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Intensity-modulated radiation therapy (IMRT) is a valuable tool in human radiation oncology, but information on its use in veterinary medicine is lacking. In this study, 12 dogs with nasal tumors were treated with IMRT at a median radiation dose of 54 Gy. Patient survival times and frequency and severity of side effects on ocular structures, oral mucosa, and skin were recorded. Eight dogs (67%) had resolution of clinical signs during radiation therapy. Median overall survival time was 446 d with a 50% 1-year and a 25% 2-year survival rate. Minimal grade 2 or 3 acute skin toxicity, no grade 2 or 3 late skin toxicity, and no grade 2 or 3 toxicity to oral mucosa or the eye opposite the tumor were identified in the dogs treated with IMRT in this study. The ipsilateral eye could not be routinely spared due to its proximity to the tumor.
Résultat clinique chez les chiens avec des tumeurs nasales traitées à la radiothérapie à modulation d’intensité. La radiothérapie à modulation d’intensité est un outil utile en radiothérapie oncologique pour les humains, mais il existe une absence d’information sur son usage en médecine vétérinaire. Dans cette étude, 12 chiens avec des tumeurs nasales ont été traités à l’aide de la radiothérapie à modulation d’intensité à une dose de radiation médiane de 54 Gy. La durée de survie des patients ainsi que la fréquence et la gravité des effets secondaires sur les structures oculaires, les muqueuses orales et la peau ont été consignées. Huit chiens (67 %) ont eu une résolution des signes cliniques durant la radiothérapie. La durée de survie médiane était de 446 jours avec un taux de survie de 1 an de 50 % et de 2 ans de 25 %. Une toxicité minime de la peau de grade de 2 ou 3, aucune toxicité de la peau de grade 2 ou 3 et aucune toxicité de grade 2 ou 3 des muqueuses orales ou de l’oeil opposé ont été identifiées chez les chiens traités à la radiothérapie à modulation d’intensité dans cette étude. L’oeil ipsilatéral ne pouvait habituellement pas être épargné en raison de sa proximité à la tumeur.
(Traduit par Isabelle Vallières)
Intensity-modulated radiation therapy (IMRT) is a method of radiation delivery that allows better dose localization to the tumor while sparing surrounding tissues. This is accomplished by constructing simulated beams and then creating a heterogeneous dose distribution for each beam by using a dynamic multi-leaf collimator (dMLC), which can be conformed to the tangential contour of the tumor. Since the contour of the tumor is different depending upon the angle at which it is viewed, beams at various angles will have a unique dMLC setting. Intensity modulation is accomplished by using multiple dMLC configurations (segments) per gantry angle, which results in variable dose fluence to different parts of the tumor as well as to the adjacent normal tissues in the field. This technique eliminates the need for other less precise beam shaping strategies such as the addition of wedges and blocks. By reducing the frequency and severity of side effects to normal tissues, IMRT plans also allow the radiation oncologist to optimize the dose to the tumor (1).
Due to complexity in the formulation of IMRT plans, standard forward treatment planning is not practical. Instead, following construction of simulated beams, important structures such as the tumor and nearby radiosensitive tissues are identified on each computed tomography (CT) image by the radiation oncologist. Each structure is then contoured using an IMRT software package, and a three-dimensional reconstruction of the scanned region is created. Dose objectives for each contoured tissue are then defined, and the computer devises a plan that will best accomplish the requested dose delivery goals. This process is referred to as inverse treatment planning and can be repeated using various beam configurations until the most favorable plan is achieved.
Over the past several years, IMRT has replaced conventional planning techniques for certain tumors in human radiation oncology centers. It is most commonly employed in treating diseases that have historically been associated with significant treatment-related side effects, such as head and neck tumors and prostate cancer. However, as various studies showing the benefits of IMRT have been completed, its use is being expanded to treat a wider variety of neoplasms. When compared with conventional therapy, the preliminary results from these IMRT trials consistently show a reduced frequency of acute side effects, along with equivalent tumor control rates. However, the relative newness of IMRT technology makes it difficult to assess its impact on delayed toxicities (2,3).
