H. Jaradat

Automatic registration of megavoltage to kilovoltage CT images in helical tomotherapy : An evaluation of the setup verification process for the special case of a rigid head phantom

Precise daily target localization is necessary to achieve highly conformal radiation delivery. In helical tomotherapy, setup verification may be accomplished just prior to delivering each fraction by acquiring a megavoltage CT scan of the patient in the treatment position. This daily image set may be manually or automatically registered to the image set on which the treatment plan was calculated, in order to determine any needed adjustments. The system was tested by acquiring 104 MVCT scans of an anthropomorphic head phantom to which translational displacements had been introduced with respect to the planning image set. Registration results were compared against an independent, optically guided positioning system. The total experimental uncertainty was within approximately 1 mm. Although the registration of phantom images is not fully analogous to the registration of patient images, this study confirms that the system is capable of phantom localization with sub-voxel accuracy. In seven registration problems considered, expert human observers were able to perform manual registrations with comparable or inferior accuracy to automatic registration by mutual information. The time to compute an automatic registration is considerably shorter than the time required for manual registration. However, human evaluation of automatic results is necessary in order to identify occasional outliers, and to ensure that the registration is clinically acceptable, especially in the case of deformable patient anatomy.

Feasibility report of image guided stereotactic body radiotherapy (IG-SBRT) with tomotherapy for early stage medically inoperable lung cancer using extreme hypofractionation.

We report on the technical feasibility, dosimetric aspects, and daily image-guidance capability with megavoltage CT (MVCT) of stereotactic body radiotherapy (SBRT) using helical tomotherapy for medically inoperable T1/2 N0 M0 non-small cell lung cancer. Nine patients underwent treatment planning with 4D-CT in a double vacuum based immobilization system to minimize tumor motion and to define a lesion-specific 4D-motion envelope. Patients received 60 Gy in 5 fractions within 10 days to a PTV defined by a motion envelope plus a 6 mm expansion for microscopic extension and setup error using tomotherapy, with daily pretreatment MVCT image guidance. The primary endpoint was technical feasibility. Secondary endpoints were defining the acute and sub-acute toxicities and tumor response. Forty three of 45 fractions were successfully delivered, with an average delivery time of 22 minutes. MVCT provided excellent tumor visualization for daily image guidance. No significant tumor regression was observed on MVCT in any patient during therapy. Median mean normalized total doses were: tumor 117 Gy10; residual lung 9 Gy3. Maximum fraction-size equivalent dose values were: esophagus 5 Gy39; cord 7 Gy36. No patient experienced ≥ grade 2 pulmonary toxicity. 3 complete, 4 partial and 2 stable responses were observed, with <3 months median follow-up. The mean tumor regression is 72%. SBRT using tomotherapy proved to be feasible, safe and free of major technical limitations or acute toxicities. Daily pretreatment MVCT imaging allows for precise daily tumor targeting with the patient in the actual treatment position, and therefore provides for precise image guidance.

Dose Escalated, Hypofractionated Radiotherapy Using Helical Tomotherapy for Inoperable Non-Small Cell Lung Cancer : Preliminary Results of a Risk-Stratified Phase I Dose Escalation Study

To improve local control for inoperable non-small cell lung cancer (NSCLC), a phase I dose escalation study for locally advanced and medically inoperable patients was devised to escalate tumor dose while limiting the dose to organs at risk including the esophagus, spinal cord, and residual lung. Helical tomotherapy provided image-guided IMRT, delivered in a 5-week hypofractionated schedule to minimize the effect of accelerated repopulation. Forty-six patients judged not to be surgical candidates with Stage I-IV NSCLC were treated. Concurrent chemotherapy was not allowed. Radiotherapy was delivered via helical tomotherapy and limited to the primary site and clinically proven or suspicious nodal regions without elective nodal irradiation. Patients were placed in 1 of 5 dose bins, all treated for 25 fractions, with dose per fraction ranging from 2.28 to 3.22 Gy. The bin doses of 57 to 80.5 Gy result in 2 Gy/fraction normalized tissue dose (NTD) equivalents of 60 to 100 Gy. In each bin, the starting dose was determined by the relative normalized tissue mean dose modeled to cause < 20% Grade 2 pneumonitis. Dose constraints included spinal cord maximum NTD of 50 Gy, esophageal maximum NTD < 64 Gy to ≤ 0.5 cc volume, and esophageal effective volume of 30%. No grade 3 RTOG acute pneumonitis (NCI-CTC v.3) or esophageal toxicities (CTCAE v.3.0 and RTOG) were observed at median follow-up of 8.1 months. Pneumonitis rates were 70% grade 1 and 13% grade 2. Multivariate analysis identified lung NTDmean (p=0.012) and administration of adjuvant chemotherapy following radiotherapy (p=0.015) to be independent risk factors for grade 2 pneumonitis. Only seven patients (15%) required narcotic analgesics (RTOG grade 2 toxicity) for esophagitis, with only 2.3% average weight loss during treatment. Best in-field gross response rates were 17% complete response, 43% partial response, 26% stable disease, and 6.5% in-field thoracic progression. The out-of-field thoracic failure rate was 13%, and distal failure rate was 28%. The median survival was 18 months with 2-year overall survival of 46.8% ± 9.7% for this cohort, 50% of whom were stage IIIB and 30% stage IIIA. Dose escalation can be safely achieved in NSCLC with lower than expected rates of pneumonitis and esophagitis using hypofractionated image-guided IMRT. The maximum tolerated dose has yet to be reached.

