The BED of 45 – 60 Gy reported, for dog and human cancers in the present study (Table 1 & 2) agrees with the report indicating that cancer control rate of 48-67% was achieved at 45 – 60 Gy. But 50% probability of causing serious complications was 54 Gy [19]. TVT was treated using 50 Gy in 3 fractions followed by 25Gy in 2 fractions over 4 days. Whereas chondrosarcoma was treated with 20 Gy [4]. Dose-response relationship of radiorays varies with mouse strain, tissue/organ and gender. Risk of radiotherapy to Macaca mulatta was not increased at 0.25 – 2.8 Gy. But the risk increased significantly from 1-45 Gy for stomach and pancreas, bladder as well as rectum (1-60 Gy) and kidney (1-15 Gy). Normal tissue tolerance to radiotherapy is a complex issue and multifunctional in nature, because 5% rate of radiotoxicity is unacceptable in some cases as 20% may be acceptable in other cases. Therefore, clinical Judgment of the physician should prevail [20]. The half-life of radiation rays is much higher in mast cell neoplasia (198 Gy), brain mass (104.2 Gy), nasal tumors (125 Gy), squamous cell carcinoma (138.9 Gy), soft tissue sarcoma (115.8 Gy) and canine soft tissue sarcoma (157.8 Gy), respectively, suggesting much higher risk of radiotoxicity that may rise from radiation therapy of the affected organs. The half-life of 90 Gy is 66 days. But the average half-life is equal to the half-life multiplied by 1.44 which equals the total dose received during treatment [21]. The relative risk of second malignant neoplasm is 0.7 - 1.8 [22]. Hemangiopericytoma is more responsible to rathiotherapy than fibrosarcoma. Dose per fraction of 2 – 20 Gy reported in the present study agrees with the report that the risk for organs is the dose above 2 Gy [23]. The use of fraction in excess of 3.5 Gy could induce osteosarcoma in dogs that received 10 fractions ranging from 3.5 – 5 Gy in three weeks. The tumor was developed in 4-5 Gy radiation therapy [24]. Also, radiotherapy of bulky soft tissue sarcomas using 20 or 25 Gy caused grade 1 skin toxicity in 3 out of 6 dogs. But chondrosarcoma (21 cm) treated with radiation ray of 20 Gy was not evaluable [4].But median survival period of 2 years has been reported for radiotherapy of canine thyroid carcinoma of 10 cm in diameter using 6.5 – 8 Gy fractions [25]. A fractional dose of 2 Gy at week 1, 3 and 4 yielded optimal relief [26] and brain glioma was tolerant to re-irradiation with median survival of 26 months [27].The intraoperative radiotherapy associated with tumor in dogs was 20-35 Gy [28]. However palliative radiotherapy which controls pains from the incurable tumor, and improves quality of life could be used [29]. Hence, palliative dose of 2 fractions for osteosarcoma; 800 cGy (lcGy = 1rad) followed by 800 cGy after 24 h making a total of 1600 cGy was used. A median survival period of 2.7 yr was reported for dogs with mast cell tumors treated with radiation therapy. But leukotrichia resulted from palliative radiotherapy of osteosarcoma 3 months after treatment [29]
This improvement might have originated from anti-metastatic immune activities by NK cells harvested from dogs treated with a dose of 9 Gy once weekly for 4 treatments. Out of the treated 10 dogs, 5 remained metastasis-free at 6 months, whereas there was regression of suspected pulmonary nodule detected at the time of diagnosis [30]. The choice of cancer therapeutic modalities is based on tumor type, histologic grade, and stage that may include surgery, radiotherapy, chemotherapy, immunotherapy, adjuvant and neo-adjuvant therapies [31]. But effective ablative radiotherapy of a local tumor requires CD8+T cells which is a dynamic strategy for cancer treatment [32]. Single radiotherapy may be more effective against bulky tumors than fractionated radiotherapy. SRT takes 4 – 6 months to shrink after which surgery may be considered. But pet owners have reduced risk of non-Hodgkin’s lymphoma as compared to non-owners [33]. Hence pet ownership may decrease the incidence of cancer in humans [34].
