A Millimeter-scale Single Charged Particle Dosimeter for Cancer Radiotherapy.

This paper presents a millimeter-scale CMOS 64×64 single charged particle radiation detector system for external beam cancer radiotherapy. A 1×1 µm2 diode measures energy deposition by a single charged particle in the depletion region, and the array design provides a large detection area of 512×512 µm2. Instead of sensing the voltage drop caused by radiation, the proposed system measures the pulse width, i.e., the time it takes for the voltage to return to its baseline. This obviates the need for using power-hungry and large analog-to-digital converters. A prototype ASIC is fabricated in TSMC 65 nm LP CMOS process and consumes the average static power of 0.535 mW under 1.2 V analog and digital power supply. The functionality of the whole system is successfully verified in a clinical 67.5 MeV proton beam setting. To our' knowledge, this is the first work to demonstrate single charged particle detection for implantable in-vivo dosimetry.

Implementation Readiness and Initial Effects of a Brief Mindfulness Audio Intervention Compared With a Brief Music Control During Daily Radiation Therapy for Prostate Cancer: A Randomized Pilot Study.

Background: The most common and debilitating side effects of radiation therapy (RT) for prostate cancer (PC) are fatigue, sleep disturbance, anxiety, and depression. Previous research has reported palliative benefits from certain self-management approaches, such as mindfulness meditation. Objective: To develop, pre-test, and evaluate the feasibility, acceptability and initial benefit of brief, audio-based mindfulness delivered during daily RT for PC compared to a relaxing music control. Methods: Following intervention development, participants were randomized to either brief guided mindfulness audio recordings or a relaxing music control during daily RT. A pre-testing phase was first conducted to determine optimal program start time, length, and content most associated with retention. A final program (n = 26) was delivered daily, starting on day one of week 2 of RT and lasting 4 consecutive weeks. Feasibility was defined as ≥70% on enrollment rate, retention, and audio program adherence. Acceptability was measured with a 12-item post-study survey. A secondary focus compared between group changes on patient reported outcomes of fatigue, anxiety, depression, sleep disturbance, and related outcomes at baseline and follow up assessments. Descriptive statistics and general linear models were used. Results: Overall, 76% (n = 38) of approached men enrolled. Pre-testing retention rates were <70% while the final program's retention rate was 89%. The majority of acceptability criteria were met in both conditions, with relatively higher ratings in the mindfulness arm. Compared to music controls, mindfulness participants demonstrated significantly less uncertainty intolerance at 4-weeks (P = .046, d = .95); and significantly lower fatigue scores (P = .049, d = 1.3) and lower sleep disturbance scores (P = .035, d = 1.1) at the 3 months follow up. Conclusion: The final intervention met feasibility and acceptability criteria. Pre-testing refinements played a key role for optimal program delivery and retention. Audio-based mindfulness delivered during RT for PC hold potential to help decrease RT-related physical and emotional side effects.

PTCOG Ocular Statement: Expert Summary of Current Practices and Future Developments in Ocular Proton Therapy.

Although rare cancers, ocular tumors are a threat to vision, quality of life, and potentially life expectancy of a patient. Ocular proton therapy (OPT) is a powerful tool for successfully treating this disease. The Particle Therapy Co-Operative Ocular Group) formulated an Evidence and Expert-Based Executive Summary of Current Practices and Future Developments in OPT: comparative dosimetric and clinical analysis with the different OPT systems is essential to set up planning guidelines, implement best practices, and establish benchmarks for eye preservation, vision, and quality of life measures. Contemporary prospective trials in select subsets of patients (eg, tumors near the optic disc and/or macula) may allow for dosimetric and clinical analysis between different radiation modalities and beamline systems to evaluate differences in radiation delivery and penumbra, and resultant tumor control, normal tissue complication rates, and overall clinical cost-effectiveness. To date, the combination of multimodal imaging (fundus photography, ultrasound, etc), ophthalmologist assessment, and clip surgery with radiation planning have been keys to successful treatment. Increased use of three-dimensional imaging (computed tomography/magnetic resonance imaging) is anticipated although its spatial resolution might be a limiting factor (eg, detection of flat diffuse tumor parts). Commercially produced ocular treatment-planning systems are under development and their future use is expected to expand across OPT centers. Future continuity of OPT will depend on the following: (1) maintaining and upgrading existing older dedicated low-energy facilities, (2) maintaining shared, degraded beamlines at large proton therapy centers, and (3) developing adapted gantry beams of sufficient quality to maintain the clinical benefits of sharp beam conformity. Option (1) potentially offers the sharpest beams, minimizing impact on healthy tissues, whereas (2) and (3) potentially offer the advantage of substantial long-term technical support and development as well as the introduction of new approaches. Significant patient throughputs and close cooperation between medical physics, ophthalmology, and radiation therapy, underpinned by mutual understanding, is crucial for a successful OPT service.

