Lisa J. Forrest

Image guidance for precise conformal radiotherapy

PURPOSE To review the state of the art in image-guided precision conformal radiotherapy and to describe how helical tomotherapy compares with the image-guided practices being developed for conventional radiotherapy. MATERIALS AND METHODS Image guidance is beginning to be the fundamental basis for radiotherapy planning, delivery, and verification. Radiotherapy planning requires more precision in the extension and localization of disease. When greater precision is not possible, conformal avoidance methodology may be indicated whereby the margin of disease extension is generous, except where sensitive normal tissues exist. Radiotherapy delivery requires better precision in the definition of treatment volume, on a daily basis if necessary. Helical tomotherapy has been designed to use CT imaging technology to plan, deliver, and verify that the delivery has been carried out as planned. The image-guided processes of helical tomotherapy that enable this goal are described. RESULTS Examples of the results of helical tomotherapy processes for image-guided intensity-modulated radiotherapy are presented. These processes include megavoltage CT acquisition, automated segmentation of CT images, dose reconstruction using the CT image set, deformable registration of CT images, and reoptimization. CONCLUSIONS Image-guided precision conformal radiotherapy can be used as a tool to treat the tumor yet spare critical structures. Helical tomotherapy has been designed from the ground up as an integrated image-guided intensity-modulated radiotherapy system and allows new verification processes based on megavoltage CT images to be implemented.

Postoperative Radiotherapy for Canine Soft Tissue Sarcoma

Thirty-five dogs with 37 soft tissue sarcoma tumors that were incompletely excised and treated with radiotherapy in the postoperative, adjuvant setting were reviewed. Variables evaluated included age, sex, tumor site, tumor histology, total tumor radiation dose, radiotherapy field size. time to recurrence, and survival. The majority of tumors were fibrosarcomas and hemangiopericytomas, but small numbers of other tumor types were also represented. Total tumor radiation dose ranged from 42 to 57 Gy given in 3- to 4.2-Gy daily fractions on a Monday through Friday schedule. Overall median survival was 1,851 days. Median time to local recurrence was greater than 798 days. Soft-tissue sarcoma tumors at oral sites had a statistically significant lower median survival (540 days) as compared to other tumor sites (2,270 days). Radiotherapy may be a useful adjuvant therapy for incompletely excised soft-tissue sarcomas with a reasonable expectation for long-term patient survival.

Clinical Implementation of Adaptive Helical Tomotherapy: A Unique Approach to Image-Guided Intensity Modulated Radiotherapy

Image-guided IMRT is a revolutionary concept whose clinical implementation is rapidly evolving. Methods of executing beam intensity modulation have included individually designed compensators, static multi-leaf collimators (MLC), dynamic MLC, and sequential (serial) tomotherapy. We have developed helical tomotherapy as an innovative solution to overcome some of the limitations of other IMRT systems. The unique physical design of helical tomotherapy allows the realization of the concepts of adaptive radiotherapy and conformal avoidance. In principle, these advances should improve normal tissue sparing and permit dose reconstruction and verification, thereby allowing significant biologically effective dose escalation. Recent radiobiological findings can be translated into altered fractionation schemes that aim to improve the local control and long-term survival. This strategy is being tested at the University of Wisconsin using helical tomotherapy with its highly precise delivery and verification system along with meticulous and practical forms of immobilization. Innovative techniques such optical guidance, respiratory gating, and ultrasound assessments are being designed and tailored for helical tomotherapy use. The intrinsic capability of helical tomotherapy for megavoltage CT (MVCT) imaging for IMRT image-guidance is being optimized. The unique features of helical tomotherapy might allow implementation of image-guided IMRT that was previously impossible or impractical. Here we review the technological, physical, and radiobiological rationale for the ongoing and upcoming clinical trials that will use image-guided IMRT in the form of helical tomotherapy; and we describe our plans for testing our hypotheses in a rigorous prospective fashion.

Four fraction palliative radiotherapy for osteosarcoma in 24 dogs.

