionation approach to standard 6-week radiation therapy with a sequential boost.

Breast radiotherapy in the prone position primarily reduces the maximum out-of-field measured dose to the ipsilateral lung.

PURPOSE To quantify the potential advantages of prone position breast radiotherapy in terms of the radiation exposure to out-of-field organs, particularly, the breast or the lung. Several dosimetric studies have been reported, based on commercial treatment planning software (TPS). These TPS approaches are not, however, adequate for characterizing out-of-field doses. In this work, relevant out-of-field organ doses have been directly measured. METHODS The authors utilized an adult anthropomorphic phantom to conduct measurements of out-of-field doses in prone and supine position, using 50 Gy prescription dose intensity modulated radiation therapy (IMRT) and 3D-CRT plans. Measurements were made using multiple MOSFET dosimeters in various locations in the ipsilateral lung, the contralateral lung and in the contralateral breast. RESULTS The closer the organ (or organ segment) was to the treatment volume, the more dose sparing was seen for prone vs supine positioning. Breast radiotherapy in the prone position results in a marked reduction in the dose to the proximal part of the ipsilateral lung, compared with treatment in the conventional supine position. This is true both for 3D-CRT and for IMRT. For IMRT, the maximum measured dose to the lung was reduced from 4 to 1.6 Gy, while for 3D-CRT, the maximum measured lung dose was reduced from 5 to 1.7 Gy. For the proximal part of the ipsilateral lung, as well as for the contralateral lung and the contralateral breast, there is little difference in the measured organ doses whether the treatment is given in the prone or the supine-position. CONCLUSIONS The decrease in the maximum dose to the proximal part of the ipsilateral lung produced by prone position radiotherapy is of potentially considerable significance. The dose-response relation for radiation-induced lung cancer increases monotonically in the zero to 5-Gy dose range, implying that a major decrease in the maximum lung dose may result in a significant decrease in the radiation-induced lung cancer risk.

SU-E-T-588: Characterization and Clinical Validation of the Varian Pivotal™ Treatment Solution for Prone Breast Care

PURPOSE To report on the clinical validation of the Varian Pivotal™ Treatment Solution for Prone Breast Care: a platform for prone breast radiation therapy. METHODS Patients treated using Breast Conserving Radiation Therapy may benefit from treatment in the prone position with the breast tissue falling freely away from the body. This geometry allows the breast tissue to be treated while avoiding the lung and heart tissue. Eighteen patients simulated and treated using the Varian Medical Systems Pivotal™ Treatment Solution for Prone Breast Care were monitored over the course of treatment for positioning integrity and reproducibility. As this carbon-fiber platform actually replaces a portion of the couch top, indexing is inherent to its design. Patients were positioned on the couch and aligned using fiducial markers and lateral SSD to the breast fiducial point. The daily couch coordinates then serves as indicators for positioning variability with this system. RESULTS The variations in couch vertical, longitudinal and lateral positions were centered on a mean value of zero with standard deviations of 0.44cm, 0.75cm and 0.79cm respectively. Other factors explored were variations in distance of mid-sternum to table edge and patient rotation into the opening. The median rotation of the chest wall was found to be 11.5 degrees at CT-Simulation with a median distance of 2.5cm from midsternum to support opening. Patient rotation was not associated with either breast size or distance from edge of platform. CONCLUSION The Pivotal™ Treatment solution consists of a couch top that replaces the standard top and as such is open from beneath without obstruction. This is a distinction from all other solutions which rely on a platform positioned above and indexed to the treatment couch. We found the reproducibility to be consistent with our historical measures while offering benefits of an integrated solution as stated above. supported by Professional Services Agreeement with Varian Medical Systems.