SPATIAL ACCURACY OF FRACTIONATED IMRT DELIVERY STUDIES IN CANINE PARASPINAL IRRADIATION

Intensity modulated radiation therapy (IMRT) theoretically allows detailed tailoring of the dose distribution in tissue. The goal of this study was to determine if a method of dynamic IMRT could be used to deliver a high dose of radiation to a concave shaped target around the cervical spinal cord. Fifteen young adult dogs from our laboratory population were randomly divided into two groups. A radiation dose of 84 Gy in 4 Gy fractions was delivered with a conventional 4 field technique for Group A dogs, and with dynamic IMRT for Group B dogs to a "C-shaped" target close to the cervical spinal cord. Neurologic status, magnetic resonance imaging results and histopathologic changes were compared among dogs in the two groups. Group A dogs developed myelomalacia with a latency period of 65 +/- 9 days. Group B dogs did not have any histologic changes to the cervical spinal cord when euthanasia was performed 12 months after irradiation. The results demonstrate that this IMRT technique can be safely and precisely delivered to a patient in a clinical situation.     

A COMPARISON OF NORMAL TISSUE COMPLICATION PROBABILITY OF BRAIN FOR PROTON AND PHOTON THERAPY OF CANINE NASAL TUMORS

This study compared the calculated normal tissue complication probability of brain in dogs with a nasal tumor, which had both photon and proton treatment planning. Nine dogs diagnosed with a variety of histologies, but all with large, caudally located nasal tumors were studied. Three-dimensional (3-D) photon dose distribution, and a proton dose distribution was calculated for each dog. To calculate the normal tissue complication probability (NTCP) for brain, the partial brain volume irradiated with the prescribed dose was determined, then a mathematic model relating complications to partial volume and radiation dose was used. The NTCP was always smaller for proton plans as compared to photon plans, indicating conformation of the dose to the target allows a higher dose to be given. If a 5% NTCP were accepted, the mean applicable dose for this group of dogs was 50.2 Gy for photons, but 58.3 Gy for protons. Not all dogs would benefit the same from proton irradiation. If a large partial brain volume has to be irradiated, the advantage becomes minimal. There is also a minimal advantage if the planning target volume (PTV) includes a small, superficial brain volume. However, for a complex PTV shape the degree of conformation is clearly superior for protons and results in smaller calculated NTCPs.     

Three‐dimensional conformal versus non‐graphic radiation treatment planning for apocrine gland adenocarcinoma of the anal sac in 18 dogs (2002–2007)

Differences in dose homogeneity and irradiated volumes of target and surrounding normal tissues between 3D conformal radiation treatment planning and simulated non‐graphic manual treatment planning were evaluated in 18 dogs with apocrine gland adenocarcinoma of the anal sac. Overall, 3D conformal treatment planning resulted in more homogenous dose distribution to target tissues with lower hot spots and dose ranges. Dose homogeneity and guarantee of not under‐dosing target tissues with 3D conformal planning came at the cost, however, of delivering greater mean doses of radiation and of irradiating greater volumes of surrounding normal tissue structures.     

A comparison of two dose calculation algorithms—anisotropic analytical algorithm and Acuros XB—for radiation therapy planning of canine intranasal tumors

Although anisotropic analytical algorithm (AAA) and Acuros XB (AXB) are both radiation dose calculation algorithms that take into account the heterogeneity within the radiation field, Acuros XB is inherently more accurate. The purpose of this retrospective method comparison study was to compare them and evaluate the dose discrepancy within the planning target volume (PTV). Radiation therapy (RT) plans of 11 dogs with intranasal tumors treated by radiation therapy at the University of Georgia were evaluated. All dogs were planned for intensity‐modulated radiation therapy using nine coplanar X‐ray beams that were equally spaced, then dose calculated with anisotropic analytical algorithm. The same plan with the same monitor units was then recalculated using Acuros XB for comparisons. Each dog's planning target volume was separated into air, bone, and tissue and evaluated. The mean dose to the planning target volume estimated by Acuros XB was 1.3% lower. It was 1.4% higher for air, 3.7% lower for bone, and 0.9% lower for tissue. The volume of planning target volume covered by the prescribed dose decreased by 21% when Acuros XB was used due to increased dose heterogeneity within the planning target volume. Anisotropic analytical algorithm relatively underestimates the dose heterogeneity and relatively overestimates the dose to the bone and tissue within the planning target volume for the radiation therapy planning of canine intranasal tumors. This can be clinically significant especially if the tumor cells are present within the bone, because it may result in relative underdosing of the tumor.     

