Proof of principle of ocular sparing in dogs with sinonasal tumors treated with intensity-modulated radiation therapy.

Intensity-modulated radiation therapy (IMRT) allows optimization of radiation dose delivery to complex tumor volumes with rapid dose drop-off to surrounding normal tissues. A prospective study was performed to evaluate the concept of conformal avoidance using IMRT in canine sinonasal cancer. The potential of IMRT to improve clinical outcome with respect to acute and late ocular toxicity was evaluated. Thirty-one dogs with sinonasal cancer were treated definitively with IMRT using helical tomotherapy and/or dynamic multileaf collimator (DMLC) delivery. Ocular toxicity was evaluated prospectively and compared with a comparable group of historical controls treated with conventional two-dimensional radiotherapy (2D-RT) techniques. Treatment plans were devised for each dog using helical tomotherapy and DMLC that achieved the target dose to the planning treatment volume and limited critical normal tissues to the prescribed dose-volume constraints. Overall acute and late toxicities were limited and minor, detectable by an experienced observer. This was in contrast to the profound ocular morbidity observed in the historical control group treated with 2D-RT. Overall median survival for IMRT-treated and 2D-treated dogs was 420 and 411 days, respectively. Compared with conventional techniques, IMRT reduced dose delivered to eyes and resulted in bilateral ocular sparing in the dogs reported herein. These data provide proof-of-principle that conformal avoidance radiotherapy can be delivered through high conformity IMRT, resulting in decreased normal tissue toxicity as compared with historical controls treated with 2D-RT.

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.

Whole brain radiotherapy with hippocampal avoidance and simultaneously integrated brain metastases boost: a planning study.

PURPOSE: To evaluate the feasibility of using tomotherapy to deliver whole brain radiotherapy with hippocampal avoidance, hypothesized to reduce the risk of memory function decline, and simultaneously integrated boost to brain metastases to improve intracranial tumor control. METHODS AND MATERIALS: Ten patients treated with radiosurgery and whole brain radiotherapy underwent repeat planning using tomotherapy with the original computed tomography scans and magnetic resonance imaging-computed tomography fusion-defined target and normal structure contours. The individually contoured hippocampus was used as a dose-limiting structure (<6 Gy); the whole brain dose was prescribed at 32.25 Gy to 95% in 15 fractions, and the simultaneous boost doses to individual brain metastases were 63 Gy to lesions >or=2.0 cm in the maximal diameter and 70.8 Gy to lesions <2.0 cm. The plans were generated with a field width (FW) of 2.5 cm and, in 5 patients, with a FW of 1.0 cm. The plans were compared regarding conformation number, prescription isodose/target volume ratio, target coverage, homogeneity index, and mean normalized total dose. RESULTS: A 1.0-cm FW compared with a 2.5-cm FW significantly improved the dose distribution. The mean conformation number improved from 0.55 +/- 0.16 to 0.60 +/- 0.13. Whole brain homogeneity improved by 32% (p <0.001). The mean normalized total dose to the hippocampus was 5.9 +/- 1.3 Gy(2) and 5.8 +/- 1.9 Gy(2) for 2.5- and 1.0-cm FW, respectively. The mean treatment delivery time for the 2.5- and 1.0-cm FW plans was 10.2 +/- 1.0 and 21.8 +/- 1.8 min, respectively. CONCLUSION: Composite tomotherapy plans achieved three objectives: homogeneous whole brain dose distribution equivalent to conventional whole brain radiotherapy; conformal hippocampal avoidance; and radiosurgically equivalent dose distributions to individual metastases.

Helical tomotherapy: image guidance and adaptive dose guidance.

Helical tomotherapy is a volumetric image-guided, fully dynamic, intensity-modulated radiation therapy (IMRT) delivery system. The daily use of its pretreatment megavoltage (MV) CT imaging for patient setup verification allows one to correct for interfraction setup error. This is a primary requirement for the accurate delivery of complex IMRT treatment plans, which give differential radiation doses to various target volumes while conformally avoiding normal critical structures. In particular, image guidance using MV CT allows for direct target position verification with the patient in the actual treatment position just prior to therapy delivery. Moreover, since helical MV CT imaging is a slow CT imaging technique, it allows for the encoding of target motion in the resulting MV CT data set, and therefore the pretreatment verification of a motion envelope defined from four-dimensional CT.

