Method to assess the need for re-planning HDR brachytherapy tandem and ring treatments.

High dose rate (HDR) brachytherapy procedures for cervical cancer require multiple applicator insertions for multiple (typically 5) fractions of a single plan, which carries a risk for variability in applicator position between fractions. Due to applicator displacement relative to patient anatomy, the dose to nearby organs-at-risk (OARs) may vary significantly from one fraction to the next. The purpose of this study was to evaluate the effect of changes in HDR tandem and ring (T&R) applicator position on doses to nearby OARs and to present a quick and simple method to estimate doses to OARs inter-fractionally without having to perform a re-plan. Ninety CT image sets for 20 patients, ages 44 to 86, undergoing T&R-based HDR for cervical cancer were used retrospectively for this study. Measures of applicator positional and angular changes relative to the bony anatomy were obtained using image fusion in MIM software, between the planning CT (plan CT) and the CT on the treatment day (CT-TX). Dosimetric data were determined, also using MIM software, using the original (first fraction) dose distribution applied to organs at risk (rectum and bladder), transferred via rigid registration from the plan CT to each CT-TX. Bladder and rectum contours were also transferred from each plan CT to each CT-TX and were tweaked manually to match anatomy on each CT-TX and examined visually for appropriateness. Differences in translation and rotation of the T&R applicator between the planning CT and subsequent individual fractions were recorded and plotted against dose differences between each fraction of treatment and the original (first) fraction. Absolute dose (D2cc) and volume (V50) differences vs positional shifts were calculated and plotted, and the Pearson Product-Moment correlation coefficient between dose parameters and measured positional shifts was determined. Average dosimetric differences between planned dose and subsequent fractional doses obtained through rigid registration were 1.48 ± 1.92 Gy, 14.91 ± 11.92 cm3, 0.56 ± 0.93 Gy, and 1.77 ± 2.18 cm3 for Bladder D2cc, Bladder V50, Rectum D2cc, and Rectum V50, respectively. Correlation between Bladder V50 and sagittal plane rotation gave an r2 of 0.4, showing the most correlation of all parameters studied. Bladder dose and volume increased by a maximum of about 2.7 Gy and 50 cm3 overall for Bladder D2cc and Bladder V50, respectively. Bladder V50 was most sensitive to T&R applicator displacements. We have quantified the effects of applicator positional changes on dose changes for the bladder and rectum. Even large changes in applicator position between fractions did not result in significant changes in dose to these normal tissues, indicating that adaptive re-planning is not necessary.

Outcomes for posterior uveal melanoma: Validation of American Brachytherapy Society Guidelines.

PURPOSE: To assess outcomes of small and medium choroidal melanoma (less than 5.0 mm in height) following Iodine-125 episcleral brachytherapy. METHODS AND MATERIALS: Patients with small and medium choroidal melanoma that underwent Iodine-125 brachytherapy with apical height of 1.0 mm to 5.0 mm and largest basal diameter of ≤16.0 mm were included. Data were extracted from the original dosimetry plans to determine doses to vision critical structures with the prescription point to the apical height (actual dose, ABS guidelines) and, after simulation, with the prescription point to the height of 5.0 mm (simulated dose, COMS protocol). Visual acuity (VA) outcomes with actual dose and that predicted with the simulated dose were estimated along with local recurrence, ocular survival, and survival at 5 years. RESULTS: A total of 339 patients with a mean age of 61.5 years with a mean follow up duration of 43.4 months were included. The mean dose reduction for lens, optic disc, and fovea was 34%, 39.4%, and 41.4%, respectively with actual dose when compared with simulated dose. The Kaplan-Meier estimations for 3 year event free rate of VA of 20/50 or better were 56% and 31% for actual dose and simulated dose, respectively. Only 3 events of local recurrence were observed (enucleated) yielding 5 year local control and ocular survival rate of 98%. Overall survival (OS) and metastasis free survival (MFS) were 95% and 87.5% at 5 years, respectively. CONCLUSIONS: Small and medium choroidal melanoma treated according to ABS has excellent outcomes. Brachytherapy planning using ABS guidelines as compared to COMS protocol may be associated with lower rates of radiation toxicity and vision loss.

