AAPM Medical Physics Practice Guideline 14.a: Yttrium-90 microsphere radioembolization.

Radioembolization using Yttrium-90 (90 Y) microspheres is widely used to treat primary and metastatic liver tumors. The present work provides minimum practice guidelines for establishing and supporting such a program. Medical physicists play a key role in patient and staff safety during these procedures. Products currently available are identified and their properties and suppliers summarized. Appropriateness for use is the domain of the treating physician. Patient work up starts with pre-treatment imaging. First, a mapping study using Technetium-99m (Tc-99m ) is carried out to quantify the lung shunt fraction (LSF) and to characterize the vascular supply of the liver. An MRI, CT, or a PET-CT scan is used to obtain information on the tumor burden. The tumor volume, LSF, tumor histology, and other pertinent patient characteristics are used to decide the type and quantity of 90 Y to be ordered. On the day of treatment, the appropriate dose is assayed using a dose calibrator with a calibration traceable to a national standard. In the treatment suite, the care team led by an interventional radiologist delivers the dose using real-time image guidance. The treatment suite is posted as a radioactive area during the procedure and staff wear radiation dosimeters. The treatment room, patient, and staff are surveyed post-procedure. The dose delivered to the patient is determined from the ratio of pre-treatment and residual waste exposure rate measurements. Establishing such a treatment modality is a major undertaking requiring an institutional radioactive materials license amendment complying with appropriate federal and state radiation regulations and appropriate staff training commensurate with their respective role and function in the planning and delivery of the procedure. Training, documentation, and areas for potential failure modes are identified and guidance is provided to ameliorate them.

Board-certified specialty training program in radiation oncology in a war-torn country: Challenges, solutions and outcomes.

BACKGROUND: Residency programs leading to board certification are important for safe and competent Radiation Oncology (RO) practice. In some developing nations, there is a gap in this field. This work addresses the experience that was accomplished to establish such a program in Iraq despite all the challenges that faces a country under war. METHODS: Descriptive report of challenges faced in a developing country that is still reeling from war, the steps taken to overcome these challenges and outcomes after graduation of two classes. RESULTS: After over 18 months of prerequisite technical and logistical preparations, a group of local and external faculty members were invited to establish the required syllabus of a structured RO residency program in Iraq. It is comprised of a total of 100 post-graduate academic credits over a 48-months period after clinical internship. First year evaluations included regular practical assessments; seven in-house papers covering RO, cancer and radiation biology, medical physics, radiological anatomy and diagnostic oncology, tumor pathology, onco-pharmacology, and medical statistics, research methodology, and cancer epidemiology, followed by a comprehensive examination. Subsequent evaluations were on an annual bases with enrollment in the American College of Radiology In-Training examination in RO. Final assessment included logbook and skills' reviews, graduation thesis or peer-review publication, two-papers' written examination, and an exit practical examination. CONCLUSIONS: Given the political, economic and social difficulties in post-war Iraq, it was a major challenge to establish a residency program in RO. Despite the significant difficulties, the first residency program leading to board certification in RO was successfully started in Iraq. The new specialists will help in addressing the shortage of radiation oncologists in the country.

The dosimetric impact of image guided radiation therapy by intratumoral fiducial markers.

