CyberKnife with integrated CT-on-rails: System description and first clinical application for pancreas SBRT.

PURPOSE: This article reports on the integration of a sliding-gantry CT-on-rails with a robotic linear accelerator. METHODS: The system consists of a SOMATOM Definition AS CT scanner (Siemens Healthcare, Forchheim, Germany) and a CyberKnife M6 FIM (Accuray, Inc., Sunnyvale, CA, USA). Additional movement programs were implemented in the robotic treatment table (RoboCouch, Accuray Inc.) to move between CT and treatment position. Acceptance testing was performed on the CT scanner according to AAPM83 guidelines, as well as safety tests for collision avoidance and electromagnetic (EM) compatibility. For the first clinical application of the system, daily dose was evaluated in five pancreas SBRT patients. A second envisioned use is the optimal alignment of the treatment beams to soft-tissue targets without the use of implanted fiducials. To this end, an offset vector feature has been implemented, which shifts the treatment center according to the daily position of the tumor relative to the spine (established by a CT scan). This offset can be applied by either moving the treatment couch (physical couch shift) or by moving the CyberKnife robot (virtual couch shift). An End-to-End (E2E) test was specifically designed to evaluate the accuracy of this feature using the Xsight Lung Tracking Phantom (Computerized Imaging Reference Systems, Inc., Norfolk, VA, USA). The position of the tumor with respect to the spine was varied by moving the insert inside the phantom and a CT scan was made for each position. The treatment plan was subsequently delivered to the phantom employing spine tracking. The test was repeated four times for a physical couch shift and four times for a virtual couch shift. RESULTS: All acceptance, safety and EM compatibility testing was successful. For the first pancreas SBRT patients treated using daily CT imaging, the volume of stomach, duodenum, or small bowel receiving >35 Gy was found to increase or remain constant during treatment; however, the clinical constraint of 5 cc was not violated. For the offset vector E2E test, the reference accuracy (without any tumor shift) was (0.74, -0.61, -0.33) mm in the inferior, left, and anterior direction respectively. The difference in deviation with respect to the reference was (-0.1 ± 0.15, 0.01 ± 0.16, -0.17 ± 0.25) mm, when applying a physical couch shift. With a virtual couch shift, the deviations were (0.02 ± 0.15, 0.06 ± 0.23, -0.4 ± 0.31) mm. CONCLUSIONS: The first combination of a CyberKnife treatment unit with a sliding-gantry CT scanner is operational in our department enabling future developments toward image-guided online-adaptive SBRT supported by diagnostic-quality CT imaging.

Fractionated stereotactic radiotherapy for uveal melanoma, late clinical results.

PURPOSE: To determine local control, late toxicity and metastatic free survival (MFS) of patients treated with fractionated stereotactic radiation therapy (fSRT) for uveal melanoma (UM). METHODS AND MATERIALS: Between 1999 and 2007, 102 UM patients were included in a prospective study of a single institution (median follow-up (FU) 32 months; median tumor thickness 6 mm); five fractions of 10 Gy were given. Primary endpoints were local tumor control and late toxicity (including visual outcome and eye preservation). Secondary endpoint was MFS. RESULTS: Local tumor control was achieved in 96% of the patients. Fifteen enucleations were performed, 2-85 months after radiation. Four eyes were enucleated because of local tumor progression. Nine patients developed grade 3 or 4 neovascular glaucoma (NVG), 19 developed severe retinopathy, 13 developed opticoneuropathy grade 3 or 4, 10 developed cataract grade 3, and 10 patients suffered from keratitis sicca. Best corrected visual acuity (BCVA) decreased from a mean of 0.26 at diagnosis to 0.16, 3 months after radiation and it gradually declined to 0.03, 4 years after therapy. The 5-year actuarial MFS was 75% (95% CIs: 62-84%). CONCLUSIONS: fSRT is an effective treatment modality for uveal melanoma with a good local control. With that, fSRT is a serious eye sparing treatment modality. However, our FU is relatively short. Also, the number of secondary enucleations is substantial, mainly caused by NVG.

