Dedicated holmium microsphere administration device for MRI-guided interstitial brain microbrachytherapy.

Microbrachytherapy with radioactive holmium-166 (166Ho) microspheres (MS) has the potential to be an effective treatment method for brain malignancies. Direct intratumoural delivery of 166Ho-MS and dose coverage of the whole tumour are crucial requirements. However, currently no dedicated instruments for controlled intratumoural delivery exist. This study presents an administration device that facilitates this novel magnetic resonance imaging (MRI) -guided intervention. The bioceramic alumina oxide cannula creates a straight channel for a superelastic nitinol precurved stylet to control spatial deposition of Ho-MS. End-point accuracy of the stylet was measured during insertions in phantoms. Imaging tests were performed in a 3 Tesla MRI-scanner to quantify instrument-induced artefacts. Additionally, the feasibility of non-radioactive holmium-165 (165Ho)-MS delivery with the administration device was evaluated in a brain tumour simulant. Absolute stylet tip error was 0.88 ± 0.61 mm, instrument distortion in MRI depended on needle material and orientation and dose delivery of 165Ho-MS in a brain tumour phantom was possible. This study shows that the administration device can accurately place the stylet for injection of Ho-MS and that visualization can be performed with MRI.

Feasibility of CT quantification of intratumoural 166Ho-microspheres.

BACKGROUND: Microspheres loaded with radioactive 166Ho (166Ho-MS) are novel particles for radioembolisation and intratumoural treatment. Because of the limited penetration of ß radiation, quantitative imaging of microsphere distribution is crucial for optimal intratumoural treatment. Computed tomography (CT) may provide high-resolution and fast imaging of the distribution of these microspheres, with lower costs and widespread availability in comparison with current standard single-photon emission tomography (SPECT) and magnetic resonance imaging. This phantom study investigated the feasibility of CT quantification of 166Ho-MS. METHODS: CT quantification was performed on a phantom with various concentrations of HoCl and Ho-MS to investigate the CT sensitivity and calibrate the CT recovery. 166Ho-MS were injected into ex vivo tissues, in VX-2 cancer-bearing rabbits, and in patients with head-neck cancer, to demonstrate sensitivity and clinical visibility. The amount of Ho-MS was determined by CT scanning, using a density-based threshold method and compared with a validated 166Ho SPECT quantification method. RESULTS: In the phantom, a near perfect linearity (least squares R2 > 0.99) between HU values and concentration of 166Ho was found. Ex vivo tissue experiments showed an excellent correlation (r = 0.99, p < 0.01) between the dose calibrator, SPECT, and CT imaging. CT recovery was on average 86.4% ex vivo, 76.0% in rabbits, and 99.1% in humans. CONCLUSION: This study showed that CT-based quantification of Ho microspheres is feasible and is a high-resolution alternative to SPECT-based determination of their local distribution.

Effect of surgical site infection on survival after limb amputation in the curative-intent treatment of canine appendicular osteosarcoma: a Veterinary Society of Surgical Oncology retrospective study.

OBJECTIVE: To determine the influence of surgical site infection (SSI) on the median disease-free interval (DFI) and median survival time (MST) in dogs after amputation in the curative-intent treatment of appendicular osteosarcoma (OSA). STUDY DESIGN: Multi-institutional retrospective cohort study. ANIMALS: Fifteen dogs with OSA and SSI, and 134 dogs with OSA and no SSI. METHODS: Medical records were reviewed, and dogs were included if the following criteria were met: histologic confirmation of OSA, no evidence of metastasis, ≥1 chemotherapy treatment, and available follow-up data. We used the definition of SSI from the Centers for Disease Control and Prevention. Kaplan-Meier estimates of median DFI and MST for the SSI and non-SSI groups were compared by log-rank test. Univariate and multivariate Cox proportional hazard regression analysis was evaluated for associations with DFI and survival. RESULTS: The median DFI and MST of all OSA dogs were 236 days (95% CI, 181-283) and 283 days (95% CI 237-355), respectively. The median DFI of dogs with SSI (292 days) did not differ from that of dogs without SSI (224 days, P = .156). The MST of dogs with SSI (292 days) did not differ from that of dogs without SSI (280 days, P = .417). Failure to complete chemotherapy was associated with decreased DFI and survival (P < .001). Adjustments for chemotherapy completion found no effect of SSI on survival. CONCLUSION: SSI did not influence the survival of dogs with appendicular OSA treated with amputation and curative-intent treatment. CLINICAL SIGNIFICANCE: The extended survival associated with SSI after limb-spare surgery for OSA does not appear to be present after amputation. Interactions between the canine immune system and OSA warrant additional study.