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 > or = 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.

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 >or=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 >or=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.

Integral radiation dose to normal structures with conformal external beam radiation.

BACKGROUND: This study was designed to evaluate the integral dose (ID) received by normal tissue from intensity-modulated radiotherapy (IMRT) for prostate cancer. METHODS AND MATERIALS: Twenty-five radiation treatment plans including IMRT using a conventional linac with both 6 MV (6MV-IMRT) and 20 MV (20MV-IMRT), as well as three-dimensional conformal radiotherapy (3DCRT) using 6 MV (6MV-3DCRT) and 20 MV (20MV-3DCRT) and IMRT using tomotherapy (6MV) (Tomo-IMRT), were created for 5 patients with localized prostate cancer. The ID (mean dose x tissue volume) received by normal tissue (NTID) was calculated from dose-volume histograms. RESULTS: The 6MV-IMRT resulted in 5.0% lower NTID than 6MV-3DCRT; 20 MV beam plans resulted in 7.7%-11.2% lower NTID than 6MV-3DCRT. Tomo-IMRT NTID was comparable to 6MV-IMRT. Compared with 6MV-3DCRT, 6MV-IMRT reduced IDs to the rectal wall and penile bulb by 6.1% and 2.7%, respectively. Tomo-IMRT further reduced these IDs by 11.9% and 16.5%, respectively. The 20 MV did not reduce IDs to those structures. CONCLUSIONS: The difference in NTID between 3DCRT and IMRT is small. The 20 MV plans somewhat reduced NTID compared with 6 MV plans. The advantage of tomotherapy over conventional IMRT and 3DCRT for localized prostate cancer was demonstrated in regard to dose sparing of rectal wall and penile bulb while slightly decreasing NTID as compared with 6MV-3DCRT.

Clinical assessment of three-dimensional ultrasound prostate localization for external beam radiotherapy.

Three-dimensional ultrasound localization has been performed for external beam prostate treatments at our institution since September 2001. This article presents data from the daily shifts for 221 patients and 5005 fractions, and the results of tests performed to assess the system's performance under clinical conditions. Three tests are presented: (1) To measure the accuracy of the shifts, eight patients treated on a helical tomotherapy machine were localized daily using both ultrasound (US) and a megavoltage computed tomography (MVCT) scan. Comparison of the shifts showed that US localization improved alignment for six of the eight patients when compared to alignment using skin marks alone. The mean US-MVCT vector for these six patients was 3.1+/-1.3 mm, compared to 5.1+/-2.1 mm between the MVCT and the skin marks. The other two patients were identified as poor candidates for US prior to their first treatment fraction. (2) To assess the extent of intrafraction motion, US localization was repeated after treatment for six patients and a total of 29 fractions. The mean intrafraction prostate shift was 1.9+/-1.0 mm, and the shift was within the 3 mm localization uncertainty [Tomé et al., Med. Phys. 29, 1781-1788 (2002); in New Technologies in Radiation Oncology, edited by W. Schlegel, T. Bortfelde, and A. Grosu (Springer, Berlin, 2005)] of the system for 25 of 29 fractions. (3) To assess the interuser variation in shifts, four experienced operators independently localized five patients for five consecutive fractions. The standard deviation of the users' shifts was found to be approximately the same as the system's localization uncertainty. For shifts larger than the system localization uncertainty, the standard deviation of the users' shifts was nearly always much smaller than the mean shift. Taken together with the results of the US-MVCT comparison, this indicates that the shifts improved patient localization despite differences between users.

Potential for radiation therapy technology innovations to permit dose escalation for non-small-cell lung cancer.

