Jacqueline Esthappan

RTOG 0529: A Phase 2 Evaluation of Dose-Painted Intensity Modulated Radiation Therapy in Combination With 5-Fluorouracil and Mitomycin-C for the Reduction of Acute Morbidity in Carcinoma of the Anal Canal

PURPOSE A multi-institutional phase 2 trial assessed the utility of dose-painted intensity modulated radiation therapy (DP-IMRT) in reducing grade 2+ combined acute gastrointestinal and genitourinary adverse events (AEs) of 5-fluorouracil (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer by at least 15% compared with the conventional radiation/5FU/MMC arm from RTOG 9811. METHODS AND MATERIALS T2-4N0-3M0 anal cancer patients received 5FU and MMC on days 1 and 29 of DP-IMRT, prescribed per stage: T2N0, 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes (PTVs) in 28 fractions; T3-4N0-3, 45 Gy elective nodal, 50.4 Gy ≤ 3 cm or 54 Gy >3 cm metastatic nodal and 54 Gy anal tumor PTVs in 30 fractions. The primary endpoint is described above. Planned secondary endpoints assessed all AEs and the investigators ability to perform DP-IMRT. RESULTS Of 63 accrued patients, 52 were evaluable. Tumor stage included 54% II, 25% IIIA, and 21% IIIB. In primary endpoint analysis, 77% experienced grade 2+ gastrointestinal/genitourinary acute AEs (9811 77%). There was, however, a significant reduction in acute grade 2+ hematologic, 73% (9811 85%, P=.032), grade 3+ gastrointestinal, 21% (9811 36%, P=.0082), and grade 3+ dermatologic AEs 23% (9811 49%, P<.0001) with DP-IMRT. On initial pretreatment review, 81% required DP-IMRT replanning, and final review revealed only 3 cases with normal tissue major deviations. CONCLUSIONS Although the primary endpoint was not met, DP-IMRT was associated with significant sparing of acute grade 2+ hematologic and grade 3+ dermatologic and gastrointestinal toxicity. Although DP-IMRT proved feasible, the high pretreatment planning revision rate emphasizes the importance of real-time radiation quality assurance for IMRT trials.

PET-GUIDED IMRT FOR CERVICAL CARCINOMA WITH POSITIVE PARA-AORTIC LYMPH NODES—A DOSE-ESCALATION TREATMENT PLANNING STUDY

PURPOSE To evaluate a treatment planning method for dose escalation to the para-aortic lymph nodes (PALNs) based on positron emission tomography (PET) with intensity-modulated radiotherapy (IMRT) for cervical cancer patients with PALN involvement. One goal of this process was not to modify the traditional treatment of the pelvic region. METHODS AND MATERIALS PET images for 4 cervical cancer patents with PALN involvement were registered with their corresponding CT scans. Positive PALNs were identified on PET images, and the surrounding critical structures were delineated on CT images. The treatment machine central axis (CAX) was placed at the level of the L4-L5 vertebral body interspace. There were two distinct treatment regions: the para-aortic bed superior to the CAX and the whole pelvis region inferior to the CAX. IMRT was used for treatment planning of PALN bed irradiation. The positive PALNs identified on PET images were defined as the gross target volume, and the para-aortic bed was defined as the clinical target volume. The radiation doses were escalated from the conventional 45 Gy to 59.4 Gy for the gross target volume and 50.4 Gy for the clinical target volume in 33 fractions. The pelvis area was treated with conventional treatment methods, AP-PA beams to 50.4 Gy in 28 fractions with a brachytherapy implant boost. The placement of the CAX allowed the two treatment regions to be abutted using the treatment machines independent jaws. RESULTS Dose escalation to positive PALNs, as identified on PET images, and the PALN bed is feasible with IMRT. Treatment plans for 4 patients revealed that escalated prescription doses could be delivered to target volumes while maintaining acceptable doses to the surrounding critical structures. Strategic placement of the treatment isocenter allows the IMRT region (PALN bed) and whole pelvis fields to be treated with a relatively uniform dose distribution in the abutment region. CONCLUSION This study indicates that PET-guided IMRT could be used in a clinical trial in an attempt to escalate doses delivered to patients with cervical cancer who have positive PALNs.