From August 2003 to July 2007, IMRT was used at the Louisiana State University Cancer Treatment Unit (LSU-CTU) to treat any definitive radiation therapy (RT) patients deemed to be at high risk of developing side effects to radiosensitive normal tissues. The most common anatomic site treated during this time period was the canine nasal cavity. While surgery (4,5) and chemotherapy (6) have been used as the sole treatment modality for canine nasal tumors, only RT, used alone or in combination with surgery or chemotherapy (7–15), has shown a significant improvement in patient survival times. However, due to the close proximity of several radiosensitive structures (eyes, oral cavity, skin), side effects such as keratitis, conjunctivitis, keratoconjunctivitis sicca (KCS), and cataracts in 1 or both eyes; oral mucositis; and erythema, ulceration, and moist desquamation of overlying skin have been reported in dogs with nasal tumors treated with RT (8–11,13,14,16,17). Every dog that received definitive RT at LSU-CTU for a malignancy of the nasal cavity after August 2003 was treated with IMRT with the intent of minimizing these radiation-induced side effects while maintaining appropriate tumor control.
The goals of this paper were to report the patient survival times and incidence of complications in this group of canine nasal tumor patients, and to compare the treatment outcomes of canine nasal tumor patients treated with IMRT and those treated with more conventional radiation techniques in historical studies in order to determine if IMRT has the potential to minimize radiation side effects while maintaining appropriate tumor control.
Medical records of all patients treated with definitive RT at the LSU-CTU from February 2003 to July 2007 were reviewed to identify dogs with tumors of the nasal cavity treated with IMRT. Intensity-modulated radiation therapy was used for all canine nasal tumors treated with definitive RT during this time interval. The prescribed radiation dose was determined by tumor type, with sarcomas and squamous cell carcinomas scheduled to receive a total dose of 63 Gy, and all others scheduled to receive a total dose of 54 Gy. All courses of RT were divided into 3 Gy fractions, and all patients were treated on a Monday/Wednesday/Friday schedule. Prior to therapy, the following staging tests were performed in all dogs: complete blood (cell) count (CBC), serum biochemical profile, urinalysis, thoracic radiographs (3-view), aspiration of regional lymph nodes (if enlarged), and tumor histopathology.
A CT study was performed at LSU for RT planning prior to initiation of RT in each patient, and treatment planning software was used to create an optimized IMRT treatment plan. The tumor, left eye, left lens, right eye, right lens, and oral cavity were contoured using the Pinnacle software (Version 6.2b; ADAC Laboratories, Milpitas, California, USA) and the planning target volume (PTV) was defined by adding a 1.5-cm margin to the gross tumor volume. Contouring of the oral cavity included the buccal mucosa, gingiva, hard and soft palate, and tongue. Tumor contouring included nasal cavity disease as well as all other areas determined to be tumor extension or metastasis on CT scan (sinus cavities, intracranial disease, and soft tissue of the head and neck). Regional lymph nodes were contoured and included in the treatment plan if enlarged on CT scan or if nodal metastasis was documented via cytology or histopathology. Plans were optimized by attempting to deliver 95% of the prescribed dose to the entire PTV while minimizing the dose to contoured structures. Patients were immobilized during the RT-planning CT scan using a vacuum-lock bag (vac-lok; Med-Tec, Orange City, Iowa, USA) which was saved and used to position the same animal throughout the course of RT. Fiducial markers and skin marking ink were also used in each patient to provide landmarks for laser-assisted positioning during therapy. Port films were generated for each patient once per week, and adjustments to patient positioning were made, if necessary, based upon evaluation of these films by the radiation clinician in charge of the case. All radiation treatments were delivered via the step and shoot (SAS) delivery method (18) using a 6-MV linear accelerator (Clinac 600C; Varian Medical Systems, Palo Alto, California, USA). All treatments were delivered with 6-MV photons only.
Tumor stage was determined using the CT images and classified according to the modified staging scheme for canine nasal tumors (8). All dogs were observed for radiation side effects to the eyes, oral cavity, skin, and central nervous system (CNS), and tumor progression throughout the radiation protocol and during post-RT rechecks at 2 wk, 6 wk, and every 2 to 3 mo thereafter. Side effects occurring during therapy or up to 90 d after the completion of RT were scored according to the Veterinary Radiation Therapy Oncology Group (VRTOG) Acute Radiation Morbidity Scoring Scheme (Table 1) (19). Side effects occurring greater than 90 d post-RT were scored according to the VRTOG Late Radiation Morbidity Scoring Scheme (Table 1) (19).