Small choroidal melanoma: outcomes following apical height dose brachytherapy.

AIM: To assess the outcomes of small choroidal melanoma following iodine-125 episcleral brachytherapy (apical height dose of 85 Gy). METHODS: Patients with small choroidal melanoma that underwent iodine-125 episcleral brachytherapy between January 2004 and December 2017 were reviewed. Inclusion criterion for this study was the COMS small tumour size (tumour apical height of 1.0-2.5 mm and largest basal diameter (LBD) <16.0 mm). Patients that received any form of prior therapy or adjuvant transpupillary thermotherapy were excluded. Outcome measures were visual acuity (VA), recurrence, ocular survival and metastasis at 3 years. Kaplan-Meier estimation was calculated for VA, recurrence, ocular survival and survival outcome (overall and metastasis-free survival rate) at 3 years. RESULTS: 161 cases of choroidal melanoma were included in this study, with the mean (SD) age of 59.6 (14.1) years, and 93 (58%) were males. The mean (SD) apical height for the tumours were 2.1 (0.4) mm and mean (SD) LBD was 8.3 (2.2) mm. The mean (SD, median) follow-up was 40.7 months (37.1, 25 months). The VA was 20/50 or better in 69%. Only one recurrence event (1%) and one enucleation event (1%) were observed. Overall survival was 97%, and no metastatic events were observed at 3 years. CONCLUSION: Small choroidal melanomas treated with iodine-125 episcleral brachytherapy have excellent outcomes. The majority (69%) of patients retained VA of 20/50 or better with very high local control and ocular survival rate (99.3%) with the absence of metastasis (100%).

Addition of magnetic resonance imaging to real time trans-rectal ultrasound-based treatment planning for prostate implants.

PURPOSE: The greater soft tissue contrast of magnetic resonance imaging (MRI) allows improved accuracy in prostate contouring compared to transrectal ultrasound (TRUS) and helps in identifying specific regions within the prostate. This study attempts to evaluate the potential benefit of MRI-TRUS fusion in treatment planning for more accurate prostate contouring and tumor dose escalation. MATERIAL AND METHODS: 14 patients with previous MRI-guided prostate biopsy and an low-dose-rate (LDR) permanent prostate seed implant have been selected. The prostate and tumor (5 patients) were contoured on the MRI images by a radiologist. The prostate was also contoured on TRUS images during LDR procedure together by a urologist and radiation oncologist. MRI and TRUS images were rigidly fused to compare prostate contours in MRI and TRUS. Prostate was then re-contoured by the radiation oncologist using this fusion. Moreover, V100, V150, and D90 differences were evaluated for localized tumor compared to prostate with negative values indicating cold tumor regions. These cases were re-planned to simulate dose escalation. RESULTS: The prostate volume was contoured 8 ±10% smaller in TRUS images, compared to MRI images. The mean percent difference in tumor (compared to prostate) V100 was 0.3 ±-0.4%, V150 was -0.7 ±-24.8%, and D90 was 0.2 ±-12.1%. For the posteriorly located tumors (2 cases), V100 was 0.0 ±-0.3%, D90 was 9.5 ±-3.0%, and V150 was 26.1 ±-5.4%. For anteriorly located tumors (3 cases), V100 was 0.4 ±-0.4%, D90 was -6.0 ±-11.9%, and V150 was -18.5 ±-14.4% (became 15.6 ±14.6% after re-plan). CONCLUSIONS: The MRI-TRUS image fusion is a feasible tool for the visualization of the prostate gland, particularly at the apex and base of the gland. Tumor identification presents the potential for dose escalation using fusion, especially for anteriorly located tumors.

Animal models of radiation retinopathy - From teletherapy to brachytherapy.