Twenty-four dogs underwent palliative radiotherapy consisting of four 8 gray (Gy) fractions of 60Co radiation on days 0, 7, 14, and 21 at 26 sites for axial (n=11) or appendicular (n=15) osteosarcoma. Response was noted in 92% of sites treated. Seventeen dogs were euthanized due to local or metastatic disease, one dog died of metastatic disease, five dogs died of unrelated causes, and one dog is alive. The four fraction protocol is effective for palliation of clinical signs associated with axial or appendicular osteosarcoma and may result in a higher response rate and longer survival time than three fraction palliative protocols.

Piroxicam, Mitoxantrone, and Coarse Fraction Radiotherapy for the Treatment of Transitional Cell Carcinoma of the Bladder in 10 Dogs: A Pilot Study

Ten dogs with transitional cell carcinoma (TCC) of the bladder were treated with a combination of once-weekly coarse fraction radiation therapy (six weekly fractions of 5.75 Gray [Gy]), mitoxantrone chemotherapy, and piroxicam. All dogs completed the radiation therapy protocol, and only minimal side effects were observed. Only two (22%) dogs achieved a measurable partial response; however, 90% of the dogs had amelioration of their urinary clinical signs. The median survival time for all dogs was 326 days. While this treatment protocol was well tolerated, the response rate and overall survival duration was not superior to reports using mitoxantrone and piroxicam without radiation therapy in dogs with TCC.

The head: Excluding the brain and orbit

Applications for computed tomography (CT) and magnetic resonance imaging (MRI) scans of the head (excluding the brain and orbit) include the evaluation of neoplastic, inflammatory, and traumatic disorders of the skull (including the cranium, maxilla, mandible, and temporomandibular joints); of the nasal and oral cavities; of the nasopharynx and paranasal sinuses; and of the tympanic bullae. CT and MRI provide information not obtained with routine radiography and should be considered whenever advanced surgical or radiation therapy is anticipated. In this article, the role of CT and MRI in the diagnosis of head disorders will be reviewed and illustrated with case examples.

Postoperative radiotherapy and mitoxantrone for anal sac adenocarcinoma in the dog: 15 cases (1991–2001)

The medical records of 15 dogs with anal sac adenocarcinoma (ASAC) treated with concurrent curative-intent radiotherapy and mitoxantrone (MX) after surgical removal of the primary tumour were reviewed retrospectively. Radiation was prescribed at 15 daily fractions of 3.2 Gy for a total dose of 48 Gy. MX was given intravenously at a dosage of 5 mg m(-2) every 3 weeks for five treatment sessions. Twelve dogs received pelvic irradiation to include the regional lymph nodes (LNs) and three received radiation only to the perineum. At the time of diagnosis, four dogs were hypercalcaemic and seven dogs presented with regional LN metastasis. All the dogs with regional LN metastasis received pelvic irradiation, and in three cases, metastatic LNs were treated in the macroscopic disease setting. The median event-free survival was 287 days, and the median overall survival was 956 days. Acute and chronic radiation complications were common and non-life threatening, although chronic complications contributed to the decision to euthanize two dogs. The results observed in this retrospective analysis compare favourably with cases of ASAC in the literature related to treatment with surgery and/or chemotherapy.

Magnetic resonance imaging findings in dogs with confirmed shoulder pathology.

OBJECTIVE To evaluate the diagnostic potential of magnetic resonance imaging (MRI) compared with a reference standard, arthroscopic and/or open surgery, in dogs with soft tissue shoulder pathology. STUDY DESIGN Retrospective study. ANIMALS Dogs (n=21). METHODS Magnetic resonance (MR) images were retrospectively evaluated in 21 dogs that had surgically identified soft tissue shoulder pathology. The musculotendinous units of the biceps, infraspinatus, teres minor, supraspinatus, subscapularis, and the medial and lateral glenohumeral ligaments (MGHL and LGHL) were graded as either normal or abnormal. Abnormal structures were further classified as being either inflamed, partially torn, or fully torn. Impingement of the biceps tendon was also evaluated. Results were reported in terms of agreement and concordance between MRI findings and surgical findings. Agreement was defined as the percentage of times MRI findings concurred with surgical findings with respect to a structure being either normal or abnormal. Concordance was defined as the percentage of times MRI concurred with the exact surgically assessed pathology when abnormality was identified. RESULTS The findings were biceps tendon: 90% agreement with 100% concordance; subscapularis: 95% agreement with 62% concordance; MGHL: 84% agreement with 83% concordance; LGHL: 88% agreement with 100% concordance; infraspinatus: 100% both agreement and concordance; biceps tendon impingement: 90% agreement with 100% concordance. CONCLUSIONS Soft tissue abnormalities of the canine shoulder were readily identified on preoperative MR images. CLINICAL RELEVANCE MRI shows great potential as a diagnostic tool in the evaluation of canine shoulder disease.

