G. Pang

Prostate stereotactic ablative body radiotherapy using a standard linear accelerator: Toxicity, biochemical, and pathological outcomes

BACKGROUND AND PURPOSE Biological dose escalation through stereotactic ablative radiotherapy (SABR) holds promise of improved patient convenience, system capacity and tumor control with decreased cost and side effects. The objectives are to report the toxicities, biochemical and pathologic outcomes of this prospective study. MATERIALS AND METHODS A phase I/II study was performed where low risk localized prostate cancer received SABR 35 Gy in 5 fractions, once weekly on standard linear accelerators. Common Terminology Criteria for Adverse Events v3.0 and Radiation Therapy Oncology Group late morbidity scores were used to assess acute and late toxicities, respectively. Biochemical control (BC) was defined by the Phoenix definition. RESULTS As of May 2012, 84 patients have completed treatment with a median follow-up of 55 months (range 13-68 months). Median age was 67 years and median PSA was 5.3 ng/ml. The following toxicities were observed: acute grade 3+: 0% gastrointestinal (GI), 1% genitourinary (GU), 0% fatigue; late grade 3+: 1% GI, 1% GU. Ninety-six percent were biopsy negative post-treatment. The 5-year BC was 98%. CONCLUSIONS This novel technique employing standard linear accelerators to deliver an extreme hypofractionated schedule of radiotherapy is feasible, well tolerated and shows excellent pathologic and biochemical control.

Phase I/II Study of a Five-fraction Hypofractionated Accelerated Radiotherapy Treatment for Low-risk Localised Prostate Cancer: Early Results of pHART3

AIMS Most men with low-risk localised prostate cancer prefer treatments with high control rates and minimal disruption to their lives. Hypofractionating external radiation treatments can theoretically maintain high bioequivalent tumour doses, decrease treatment visits and decrease acute and late toxicities. The aim of this study was to assess the toxicity and feasibility of a hypofractionated accelerated regimen for these patients. MATERIALS AND METHODS The present study was a phase I/II study in which patients with T1-2b, Gleason < or = 6 and prostate-specific antigen (PSA) < or = 10 ng/ml prostate cancer received 35Gy in five fractions, once a week over 29 days. Treatment was delivered with intensity-modulated radiotherapy on standard linear accelerators, with daily image guidance using gold seed fiducials, and a 4mm clinical target volume to planning target volume margin. RESULTS As of January 2008, the target accrual of 30 patients had been reached and all had completed treatment and at least 6 months of follow-up. Dose-volume histogram objectives were achievable in all patients. Treatment was very well tolerated with no grade 3 or 4 genitourinary toxicity, gastrointestinal toxicity nor fatigue observed (95% confidence interval 0-12%). As a group, compared with baseline, the following additional grade 2 toxicities were observed: 13% genitourinary, 7% gastrointestinal and 10% fatigue. At 6 months all scores had returned to or improved over baseline. The median PSA before treatment was 6.0 ng/ml. At 6 months, the median PSA was 1.8 ng/ml and 75% had a PSA < or = 3.0 ng/ml. CONCLUSIONS This novel technique using standard linear accelerators seems feasible and is well tolerated. Further follow-up will be carried out to document late toxicity and efficacy.

Hypofractionated concomitant intensity-modulated radiotherapy boost for high-risk prostate cancer: late toxicity.

PURPOSE To report the acute and late toxicities of patients with high-risk localized prostate cancer treated using a concomitant hypofractionated, intensity-modulated radiotherapy boost combined with long-term androgen deprivation therapy. METHODS AND MATERIALS A prospective Phase I-II study of patients with any of the following: clinical Stage T3 disease, prostate-specific antigen level ≥ 20 ng/mL, or Gleason score 8-10. A dose of 45 Gy (1.8 Gy/fraction) was delivered to the pelvic lymph nodes with a concomitant 22.5 Gy prostate intensity-modulated radiotherapy boost, to a total of 67.5 Gy (2.7 Gy/fraction) in 25 fractions within 5 weeks. Image guidance was performed using three gold seed fiducials. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, and Radiation Therapy Oncology Group late morbidity scores were used to assess the acute and late toxicities, respectively. Biochemical failure was determined using the Phoenix definition. RESULTS A total of 97 patients were treated and followed up for a median of 39 months, with 88% having a minimum of 24 months of follow-up. The maximal toxicity scores were recorded. The grade of acute gastrointestinal toxicity was Grade 0 in 4%, 1 in 59%, and 2 in 37%. The grade of acute urinary toxicity was Grade 0 in 8%, 1 in 50%, 2 in 39%, and 3 in 4%. The grade of late gastrointestinal toxicity was Grade 0 in 54%, 1 in 40%, and 2 in 7%. No Grade 3 or greater late gastrointestinal toxicities developed. The grade of late urinary toxicity was Grade 0 in 82%, 1 in 9%, 2 in 5%, 3 in 3%, and 4 in 1% (1 patient). All severe toxicities (Grade 3 or greater) had resolved at the last follow-up visit. The 4-year biochemical disease-free survival rate was 90.5%. CONCLUSIONS A hypofractionated intensity-modulated radiotherapy boost delivering 67.5 Gy in 25 fractions within 5 weeks combined with pelvic nodal radiotherapy and long-term androgen deprivation therapy was well tolerated, with low rates of severe toxicity. The biochemical control rate at early follow-up has been promising. Additional follow-up is needed to determine the long-term biochemical control and prostate biopsy results.