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.     

Laparoscopically implanted tissue expander radiotherapy in canine transitional cell carcinoma

Organ motion and injury to adjacent structures limit curative treatment of intraabdominal tumors with external beam radiotherapy. We evaluated the use of Laparoscopically Implanted Tissue Expander Radiotherapy (LITE-RT) to exclude critical structures during irradiation of the urinary bladder in two dogs with transitional cell carcinoma (TCC) using helical tomotherapy. Dogs had histologically confirmed bladder TCC with no metastasis. A custom-shaped tissue expander was placed between the colon and bladder laparoscopically in one dog and during laparotomy in the other. The prescribed radiation dose was 45 Gy to 98% volume of the bladder in 18 fractions of 2.5 Gy. Tumor response and normal tissue effects were monitored with cystoscopy and colonic biopsies before treatment and 3, 6, and 15 months after treatment. Based on treatment plans from inflated vs. deflated tissue expander CT images, there was a mean dose reduction to the colon of 53% and 31% for the two dogs. Interfractional target repositioning was possible by using volumetric megavoltage computed tomography helical tomotherapy. Both dogs had no clinical signs of chronic colitis but did experience mild cystitis during treatment. Tissue expanders became detached, requiring an additional surgery for reattachment, in both dogs. One dog developed a fibrous adhesion resulting in bladder rupture during inflation, which necessitated early device removal. One dog was euthanized for tumor-associated ureteral obstruction at 8 months while the other is alive at 21 months. We conclude that LITE-RT shows promise in treatment of canine bladder TCC due to lack of acute colitis and enteritis.     

192iridium brachytherapy, using an intracavitary afterload device, for treatment of intranasal neoplasms in dogs.

After surgical removal of a primary intranasal neoplasm, an implant device, designed to deliver 192iridium (192Ir) brachytherapy, was positioned in the nasal cavity of 8 dogs. Ribbons containing 192Ir seeds were placed in the device, using an afterloading technique. Dosimetry, to a dose of 7,000 to 10,000 centiGray (cGy), was calculated to encompass the site previously occupied by the tumor and a 1-cm margin of surrounding normal tissue. The quantity of 192Ir implanted varied between 16.69 and 100.80 mg of radium equivalent. The duration of implantation ranged from 90 to 168 hours. All dogs tolerated the implant well, but had a mucoid nasal discharge after radiotherapy. The implant device allowed rapid application and removal of the radioactive ribbons. Mean (+/- SD) radiation exposure to each radiotherapist during seed loading and unloading was 14.4 (+/- 5.3) and 4.5 (+/- 0.9) mrem, respectively. A uniform dose distribution around the intranasal implant device was achieved; however, dogs that received doses in excess of 9,400 cGy at the dorsolateral surface of the nose and/or hard palate had bone and soft tissue necrosis between 70 and 120 days after treatment. One dog was euthanatized 50 days after treatment because of metastatic disease, and 2 dogs were euthanatized because of local tumor recurrence at 125 and 212 days. Death, considered unrelated to treatment, occurred in 1 dog that was euthanatized 27 days after treatment and in 3 dogs that died 30, 93, and 456 days after treatment. Necropsy was performed on 3 of these dogs and evidence of intranasal neoplasia was not observed. One dog remained disease-free at 587 days after treatment.     

Frameless stereotactic radiosurgery for the treatment of primary intracranial tumours in dogs

Stereotactic radiosurgery (SRS) is a procedure that delivers a single large radiation dose to a well‐defined target. Here, we describe a frameless SRS technique suitable for intracranial targets in canines. Medical records of dogs diagnosed with a primary intracranial tumour by imaging or histopathology that underwent SRS were retrospectively reviewed. Frameless SRS was used successfully to treat tumours in 51 dogs with a variety of head sizes and shapes. Tumours diagnosed included 38 meningiomas, 4 pituitary tumours, 4 trigeminal nerve tumours, 3 gliomas, 1 histiocytic sarcoma and 1 choroid plexus tumour. Median survival time was 399 days for all tumours and for dogs with meningiomas; cause‐specific survival was 493 days for both cohorts. Acute grade III central nervous system toxicity (altered mentation) occurred in two dogs. Frameless SRS resulted in survival times comparable to conventional radiation therapy, but with fewer acute adverse effects and only a single anaesthetic episode required for therapy.     

