Adaptive radiation therapy using weekly hypofractionation for thymoma treatment: A retrospective study of 10 rabbits.

Radiation therapy (RT) is being utilized more commonly for rabbit thymomas due to high perioperative mortality rates with surgery. Median overall survival times reported for rabbit thymomas treated with a variety of RT protocols and techniques range from 6 months to greater than 2 years. As thymomas are radiation-responsive tumours and may shrink rapidly after RT, adaptive radiotherapy (ART) is often warranted. The purpose of this single-institution retrospective case series was to investigate the tumour volume reduction during RT, the frequency of replanning during RT, and survival time in rabbit thymomas treated using intensity-modulated/image-guided radiation therapy (IMRT/IGRT) and a weekly hypofractionated protocol delivering a total dose of 30 Gy. Ten rabbits met the inclusion criteria from October 2014 to October 2019. The median progression-free survival was 561 days and the median overall survival was 634 days (range: 322-1118 days). The tumour volume gradually decreased with each RT fraction. On post-hoc analysis, only the first RT fraction was associated with a significant GTV reduction (of more than 50% on average, p < .001). All subsequent RT fractions did not further reduce the GTV significantly (p > .06). Hypofractionated RT using a weekly protocol of 5 fractions of 6 Gy is a reasonable option to treat rabbit thymomas and replanning should be anticipated. The results of this study support the use of RT to rapidly relieve thymoma-induced dyspnoea in rabbits.

Patterns of local residual disease and local failure after intensity modulated/image guided radiation therapy for sinonasal tumors in dogs.

BACKGROUND: Most dogs with sinonasal tumors (SNT) treated with radiation therapy (RT) died because of local disease progression. HYPOTHESIS/OBJECTIVES: Our hypothesis is that the majority of local failure and residual disease would occur within the radiation field. ANIMALS: Twenty-two dogs with SNT treated with RT. METHODS: Retrospective cohort study. INCLUSION CRITERIA: dogs with SNT receiving 10 daily fractions of 4.2 Gy with intensity modulated radiation therapy (IMRT)/image guided radiation therapy (IGRT) and follow-up cone beam computed tomography (CBCT). Each CBCT was registered with the original radiation planning CT and the gross tumor volume (GTV) contoured. The GTV was classified as residual (GTVr) or a failure (GTVf). The dose statistic for each GTV was calculated with the original IMRT plan. For GTVf, failures were classified as "in-field," "marginal," or "out-field" if at least 95, 20-95, or less than 20% of the volume of failure was within 95% (D95) of the total prescription dose, respectively. RESULTS: There were 52 follow-up CBCT/CTs. Overall there was a GTVr for 20 dogs and GTVf for 16 dogs. The majority of GTVr volume was within the original GTV. GTVf analysis showed that 75% (12/16) were "in-field," 19% (3/16) were "marginal" and 6% (1/16) were "out-field." CONCLUSION AND CLINICAL IMPORTANCE: In-field failures are the main pattern for local recurrence, and there is evidence of radioresistant subvolumes within the GTV.

Clinical-dosimetric relationship between lacrimal gland dose and keratoconjunctivitis sicca in dogs with sinonasal tumors treated with radiation therapy.

BACKGROUND: Dogs with sinonasal tumor can develop keratoconjunctivitis sicca (KCS) after radiation therapy (RT). In humans, the incidence of xerophtalmia is associated with the mean radiation dose received by the ipsilateral lacrimal gland (LG). HYPOTHESIS/OBJECTIVES: The eyes receiving a higher mean LG dose are more likely to develop KCS. The aim of the study was to determine a starting threshold dose to use as dose constraint for intensity-modulated radiation therapy (IMRT). ANIMALS: Dogs with nasal tumors treated with RT between August 2013 and December 2016. METHODS: Case control retrospective study of dogs with sinonasal tumor treated with 42 Gray (Gy) in 10 fractions using IMRT. Dogs were included if development of KCS after RT was documented (cases) or adequate follow-up information with Schirmer tear test (STT) result for ≥6 months after RT was available (controls). Lacrimal glands were contoured and dose distribution was calculated using the original treatment plan to determine prescribed doses to LGs. RESULTS: Twenty-five dogs were treated with RT and 5 dogs (20%) developed KCS. Fifteen dogs met the inclusion criteria including 5 unilateral KCS and 10 control dogs, resulting in 5 KCS eyes and 25 control eyes. KCS developed at a median of 111 days (84-122) after 1st RT. The mean LG dose reached using a 4.2 Gy per fraction was 33.08 Gy (range: 23.75-42.33) for KCS eyes and 10.33 Gy (1.8-24.77) for control eyes (P < .001). The minimum LG mean dose for developing KCS was 23.75 Gy. No eyes that received a mean LG dose <20 Gy developed KCS versus 5/7 (71%) developed with >20 Gy. CONCLUSION AND CLINICAL IMPORTANCE: Contouring and applying a dose constraint on LGs should be performed when using IMRT in dogs with sinonasal tumors to reduce the risk of KCS.