Previously published articles reporting radiation side effects in canine nasal tumor patients reveal that dogs were treated with many different fractionation schemes and a wide variety of total doses (8,11–16,20). While it is not possible to directly compare these protocols, we can compare the predicted biologically effective doses (BEDs) of the various historical protocols and the protocols in the current study using the Nominal Standard Dose methodology (21). This technique is used for comparison of multiple radiation protocols of varying dose per fraction, total dose, and treatment times in order to determine which protocol has the highest dose intensity and thus would be expected to result in the best tumor control, but also cause the most damage to nearby radiosensitive tissues. The higher the BED, the “hotter” the protocol is predicted to be. In this study, the BED for acute and late responding tissues (BED10 and BED3, respectively), as well as the BED10 corrected for proliferation were determined for all prescribed radiation protocols (some studies included multiple protocols). Calculation of the BED10 corrected for proliferation was needed due to the potential for repopulation and healing of acutely affected tissues during the more protracted protocols. Biologically effective dose values were calculated using the equation:
where: E/α = BED, nd = total dose, d = dose/fraction, t = total time of the protocol, Tpot = the potential doubling time of the tumor, and 0.693/α(t/Tpot) represents the correction for proliferation. Assumptions in calculation of BEDs were taken from published standard values as follows: α/β for acutely responding tissues = 10, α/β for late responding tissues = 3, α for the proliferation correction = 0.3, and Tpot = 5 days (21). A potential doubling time of 5 d was used since the median doubling time for head and neck cancer in humans has been given as 4 to 6 d. (22,23) Since some dogs in all studies failed to complete the prescribed protocol, and since some reported cohorts of dogs in historical references were treated with varying dose/fraction, median total dose, median dose/fraction, and median time of protocol were used when available. If total time of protocol was not explicitly stated, dogs were assumed to have completed the protocol in the shortest possible time (with no treatment delays). In studies reporting on multiple cohorts of dogs receiving different prescribed radiation doses, each cohort was evaluated independently.
Statistical analysis of patient survival times was performed using the Kaplan-Meier method (24). Dogs alive at the end of the study period, those lost to follow up, and those that died for reasons unrelated to their nasal tumors were censored from analysis at the study’s end date, date of last contact, or date of death, respectively. Survival times were measured from the date of the last radiation treatment to time of death or euthanasia.
Ten male and 2 female dogs were included in the study. Patient ages ranged from 4 to 14 y (median, 10 y). Ten dogs were purebred with 9 breeds represented [Finnish spitz, miniature schnauzer, German shepherd (2), Shetland sheepdog, cocker spaniel, Scottish terrier, Welsh corgi, Labrador retriever, Siberian husky]; 2 dogs were mixed-breed. Five dogs were diagnosed with squamous cell carcinoma, 4 with adenocarcinoma, 1 with chondrosarcoma, 1 with undifferentiated sarcoma, and 1 with mast cell tumor. Seven dogs initially presented for epistaxis alone, while 3 dogs presented for bony facial deformity and epistaxis. All dogs with bony facial deformity had squamous cell carcinoma. One dog (adenocarcinoma) presented with excessive sneezing as the only clinical sign, and 1 dog (mast cell tumor) presented for facial soft tissue swelling. Based on initial CT scan results, 7 dogs were classified as stage 2, and 5 dogs were classified as stage 1. Dogs with stage 2 disease included 4 with squamous cell carcinoma, 1 with an adenocarcinoma, 1 with a chondrosarcoma, and 1 with a mast cell tumor. Dogs with stage 1 disease included 1 squamous cell carcinoma, 3 adenocarcinomas, and 1 undifferentiated sarcoma. Seven dogs had predominantly left-sided tumors, while 5 had predominantly right-sided disease. Cribriform plate involvement was noted in 5 dogs (2 squamous cell carcinomas, 1 adenocarcinoma, 1 chondrosarcoma, and 1 mast cell tumor). One dog with adenocarcinoma presented with metastasis to the right and left mandibular lymph nodes. Metastatic disease was not detected in any other patient on initial staging.
Four dogs received 1 or more doses of chemotherapy. One dog with squamous cell carcinoma received 5 doses (30 mg/m2 q3wk) of doxorubicin (Adriamycin; Pharmacia and Upjohn, Kalamazoo, Michigan, USA), while another dog with squamous cell carcinoma received 4 doses (300 mg/m2 q3wk) of carboplatin (Paraplatin; Bristol-Myers Squibb, New York, New York, USA). Both protocols were given concurrently with RT. Another dog with adenocarcinoma received 1 dose of carboplatin at a dose of 300 mg/m2, given concurrently with the 1st RT fraction. The 4th dog had a mast cell tumor and received lomustine (CeeNU; Bristol-Myers Squibb, Princeton, New Jersey, USA) at a dose of 70 mg/m2, q3wk for 7 treatments, initiated upon detection of metastatic disease 7 mo after completing RT.