Effectiveness of fractionated stereotactic radiotherapy for uveal melanoma.

PURPOSE: To study the effectiveness and acute side effects of fractionated stereotactic radiation therapy (fSRT) for uveal melanoma. METHODS AND MATERIALS: Between 1999 and 2003, 38 patients (21 male, 17 female) were included in a prospective, nonrandomized clinical trial (mean follow-up of 25 months). A total dose of 50 Gy was given in 5 consecutive days. A blinking light and a camera (to monitor the position of the diseased eye) were fixed to a noninvasive relocatable stereotactic frame. Primary end points were local control, best corrected visual acuity, and toxicity at 3, 6, 12, and 24 months, respectively. RESULTS: After 3 months (38 patients), the local control was 100%; after 12 months (32 patients) and 24 months (15 patients), no recurrences were seen. The best corrected visual acuity declined from a mean of 0.21 at diagnosis to 0.06 2 years after therapy. The acute side effects after 3 months were as follows: conjunctival symptoms (10), loss of lashes or hair (6), visual symptoms (5), fatigue (5), dry eye (1), cataract (1), and pain (4). One eye was enucleated at 2 months after fSRT. CONCLUSIONS: Preliminary results demonstrate that fSRT is an effective and safe treatment modality for uveal melanoma with an excellent local control and mild acute side effects. The follow-up should be prolonged to study both long-term local control and late toxicity.

Optimal source position for irradiation of coronary bifurcations in endovascular brachytherapy with catheter based beta or iridium-192 sources.

BACKGROUND AND PURPOSE: Intracoronary brachytherapy after percutaneous transluminal coronary angioplasty (PTCA) is usually performed with catheter-based treatment techniques in a straight vessel segment. There is a growing interest for treatment of bifurcations, which requires consecutive positioning of the source in main vessel and side branch. MATERIALS AND METHODS: In-house developed software (IC-BT doseplan) is used to explore the optimal positioning of the source in modelled bifurcations with different shape for the source types available in our hospital, i.e. (90)Sr/(90)Y, (32)P and (192)Ir. The results were summarised in look-up tables. The usefulness of these look-up tables was tested on various clinical examples. RESULTS: Tabulated results for the modelled bifurcations yield an estimation of the distance between the sources (gap width) in relation to the geometry and source type: (90)Sr/(90)Y gap range 3-8.5 mm, (32)P gap range 2-7 mm and (192)Ir gap range 3.5-8 mm. The average dose relative to 2 mm from the source axis is: (90)Sr/(90)Y, (mean+/-SD) 120+/-40%; (32)P, 125+/-50% and (192)Ir, 120+/-22%. The look-up tables also provide the coarse location and value of maximum and minimum dose: (90)Sr/(90)Y, 220-60%, (32)P, 230-55% and (192)Ir, 170-85%. It appeared that the look-up tables provide a good approximation of the optimal gap width in the clinical examples. CONCLUSIONS: Tabulated optimal gap widths are very useful for quick estimation of the required gap width for a given bifurcation and source type, in case the prescribed dose in both vessels is the same. In unfavourable geometries there is a risk of local underdosage. Individual treatment planning using a program such as IC-BT doseplan is then recommended.

A modified relocatable stereotactic frame for irradiation of eye melanoma: design and evaluation of treatment accuracy.