Biodistribution and Physiologically-Based Pharmacokinetic Modeling of Gold Nanoparticles in Mice with Interspecies Extrapolation.

Gold nanoparticles (AuNPs) are a focus of growing medical research applications due to their unique chemical, electrical and optical properties. Because of uncertain toxicity, "green" synthesis methods are emerging, using plant extracts to improve biological and environmental compatibility. Here we explore the biodistribution of green AuNPs in mice and prepare a physiologically-based pharmacokinetic (PBPK) model to guide interspecies extrapolation. Monodisperse AuNPs were synthesized and capped with epigallocatechin gallate (EGCG) and curcumin. 64 CD-1 mice received the AuNPs by intraperitoneal injection. To assess biodistribution, groups of six mice were sacrificed at 1, 7, 14, 28 and 56 days, and their organs were analyzed for gold content using inductively coupled plasma mass spectrometry (ICP-MS). A physiologically-based pharmacokinetic (PBPK) model was developed to describe the biodistribution data in mice. To assess the potential for interspecies extrapolation, organism-specific parameters in the model were adapted to represent rats, and the rat PBPK model was subsequently evaluated with PK data for citrate-capped AuNPs from literature. The liver and spleen displayed strong uptake, and the PBPK model suggested that extravasation and phagocytosis were key drivers. Organ predictions following interspecies extrapolation were successful for rats receiving citrate-capped AuNPs. This work lays the foundation for the pre-clinical extrapolation of the pharmacokinetics of AuNPs from mice to larger species.

Proposed expansion margins for planning organ at risk volume for lenses during radiation therapy of the nasal cavity in dogs and cats.

Radiation therapy protocols for the feline or canine nasal cavity can damage epithelial cells of the posterior pole of the lens and lead to the development of cataracts. Aims of this retrospective, descriptive study were to calculate movements of the lens during radiation therapy of the nasal cavity in a sample of cats and dogs, and to propose species-specific expansion margins for planning organ at risk volume (PRV) to minimize radiation doses to the lens. All included patients were immobilized with an indexed bite block and positioned in a vacuum positioning cushion for head irradiation. On-board cone beam CT (CBCT) imaging was used for patient alignment. Both ocular lenses were contoured on the therapeutic CBCTs. Coregistration (fusion) between the planning CT and CBCTs was used to measure the movements of the lens. Two measurements were made: the differences between the centroid point of each lens as well as the displacement of the coregistrations. A total of 496 different observations were recorded from 14 cats and 52 dogs. Using the displacement results, we calculated how often the lens would be within the lens-PRV contour. We proposed that an optimal expansion margin from the lens volume of 2 mm in cats and 3 mm in dogs may be necessary in generating PRV expansion for the lens. From our results, we expect the lens would therefore be within these proposed PRV expansions in 92% of the feline measurements and 95% of the canine measurements.

Dosimetric evaluation of whole-breast radiation therapy: clinical experience.