PURPOSE: Pancreatic fiducials have proven superior over other isocenter localization surrogates, including anatomical landmarks and intratumoral or adjacent stents. The more clinically relevant dosimetric impact of image guided radiation therapy (IGRT) using intratumoral fiducial markers versus bony anatomy has not yet been described and is therefore the focus of the current study. METHODS AND MATERIALS: Using daily orthogonal kV or cone beam computed tomography (CBCT) images and positional and dosimetric data were analyzed for 12 consecutive patients treated with fiducial based IGRT and volumetric modulated arc therapy to the intact pancreas. The shifts from fiducial to bone (ΔFid-Bone) required to realign the daily fiducial-matched pretreatment images (kV, CBCTs) to the planning computed tomography (CT) using bony anatomic landmarks were recorded. The isocenter was then shifted by (ΔFid-Bone) for 5 evenly spaced treatments, and the dosimetric impact of ΔFid-Bone was calculated for planning target volume coverage (PTV50.4 and PTV47.9) and organs at risk (liver, kidney, and stomach/duodenum). RESULTS: The ΔFid-Bone were greatest in the superoinferior direction (ΔFid-Bone anteroposterior, 2.7 ± 3.0; left-right, 2.8 ± 2.8; superoinferior, 6.3 ± 7.9 mm; mean ± standard deviation; P = .03). PTV50.4 coverage was reduced by 13% (fiducial plan 95 ± 2.0 vs bone plan 82 ± 12%; P = .005; range, 5%-52%; >5% loss in all; and >10% loss in 42% of patients), and to a lesser degree for PTV47.9 (difference, -8%; range, 1%-30%; fiducial plan 100 ± 0.3% vs bone plan 92 ± 7.6%; P = .003; with reductions of >5% in 66% and >10% in 33% of patients). The dosimetric impact of ΔFid-Bone on the organs at risk was not significant. Positional shifts for kV- and CBCT-based realignments were nearly identical. CONCLUSION: Compared with matching by fiducial markers, IGRT matched by bony anatomy substantially reduces the PTV50.4 and PTV47.9 coverage, supporting the use of intratumoral pancreatic markers for improved targeting in IGRT for pancreatic cancer.

The use of RapidArc volumetric-modulated arc therapy to deliver stereotactic radiosurgery and stereotactic body radiotherapy to intracranial and extracranial targets.

Twenty-three targets in 16 patients treated with stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT) were analyzed in terms of dosimetric homogeneity, target conformity, organ-at-risk (OAR) sparing, monitor unit (MU) usage, and beam-on time per fraction using RapidArc volumetric-modulated arc therapy (VMAT) vs. multifield sliding-window intensity-modulated radiation therapy (IMRT). Patients underwent computed tomography simulation with site-specific immobilization. Magnetic resonance imaging fusion and optical tracking were incorporated as clinically indicated. Treatment planning was performed using Eclipse v8.6 to generate sliding-window IMRT and 1-arc and 2-arc RapidArc plans. Dosimetric parameters used for target analysis were RTOG conformity index (CI(RTOG)), homogeneity index (HI(RTOG)), inverse Paddick Conformity Index (PCI), D(mean) and D5-D95. OAR sparing was analyzed in terms of D(max) and D(mean). Treatment delivery was evaluated based on measured beam-on times delivered on a Varian Trilogy linear accelerator and recorded MU values. Dosimetric conformity, homogeneity, and OAR sparing were comparable between IMRT, 1-arc RapidArc and 2-arc RapidArc plans. Mean beam-on times ± SD for IMRT and 1-arc and 2-arc treatments were 10.5 ± 7.3, 2.6 ± 1.6, and 3.0 ± 1.1 minutes, respectively. Mean MUs were 3041, 1774, and 1676 for IMRT, 1-, and 2-arc plans, respectively. Although dosimetric conformity, homogeneity, and OAR sparing were similar between these techniques, SRS and SBRT fractions treated with RapidArc were delivered with substantially less beam-on time and fewer MUs than IMRT. The rapid delivery of SRS and SBRT with RapidArc improved workflow on the linac with these otherwise time-consuming treatments and limited the potential for intrafraction organ and patient motion, which can cause significant dosimetric errors. These clinically important advantages make image-guided RapidArc useful in the delivery of SRS and SBRT to intracranial and extracranial targets.

Prospective evaluation of an in vitro radiation resistance assay in locally advanced cancer of the uterine cervix: a Southwest Oncology Group Study.