Dosimetry of therapeutic photon beams using an extended dose range film

For intensity modulated radiation therapy (IMRT) dose distribution verification, multidimensional measurements are required to quantify the steep dose-gradient regions. High resolution, two-dimensional dose distributions can be measured using radiographic film. However, the photon energy response of film is known to be a function of depth, field size, and photon beam energy, potentially reducing the accuracy of dose distribution measurements. The dosimetric properties of the recently developed Kodak EDR2 film were investigated and compared to those of Kodak XV film. The dose responses of both film types to 6 MV and 18 MV photon beams were investigated for depths of 5 cm, 10 cm, and 15 cm and field sizes of 4x4 cm2 and 15x15 cm2. This analysis involved the determination of sensitometric curves for XV and EDR2 films, the determination of dose profiles from exposed XV and EDR2 films, and comparison of the film-generated dose profiles to ionization chamber measurements. For the combinations of photon beam energy, depth, and field size investigated here, our results indicate that the sensitometric curves are nearly independent of field size and depth of calibration. For a field size of 4x4 cm2, a single sensitometric curve for either EDR2 and XV film can be used for the determination of relative dose profiles. For the larger field size, the sensitometric curve for EDR2 film is superior to XV film in regions where the dose falls below 20% of the central axis dose, due to the effects that the increased low energy scattered photon contributions have on film response. The limited field size and depth dependence of sensitometric data measured using EDR2 film, along with the inherently wide linear dose-response range of EDR2 film, makes it better suited to the verification of IMRT dose distributions.

Prospective Clinical Trial of Positron Emission Tomography/Computed Tomography Image-Guided Intensity-Modulated Radiation Therapy for Cervical Carcinoma With Positive Para-Aortic Lymph Nodes

PURPOSE To describe a more aggressive treatment technique allowing dose escalation to positive para-aortic lymph nodes (PALN) in patients with cervical cancer, by means of positron emission tomography (PET)/computed tomography (CT)-guided intensity-modulated radiation therapy (IMRT). Here, we describe methods for simulation and planning of these treatments and provide objectives for target coverage as well as normal tissue sparing to guide treatment plan evaluation. METHODS AND MATERIALS Patients underwent simulation on a PET/CT scanner. Treatment plans were generated to deliver 60.0 Gy to the PET-positive PALN and 50.0 Gy to the PALN and pelvic lymph node beds. Treatment plans were optimized to deliver at least 95% of the prescribed doses to at least 95% of each target volume. Dose-volume histograms were calculated for normal structures. RESULTS The plans of 10 patients were reviewed. Target coverage goals were satisfied in all plans. Analysis of dose-volume histograms indicated that treatment plans involved irradiation of approximately 50% of the bowel volume to at least 25.0 Gy, with less than 10% receiving at least 50.0 Gy and less than 1% receiving at least 60.0. With regard to kidney sparing, approximately 50% of the kidney volume received at least 16.0 Gy, less than 5% received at least 50.0 Gy, and less than 1% received at least 60.0 Gy. CONCLUSIONS We have provided treatment simulation and planning methods as well as guidelines for the evaluation of target coverage and normal tissue sparing that should facilitate the more aggressive treatment of cervical cancer.

FIDUCIAL-BASED TRANSLATIONAL LOCALIZATION ACCURACY OF ELECTROMAGNETIC TRACKING SYSTEM AND ON-BOARD KILOVOLTAGE IMAGING SYSTEM

PURPOSE The Calypso medical four-dimensional localization system uses AC electromagnetics, which do not require ionizing radiation, for accurate, real-time tumor tracking. This investigation compared the static and dynamic tracking accuracy of this system to that of an on-board imaging kilovoltage X-ray system for concurrent use of the two systems. METHODS AND MATERIALS The localization accuracies of a kilovoltage imaging system and a continuous electromagnetic tracking system were compared. Using an in-house developed four-dimensional stage, quality-assurance fixture containing three radiofrequency transponders was positioned at a series of static locations and then moved through the ellipsoidal and nonuniform continuous paths. The transponder positions were tracked concurrently by the Calypso system. For static localization, the transponders were localized using portal images and digitally reconstructed radiographs by commercial matching software. For dynamic localization, the transponders were fluoroscopically imaged, and their positions were determined retrospectively using custom-written image processing programs. The localization data sets were synchronized with and compared to the known quality assurance fixture positions. The experiment was repeated to retrospectively track three transponders implanted in a canine lung. RESULTS The root mean square error of the on-board imaging and Calypso systems was 0.1 cm and 0.0 cm, respectively, for static localization, 0.22 mm and 0.33 mm for dynamic phantom positioning, and 0.42 mm for the canine study. CONCLUSION The results showed that both localization systems provide submillimeter accuracy. The Calypso and on-board imaging tracking systems offer distinct sets of advantages and, given their compatibility, patients could benefit from the complementary nature of the two systems when used concurrently.