Mindfulness-Based Group Medical Visits: Strategies to Improve Equitable Access and Inclusion for Diverse Patients in Cancer Treatment.

Background: Mindfulness-based interventions (MBIs) are supported by clinical practice guidelines as effective non-pharmacologic interventions for common symptoms experienced by cancer patients, including anxiety, depression, and fatigue. However, the evidence predominately derives from White breast cancer survivors. Racial and ethnic minority patients have less access to integrative oncology care and worse cancer outcomes. To address these gaps, we designed and piloted a series of mindfulness-based group medical visits (MB-GMVs), embedded into comprehensive cancer care, for racially and ethnically diverse patients in cancer treatment. Methods: As a quality improvement project, we launched a telehealth MB-GMV series for patients undergoing cancer treatment, delivered as four weekly 2-hour visits billable to insurance. Content was concordant with evidence-based guidelines and established MBIs and adapted to improve cultural relevance and fit (eg, access-centered, trauma-informed, with inclusive communication practices). Program structure was adapted to address barriers to participation, with ≥50% slots per series reserved for racial and ethnic minority patients. Intake surveys incorporated a demographic questionnaire and symptom assessments. Evaluations were sent following the visits. Results: In our first ten cohorts (n = 78), 80% of referred patients enrolled. Participants were: 22% Asian, 14% Black, 17% Latino, 45% non-Latino White; 65% female; with a median age of 54 years (range 27-79); and 80% had metastatic cancer. Common baseline symptoms included lack of energy, difficulty sleeping, and worrying. Most patients (90%) attended ≥3 visits. On final evaluations, 87% patients rated the series as "excellent"; 81% "strongly agreed" that they liked the GMV format; and 92% would "definitely" recommend the series to others. Qualitative themes included empowerment and connectedness. Conclusion: Telehealth GMVs are a feasible, acceptable, and financially sustainable model for increasing access to MBIs. Diverse patients in active cancer treatment were able to participate and reported high levels of satisfaction with this series that was tailored to center health equity and inclusion.

Phase II TPDCV protocol for pediatric low-grade hypothalamic/chiasmatic gliomas: 15-year update.

To report long-term results for children with low-grade hypothalamic/chiasmatic gliomas treated on a phase II chemotherapy protocol. Between 1984 and 1992, 33 children with hypothalamic/chiasmatic LGGs received TPDCV chemotherapy on a phase II prospective trial. Median age was 3.0 years (range 0.3-16.2). Twelve patients (36%) underwent STRs, 14 (42%) biopsy only, and seven (21%) no surgery. Twenty patients (61%) had pathologic JPAs, nine (27%) grade II gliomas, and four (12%) no surgical sampling. Median f/u for surviving patients was 15.2 years (range 5.3-20.7); 20 of the 23 surviving patients had 14 or more years of follow-up. Fifteen-year PFS and OS were 23.4 and 71.2%, respectively. Twenty-five patients progressed, of whom 13 are NED, two are AWD, and 10 have died. All children who died were diagnosed and first treated at age three or younger. Age at diagnosis was significantly associated with relapse and survival (P = 0.004 for PFS and P = 0.037 for OS). No PFS or OS benefit was seen with STR versus biopsy/no sampling (P = 0.58 for PFS, P = 0.59 for OS). For patients with JPAs and WHO grade II tumors, the 15-year PFS was 18.8 and 22.2% (P = 0.95) and 15-year OS was 73.7 and 55.6% (P = 0.17), respectively. Upfront TPDCV for children with hypothalamic/chiasmatic LGGs resulted in 15-year OS of 71.2% and 15-year PFS of 23.4%. No survival benefit is demonstrated for greater extent of resection. Age is a significant prognostic factor for progression and survival.

Fundus image fusion in EYEPLAN software: an evaluation of a novel technique for ocular melanoma radiation treatment planning.