Digital radiology using active matrix readout of amorphous selenium: Geometrical and effective fill factors

Flat panel self-scanned x-ray detectors using amorphous selenium (a-Se) as the photoconductor are being developed to replace both film/screen cassette systems for radiography and image intensifier (XRII)/video systems for fluoroscopy. These use a two-dimensional array of pixel electrodes to collect and readout the latent image charges formed on the photoconductor surface. The percentage of the area covered by the pixel electrodes (i.e., the geometrical fill factor fg) is always less than unity. In this paper, a novel approach is introduced to make the charge collection by pixel electrodes almost complete (i.e., a close to unity effective fill factor). The idea is to bend the electric field lines in the a-Se layer in such a way that image charges cannot land in the gap region between electrodes. This is achieved by depositing holes in the gap region, which is possible because there are charge traps available at the a-Se/insulator interface. The distribution of holes required in the gap region is calculated. Various factors associated with the feasibility of this approach as well as a method to deposit these holes are discussed. Application of the approach to the case of mammography is also included.

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.

Development of high quantum efficiency, flat panel, thick detectors for megavoltage x-ray imaging: a novel direct-conversion design and its feasibility.

Most electronic portal imaging devices (EPIDs) developed to date, including recently developed flat panel systems, have low x-ray absorption, i.e., low quantum efficiency (QE) of 2%-4% as compared to the theoretical limit of 100%. A significant increase of QE is desirable for applications such as a megavoltage cone-beam computed tomography (MVCT) and megavoltage fluoroscopy. However, the spatial resolution of an imaging system usually decreases significantly with an increase of QE. The key to the success in the design of a high QE detector is therefore to maintain the spatial resolution. Recently, we demonstrated theoretically that it is possible to design a portal imaging detector with both high QE and high resolution [see Pang and Rowlands, Med. Phys. 29, 2274 (2002)]. In this paper, we introduce such a novel design consisting of a large number of microstructured plates (made by, e.g., photolithographic patterning of evaporated or electroplated layers) packed together and aligned with the incident x rays. On each plate, microstrip charge collectors are focused toward the x-ray source to collect charges generated in the ionization medium (e.g., air or gas) surrounded by high-density materials that act as x-ray converters. The collected charges represent the x-ray image and can be read out by various means, including a two-dimensional (2-D) active readout matrix. The QE, spatial resolution, and sensitivity of the detector have been calculated. It has been shown that the new design will have a QE of more than an order of magnitude higher and a spatial resolution equivalent to that of flat panel systems currently used for portal imaging. The new design is also quantum noise limited down to very low doses (approximately 1-2 radiation pulses of the linear accelerator).

Electronic portal imaging based on cerenkov radiation: a new approach and its feasibility.

Most electronic portal imaging devices (EPIDs) developed so far use a Cu plate/phosphor screen to absorb x rays and convert their energies into light, and the light image is then read out. The main problem with this approach is that the Cu plate/phosphor screen must be thin (approximately 2 mm thick) in order to obtain a high spatial resolution, resulting in a low x-ray absorption or low quantum efficiency for megavoltage x rays (typically 2-4%). In addition, the phosphor screen contains high atomic number (high-Z) materials, resulting in an over-response of the detector to low-energy x rays in dosimetric verification. In this paper, we propose a new approach that uses Cerenkov radiation to convert x-ray energy absorbed by the detector into light for portal imaging applications. With our approach, a thick (approximately 10-30 cm) energy conversion layer made of a low-Z dielectric medium, such as a large-area, thick fiber-optic taper consisting of a matrix of optical fibers aligned with the incident x rays, is used to replace the thin Cu plate/phosphor screen. The feasibility of this approach has been investigated using a single optical fiber embedded in a solid material. The spatial resolution expressed by the modulation transfer function (MTF) and the sensitivity of the detector at low doses (approximately one Linac pulse) have been measured. It is predicted that, using this approach, a detective quantum efficiency of an order of magnitude higher at zero frequency can be obtained while maintaining a reasonable MTF, as compared to current EPIDs.