BACKGROUND: Innovations in radiation therapy (RT) technology could have the potential to allow for radiation dose escalation by evaluating tumor motion, minimizing and compensating for motion, and evaluating delivery technologies such as 3-dimensional (3D) conformal radiation therapy (CRT) and intensity-modulated RT (IMRT) using tomotherapy. MATERIALS AND METHODS: Ninety different RT plans were generated using 3 different treatment techniques for 10 patients. These were evaluated using dosimetric tools such as dose-volume histogram (DVH) analysis, tumor equivalent uniform dose (EUD), and dosimetric parameters predictive for lung toxicity, such as the volume of lung receiving > 20 Gy of radiation (V20) and the normalized mean total radiation dose to the lung (NTDmean). The 3 techniques studied included free breathing using 3D CRT, 3D CRT with maximum-inspiration breath-hold (MIBH) to minimize tumor motion, and IMRT delivery with MIBH; the combination of 3 separate planning treatment-volume sets resulted in the generation of 90 different treatment plans. To plan these, patients underwent treatment-planning computed tomography in MIBH and free breathing followed by simulation with measurement of tumor motion and generation/evaluation of DVHs, EUDs, V20, and NTDmean. RESULTS: Average tumor motion was 1.54 cm in the cephalocaudad directions, 1.26 cm in the anteroposterior directions, and 0.56 cm in the lateral directions between maximum inspiration and expiration. Maximum-inspiration breath-hold produced superior lung sparing evidenced by lower V20 and NTDmean values, and these parameters predicted lower modeled pneumonitis rates. Tomotherapy-based IMRT provided further lung sparing. CONCLUSION: Treatment in MIBH results in lower V20 and NTDmean values and lower modeled pneumonitis rates. This effect is enhanced by the use of IMRT. The use of MIBH with IMRT may therefore aid in escalating the dose in RT.

Total scalp irradiation using helical tomotherapy.

Homogeneous irradiation of the scalp poses technical and dosimetric challenges due to the extensive, superficial, curved treatment volume. Conventional treatments on a linear accelerator use multiple matched electron fields or a combination of electron and photon fields. Problems with these techniques include dose heterogeneity in the target due to varying source-to-skin distance (SSD) and angle of beam incidence, significant dose to the brain, and the potential for overdose or underdose at match lines between the fields. Linac-based intensity-modulated radiation therapy (IMRT) plans have similar problems. This work presents treatment plans for total scalp irradiation on a helical tomotherapy machine. Helical tomotherapy is well-suited for scalp irradiation because it has the ability to deliver beamlets that are tangential to the scalp at all points. Helical tomotherapy also avoids problems associated with field matching and use of more than one modality. Tomotherapy treatment plans were generated and are compared to plans for treatment of the same patient on a linac. The resulting tomotherapy plans show more homogeneous target dose and improved critical structure dose when compared to state-of-the-art linac techniques. Target equivalent uniform dose (EUD) for the best tomotherapy plan was slightly higher than for the linac plan, while the volume of brain tissue receiving over 30 Gy was reduced by two thirds. Furthermore, the tomotherapy plan can be more reliably delivered than linac treatments, because the patient is aligned prior to each treatment based on megavoltage computed tomography (MVCT).

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.

The utility of megavoltage computed tomography images from a helical tomotherapy system for setup verification purposes.

PURPOSE: To evaluate the utility of relatively low-dose megavoltage computed tomography (MVCT) images from a clinical helical tomotherapy system for setup verification purposes. METHODS AND MATERIALS: Cross-sectional kilovolt computed tomography (kVCT) images were obtained for treatment planning purposes on a diagnostic third-generation CT scanner, followed by MVCT images from a helical tomotherapy system in 8 pet dogs with spontaneously occurring tumors. The kVCT and MVCT images were aligned for setup verification purposes, allowing repositioning before treatment delivery. RESULTS: Tumors are readily visualized on the MVCT images. At a dose of 2-3 cGy, the MVCT images are of sufficient quality for verification of treatment setup, but soft-tissue contrast is inferior to that with conventional kVCT. The MV and kVCT images were successfully aligned. When necessary, patients undergoing helical tomotherapy were repositioned before treatment. CONCLUSIONS: Megavoltage CT image quality is sufficient for tumor identification and three-dimensional setup verification in dogs with spontaneous tumors. The MVCT images can be aligned with the planning kVCT to ensure proper patient registration before treatment. Image alignment was successful in these canine patients, despite no skin markings defining patient positioning between the two scans. MVCT images facilitate setup verification, and their tomographic nature offers improvements over conventional portal imaging.

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.