Intratumoral injection of radioactive holmium ( 166 Ho) microspheres for treatment of oral squamous cell carcinoma in cats.

BACKGROUND & AIMS: A "microbrachytherapy" was developed as treatment option for inoperable tumours by direct intratumoral injection of radioactive holmium-166 ( 166 Ho) microspheres (MS). 166 Ho emits ß-radiation which potentially enables a high, ablative, radioactive-absorbed dose on the tumour tissue while sparing surrounding tissues. MATERIALS & METHODS: Safety and efficacy of 166 Ho microbrachytherapy were evaluated in a prospective cohort study of 13 cats with inoperable oral squamous cell carcinoma without evidence of distant metastasis. RESULTS: Local response rate was 55%, including complete response or partial response (downstaging) enabling subsequent marginal resection. Median survival time was 113 days overall, and 296 days for patients with local response. Side effects were minimal. Tumour volume was a significant predictor of response. DISCUSSION: Response rate may be further improved by optimizing the intratumoral spatial distribution of 166 Ho MS. CONCLUSION: 166 Ho microbrachytherapy has potential as a minimally invasive, single procedure radio-ablation treatment of unresectable tumours with minimal morbidity.

Nd:YAG surgical laser effects in canine prostate tissue: temperature and damage distribution.

An in vitro model was used to predict short-term, laser-induced, thermal damage in canine prostate tissue. Canine prostate tissue samples were equipped with thermocouple probes to measure tissue temperature at 3, 6, 9 and 12 mm depths. The tissue surface was irradiated with a Nd:YAG laser in contact or non-contact mode for up to 20 s, using powers from 5 to 20 W. Prediction of thermal damage using Arrhenius theory was discussed and compared to the in vitro damage threshold, determined by histological evaluation. The threshold temperature for acute thermal tissue damage was 69 +/- 6 degrees C (means +/- SD), irrespective of exposure time. Contact mode laser application caused vaporization of tissue, leaving a crater underneath the fiber tip. The mean extent of tissue damage underneath the vaporization crater floor was 0.9 +/- 0.6 mm after 5, 10 or 20 s of contact mode laser irradiation at 10 W, whereas 20 W non-contact exposure up to 20 s causes up to 4.7 +/- 0.2 mm coagulation necrosis. It was concluded that short-term acute thermal tissue damage can be comprehensively described by a single threshold temperature.

Preliminary results of intraoperative photodynamic therapy with 5-aminolevulinic acid in dogs with prostate carcinoma.

Six client-owned dogs with prostate carcinoma were treated with a combination of (1) partial subcapsular prostatectomy using an Nd:YAG laser, (2) intraoperative photodynamic therapy using a halogen broad band lamp after local administration of a photosensitiser, and (3) systemic treatment with meloxicam. Median survival time was 41days (range 10-68days), which compared negatively with previous reports of subtotal laser prostatectomy combined with topical interleukin-2 administration, and photodynamic therapy alone. Despite treatment, the disease progressed locally, causing signs of stranguria to recur, and in the form of distant metastases. The recurrence of clinical signs due to the primary tumour despite photodynamic therapy is probably largely explained by insufficient penetration of light into the tissue. Better results may be obtained using other light sources (e.g. laser) and alternative techniques of light delivery, such as fibres or catheters allowing interstitial diffusion of light.