OBJECTIVES: To investigate the feasibility of performing a fresh-tissue, in vitro radiation resistance assay (IVRRA) in a cooperative group setting and to assess the association of IVRRA results with clinical outcomes. METHODS: Women with Stages IIB-IVA carcinoma of the uterine cervix without obvious para-aortic lymphadenopathy on imaging were eligible. Primary tumor biopsies were shipped to a central testing facility where agar-based cell suspensions were exposed to 300 cGy of RT ± cisplatin and cultured for 5 days. ³H-thymidine incorporation was used to determine percent cell inhibition (PCI) of test specimen compared to that of the untreated control. Tumors were considered to exhibit extreme radiation resistance (ERR), intermediate radiation resistance (IRR) or low radiation resistance (LRR) based on a standard data set from 39 previously studied specimens. Standardized doses of external beam radiation and intracavitary brachytherapy, when feasible, in addition to platinum-based chemotherapy were mandated. Progression-free survival (PFS) was the primary endpoint. Clinical response and overall survival (OS) were secondary endpoints. Clinical investigators were blinded to assay data and vice versa. RESULTS: Thirty-six patients were enrolled, but analysis was limited to 17 patients whose specimens were adequate for IVRRA. The median follow-up time among patients still alive at last contact was 40 months (range: 0-56 months). There was no association between IVRRA and response. In the Cox model, IRR/ERR tumors showed worse PFS [HR = 11.2 (95% CI 1.3-96, p = 0.03)] and worse OS [HR=11.7 (95% CI 1.4-99.6, p = 0.03)] compared to LRR tumors when IVRRA was performed with RT alone, but there were no associations between IVRRA and PFS or OS when cisplatin was added to the IVRRA. CONCLUSIONS: IVRRA (RT alone) results correlated with PFS and OS in this prospective trial, but follow-up trials are indicated to address feasibility and to confirm results in an expanded cohort. If confirmed, IVRRA could potentially direct molecular identification of novel targeted therapeutic approaches which might counteract radiation resistance.

Experimental investigation of the implementation of Fermi-Eyges-Hogstrom electron beam model of the Pinnacle3 system at extended SSDs.

A commercially available ADAC Pinnacle(3) radiation treatment planning system has been used to model electron beams from a Varian Clinac 2300C/D in the energy range of 6 to 22 MeV. Prior to clinical use, the dosimetric characteristics of the beams have to be modeled accurately. As a first step for beam modeling, a number of dose profile and depth dose measurements were taken at standard source-to-surface distance (SSD) of 100 cm. Dose profiles and depth dose measurements at extended SSDs up to 120 cm are important for ascertaining accuracy of the model, as well as their clinical usefulness in the treatment of some sites (e.g., head-and-neck tumors). Modeled and measured beam data were compared. Over 98% of comparison points (modeled vs. measured) at 100-cm SSD were within 2.5% or 2.5 mm. At 110 cm SSD, over 98% of compared points were within 4% or 4 mm, and at 120-cm SSD, over 98% of compared points were within 5% or 5 mm. Overall, more than 98% of compared points were within 4% or 4 mm. Better models were produced for lower energies (6 to 15 MeV) than higher energies (18 and 22 MeV). For 6, 9, 12, and 15 MeV, 89% of compared points were within 2% or 2 mm. For 18- and 22-MeV electron energies, 75% and 67%, respectively, were within 2% or 2 mm. These results are consistent with the recommendations of AAPM Task Group Report 53.

Real-time tumor tracking using implanted positron emission markers: concept and simulation study.