Optimized IMRT plans consisted of either 7 beams (10 dogs) or 9 beams (2 dogs). A prescribed dose of 63 Gy was planned for 7 dogs, and a dose of 54 Gy was planned for the remaining 5 dogs. Four patients failed to complete the prescribed radiation protocol, 3 of which (both squamous cell carcinomas) had progression of nasal cavity disease and received 51 Gy and 48 Gy. One dog (chondrosarcoma) received 42 Gy before treatment was discontinued by the owner due to lack of tumor response and owner concerns over exacerbation of osteoarthritis due to repeated positioning for RT. One other dog (adenocarcinoma) received 51 Gy before progressive systemic metastasis was observed. The remaining 8 patients had resolution of their clinical signs during the course of RT. Recheck CT scans were performed in 6 dogs, 4 of which had a PR (2 adenocarcinoma, 1 undifferentiated sarcoma, and 1 squamous cell carcinoma) and 2 had a CR (1 squamous cell carcinoma, 1 mast cell tumor).
Nine dogs were euthanized due to tumor progression, 4 of which lived < 90 d post-RT and thus could not be evaluated for late side effects. One dog with progressive disease was lost to follow up at 45 d post-RT, 1 dog died due to causes unrelated to the nasal tumor 24 mo after completing RT, and 1 dog was still alive at the end of the study period (514 d post-RT). Overall survival times ranged from 8 to 991 d with a median of 446 d (Figure 1). The 1-year survival rate was 50%, and the 2-year survival rate was 25%.
Acute ocular side effects were detected in 6 dogs. These consisted of 5 dogs with grade 2 side effects (KCS in all 5) and 1 dog with grade 2 and 3 side effects (corneal ulceration), all of which occurred in the eye ipsilateral to the bulk of the tumor. One of the dogs with grade 2 effects received 5 doses of doxorubicin concurrently. Median cumulative radiation dose given before development of acute ocular side effects was 48 Gy. One dog had grade 2 and 3 late toxicity to the ipsilateral eye (symptomatic cataract formation, blindness, phthisis bulbi) 31 mo post-RT. This was the same dog that had grade 3 acute effects and also the dog that received 4 doses of carboplatin concurrently. One other dog had grade 2 late toxicity to the ipsilateral eye (keratitis) 4 mo post-RT. This dog had received 5 doses of doxorubicin concurrently. No side effects were detected in the eye contralateral to the tumor in any patient. Grade 1 mucositis developed during RT in 2 dogs (16.7%). No adverse effects related to mucositis were seen in any of these patients, and none required therapy. Median cumulative radiation dose given before development of mucositis was 45 Gy. Acute cutaneous side effects were seen in 3 dogs (25%), consisting of grade 1 skin toxicity in 2 dogs and grade 2 toxicity in 1 dog. All 3 of these patients initially presented with facial deformity, and these 3 dogs were the only patients to develop late cutaneous effects (all grade 1). The median cumulative radiation dose given before development of cutaneous toxicity was 30 Gy. Clinical signs consistent with side effects on the CNS were not seen in any patient.
Results of the BED calculations for previously published radiation protocols and those used in this study are given in Figure 2. Average BED10 for previously reported protocols was 66.3 Gy10, average BED3 was 108.0 Gy3, and average BED10 corrected for proliferation was 55.7 Gy10. The BED10 for both protocols used in the current study was higher than the calculated average for historical protocols, but when corrected for proliferation, the BED10 for the prescribed dose of 54 Gy fell below average, although it was still higher than that of 2 of the historical protocols. The BED10 for the prescribed dose of 63 Gy remained higher than the historical average when corrected for proliferation. The BED3 for the protocol that prescribed a total dose of 63 Gy in this study was the highest of any protocol, while the BED3 for the protocol that prescribed 54 Gy was equivalent to the historical average (Table 2). Thus, the dose intensity of the treatments given in the current study is within the range of that used in previous studies, which indicates that a general comparison of side effects can be reasonably performed.