Radiation retinopathy is a serious vision-impairing complication of radiation therapy used to treat ocular tumors. Characterized by retinal vasculopathy and subsequent retinal damage, the first sign of radiation retinopathy is the preferential loss of vascular endothelial cells. Ensuing ischemia leads to retinal degradation and late stage neovascularization. Despite the established disease progression, the pathophysiology and cellular mechanisms contributing to radiation retinopathy remain unclear. Clinical experience and basic research for other retinal vasculopathies, such as diabetic retinopathy and retinopathy of prematurity, can inform our understanding of radiation retinopathy; however, the literature investigating the fundamental mechanisms in radiation retinopathy is limited. Treatment trials have shown modest success but, ultimately, fail to address the cellular events that initiate radiation retinopathy. Animal models of radiation retinopathy could provide means to identify effective therapies. Here, we review the literature for all animal models of radiation retinopathy, summarize anatomical highlights pertaining to animal models, identify additional physiological factors to consider when investigating radiation retinopathy, and explore the use of clinically relevant tests for studying in vivo models of radiation retinopathy. We encourage further investigation into the mechanistic characterization of radiation retinopathy in the hope of discovering novel treatments.

Principles and practice of high-dose rate penile brachytherapy: Planning and delivery techniques.

PURPOSE: To allow for organ preservation, high-dose rate (HDR) brachytherapy may be used in the treatment of localized penile cancer. Penile cancer is a rare malignancy that accounts for <1% of cancers in men in the United States. The standard treatment for localized disease is partial amputation of the penis. However, patients with T1b or T2 disease <4 cm in maximum dimension and confined to the glans penis may be treated with brachytherapy as an organ-sparing approach. Previous works have described the technique involved for low-dose rate brachytherapy; however, we detail the techniques involved with HDR brachytherapy. METHODS AND MATERIALS: Circumcision should precede brachytherapy. Interstitial brachytherapy needles are placed in the operating room under general anesthesia with the goal to allow for appropriate target coverage. Target definition is done via computed tomography-based simulation and planning. Radiation is delivered using a prescription dose of 3840 cGy in 12 fractions twice daily over a course of 6 days. RESULTS: Acute toxicities peak upon completion of the radiation therapy and may include dermatitis, sterile urethritis, and adhesions in the urethra. These toxicities are reversible and generally take 2 to 3 months to heal. The two most common and significant late complications of radiation therapy for penile cancer are soft tissue necrosis and meatal stenosis. An increased risk of necrosis has been reported with T3 tumors and higher-volume implants (>30 cm3). Erectile function is generally maintained because the erectile tissues including the penile shaft and corpora have not been irradiated. CONCLUSIONS: Organ preservation is feasible using HDR brachytherapy with favorable acute and late toxicities.

Local Failure After Episcleral Brachytherapy for Posterior Uveal Melanoma: Patterns, Risk Factors, and Management.

PURPOSE: To evaluate the patterns, the risk factors, and the management of recurrence following brachytherapy in patients with posterior uveal melanoma, given that an understanding of the recurrence patterns can improve early recognition and management of local treatment failure in such patients. DESIGN: Retrospective cohort study. METHODS: Setting: Multispecialty tertiary care center. PARTICIPANTS: A total of 375 eyes treated with episcleral brachytherapy for posterior uveal melanoma from January 2004 to December 2014. Exclusion criteria included inadequate follow-up (<1 year) and previous radiation therapy. Main Outcomes and Measures: Local control rate and time to recurrence were the primary endpoints. Kaplan-Meier estimation and Cox proportional hazards models were conducted to identify risk factors for recurrence. RESULTS: Twenty-one patients (5.6%) experienced recurrence (follow-up range 12-156 months; median 47 months). The median time to recurrence was 18 months (range 4-156 months). Five-year estimated local recurrence rate was 6.6%. The majority (90.5%) of the recurrences occurred within the first 5 years. The predominant site of recurrence was at the tumor margin (12 patients, 57.1%). Univariate analysis identified 3 statistically significant recurrence risk factors: advanced age, largest basal diameter, and the use of adjuvant transpupillary thermotherapy (TTT). Recurrent tumors were managed by repeat brachytherapy, TTT, or enucleation. CONCLUSIONS: Local recurrences following brachytherapy are uncommon 5 years after episcleral brachytherapy. Follow-up intervals can be adjusted to reflect time to recurrence. Most of the eyes with recurrent tumor can be salvaged by conservative methods.