The delivery accuracy of radiation therapy for pulmonary and abdominal tumors suffers from tumor motion due to respiration. Respiratory gating should be applied to avoid the use of a large target volume margin that results in a substantial dose to the surrounding normal tissue. Precise respiratory gating requires the exact spatial position of the tumor to be determined in real time during treatment. Usually, fiducial markers are implanted inside or next to the tumor to provide both accurate patient setup and real-time tumor tracking. However, current tumor tracking systems require either substantial x-ray exposure to the patient or large fiducial markers that limit the value of their application for pulmonary tumors. We propose a real-time tumor tracking system using implanted positron emission markers (PeTrack). Each marker will be labeled with low activity positron emitting isotopes, such as 124I, 74As, or 84Rb. These isotopes have half-lives comparable to the duration of radiation therapy (from a few days to a few weeks). The size of the proposed PeTrack marker will be 0.5-0.8 mm, which is approximately one-half the size of markers currently employed in other techniques. By detecting annihilation gammas using position-sensitive detectors, multiple positron emission markers can be tracked in real time. A multimarker localization algorithm was developed using an Expectation-Maximization clustering technique. A Monte Carlo simulation model was developed for the PeTrack system. Patient dose, detector sensitivity, and scatter fraction were evaluated. Depending on the isotope, the lifetime dose from a 3.7 MBq PeTrack marker was determined to be 0.7-5.0 Gy at 10 mm from the marker. At the center of the field of view (FOV), the sensitivity of the PeTrack system was 240-320 counts/s per 1 MBq marker activity within a 30 cm thick patient. The sensitivity was reduced by 45% when the marker was near the edge of the FOV. The scatter fraction ranged from 12% (124I, 74As) to 16% (84Rb). In addition, four markers (labeled with 124I) inside a 30 cm diameter water phantom were simulated to evaluate the feasibility of the multimarker localization algorithm. Localization was considered successful if a marker was localized to within 2 mm from its true location. The success rate of marker localization was found to depend on the number of annihilation events used and the error in the initial estimate of the marker position. By detecting 250 positron annihilation events from 4 markers (average of 62 events per marker), the marker success rates for initial errors of +/-5, +/-10, and +/-15 mm were 99.9%, 99.6%, and 92.4%, respectively. Moreover, the average localization error was 0.55 (+/-0.27) mm, which was independent of initial error. The computing time for localizing four markers was less than 20 ms (Pentium 4, 2.8 GHz processor, 512 MB memory). In conclusion, preliminary results demonstrate that the PeTrack technique can potentially provide real-time tumor tracking with low doses associated with the marker's activity. Furthermore, the small size of PeTrack markers is expected to facilitate implantation and reduce patient risk.

Gene expression profiling of in vitro radiation resistance in cervical carcinoma: a feasibility study.

OBJECTIVE(S): To determine the feasibility of integrating an in vitro chemo-radiation response assay (IVRRA) with a gene microarray system to investigate the molecular patterns of expression that contribute to radiation resistance in cervical cancer. METHODS: Viable primary untreated cervical cancer specimens were obtained and exposed to gamma irradiation at a dose of 3 Gy in the IVRRA to determine in vitro radiation sensitivity. RNA was purified for microarray analysis with the Affymetrix Human Genome U95A Array carrying more than 12,000 gene probes. Gene expression analysis was performed, and specimen transcript patterns were correlated with radiation response using an iteration analysis model and Pearson's correlation coefficient. RESULTS: A feasibility set of eight tumor specimens was studied. Tumors were classified into 4 extreme (ERR), 2 intermediate (IRR) and 2 low radiation resistance (LRR) categories. An intrinsic radiation response gene set of 54 genes transcripts with 100% accuracy for the classification of each tumor's radiation response category was identified. CONCLUSION(S): Gene sets associated with in vitro radiation response profiles in cervical cancer can be generated using the IVRRA and microarray technology. This has direct applications to the study of the biological pathways contributing to radiation resistance and may lead to the development of alternative treatment modalities. The potential of these technologies for cancers in which radiotherapy is employed warrants further investigation.

Use of Yttrium-90 TheraSphere for the treatment of unresectable hepatocellular carcinoma.