SLOW RELEASE CISPLATIN COMBINED WITH RADIATION FOR THE TREATMENT OF CANINE NASAL TUMORS

Thirteen dogs with malignant tumors of the nasal cavity were treated with a combination of slow release cisplatin and megavoltage radiation. Radiation was delivered on a Monday through Friday schedule using a 6 MV linear accelerator. The median total dose was 49.5 Gy (range 49.5-56 Gy). Cisplatin was given using an open-cell polylactic acid polymer, impregnated with the drug and implanted intramus-cularly at a distant site, as a slow release delivery system (OPLAn-Pt [THM Biomedical, Inc]). The median dose used was 60 mg/m2 (range 60–100 mg/m2). When combined with radiation, this delivery system caused no systemic drug toxicity, and a local tissue reaction was seen in only two dogs. Acute side effects to normal tissue from radiation were not enhanced, as measured by subjective assessment. When compared to a group of historical controls that received radiation without OPLA-Pt, the dogs that received combined radiation and cisplatin had longer overall survival times, with a median of 580 days. The control group had a median survival of 325 days. Previously reported median survival times for comparable megavoltage radiation treatment range from 6 to 13 months. Some dogs in both groups also received adjubant chemotherapy but this did not influence survival time. By multivariate analysis, only the use of OPLA-Pt was found to significantly influence survival, with a p value of p = 0.023. Mega-voltage radiation and slow release cisplatin appears to be a well tolerated combination that may favorably affect survival of dogs with nasal tumors.     

Stereotactic radiosurgery for treatment of osteosarcomas involving the distal portions of the limbs in dogs

Stereotactic radiosurgery (SRS) involves precise delivery of a single large dose of radiation to a designated tumor target. This report describes use of SRS in combination with a frameless stereotactic localization system to treat 11 dogs with appendicular osteosarcomas. Five dogs were treated with SRS alone; 6 were treated with a combination of SRS and chemotherapy. Overall median survival time was 363 days (range, 145 to 763 days), with 6 dogs still alive 90, 142, 234, 367, 633, and 763 days after SRS. Limb function was good or excellent in all 6 dogs that were still alive. Results in these dogs suggest that SRS may be a viable option for dogs with appendicular osteosarcoma, with the potential to provide long-term local tumor control and improvement in limb function, especially when combined with chemotherapy. Because of the destructive nature of osteosarcoma and limitations of SRS, dogs with tumors that are small and have caused minimal bone destruction would likely be the best candidates for this procedure.     

Radiation therapy for the treatment of tumours in small companion animals

Radiation is becoming widely available to treat tumours in veterinary patients. Orthovoltage machines capable of delivering low energy external beam radiation are less versatile than linear accelerators and cobalt-60 machines that deliver megavoltage radiation. In addition, electron beam capabilities that are available with some linear accelerators allow more targeted treatment in smaller patients. Acute effects of radiation are to be expected, but in nearly all cases such side effects resolve without limiting protocols. In contrast, late effects of radiation are dose limiting and are more likely with higher doses per treatment fraction. Protocols that use smaller doses per fraction have a lower risk of late effects thereby allowing higher total doses to be delivered which leads to higher tumour control rates. It is possible to provide long-term tumour control in cats and dogs using radiation therapy, particularly for mast cell tumours, soft tissue sarcomas, oral tumours and brain tumours in dogs and soft tissue sarcomas and skin tumours in cats. Individualization of treatments for tumours based on tumour staging and proliferative fraction should be considered, rather than making blanket assumptions about the behaviour of histologically determined tumour types.     

Single fraction stereotactic radiation therapy (stereotactic radiosurgery) is a feasible method for treating intracranial meningiomas in dogs

The aim of this retrospective, pilot study was to evaluate stereotactic radiosurgery as a method for treating intracranial meningiomas in dogs. Included dogs had an imaging diagnosis of presumed intracranial meningioma, were treated using a standardized stereotactic radiosurgery protocol, and had a follow‐up time of >6 months after stereotactic radiosurgery. A single fraction of 16 Gy stereotactic radiosurgery was delivered to the tumor, with an internal simultaneously integrated boost to a total dose of 20–24 Gy to the central portion of the tumor. Thirty‐two dogs were sampled. One dog was euthanized in the periprocedural period, and 10 of the remaining 31 dogs (31%) experienced an acute adverse event (defined as declining neurologic function due to tumor progression or treatment‐associated complication within the first 6 months after stereotactic radiosurgery), three of which were fatal. Too few subjects (n = 6) had cross‐sectional imaging after stereotactic radiosurgery to determine an objective response rate; however, 17/30 (57%) dogs assessed for response had a perceived clinical benefit from treatment. The overall median survival time was 519 days (95% confidence interval: 330–708 days); 64% and 24% of dogs were alive at 1 and 2 years after stereotactic radiosurgery, respectively. Dogs with infratentorial tumor location and high gradient indices had shorter survival. There were no factors identified which were predictive of acute adverse event. Survival times reported herein are similar to what has previously been reported for other stereotactic and traditional fractionated radiotherapy protocols. Findings therefore supported the use of stereotactic radiosurgery as an alternative method for treating dogs with presumed intracranial meningiomas.     