Neoplasm was the most common terminal disease in 73 out of 82 canine breeds and the most common cause of death in dogs greater than 1 yr of age with an incidence greater than 3 times that of traumatic injury [35]. Unluckily, not all cancers respond well to radiation therapy including soft tissue sarcoma [36]. Prostate tumors of dogs, most commonly, adenocarcinomas are models of prostate neoplasia in humans [37]. Prostate carcinoma in dog treated with intraoperative orthovoltage resulted in median survival time of 114 days [38]. But intensity-modulated and image-guided radiation therapy on genitourinary carcinomas showed clinical benefit in 9 out of 10 dogs with median survival time of 654 days and dogs with prostate carcinoma had survival time of 317 days [39]. Ameloblastoma and keratinizing ameloblastoma observed in 3-13 years-old dogs were treated with radiation rays and one survived for 4.8 months with no-evidence of tumor regrowth. But regrowth was observed in 3 dogs at 6, 21, 34 months after completion of radiotherapy [40]. Stereotactic body radiation therapy (SBRT) for heart-base tumors in dogs resulted in median survival day of 408 – 751 days [41]. Canine soft tissue dose per fraction daily, resulted in median survival of 1,851 days, but median time to local recurrence was 540 days as compared to other tumors (2, 270 days). Hence radiotherapy could be used as an adjuvant therapy for incompletely excized soft-tissue sarcomas with long-term median survival in the affected patients [42]. One gray is equal to 100 rads (Dabielzig and Thrall, 1982). Exposure to weekly radiation of 8 Gy with carboplatin every 21 days for 4 times resulted in mean survival time (390 days) for stage I, stage II (1, 286 days), stage III (159 days) and stage IV (90 days) respectively. Hence radiotherapy is a viable palliative treatment of canine oral melanoma [43]. But acute radiation side-effects are completely healed 4-week post radiation treatment in nontonsillar squamous cell carcinoma [44]. A total dose of radiation (48 Gy) of 12 fractions given 4 Gy per fraction thrice weekly led to continuous decrease in tumor size after completion of treatment [45]. Late toxicity is a major concern for patients treated with adjuvant radiotherapy [46]. But single radiotherapeutic dose of 24 Gy not 3 x 9 Gy fractions coupled early tumor ischaemia and or reperfusion to human cancer ablation [47]. Diffusion-weighted and positron emission tomography (PET)/magnetic resonance imaging (MRI) may reveal radiotherapy induced changes and complications [48]. Primary or adjunctive radiotherapy has become a mainstay for intracranial neoplasia and more beneficial than surgery in case of meningiomas [49]. Median survival time of radiation treatment is 33 – 49 weeks [50]. Radiotherapeutic dose of 2 – 5 fractions are referred to as stereotactic radiosurgery compared to 16 – 20 fractions for standard radiation protocols [51]. Since salinomycin can kill cancer stem cells and therapy resistant cancer cells [52], it may be used in combination with radiotherapy in treatment of very resistant cancers. Radiotherapy enhances natural killer cell and cytotoxicity in canine sarcoma [53]. Canine models of malignant cancers such as osteosarcomas are more advantageous and reliable than current murine models [54]. Combination of doxorubicin, cisplatin vinblastine or cyclophosphamide with radiotherapy of tonsillar squamous carcinoma of dog yielded a favourable higher rate of therapeutic response and significantly longer survival times [54]. But radiotherapy is a viable alternative for the palliative treatment of canine oral melanoma [43], in spite of the fact that hypoxia has negative influence on determining response to conventional therapy [56], suggesting that substantial differences in intrinsic radio-sensitivity exist in canine cancers [57]. Fluorodeoxyglucose (FDG)/PET is an effective imaging technique for lymph mode staging of locally advanced cervical carcinoma with negative computed tomography (CT) findings, despite PET-CT could customize and guide brachytherapy planning [58]. However, choline PET/CT is complementary to imaging modalities with the advantage of restaging prostate cancer in a single step [59]. But FDG-PET is mainly used for diagnosis, staging, early response prediction and re-staging of different gastrointestinal tumors [60] and allow more thorough staging avoiding unnecessary radiotherapy [61]. FDG-PET is also recommended in case of cervical metastases from an unknown primary tumor [62]. Whereas the intensity modulated radiotherapy (IMRT) combined with treatment plan based on imaging is individualized, the phenomenon called customized radiation therapy or dose painting [63]. Hence individual adaptation based on functional PET imaging is highly promising [64]. Respiratory gated (RD) 4D-PET/CT improved diagnostic performance of PET/CT and defines better, the target volume for radiation therapy [65]. Quantitative analysis with PET-imaging protocols could help in tumor diagnosis [66]. But segmentation of PET-images could delineate target cancer cells during radiation therapy [67]. Accurate positioning and immobilization is very vital for effective radiotherapy [68], which is a function of nuclear medicine [69]. This requires potential radiopharmaceuticals that include tracers, monitoring proliferation, aminoacid metabolism, hypoxia, lipid metabolism and receptor expression [70]. Really personalized approach of radiation target volume delineation requires many parameters [71], suggesting that the use of PET requires awareness among radiotherapists and oncologists [72]. Intensity modulated radiotherapy (IMRT) of 0.3-3.5 Gy and 3D tangetial beams of 0.4-4.3 Gy have been suggested for heart and lung. The median dose to the lung of IMRT was 4.9-5 Gy and 5.6 Gy for the 3D tangetial beams, respectively. Hence, IMRT technique for early breast cancer allows more homologous dose distribution in target volume, but reducing the dose to critical organ.