Episcleral brachytherapy of uveal melanoma: role of intraoperative echographic confirmation.

PURPOSE: To compare the rates of tumour recurrence following episcleral brachytherapy for uveal melanoma before and after implementation of intraoperative echographic confirmation of plaque placement. MATERIALS AND METHODS: All patients with primary single ciliary body or choroidal melanoma treated with iodine-125 or ruthenium-106 plaque brachytherapy between 1 January 2004 and 30 December 2013 were included. Exclusion criteria were patients with previous radiation treatment and patients who received adjuvant transpupillary thermotherapy. Since February 2007, intraoperative echographic confirmation was initiated to ensure that the plaque was centred on the tumour base and/or all tumour margins were covered by the plaque. RESULTS: 252 patients were included in the study. Local tumour control after primary brachytherapy was achieved in 242/252 (96.0%). Of the 10 patients with treatment failure, 8 patients had local recurrence and 2 patients had failure to response. With the incorporation of the intraoperative echographic confirmation for plaque positioning the treatment failure rate decreased from 9.3% (5/54 patients) to 1.5% (3/198 patients). Continuous and categorical univariable predictors of recurrence were analysed for statistical significance. The only statistically significant variable was the intraoperative echographic confirmation (HR: 0.16; p=0.032) for recurrence within the first 24 months. CONCLUSIONS: Intraoperative echographic confirmation of plaque placement during episcleral brachytherapy for choroidal melanoma reduces the risk of early local recurrence.

Vision Loss Following Episcleral Brachytherapy for Uveal Melanoma: Development of a Vision Prognostication Tool.

IMPORTANCE: Vision loss following episcleral brachytherapy for uveal melanoma is difficult to predict for individual patients. OBJECTIVE: To generate a risk calculator for vision loss following episcleral brachytherapy for uveal melanoma. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of data was conducted at a multispecialty tertiary care center in Cleveland, Ohio. All patients with primary ciliary body or choroidal melanoma treated with iodine 125 or ruthenium 106 episcleral brachytherapy between January 1, 2004, and December 30, 2013, were included. Univariate and multivariable Cox proportional hazards were used to determine the influence of baseline patient factors on vision loss. Kaplan-Meier curves (log-rank analyses) were used to estimate freedom from vision loss. Bootstrap resampling was performed to bias correct this estimate. MAIN OUTCOMES AND MEASURES: Vision loss (to visual acuity [VA] worse than 20/50 and worse than 20/200). RESULTS: A total of 311 patients were included in the study, with a mean (SD) age of 62 (14.7) years at start of treatment and a median follow-up of 36 months (interquartile range, 18-60 months). At presentation, VA was better than or equal to 20/50 in 199 patients (64%) and better than or equal to 20/200 in 289 patients (93%). By Kaplan-Meier analysis, VA less than 20/200 at 3 years was not associated with sex, diabetes, systemic hypertension, or hypercholesterolemia but was associated with history of ocular comorbidities, type of isotope (ruthenium 106 or iodine 125), and initial VA ( >20/50 or <20/50). By multivariable analysis, age (hazard ratio [HR], 0.97; 95% CI, 0.94-1.00; P = .06), largest basal diameter (HR, 1.25; 95% CI, 1.16-1.34; P = <.001), total radiation dose to the fovea (HR, 1.03; 95% CI, 1.01-1.04; P = .001) and optic disc (HR, 1.01; 95% CI, 1.00-1.01; P = .005), and initial VA worse than 20/50 (HR, 1.85; 95% CI, 1.20-2.85; P = .005) were predictive of vision loss to a VA of less than 20/200. The concordance index for the full data set was 0.77. Using these data, an online risk calculator was developed to predict vision loss following episcleral brachytherapy. CONCLUSIONS AND RELEVANCE: The vision prognostication tool presented herein needs to be validated by independent data sets. This tool may improve counseling for patients being evaluated for episcleral brachytherapy. At-risk individuals identified by this tool could be considered for inclusion into trials exploring prevention or treatment of radiation retinopathy and alternative therapies of uveal melanoma.