USE OF PHOTON FIELDS WITH NONCOINCIDENT ISOCENTERS TO IMPROVE HOMOGENEITY OF DOSE DISTRIBUTION

To compare changes in dose distribution in irregularly shaped volumes treated using fields with noncoincident isocenters compared with fields with coincident isocenters. The hypothesis was that use of fields with noncoincident isocenters would result in improved homogeneity of dose distribution. We chose to test the hypothesis in canine nasal tumors because of the increased dorsoventral thickness of the caudal compared with the rostral nasal cavity. Computed tomography images from eight dogs with nasal tumors were selected. A tissue-contouring program was used to outline contours, including the mandible as a normal tissue structure and the planning target volume (PTV), divided into a rostral and caudal volume. A traditional computerized treatment plan consisting of two parallel-opposed fields was constructed for each dog. A second treatment plan using a third caudally located field having a different isocenter was constructed for comparison. Dose-volume histograms were generated and compared for each contoured structure in both plans. In all dogs the use of noncoincident fields resulted in increased dose to the ethmoid region through the caudal field. Minimum dose in the caudal tumor PTV increased as well. At the same time, dose delivered to the mandible, prone to develop significant side effects, was lower in all dogs with the use of noncoincident fields, as it was possible to reduce the dose delivered from the ventral field. Use of photon fields with noncoincident isocenters can improve the dose distribution in irregularly shaped volumes in comparison with fields with coincident isocenters. Improved tumor dose distribution was achieved with the addition of a smaller field having a different isocenter.     

RADIATION PNEUMONITIS IN THREE DOGS

Radiation pneumonitis developed within the radiation treatment field in three dogs with soft tissue sarcomas located on or adjacent to the thoracic wall. Radiographic signs compatible with a diagnosis of radiation pneumonitis developed from one (n = 2 dogs) to two (n = 1 dog) months after completion of therapy. The initial radiographic sign was an alveolar infiltrate in all three dogs. At subsequent examinations at variable time periods after treatment, radiographic findings included: bronchiectasis (n = 3 dogs), alveolar infiltrate (n = 2 dogs), decreased lung volume (n = 2 dogs), and unstructured interstitial opacification (n = 1 dog). Necropsy examination of one dog at fourteen months after the completion of radiotherapy showed evidence of pulmonary fibrosis within the irradiated lung. Necropsy examination of the second dog did not show any evidence of radiation induced changes. It is possible that histopathologic examination did not include irradiated lung. No clinical signs that could be attributed to the radiation pneumonitis were observed in any dog. It appears that approximately 25% of the lung can be safely irradiated to high doses, if indicated, in order to deliver an adequate dose of radiation to a primary tumor site.     

Hypofractionated Radiation Therapy of Brain Masses in Dogs: A Retrospective Analysis of Survival of 83 Cases (1991–1996)

There are few reports of radiation treatment for brain tumors in dogs, and the optimal treatment protocol has yet to be established. We completed a retrospective analysis of the survival times of a series of 83 dogs with intracranial masses that were treated by hypofractionated megavoltage radiation therapy. A total tumor dose of 38 Gray was given over 5 weeks as once weekly fractions via 3 perpendicular portals. The median survival time from the start of radiotherapy for the whole cohort was 43.7 weeks (range, 0.1-172 weeks). Extra-axial masses had a better survival time (49.7 weeks) than did other intracranial masses (intra-axial, 40.4 weeks; pituitary, 21.0 weeks). Delayed radiation toxicity was suspected as the cause of death or reason for euthanasia in 12 dogs. The hypofractionated radiation protocol resulted in survival times similar to those obtained using more conventional multifractionated regimens, and this protocol may be a useful, less intensive alternative treatment for brain tumors in dogs.     