This is a retrospective analysis of a new treatment modality, intra-arterial administration of Yttrium-90 TheraSphere, for unresectable hepatocellular carcinoma (HCC). Patients with HCC not amenable to surgical treatment who had satisfactory physiological function without comorbid disease or significant pulmonary shunting were eligible for treatment. Patients were categorized into complete, partial, or no response based on serum alpha-fetoprotein (AFP) levels and CT or MRI imaging. Fourteen patients were considered candidates for treatment. Three patients were excluded due to significant hepatopulmonary shunting. Eleven patients were treated with TheraSphere. One patient (9%) had a complete response, eight patients (78%) had a partial response, and two patients (18%) showed no response. Partial and complete responders with AFP-associated HCC demonstrated a median decrease in AFP levels of 79 per cent at 73 days. No patients developed liver toxicity nor died due to treatment. Five patients (45%) died of progressive disease at a median of 7 months post-treatment. Six patients (54%) were alive at a median of 11 months (range, 9 to 20 months). Okuda stage 2 and 3 patients showed a median survival of 11 months and 7 months, respectively. Yttrium-90 TheraSphere treatment for unresectable hepatocellular carcinoma is well tolerated and appears to extend survival.

Treatment planning considerations of reshapeable automatic intensity modulator for intensity modulated radiation therapy.

As compared with multi-leaf collimator based intensity modulated radiation therapy (IMRT) techniques, physical modulators have the major advantage of temporally invariant intensity map delivery which makes it more flexible with monitor unit rate, simpler resolution of interrupted treatment and easier implementation and use with respiratory gating. However, traditional physical modulator techniques require long fabrication time and operator intervention during treatments. It has been previously proposed [Xu et al., Med. Phys. 29, 2222-2229 (2002)] that a reshapeable automatic intensity modulator (RAIM) can automatically produce physical modulators by molding a deformable high x-ray attenuation material using a matrix of computer-controlled pistons. RAIM can potentially eliminate the limitations of traditional physical modulators. The present study addresses the treatment planning considerations of RAIM for IMRT. In this study, a 3D treatment-planning system (PLUNC) was modified to include the capability of providing treatment planning using RAIM. Two clinically representative cases were studied: nasopharyngeal and prostate tumors. First, the RAIM system with two different spatial resolutions at isocenter, 1 x 1 cm2 and 0.5 x 0.5 cm2, were evaluated. The treatment planning results of RAIM were then compared with other IMRT techniques such as smooth modulator with ideal (100%-2%) and limited (100%-13%) intensity modulation ranges, segmental multi-leaf collimator (SMLC) with ten intensity levels, 1 cm leaf width and 0.5 cm step size and serial tomotherapy using the Peacock system. Bringing the spatial resolution of RAIM down to 0.5 x 0.5 cm2 did not show improvement due to the effect of penumbra. The RAIM system with 1 x 1 cm2 proved slightly inferior as compared to the ideal smooth physical modulator but better than the SMLC technique and the smooth modulator with limited modulation range. When compared to serial tomotherapy, RAIM is only inferior in brain stem sparing for the nasopharynx case. Furthermore, the RAIM system with 1 x 1 cm2 resolution required significantly lower monitor units as compared to the other IMRT techniques for the two cases studied.

Reshapable physical modulator for intensity modulated radiation therapy.