Quality assurance for clinical implementation of an electromagnetic tracking system

The Calypso Medical 4D localization system utilizes alternating current electromagnetics for accurate, real-time tumor tracking. A quality assurance program to clinically implement this system is described here. Testing of the continuous electromagnetic tracking system (Calypso Medical Technologies, Seattle, WA) was performed using an in-house developed four-dimensional stage and a quality assurance fixture containing three radiofrequency transponders at independently measured locations. The following tests were performed to validate the Calypso system: (a) Localization and tracking accuracy, (b) system reproducibility, (c) measurement of the latency of the tracking system, and (d) measurement of transmission through the Calypso table overlay and the electromagnetic array. The translational and rotational localization accuracies were found to be within 0.01 cm and 1.0 degree, respectively. The reproducibility was within 0.1 cm. The average system latency was measured to be within 303 ms. The attenuation by the Calypso overlay was measured to be 1.0% for both 6 and 18 MV photons. The attenuations by the Calypso array were measured to be 2% and 1.5% for 6 and 18 MV photons, respectively. For oblique angles, the transmission was measured to be 3% for 6 MV, while it was 2% for 18 MV photons. A quality assurance process has been developed for the clinical implementation of an electromagnetic tracking system in radiation therapy.

Peripheral dose distributions for a linear accelerator equipped with a secondary multileaf collimator and universal wedge

The American Association of Physicists in Medicine Task Group 36 (AAPM TG‐36) data can be used to estimate peripheral dose (PD) distributions outside the primary radiation field. However, the report data does not apply to linear accelerators equipped with a multileaf collimator (MLC) and universal wedge (UW). Tertiary multileaf collimators have been shown to significantly affect PD distributions and TG‐36 reported data. Measurements were performed to evaluate PD distributions for a linear accelerator equipped with a secondary MLC, backup diaphragms, and UW. This data can be used to compliment the TG‐36 report for estimation of doses to critical structures outside primary radiation fields. For the evaluated linear accelerator, an MLC is incorporated in the upper secondary collimator jaws. Backup shielding diaphragms are located underneath the MLC. At the nominal collimator position, the MLC and the backup diaphragm provide collimation primarily in the transverse direction. Conventional, solid tungsten‐alloy jaws, located underneath the backup diaphragms, provide secondary collimation in the longitudinal direction. The universal wedge provides dose modulation in the direction of the conventional jaws. Measurements were made with an ionization chamber inserted into a 20×40×120cm3 water‐equivalent plastic phantom with the secondary collimator and MLC settings of 5×5,10×10,15×15, and 25×25cm2 with and without UW. Data was acquired along the machines longitudinal axis for 6, 10, and 18 MV photons. Peripheral dose distributions were measured with the collimator rotated to 0° and 270° for open field measurements and to 0°, 180°, and 270° for wedged fields (IEC 1217). This allowed evaluation of peripheral dose distributions as a function of collimator rotation. Wedged fields were normalized to deliver the same dose at the depth of maximum dose on the central axis as open fields. The measured PD distributions were generally comparable to data reported by TG‐36. At distances close to the field edge (less than 30 or 40 cm), the measured PD distributions were lower when the measurement point was shielded by solid jaws than with MLC and backup diaphragm. At longer distances, this trend reversed for all energies and evaluated field sizes. However, the difference in PD distribution with collimator rotation was not large enough to warrant strategic positioning of the collimator to reduce dose to critical structures outside the primary radiation field. Because internal scatter dominates close to the field edge, wedged PD distributions were comparable to open field doses at distances closer than 30 cm. However, at distances larger than 30 cm from the field edge, wedged PD distributions were significantly grater than those for open fields due to increased contribution of leakage radiation. Increased leakage radiation is due to the increase in wedged field monitor units, which is related to a small wedge factor (0.27 to 0.29). PACS number(s): 87.53.–j, 87.66.–a

Tumor volume and subvolume concordance between FDG-PET/CT and diffusion-weighted MRI for squamous cell carcinoma of the cervix.