PURPOSE: To describe a reliable, patient-friendly relocatable stereotactic frame for irradiation of eye melanoma and to evaluate the repositioning accuracy of the stereotactic treatment. METHODS AND MATERIALS: An extra construction with a blinking light and a camera is attached to a noninvasive relocatable Gill-Thomas-Cosman stereotactic frame. The position of the blinking light is in front of the unaffected eye and can be adjusted to achieve an optimal position for irradiation. The position of the diseased eye is monitored with a small camera. A planning CT scan is performed with the affected eye in treatment position and is matched with an MR scan to improve the accuracy of the delineation of the tumor. Both the translation and rotation of the affected eye are calculated by comparing the planning CT scan with a control CT scan, performed after the radiation therapy is completed. RESULTS: Nineteen irradiated eye melanoma patients were analyzed. All patients received 5 fractions of 10 Gy within 5 days. The depth-confirmation helmet measurements of the day-to-day treatment position of the skull within the Gill-Thomas-Cosman frame were analyzed in the anteroposterior, lateral, and vertical directions and were 0.1 +/- 0.3, 0.0 +/- 0.2, and 0.2 +/- 0.2 mm (mean +/- SD), respectively. The average translations of the eye on the planning and control CT scan were 0.1 +/- 0.3 mm, 0.1 +/- 0.4, and 0.1 +/- 0.5 mm, respectively. The median rotation of the diseased eye was 8.3 degrees. CONCLUSIONS: The described Rotterdam eye fixation system turned out to be a feasible, reliable, and patient-friendly system.

A comparison of intravascular source designs based on the beta particle emitter 114mIn/114In. Line source versus stepping source.

BACKGROUND: Catheter-based intravascular brachytherapy (IVB) sources of the next generation will have to meet high demands in terms of miniaturization, flexibility, safety, reliability, costs and versatility. The radionuclide pair 114mIn/114In (half-life 49.51 days, maximum beta energy 2.0 MeV, average beta energy 0.78 MeV) is an attractive beta emitter for application in such a source. METHODS: Since metallic indium is unfit for the manufacture of a brachytherapy source, the feasibility, safety and dosimetric properties of a design concept comprising a linear array of ceramic In2O3 spheres within a thin-walled, superelastic Ni/Ti capsule are investigated. RESULTS: Neutron activation of enriched In2O3 spheres yields a specific activity sufficiently high for the manufacture of a stepping source, keeping treatment times limited to a few minutes. Although 114mIn/114In also emits some gamma radiation, the effective doses received by members of the medical staff are an order of magnitude lower than those received from fluoroscopy. The dose distributions about a 40-mm line source and a 5-mm stepping source (outer diameter 0.36 mm) are calculated using MCNP4C. Dose-volume histograms (DVHs) are calculated for the line source (centered and noncentered) and the stepping source (centered) using the geometry of a human coronary artery. CONCLUSION: The results show that a centered stepping source with optimized dwell times delivers the most homogenous dose within the target volume.

Dosimetric comparison between high-precision external beam radiotherapy and endovascular brachytherapy for coronary artery in-stent restenosis.

PURPOSE: Several drawbacks of endovascular brachytherapy for the treatment of coronary artery in-stent restenosis may be addressed by high-precision external beam radiotherapy (EBRT). The dosimetric characteristics of both treatment techniques were compared. METHODS AND MATERIALS: The traversed volume of 10 coronary artery stents during the cardiac cycle was determined by electrocardiographically gated multislice spiral CT in 10 patients. By use of this traversed volume, high-precision EBRT treatment plans were generated for stents in the left circumflex (LCx), left anterior descending (LAD), and right coronary artery (RCA). The maximum dose to the nontargeted major coronary arteries was determined and compared to similar data calculated for endovascular brachytherapy. RESULTS: High-precision EBRT targeted at LCx stents contributed a mean maximum dose (D(max)) of 83.5% (range: 71.6-95.3%) and 16.3% to the LAD and RCA, respectively. Targeted LAD stents contributed a mean D(max) of 39.3% (range: 14.5-94.8%) and 5.2% (range: 0-13.4%) to the LCx and RCA, respectively. Targeted RCA stents contributed a mean D(max) of 6.2% (range: 0-12.4%) and 5.8% (range: 0-11.5%) to the LCx and LAD, respectively. Endovascular brachytherapy targeted at LCx stents contributed a mean D(max) of 1.7% (range: 0.7-2.7%) and 1.0% (range: 0.6-1.4%) to the LAD and RCA, respectively. Targeted LAD stents contributed a mean D(max) of 5.2% (range: 0.5-11.4%) and 0.7% (range: 0.4-1.1%) to the LCx and RCA, respectively; targeted RCA stents contributed a mean D(max) of 0.3% (range: 0.2-0.5%) and 0.2% (range: 0.1-0.3%) to the LCx and LAD, respectively. CONCLUSIONS: Although the doses distributed throughout the heart were higher for high-precision EBRT compared to endovascular brachytherapy, they are expected to be clinically irrelevant when nontargeted major coronary arteries are not closely situated to the targeted vessel segment. These encouraging results warrant further investigation of high-precision EBRT as a potential alternative to endovascular brachytherapy for the treatment of coronary artery in-stent restenosis.