Imaging of 1.0-mm-diameter radiopaque markers with megavoltage X-rays: An improved online imaging system

PURPOSE To improve an online portal imaging system such that implanted cylindrical gold markers of small diameter (no more than 1.0 mm) can be visualized. These small markers would make the implantation procedure much less traumatic for the patient than the large markers (1.6 mm in diameter), which are usually used today to monitor prostate interfraction motion during radiation therapy. METHODS AND MATERIALS Several changes have been made to a mirror-video based online imaging system to improve image quality. First, the conventional camera tube was replaced by an avalanche-multiplication-based video tube. This new camera tube has very high gain at the target such that the camera noise, which is one of the main causes of image degradation of online portal imaging systems, was overcome and effectively eliminated. Second, the conventional linear-accelerator (linac) target was replaced with a low atomic number (low-Z) target such that more diagnostic X-rays are present in the megavoltage X-ray beam. Third, the copper plate buildup layer for the phosphor screen was replaced by a thin plastic layer for detection of the diagnostic X-ray components in the beam generated by the low-Z target. RESULTS Radiopaque fiducial gold markers of different sizes, i.e., 1.0 mm (diameter) x 5 mm (length) and 0.8 mm (diameter) x 3 mm (length), embedded in an Alderson Rando phantom, can be clearly seen on the images acquired with our improved system. These markers could not be seen on images obtained with any commercial system available in our clinic. CONCLUSION This work demonstrates the visibility of small-diameter radiopaque markers with an improved online portal imaging system. These markers can be easily implanted into the prostate and used to monitor the interfraction motion of the prostate.

Intra-fraction motion during extreme hypofractionated radiotherapy of the prostate using pre- and post-treatment imaging.

AIMS To determine intra-fraction displacement of the prostate during extreme hypofractionated radiotherapy using pre- and post-treatment orthogonal images with three implanted gold seed fiducial markers. MATERIALS AND METHODS In total, 265 image pairs were obtained from 53 patients who underwent extreme hypofractionated radiotherapy to a dose of 35 Gy in five fractions on standard linear accelerators. Position verification was obtained with orthogonal X-rays before and after treatment and were used to determine intra-fraction prostate displacement. RESULTS The mean intra-fraction prostate displacements were -0.03 ± 0.61 mm (one standard deviation), 0.21 ± 1.50 mm and -0.86 ± 1.73 mm in the left-right, superior-inferior and anterior-posterior directions, respectively. The mean intra-fraction displacement during the first two fractions was moderately correlated with the displacement in the remaining three fractions, with correlation coefficients of 0.63 (95% confidence interval 0.43-0.77) and 0.47 (95% confidence interval 0.22-0.65) in the superior-inferior and anterior-posterior directions, respectively. There was no significant correlation in the left-right direction with a coefficient of -0.04 (95% confidence interval -0.31-0.23). CONCLUSIONS The mean intra-fraction prostate displacement during a course of extreme hypofractionated radiotherapy is small. A strategy using the first two fractions to predict future displacements >5 mm warrants further validation.

Megavoltage cone beam digital tomosynthesis (MV-CBDT) for image-guided radiotherapy: a clinical investigational system

Cone beam digital tomosynthesis (CBDT) is a new imaging technique proposed recently as a rapid approach for creating tomographic images of a patient in the radiotherapy treatment room. The purpose of this work is to investigate the feasibility of performing megavoltage (MV) CBDT clinically. A clinical investigational MV-CBDT system was installed on an existing LINAC. After the installation, the treatment machine can be operated in two distinct modes: (1) normal clinical treatment mode; (2) CBDT mode, in which tomographic images of the patient can be obtained using MV-CBDT. Various calibration and phantom measurements were performed on the system, followed by a patient study. Our phantom measurements have shown that: (1) for the same imaging dose, MV-CBDT has the same signal-difference-to-noise ratio as megavoltage cone beam computed tomography (MV-CBCT); (2) MV-CBDT has a better spatial resolution than MV-CBCT in the planes of reconstruction but a worse spatial resolution in the direction perpendicular to the planes of reconstruction. MV-CBDT patient images were also obtained and compared to that of MV-CBCT. We have demonstrated that it is clinically feasible to perform MV-CBDT in the treatment room for image-guided radiotherapy.