Radiation therapy for incompletely excised grade II canine mast cell tumors.

Forty-five dogs with incompletely excised grade II mast cell tumors were treated with radiation using a cobalt 60 teletherapy unit (15 fractions of 3.2 Gy for a total of 48 Gy). Twenty-four of the dogs underwent prophylactic regional lymph node irradiation. Three (6.7%) dogs had tumor recurrence, two (4.4%) dogs developed metastasis, and 14 (31%) dogs developed a second cutaneous mast cell tumor. No difference in overall survival rate was observed between the dogs receiving and not receiving prophylactic irradiation of the regional lymph node.

Heterogeneity in Intratumor Correlations of 18F-FDG, 18F-FLT, and 61Cu-ATSM PET in Canine Sinonasal Tumors

Intratumor heterogeneity in biologic properties and in relationships between various phenotypes may present a challenge for biologically targeted therapies. Understanding the relationships between different phenotypes in individual tumor types could help inform treatment selection. The goal of this study was to characterize spatial correlations of glucose metabolism, proliferation, and hypoxia in 2 histologic types of tumors. Methods: Twenty canine veterinary patients with spontaneously occurring sinonasal tumors (13 carcinomas and 7 sarcomas) were imaged with 18F-FDG, 18F-labeled 3′-deoxy-3′-fluorothymidine (18F-FLT), and 61Cu-labeled diacetyl-bis(N4-methylthiosemicarbazone) (61Cu-ATSM) PET/CT on 3 consecutive days. Precise positioning and immobilization techniques coupled with anesthesia enabled motionless scans with repeatable positioning. Standardized uptake values (SUVs) of gross sarcoma and carcinoma volumes were compared by use of Mann–Whitney U tests. Patient images were rigidly registered together, and intratumor tracer uptake distributions were compared. Voxel-based Spearman correlation coefficients were used to quantify intertracer correlations, and the correlation coefficients of sarcomas and carcinomas were compared. The relative overlap of the highest uptake volumes of the 3 tracers was quantified, and the values were compared for sarcomas and carcinomas. Results: Large degrees of heterogeneity in SUV measures and phenotype correlations were observed. Carcinoma and sarcoma tumors differed significantly in SUV measures, with carcinoma tumors having significantly higher 18F-FDG maximum SUVs than sarcoma tumors (11.1 vs. 5.0; P = 0.01) as well as higher 61Cu-ATSM mean SUVs (2.6 vs. 1.2; P = 0.02). Carcinomas had significantly higher population-averaged Spearman correlation coefficients than sarcomas in comparisons of 18F-FDG and 18F-FLT (0.80 vs. 0.61; P = 0.02), 18F-FLT and 61Cu-ATSM (0.83 vs. 0.38; P < 0.0001), and 18F-FDG and 61Cu-ATSM (0.82 vs. 0.69; P = 0.04). Additionally, the highest uptake volumes of the 3 tracers had significantly greater overlap in carcinomas than in sarcomas. Conclusion: The relationships of glucose metabolism, proliferation, and hypoxia were heterogeneous across different tumors, with carcinomas tending to have high correlations and sarcomas having low correlations. Consequently, canine carcinoma tumors are robust targets for therapies that target a single biologic property, whereas sarcoma tumors may not be well suited for such therapies. Histology-specific PET correlations have far-reaching implications for the robustness of biologic target definition.