A new method of generating beam intensity modulation filters for intensity modulated radiation therapy (IMRT) is presented. The modulator was based on a reshapable material, which is not compressible but can be deformed under pressure. A two-dimensional (2D) piston array was used to repeatedly shape the attenuating material. The material is a mixture of tungsten powder and a silicon-based binder. The linear attenuation coefficient of the material was measured to be 0.409 cm(-1) for a 6 MV x-ray beam. The maximum thickness of the physical modulator is 10.2 cm, allowing a transmission of 1.5%. A 16 x 16 square piston array was used to generate a depth pattern in the deformable attenuating material. Each piston has a cross section of 6.37 x 6.37 mm2. The modulator was placed 65 cm from the radiation source of the linear accelerator in the position of the shielding tray. At this position, each piston projects to a 1.0 x 1.0 cm2 area at the isocenter, giving a treatment field of 16 x 16 cm2. The percent depth dose curve and output factor measurement show a slight beam hardening and a 1%-4% increase in scatter fraction when 2.2-4.4 cm uniform thickness filters are in the beam. The surface dose was decreased with the filter in the beam. Ion chamber and verification films were used to verify the entrance dose. The measured absolute and relative doses were compared with the calculated dose. The agreement of measurements and calculations is within 3%. In order to verify the spatial modulation of dose, 1-D dose profiles were obtained using dose calculations. Calculated and measured profiles were compared. The 20%-80% penumbra of the modulator was measured to be 5.5-10 mm. The results show that a physical modulator formed using a 16 x 16 piston array and a deformable attenuation material can provide intensity modulation for IMRT comparable with those provided by currently available commercial MLC techniques.

Intensity-modulated radiation therapy for the spine at the University of California, Irvine.

Radiation treatment of malignant diseases of the spine poses unique challenges to the radiation oncology treatment team. Intensity-modulated radiation therapy (IMRT) offers the capability of delivering high doses to targets near the spine while respecting spinal cord tolerance. At the University of California, Irvine, 8 patients received a total of 10 courses to the spine for a variety of primary and metastatic malignant conditions. This paper discusses anatomical considerations, spinal cord radiation myelopathy, and treatment planning issues as it relates to the treatment of spinal cord lesions. Between October 1997 and August 2001, a total of 8 patients received 10 courses of IMRT for primary or metastatic disease of the spine. Cancers treated included metastatic lung, renal, adrenocortical cancers, and primary sarcomas and giant cell tumor. Five cases had 6 courses given for re-irradiation of symptomatic disease and 3 cases had 4 courses of IMRT as primary management of their spinal lesions. Although 3 courses were given postoperatively, these were for grossly residual disease. For the re-irradiation patients, the mean follow-up interval was 4 months. The local control was estimated at 14%. Of the patients treated with primary intent, the mean follow-up was 9 months and the local control rate 75%. No patients developed spinal cord complications.

Intensity-modulated radiotherapy for previously irradiated, recurrent head-and-neck cancer.

The purpose of this work is to evaluate our initial experience in treating previously irradiated, recurrent head-and-neck cancers using intensity-modulated radiotherapy (IMRT). Between July 1997 and September 1999, 12 patients with previously irradiated, locally recurrent head-and-neck cancers were treated with IMRT. These included cancers of the nasopharynx, oropharynx, hypopharynx, larynx, paranasal sinus, skin of the head-and-neck region, and malignant melanoma. Five of these 12 patients had received radiation as the primary treatment, with doses ranging from 66.0 to 126.0 Gy, and the remaining 7 patients had undergone definitive surgeries followed by an adjuvant course of radiation treatment, with doses ranging between 36.0 and 64.8 Gy. Recurrence after the initial course of radiation occurred in periods ranging from 4 to 35 months, with 11 of 12 cases recurring fully in the fields of previous irradiation. Recurrent tumors were treated with IMRT to total doses between 30 to 70 Gy (> 50 Gy in 10 cases) prescribed at the 75% to 92% isodose lines with daily fractions of 1.8 to 2 Gy. The results revealed that acute toxicities were acceptable except in 1 patient who died of aspiration pneumonia during the course of retreatment. There were 4 complete responders, 2 partial responders, and 2 patients with stable disease in the IMRT-treated volumes. Three patients received IMRT as adjuvant treatment following salvage surgery. At 4 to 16 months of follow-up, 7 patients were still alive, with 5 revealing no evidence of disease. In conclusion, this pilot study demonstrates that IMRT offers a viable mode of re-irradiation for recurrent head-and-neck cancers in previously irradiated sites. Longer follow-up time and a larger number of patients are needed to better define the therapeutic advantage of IMRT in recurrent, previously irradiated head-and-neck cancers.