A novel method to correct for pitch and yaw patient setup errors in helical tomotherapy

An accurate means of determining and correcting for daily patient setup errors is important to the cancer outcome in radiotherapy. While many tools have been developed to detect setup errors, difficulty may arise in accurately adjusting the patient to account for the rotational error components. A novel, automated method to correct for rotational patient setup errors in helical tomotherapy is proposed for a treatment couch that is restricted to motion along translational axes. In tomotherapy, only a narrow superior/inferior section of the target receives a dose at any instant, thus rotations in the sagittal and coronal planes may be approximately corrected for by very slow continuous couch motion in a direction perpendicular to the scanning direction. Results from proof-of-principle tests indicate that the method improves the accuracy of treatment delivery, especially for long and narrow targets. Rotational corrections about an axis perpendicular to the transverse plane continue to be implemented easily in tomotherapy by adjustment of the initial gantry angle.

Pelvic nodal dose escalation with prostate hypofractionation using conformal avoidance defined (H-CAD) intensity modulated radiation therapy

The management of prostate cancer patients with a significant risk of pelvic lymph node involvement is controversial. Both whole pelvis radiotherapy and dose escalation to the prostate have been linked to improved outcome in such patients, but it is unclear whether conventional whole pelvis doses of only 45–50 Gy are optimal for ultimate nodal control. The purpose of this study is to examine the dosimetric and clinical feasibility of combining prostate dose escalation via hypofractionation with conformal avoidance-based IMRT (H-CAD) dose escalation to the pelvic lymph nodes. One conformal avoidance and one conventional plan were generated for each of eight patients. Conformal avoidance-based IMRT plans were generated that specifically excluded bowel, rectum, and bladder. The prostate and lower seminal vesicles (PTV 70) were planned to receive 70 Gy in 2.5 Gy/fraction while the pelvic lymph nodes (PTV 56) were to concurrently receive 56 Gy in 2 Gy/fraction. The volume of small bowel receiving ≥45 Gy was restricted to 300 ml or less. These conformal avoidance plans were delivered using helical tomotherapy or LINAC-based IMRT with daily imaging localization. All patients received neoadjuvant and concurrent androgen deprivation with a planned total of two years. The conventional, sequential plans created for comparison purposes for all patients consisted of a conventional 4-field pelvic box prescribed to 50.4 Gy (1.8 Gy/fraction) followed by an IMRT boost to the prostate of 25.2 Gy (1.8 Gy/fraction) yielding a final prostate dose of 75.6 Gy. For all plans, the prescription dose was to cover the target structure. Equivalent uniform dose (EUD) analyses were performed on all targets and dose-volume histograms (DVH) were displayed in terms of both physical and normalized total dose (NTD), i.e. dose in 2 Gy fraction equivalents. H-CAD IMRT plans were created for and delivered to all eight patients. Analysis of the H-CAD plans demonstrates prescription dose coverage of >95% of both the PTV 70 (prostate) and PTV 56 (nodes). The EUDs for PTV 70 and PTV 56 were greater than prescription dose for all eight plans. Analysis of bio-effective DVHs demonstrated similar amounts of small bowel receiving ≥45 Gy for H-CAD and sequential plans, in spite of the significantly higher dose to which H-CAD treated the pelvic nodes. The treatment was well tolerated in the eight treated patients in that no grade 2 or higher acute gastrointestinal toxicities were seen. Prostate hypofractionation with concurrent conformal avoidance-based pelvic IMRT for high risk prostate cancer represents an efficient and promising method for achieving dose escalation both of pelvic lymph nodes and the prostate with modest acute toxicity. Unlike a vascular-guided targeting approach, conformal avoidance has the potential advantage of also encompassing at-risk nodes that are not contained within major nodal chains. A phase II trial to more thoroughly examine this treatment approach is currently underway.

Megavoltage computed tomography: an emerging tool for image-guided radiotherapy.