Interest in IMRT has begun to arise in the veterinary literature, as evidenced by recent studies looking at the potential for using IMRT to create a “C-shaped” paraspinal radiation field without development of myelomalacia (25), use of IMRT to treat a canine lung tumor (26), and the potential for dose escalation (27) or boost therapy (28) in canine nasal tumors treated with IMRT. With the exception of the treated lung tumor, no studies have given information on long-term follow-up in animals with spontaneous neoplasms treated with IMRT. The lung tumor in the case report was treated with a relatively low cumulative dose of 30 Gy, but the patient had no detectable radiation side effects to the surrounding lung tissue at necropsy 22 mo post-treatment. With the exception of the dog lost to follow-up at 45 d and the dog still alive at 514 d, all dogs in the current study were followed until their death, which allowed for assessment of late side effects in those that survived > 90 d.
Previous studies evaluating the efficacy of RT in the treatment of canine nasal tumors have reported median survival times ranging from 5.5 mo to 23 mo (median, 13.2 mo) (7–15, 29–31). One of these reports included only dogs with nasal adenocarcinoma (10), one included only dogs with squamous cell carcinoma (31), and the remainder included dogs with tumors of varying histologies. No consistent method of tumor treatment was used for the patients in these studies. Cumulative radiation doses ranged from 25 Gy to 67.5 Gy (generally ≤ 54 Gy) and were given on either a Monday/Wednesday/Friday or Monday to Friday schedule using orthovoltage or megavoltage (cobalt-60, 6-MV linear accelerator) radiation, with these parameters often varying among dogs within a single study. Adjunctive chemotherapy and surgical cytoreduction of the tumor prior to RT were part of the treatment protocol in approximately 21% and 43%, respectively, of the previously reported canine nasal tumor patients.
In the current study, the total radiation dose, treatment schedule, tumor types, and percentage of patients receiving adjuvant chemotherapy (33%) match up well with those of previous reports, so a general comparison of survival times and radiation side effects to those found in earlier studies seems appropriate. In patients treated with IMRT, the beam is shaped to the exact size and shape of the tumor to be treated and the dose is designed to fall off rapidly outside the target volume. Therefore, patient positioning becomes even more crucial than in conventional RT planning, and if the patient is not in exactly the same position each time a dose is delivered, not only will local structures potentially receive a higher than normal dose, but the tumor itself may be undertreated, resulting in loss of tumor control. This could, in turn, lead to decreased survival times in IMRT patients when compared with those treated with more conventional techniques (32). In the current study, the median survival time of 446 d (14.9 mo) in dogs treated with IMRT is consistent with the survival times previously reported, which implies that these tumors were targeted effectively and received an appropriate radiation dose.
Various radiation toxicity grading schemes have been used for evaluation of side effects in previous studies involving canine nasal tumors treated with RT (8,11–16,20). The results of adjusting the toxicity scores in these studies to correspond with the VRTOG scoring scheme for acute and late radiation morbidity (Table 1) are summarized in Table 3. Acute ocular toxicity in IMRT patients was comparable to that seen in earlier studies with only modest improvement seen over dogs treated with conventional radiation techniques. However, most previous reports do not discuss whether these side effects were unilateral or bilateral. In the current study, all ocular side effects were unilateral and affected the eye ipsi-lateral to the tumor. Comparison of late ocular side effects shows similar results. Intensity-modulated radiation therapy is not able to significantly improve side effects to the eye on the side of the tumor because the planning target volume (PTV) for the tumor in question will often need to include adjacent tissues if appropriate tumor control is to be achieved. Our findings are in accord with those of a recent study in which predicted complications in the ipsi-lateral eye were not significantly less with IMRT plans than with conventional planning techniques (26). Few grade 2–3 acute side effects to the skin were seen in patients in this study. All dogs that exhibited cutaneous side effects originally presented with facial deformity, which indicates that the tumor had eroded through the bony structures of the nasal cavity and invaded the soft tissues of the face prior to treatment, thus becoming intimately associated with the overlying cutaneous structures. In such cases, it is not possible to spare the skin and still deliver an effective dose to the tumor, even with the most sophisticated beam-shaping strategies. No grade 2–3 late radiation toxicity to the skin was observed.