POTENTIAL FOR INTENSITY-MODULATED RADIATION THERAPY TO PERMIT DOSE ESCALATION FOR CANINE NASAL CANCER

We evaluated the impact of inverse planned intensity-modulated radiation therapy (IMRT) on the dose-volume histograms (DVHs) and on the normal tissue complication probabilities (NTCPs) of brain and eyes in dogs with nasal tumors. Nine dogs with large, caudally located nasal tumors were planned using conventional techniques and inverse planned IMRT for a total prescribed dose of 52.5 Gy in 3.5 Gy fractions. The equivalent uniform dose for brain and eyes was calculated to estimate the normal tissue complication probability (NTCP) of these organs. The NTCP values as well as the DVHs were used to compare the treatment plans. The dose distribution in IMRT plans was more conformal than in conventional plans. The average dose delivered to one-third of the brain was 10 Gy lower with the IMRT plan compared with conventional planning. The mean partial brain volume receiving 43.6 Gy or more was reduced by 25.6% with IMRT. As a consequence, the NTCPs were also significantly lower in the IMRT plans. The mean NTCP of brain was two times lower and at least one eye could be saved in all patients planed with IMRT. Another possibility with IMRT is dose escalation in the target to improve tumor control while keeping the NTCPs at the same level as for conventional planning. Veterinary     

USE OF A PETROLEUM-BASED BOLUS FOR PHOTON RADIATION THERAPY OF DISTAL EXTREMITIES IN DOGS

While skin sparing is an advantage of megavoltage beams, in certain clinical situations the planning target volume includes the skin surface and a skin sparing effect is not desirable. A tissue equivalent material, termed build up bolus, is used in these situations to provide adequate absorbed dose at the surface of the skin. However, an irregular patient contour can lead to air gaps between the build up bolus and the skin surface, which may result in variability in radiation dose across the target volume. The shape of the canine distal hind extremity is irregular, and commercially available bolus materials do not conform well to this region. The purpose of this study was to assess the dose homogeneity achieved using a petroleum-based bolus material, in combination with a commercially available sheet bolus, for radiation treatment of the canine tarsus. Repeated setups were performed to mimic daily treatment setups in the clinic setting, and computed tomographic scans were performed after each setup. Dose distribution achieved with a cobalt therapy machine and a 6 MV linear accelerator was assessed using three-dimensional treatment planning software. The dose to the clinical target volume fell within 95% and 107% of the prescribed dose for both treatment machines, which is considered clinically acceptable by the authors. This petroleum-based bolus is equivalent to water in its photon attenuation, conforms well to an irregular patient contour, and retains its shape after positioning. Applications to other anatomical sites could be considered.     

UNEXPECTED TOXICITY FOLLOWING USE OF GEMCITABINE AS A RADIOSENSITIZER IN HEAD AND NECK CARCINOMAS: A VETERINARY RADIATION THERAPY ONCOLOGY GROUP PILOT STUDY

Gemcitabine (2',2'-difluorodeoxycytidine) was given intravenously twice weekly to 10 cats with oral squamous cell carcinoma and 15 dogs with nasal carcinoma undergoing radiotherapy as a radiosensitizing agent. The average total radiation dose was 50 Gy for dogs and 54 Gy for cats given Monday-Friday (planned dose of 54 and 57 Gy, respectively). Dogs received an average of five doses of gemcitabine beginning at 50 mg/m2, and cats received an average of five doses of gemcitabine beginning at 25 mg/m2. Twelve of 15 dogs and five of 10 cats required chemotherapy dose reduction or postponement because of hematologic or normal tissue toxicity. The results herein do not support the use of gemcitabine at the studied dose and schedule, as significant hematologic and local tissue toxicity was observed in the studied patients. Pharmacokinetic data are necessary to best define the efficacy and optimal dose and schedule of gemcitabine in combination with traditional radiotherapy.     

Vertebral plasma cell tumors in 8 dogs

The case histories of 8 dogs with spinal pain and neurologic deficits associated with vertebral plasma cell tumor are reviewed. Four dogs had solitary plasmacytoma, 3 had multiple myeloma, and 1 dog had 2 vertebral lesions with no evidence of disseminated disease. Four dogs were treated: 2 with multiple myeloma received chemotherapy only and survived 17 and 26 months, respectively. Two dogs with solitary plasmacytomas of the spine had chemotherapy and radiotherapy: the 1st survived 4 months and was euthanized after developing radiation myelopathy; the 2nd survived 65 months before developing multiple myeloma. The diagnosis of solitary plasmacytoma of the spine versus multiple myeloma is discussed.