Radiation therapy of the intact breast is the standard therapy for preventing local recurrence of early-stage breast cancer following breast conservation surgery. To improve patient standard of care, there is a need to define a consistent and transparent treatment path for all patients that reduces significance variations in the acceptability of treatment plans. There is lack of consistency among institutions or individuals about what is considered an acceptable treatment plan: target coverage vis-à-vis dose to organs at risk (OAR). Clinical trials usually resolve these issues, as the criteria for an acceptable plan within the trial (target coverage and doses to OAR) are well defined. We developed an institutional criterion for accepting breast treatment plans in 2006 after analyzing treatment data of approximately 200 patients. The purpose of this article is to report on the dosimetric review of 623 patients treated in the last 18 months to evaluate the effectiveness of the previously developed plan acceptability criteria and any possible changes necessary to further improve patient care. The mean patient age is 61.6 years (range: 25.2 to 93.0 years). The mean breast separation for all the patients is 21.0cm (range: 12.4 to 34.9cm), and the mean planning target volume (PTV_eval) (breast volume for evaluation) is 884.0cm(3) (range: 73.6 to 3684.6cm(3)). Overall, 314 (50.4%) patients had the disease in the left breast and 309 (49.6%) had it in the right breast. A total of 147 (23.6%) patients were treated using the deep inspiration breath-hold (DIBH) technique. The mean normalized PTV_eval receiving at least 92% (V92% PD) and 95% (V95% PD) of the prescribed dose (PD) are more than 99% and 97%, respectively, for all patients. The mean normalized PTV_eval receiving at least 105% (V105% PD) of the PD is less than 1% for all groups. The mean homogeneity index (HI), uniformity index (UI), and conformity index (CI) for the PTV_eval are 0.09 (range: 0.05 to 0.15), 1.07 (range: 0.46 to 1.11), and 0.98 (range: 0.92 to 1.0), respectively. Our data confirm the significant advantage of using DIBH to reduce heart dose when compared with the free-breathing technique. The p values analyses of the results for the V5Gy, V10Gy, V15Gy, V20Gy, and V30Gy for the heart comparing DIBH and free-breathing techniques are well less than 0.05 (i.e., p < 0.05). However, similar analyses for the lung give values greater than 0.05 (i.e., p > 0.05), indicating that there is no significant difference in lung dose comparing the 2 treatment techniques.

On bolus for megavoltage photon and electron radiation therapy.

Frequently, in radiation therapy one must treat superficial lesions on cancer patients; these are at or adjacent to the skin. Megavoltage photon radiotherapy penetrates through the skin to irradiate deep-seated tumors, with skin-sparing property. Hence, to treat superficial lesions, one must use a layer of scattering material to feign as the skin surface. Although megavoltage electron beams are used for superficial treatments, one occasionally needs to enhance the dose near the surface. Such is the function of a "bolus," a natural or synthetically developed material that acts as a layer of tissue to provide a more effective treatment to the superficial lesions. Other uses of boluses are to correct for varying surface contours and to add scattering material around the patient's surface. Materials used as bolus vary from simple water to metal and include various mixtures and compounds. Even with the modernization of the technology for external-beam therapy and the emergence of various commercial boluses, the preparation and utilization of a bolus in clinical radiotherapy remains an art. Considering the varying experiences and practices, this paper briefly summarizes available boluses that have been proposed and are employed in clinical radiotherapy. Although this review is not exhaustive, it provides some initial guidance and answers questions that may arise in clinical practice.

Dose assessment from an online kilovoltage imaging system in radiation therapy.

We have investigated the dosimetric properties of a commercial kilovoltage cone beam computerised tomography (kV-CBCT) system. The kV-CBCT doses were measured in 16 and 32 cm diameter standard cylindrical Perspex computerised tomography (CT) and Rando anthropomorphic phantoms using 125 kVp and 1.0-2.0 mA s per projection. We also measured skin doses using thermoluminescence dosimeters placed on the skin surfaces of prostate cancer patients undergoing kV-kV image matching for daily set-up. The skin doses from kV-kV image matching of prostate cancer patients on the anterior and lateral skin surfaces ranged from 0.03 +/- 0.01 to 0.64 +/- 0.01 cGy depending on the beam filtration and technique factors employed. The mean doses on the Rando phantom ranged from 3.0 +/- 0.1 to 5.1 +/- 0.3 cGy for full-fan scans and from 3.8 +/- 0.1 to 6.6 +/- 0.2 cGy for half-fan scans using 125 kVp and 2 mA s per projection. The isocentre cone beam dose index (CBDI) in the 16 and 32 cm Perspex phantoms is 4.65 and 1.81 cGy, respectively (using a 0.6 cm(3) Capintec PR06C Farmer chamber) for full-fan scans, and the corresponding normalised CBDIs are 0.72 and 0.28 cGy/100 mA s, respectively. The mean weighted CBDIs are 4.93 and 2.14 cGy, and the normalised weighted CBDIs are 0.76 and 0.33 cGy/100 mA s for the 16 and 32 cm phantoms, respectively (full-fan scans). The normalised weighted CBDI for the half-fan scan is 0.41 cGy/100 mA s for the 32 cm diameter phantom. All measurements of the CBDI using the 0.6 cm(3) Farmer chamber are within 2-5% of measurements taken with the 100 mm CT chamber. The CBDI technique and definitions can be used to benchmark CBCT systems and to provide estimates of imaging doses to patients undergoing on-board imager (OBI)/CBCT image guided radiation therapy.