Background:Helical tomotherapy is a unique approach to image-guided IMRT that combines features of a linear accelerator and a CT scanner. This design allows generation of megavoltage CT (MVCT) images, which among other uses, are used to verify daily setup. In this study, we assessed the image-quality, absorbed radiation doses, and clinical practicality of MVCT from our helical tomotherapy prototype unit. Materials and Methods:Phantom studies were first performed to assess the capabilities of MVCT. Next, MVCT images from human patients prospectively enrolled on institutional review board-approved imaging and treatment protocols were analyzed. MVCT was obtained using a 4-MV beam from the University of Wisconsin helical tomotherapy prototype device. These scans were compared with conventional kilovoltage (kVCT) images from a diagnostic CT scanner. Results:MVCT images in phantoms demonstrate an ability to detect contrast differences as small as 3%. Small objects, 1.2 to 1.6 mm, were seen with good resolution. In human subjects, MVCT imaging of tumor targets and normal anatomy revealed sufficient detail for patient repositioning. MVCT imaging of metallic objects showed minimal artifact in comparison with kVCT. Patient scans were obtained in about 1 to 5 minutes and resulted in absorbed radiation doses of 1.5 to 3 cGy. Conclusions:MVCT is an elegant pretreatment position and setup verification tool. MVCT images of human subjects obtained from the helical tomotherapy unit showed good resolution and contrast. The high-quality three-dimensional information permits its use in day-to-day setup verification. The unique properties of MVCT also provide the potential for primary imaging of anatomic regions near metal prostheses as well as nonmedical applications. Additional investigations are underway to improve image quality, further reduce patient dose, and aid adaptive radiotherapy and dose reconstruction.

On the Incorporation of Multi-Modality Image Registration into the Radiotherapy Treatment Planning Process

A technique is presented that allows the direct use of physiological image sets in the radiation therapy treatment planning process. When fused to the treatment planning CT, physiological image studies may allow one to define physiological tumor subvolumes consisting of areas of possible chronic hypoxia, areas of high perfusion, areas of high diffusion, and areas containing high choline concentrations. These physiological tumor subvolumes could be selectively boosted to increase local control of malignant brain tumors once one has determined which of these physiological tumor subvolumes predicts for local tumor recurrence after conventional radiotherapy. In this technique a user assisted automatic registration technique is used that is based on an analytical estimate for the transformation matrix needed to register two rigid bodies. The only user input needed is three non-collinear points selected based on landmarks in the primary image and the corresponding three points in the secondary image. Since this registration technique uses two sets of at least three user-defined landmark points each of which has some selection error associated with it, the final registration will have an error that depends only on the selection error associated with the point sets. Since physiological image studies are acquired at the same setting as the T1- w MRI their spatial orientation with respect to the T1- w MRI is known. Therefore, the registration of multiple physiological image studies to the treatment planning CT can be accomplished by first correlating them to the T1- w MRI, and in a second step the T1- w MRI is then registered to the treatment planning CT. The desired registration of the physiological image studies to the treatment planning CT is then accomplished by simply composing the appropriate transformation matrices.

Measurements of light nuclei production in 11.5a GeV/c Au+Pb heavy-ion collisions

We report on measurements by the E864 experiment at the BNL-AGS of the yields of light nuclei in collisions of Au(197) with beam momentum of 11.5 A GeV/c on targets of Pb(208) and Pt(197). The yields are reported for nuclei with baryon number A=1 up to A=7, and typically cover a rapidity range from y(cm) to y(cm)+1 and a transverse momentum range of approximately 0.1<p(T)/A<0.5 GeV/c. We calculate coalescence scale factors B(A) from which we extract model dependent source dimensions and collective flow velocities. We also examine the dependences of the yields on baryon number, spin, and isospin of the produced nuclei.

Helical Tomotherapy as a Means of Delivering Scalp-sparing Whole Brain Radiation Therapy

We read with interest, “Treating the

Antideuteron yield at the AGS and coalescence implications

We present Experiment 864s measurement of invariant antideuteron yields in 11.5A GeV/c Au + Pt collisions. The analysis includes 250 million triggers representing 14 billion 10% central interactions sampled for events with high mass candidates. We find (1/2 pi pt) d^(2)N/dydpt = 3.5 +/- 1.5 (stat.) +0.9,-0.5 (sys.) x 10^(-8) GeV^(-2)c^(2) for 1.8=0.35 GeV/c (y(cm)=1.6) and 3.7 +/- 2.7 (stat.) +1.4,-1.5 (sys.) x 10^(-8) GeV^(-2)c^(2) for 1.4=0.26 GeV/c, and a coalescence parameter B2-bar of 4.1 +/- 2.9 (stat.) +2.3,-2.4 (sys.) x 10^(-3) GeV^(2)c^(-3). Implications for the coalescence model and antimatter annihilation are discussed.