Brachytherapy.

Brachytherapy is the preferred radiation treatment modality for various intraocular tumors, most commonly, uveal melanoma. Radioactive sources are placed directly onto or around the tumor with the aid of episcleral plaques, whereby the employed sources exhibit an extremely sharp fall-off of dosage outside the few millimeters around the tumor. With such high focality, radiation dose to vision critical structures is minimized. Various sources have been used over the years, with iodine-125 being the most common. This chapter will highlight the history of brachytherapy for the treatment of intraocular tumors, current practice including isotopes and plaques utilized, as well as a comprehensive treatment planning and physics review.

Lung dose calculation with SPECT/CT for 9°Yittrium radioembolization of liver cancer.

PURPOSE: To propose a new method to estimate lung mean dose (LMD) using technetium-99m labeled macroaggregated albumin ((99m)Tc-MAA) single photon emission CT (SPECT)/CT for (90)Yttrium radioembolization of liver tumors and to compare the LMD estimated using SPECT/CT with clinical estimates of LMD using planar gamma scintigraphy (PS). METHODS AND MATERIALS: Images of 71 patients who had SPECT/CT and PS images of (99m)Tc-MAA acquired before TheraSphere radioembolization of liver cancer were analyzed retrospectively. LMD was calculated from the PS-based lung shunt assuming a lung mass of 1 kg and 50 Gy per GBq of injected activity shunted to the lung. For the SPECT/CT-based estimate, the LMD was calculated with the activity concentration and lung volume derived from SPECT/CT. The effect of attenuation correction and the patient's breathing on the calculated LMD was studied with the SPECT/CT. With these effects correctly taken into account in a more rigorous fashion, we compared the LMD calculated with SPECT/CT with the LMD calculated with PS. RESULTS: The mean dose to the central region of the lung leads to a more accurate estimate of LMD. Inclusion of the lung region around the diaphragm in the calculation leads to an overestimate of LMD due to the misregistration of the liver activity to the lung from the patient's breathing. LMD calculated based on PS is a poor predictor of the actual LMD. For the subpopulation with large lung shunt, the mean overestimation from the PS method for the lung shunt was 170%. CONCLUSIONS: A new method of calculating the LMD for TheraSphere and SIR-Spheres radioembolization of liver cancer based on (99m)Tc-MAA SPECT/CT is presented. The new method provides a more accurate estimate of radiation risk to the lungs. For patients with a large lung shunt calculated from PS, a recalculation of LMD based on SPECT/CT is recommended.

Dosimetric benefit of a new ophthalmic radiation plaque.

PURPOSE: To determine whether the computed dosimetry of a new ophthalmic plaque, EP917, when compared with the standard Collaborative Ocular Melanoma Study (COMS) plaques, could reduce radiation exposure to vision critical structures of the eye. METHODS AND MATERIALS: One hundred consecutive patients with uveal melanoma treated with COMS radiation plaques between 2007 and 2010 were included in this study. These treatment plans were generated with the use of Bebig Plaque Simulator treatment-planning software, both for COMS plaques and for EP917 plaques using I-125. Dose distributions were calculated for a prescription of 85 Gy to the tumor apex. Doses to the optic disc, opposite retina, lens, and macula were obtained, and differences between the 2 groups were analyzed by standard parametric methods. RESULTS: When compared with the COMS plaques, the EP917 plaques used fewer radiation seeds by an average difference of 1.94 (P<.001; 95% confidence interval [CI], -2.8 to -1.06) and required less total strength of radiation sources by an average of 17.74 U (air kerma units) (P<.001; 95% CI, -20.16 to -15.32). The total radiation doses delivered to the optic disc, opposite retina, and macula were significantly less by 4.57 Gy, 0.50 Gy, and 11.18 Gy, respectively, with the EP917 plaques vs the COMS plaques. CONCLUSION: EP917 plaques deliver less overall radiation exposure to critical vision structures than COMS treatment plaques while still delivering the same total therapeutic dose to the tumor.