To compare [18F]fluorodeoxyglucose (FDG) / positron emission tomography (PET) / computed tomography (CT) and magnetic resonance imaging (MRI) for evaluating patients with cervical cancer. We compared tumor characteristics on FDG‐PET and apparent diffusion coefficient (ADC) maps on diffusion‐weighted MRI (DWI) to evaluate concordance of two functional imaging techniques.

Surface and buildup dose characteristics for 6, 10, and 18 MV photons from an Elekta Precise linear accelerator

Understanding head scatter characteristics of photon beams is vital to properly commission treatment planning (TP) algorithms. Simultaneously, having definitive surface and buildup region dosimetry is important to optimize bolus. The Elekta Precise linacs have unique beam flattening filter configurations for each photon beam (6, 10, and 18 MV) in terms of material and location. We performed a comprehensive set of surface and buildup dose measurements with a thin window parallel‐plate (PP) chamber to examine effects of field size (FS), source‐to‐skin distance (SSD), and attenuating media. Relative ionization data were converted to fractional depth dose (FDD) after correcting for bias effects and using the Gerbi method to account for chamber characteristics. Data were compared with a similar vintage Varian linac. At short SSDs the surface and buildup dose characteristics were similar to published data for Varian and Elekta accelerators. The FDD at surface (FDD0) for 6, 10, and 18 MV photons was 0.171, 0.159, and 0.199, respectively, for a 15×15 cm2, 100 cm SSD field. A blocking tray increased FDD0 to 0.200, 0.200, and 0.256, while the universal wedge decreased FDD0 to 0.107, 0.124, and 0.176. FDD0 increased linearly with FS (~1.16%/cm). FDD0 decreased exponentially for 10 and 18 MV with increasing SSD. However, the 6 MV FDD0 actually increased slightly with increasing SSD. This is likely due to the unique distal flattening filter for 6 MV The measured buildup curves have been used to optimize TP calculations and guide bolus decisions. Overall the FDD0 and buildup doses were very similar to published data. Of interest were the relatively low 10 MV surface doses, and the 6 MV FDD0s dependence on SSD.

Outcomes of iodine-125 plaque brachytherapy for uveal melanoma with intraoperative ultrasonography and supplemental transpupillary thermotherapy

PURPOSE To assess the impact on local tumor control of intraoperative ultrasonographic plaque visualization and selective application of transpupillary thermotherapy (TTT) in the treatment of posterior uveal melanoma with iodine-125 (I-125) episcleral plaque brachytherapy (EPB). METHODS AND MATERIALS Retrospective analysis of 526 patients treated with I-125 EPB for posterior uveal melanoma. Clinical features, dosimetric parameters, TTT treatments, and local tumor control outcomes were recorded. Statistical analysis was performed using Cox proportional hazards and Kaplan-Meier life table method. RESULTS The study included 270 men (51%) and 256 women (49%), with a median age of 63 years (mean, 62 years; range, 16-91 years). Median dose to the tumor apex was 94.4 Gy (mean, 97.8; range, 43.9-183.9) and to the tumor base was 257.9 Gy (mean, 275.6; range, 124.2-729.8). Plaque tilt >1 mm away from the sclera at plaque removal was detected in 142 cases (27%). Supplemental TTT was performed in 72 patients (13.7%). One or 2 TTT sessions were required in 71 TTT cases (98.6%). After a median follow-up of 45.9 months (mean, 53.4 months; range, 6-175 months), local tumor recurrence was detected in 19 patients (3.6%). Local tumor recurrence was associated with lower dose to the tumor base (P=.02). CONCLUSIONS Ultrasound-guided plaque localization of I-125 EPB is associated with excellent local tumor control. Detection of plaque tilt by ultrasonography at plaque removal allows supplemental TTT to be used in patients at potentially higher risk for local recurrence while sparing the majority of patients who are at low risk. Most patients require only 1 or 2 TTT sessions.