M. Al-Ghazi

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 markers activity. Furthermore, the small size of PeTrack markers is expected to facilitate implantation and reduce patient risk.

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.

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.

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.

The University of California, Irvine experience with tomotherapy using the Peacock system ☆

Our institutional experience using the Peacock system for intensity-modulated radiation therapy (IMRT) is summarized. Over 100 patients were treated using this system, which is fitted to a Clinac 600C linac. Both cranial and extracranial lesions have been treated using this modality. Immobilization is achieved either with the Talon system for cranial sites or an Aquaplast cast. Target volumes up to 500 cm3 have been treated. Multiple lesions (up to 3) were treated in one setup. The range of dose/fractionation schemes used was 15 Gy/1 fx (radiosurgical treatment) - 80 Gy/40 fx. Dose validation studies were carried out using film and ion chamber dosimetry in a specially designed phantom. Optimal dose distributions were attainable using inverse treatment planning for IMRT delivery. These were found to encompass the target volumes accurately using dose validation phantom studies. Immobilization methods used were accurate to within 1 mm, as evidenced by daily portal films. IMRT using the Peacock system offers the advantage of delivery of conformal therapy to high doses safely and accurately. This provides the opportunity for dose escalation studies, retreatment of previously treated tumors, as well as treating multiple targets in one setup. The system may be fitted to a conventional linac without major modifications.

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.

A practical method for the calculation of multileaf collimator shaped fields output factors

Output factors of multileaf-collimator (MLC) shaped radiation fields were measured for a commercial linear accelerator whose MLC leaves form parts of the upper collimator system. The approach of taking into account the reduced phantom scatter due to the MLC shaping on the output factor has previously been shown to be inadequate for this type of machine because of the effect of the MLC leaves on the collimator factor [Palta et al., Med. Phys. 23, 1219-1224(1996)]. In this article, we present two forms of the collimator factor that give satisfactory agreement with measured values of the output factors of MLC-shaped fields. The present method should be directly applicable to other linacs of similar MLC configuration. For clinical treatment planning, we believe the method is practical and accurate enough to be satisfactory. The equation for calculating the output factor requires only peak scatter and output factors of the machine. These are normally measured during machine commissioning.

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.

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.