Inaccuracy in manual multisegmental irradiation in coronary arteries.

PURPOSE: Retrospective evaluation of the accuracy of manual multisegmental irradiation with a source train for irradiation of long (re)stenotic lesions in coronary arteries, following percutaneous transluminal coronary angioplasty (PTCA). MATERIAL AND METHODS: Thirty-six patients were treated with intracoronary irradiation following PTCA with manual multisegmental irradiation. These patients were included in the multicenter, multinational 'European Surveillance Registry with the Novoste Beta-Cath system' (RENO). In all 36 patients the target length (i.e. PTCA length plus 5-mm margin at each side) was too long for the available source train lengths (30 and 40 mm). In 33 patients the radiation delivery catheter was manually positioned twice and in three patients three times in series, trying to avoid any gap or overlap. The total number of junctions was 39. Following a successful PTCA procedure the site of angioplasty was irradiated using the Novoste Beta-Cath afterloader with a 5-F non-centered catheter which accommodates the sealed beta-emitting (90)Sr/(90)Y source train or dummy source train. Radiation was delivered first to the distal part of the target length. Fluoroscopic images of this source position were stored in the computer memory. For irradiation of the proximal part of the target length, the delivery catheter had to be retracted over a distance equal to the source length used for the distal part. This was done by a continuous overlay video loop with ECG-gated replay of the image stored in the computer memory. The dummy source was used to position the delivery catheter so that the junction between both source positions was as precise as possible. Measurements of gap or overlap between the source positions were performed retrospectively on printed images. Doses were calculated, in accordance with the Novoste study protocol, at a distance of 2 mm from the source axis (=dose prescription distance) in several points along the irradiated length. RESULTS: Interventional or PTCA length varied between 33 and 95 mm. The lesion sites were in the left anterior descending artery, (n=6), right coronary artery (n=20), left circumflex artery (n=6) and one vein graft. The administered radiation dose was determined by the vessel diameter and the presence of a stent. This dose, prescribed at a distance of 2 mm from the source axis, varied between 16 and 22 Gy. No gap or overlap was seen between the two source trains in only two out of 39 cases. In 16 cases there was a gap ranging between 0.6 and 9.6 mm and 18 cases showed an overlap of 0.5-14.4 mm. In three patients the measurement was not possible. In case of a gap the minimal dose calculated at 2 mm from the source axis varies between 0 and 87% of the prescribed dose, depending on the distance between both sources. In case of overlap the maximal dose varies between 110 and 200% of the prescribed dose at 2 mm from the source axis. CONCLUSIONS: The results show the inaccuracy of manual multisegmental irradiation using a source train in coronary arteries, causing unacceptable dose inhomogeneities at a distance of 2 mm from the source axis at the junction between both source positions. Moreover, a perfect junction will never be possible due to movement of the non-centered radiation delivery catheter in the vessel lumen, as applied in this study. Manual multisegmental irradiation is therefore not recommended. Using longer line sources or source trains or preferably an automated stepping source is a more reliable and safer technique for treatment of long lesions.