Only a small amount of acute side effects were observed in the oral cavity of dogs in this study. None of the dogs treated with IMRT had grade 2–3 mucositis, and no therapy was necessary to treat side effects to the oral mucosa in any dog. Part of the reason for this minimal toxicity may be the relatively low dose per fraction and protracted treatment interval used in these dogs compared with the fractionation schemes in historical studies in which severe mucositis was more frequent (Table 3). However, to the authors’ knowledge, no definitive comparison has been made between canine nasal tumors treated with 3 d per wk fractionation schemes and those treated with 5 d per wk fractionation schemes to determine if a significant difference in acute radiation side effects could be shown. In 1 study that evaluated various radiation treatment protocols including some dogs treated Monday/Wednesday/Friday at variable dose per fraction, some treated Monday-Friday at variable dose per fraction, and some treated with a boost technique that included some days where dogs were treated more than once, dose per fraction did not significantly affect development or severity of acute side effects (12). Unfortunately, the lack of controlled studies prevents us from determining whether or not the treatment schedule in the current study played a role in minimizing the degree of mucositis seen. However, if the more protracted treatment interval and lower dose per fraction helped to decrease acute side effects, then it is reasonable to assume that it would also lead to poor tumor control due to repopulation of tumor cells between treatments. This should result in shorter tumor response duration and survival times when compared with previous studies, which did not occur. Also, when the BED for acutely responding tissues is compared, both with and without a correction for proliferation during the course of therapy, the IMRT protocols used herein have BEDs that compare favorably to those of the historical protocols presented for comparison. This would suggest that any decrease in acute toxicities cannot be explained by fractionation alone.
Overall, side effects on local radiosensitive structures were minimal in canine nasal tumor patients treated with IMRT. Moderate to severe late-term side effects were observed in only 2 dogs in the current study, both of which received chemotherapy concurrently with the radiation treatments. Both doxorubicin and carboplatin have been shown to have radiosensitization properties (33,34), so it is possible that the addition of these agents to the treatment protocol resulted in more severe tissue damage than would be expected with radiation alone.
Recent articles have evaluated the possibility of using IMRT to treat canine nasal tumors more aggressively by increasing the prescribed tumor dose or using boost therapy to increase dose intensity. One study used normal tissue complication probabilities (NTCP) to illustrate that a simultaneously integrated boost of radiation therapy can theoretically be safely administered to dogs with nasal tumors by use of image-guided IMRT planning (helical tomotherapy) (28). These results predicted improved tumor control probability in 8 dogs without an increase in radiation-induced side effects to the eyes and brain. In another study, IMRT plans were created for 9 canine nasal tumors, and the NTCP for the eyes and brain were compared with those generated in conventional 3-dimensional planning techniques (27). Intensity-modulated radiation therapy plans were found to predict fewer radiation-induced side effects than conventional plans. The comparable survival times and reduced side effects noted in the current study compared with historical canine nasal tumor patients treated by conventional radiation planning techniques support the theoretical benefits of IMRT claimed by these initial reports.
Limitations to this study include the small patient number and the difficulty in obtaining accurate BED values for true dose intensity comparisons among the protocols used here and in historical studies. Unfortunately, it is very uncommon to be able to treat all dogs uniformly with a prescribed protocol (due to tumor progression, owner concerns, etc.); therefore, these calculations will likely remain useful only as a general comparison. Further investigation with a larger number of dogs would be beneficial in confirming the results seen in this study.
In conclusion, IMRT has improved tumor control and minimized radiation-induced side effects to nearby radiosensitive tissues in many human trials. Canine nasal tumors are a good starting point for evaluation of this technology in veterinary medicine due to their poor response to chemotherapy, their surgically inaccessible location, and the proximity of sensitive structures such as the eyes, oral cavity, and brain. Dogs treated in this study experienced survival times similar to those in previously published reports of nasal tumor patients treated with RT, indicating that tumor control was acceptable. Moderate to severe side effects were uncommon except in the eye ipsi-lateral to the bulk of the tumor and in the skin of patients that had facial deformity, which implies that IMRT cannot be used to spare tissues that are intimately associated with the tumor. Patients receiving concurrent cytotoxic doses of chemotherapy may also have had more severe complications. Overall, IMRT spared the contralateral eye completely in all canine nasal tumor patients, showed modest improvement in late ocular toxicity to the ipsi-lateral eye, and resulted in considerable improvement in acute toxicity to the skin and oral mucous membranes when compared with dogs in previous studies treated with conventional radiation techniques. These findings suggest that IMRT could be used to treat canine nasal tumors with higher cumulative doses of radiation without increasing acute or delayed toxicity beyond levels that are currently considered acceptable. Additional studies with long term follow-up are needed to determine whether this will be a more effective approach to treatment for this tumor. CVJ
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