PURPOSE: The purpose of this study is to evaluate a novel approach for treatment planning using digital fundus image fusion in EYEPLAN for proton beam radiation therapy (PBRT) planning for ocular melanoma. The authors used a prototype version of EYEPLAN software, which allows for digital registration of high-resolution fundus photographs. The authors examined the improvement in tumor localization by replanning with the addition of fundus photo superimposition in patients with macular area tumors. METHODS: The new version of EYEPLAN (v3.05) software allows for the registration of fundus photographs as a background image. This is then used in conjunction with clinical examination, tantalum marker clips, surgeon's mapping, and ultrasound to draw the tumor contour accurately. In order to determine if the fundus image superimposition helps in tumor delineation and treatment planning, the authors identified 79 patients with choroidal melanoma in the macular location that were treated with PBRT. All patients were treated to a dose of 56 GyE in four fractions. The authors reviewed and replanned all 79 macular melanoma cases with superimposition of pretreatment and post-treatment fundus imaging in the new EYEPLAN software. For patients with no local failure, the authors analyzed whether fundus photograph fusion accurately depicted and confirmed tumor volumes as outlined in the original treatment plan. For patients with local failure, the authors determined whether the addition of the fundus photograph might have benefited in terms of more accurate tumor volume delineation. RESULTS: The mean follow-up of patients was 33.6 +/- 23 months. Tumor growth was seen in six eyes of the 79 macular lesions. All six patients were marginal failures or tumor miss in the region of dose fall-off, including one patient with both in-field recurrence as well as marginal. Among the six recurrences, three were managed by enucleation and one underwent retreatment with proton therapy. Three patients developed distant metastasis and all three patients have since died. The replanning of six patients with their original fundus photograph superimposed showed that in four cases, the treatment field adequately covered the tumor volume. In the other two patients, the overlaid fundus photographs indicated the area of marginal miss. The replanning with the fundus photograph showed improved tumor coverage in these two macular lesions. For the remaining patients without local failure, replanning with fundus photograph superimposition confirmed the tumor volume as drawn in the original treatment plan. CONCLUSIONS: Local control was excellent in patients receiving 56 GyE of PBRT for uveal melanomas in the macular region, which traditionally can be more difficult to control. Posterior lesions are better defined with the additional use of fundus image since they can be difficult to mark surgically. In one-third of treatment failing patients, the superposition of the fundus photograph would have clearly allowed improved localization of tumor. The current practice standard is to use the superimposition of the fundus photograph in addition to the surgeon's clinical and clip mapping of the tumor and ultrasound measurement to draw the tumor volume.

Oral isotretinoin and topical retinoid use in a series of young patients with ocular melanoma.

PURPOSE: To describe the first series of six young uveal melanoma (UM) patients with oral isotretinoin and/or topical retinoid therapy prior to diagnosis. OBSERVATIONS: The case series is based on clinical observations at our UM quaternary referral center. Six UM patient cases are reported, ages 16-44 years old. All had been using either oral (isotretinoin) and/or topical (tretinoin or tazarotene) retinoid treatment (3 months-~10 years) prior to or at the time of diagnosis (3 of 6 cases). All patients had ocular complaints on presentation, and the onset of certain symptoms corresponded with the course of retinoids. Other potential risk factors or relevant history included Caucasian background, cone-rod dystrophy and active smoker status (Case 2), family history of UM and pregnancy at time of diagnosis (Case 3), past smoking and possible secondary Chernobyl exposure as a baby (Case 5). All patients were treated with proton beam radiotherapy and currently have no sign of recurrent or metastatic disease. CONCLUSIONS AND IMPORTANCE: Retinoid therapy has been linked to various benign and/or reversible effects on the anterior and posterior eye, though pathophysiology remains not well understood. Uveal melanoma (UM) is a rare cancer diagnosis in young adults. We report here the first case series of young UM patients with a history of retinoid use and ocular complaints. No causal link is claimed and further systematic epidemiologic and biologic study of retinoid therapy and ocular impact may provide additional relevant data, particularly in young ocular melanoma patients.

Practice Considerations for Proton Beam Radiation Therapy of Uveal Melanoma During the Coronavirus Disease Pandemic: Particle Therapy Co-Operative Group Ocular Experience.

Uveal melanoma (UM) is a rare but life-threatening cancer of the eye. In light of the coronavirus disease (COVID-19) pandemic, hospitals and proton eye therapy facilities must analyze several factors to ensure appropriate treatment protocols for patients and provider teams. Practice considerations to limit COVID-19 transmission in the proton ocular treatment setting for UM are necessary. The Particle Therapy Co-Operative Group is the largest international community of particle/proton therapy providers. Participating experts have current or former affiliation with the member institutions of the Particle Therapy Co-Operative Group Ocular subcommittee with long-standing high-volume proton ocular programs. The practices reviewed in this document must be taken in conjunction with local hospital procedures, multidisciplinary recommendations, and regional/national guidelines, as each community may have its unique needs, supplies, and protocols. Importantly, as the pandemic evolves, so will the strategies and recommendations. Given the unique circumstances for UM patients, along with indications of potential ophthalmologic transmission as a result of health care providers working in close proximity to patients and intrinsic infectious risk from eyelashes, tears, and hair, practice strategies may be adapted to reduce the risk of viral transmission. Certainly, providers and health care systems will continue to examine and provide as safe and effective care as possible for patients in the current environment.

Ultrasonography and transillumination for uveal melanoma localisation in proton beam treatment planning.

BACKGROUND/OBJECTIVE: The success of proton beam treatment (PBT) in uveal melanoma depends in part on the accuracy of tumour localisation. This study determined if using ultrasonography (US) to measure the distance between tumour margin and tantalum ring (DTR) in PBT planning improves local treatment success when compared with using intraoperative transillumination (TI) alone. METHODS: Retrospective analysis of patients with uveal melanoma treated at one centre between January 2006 and June 2017 with ≥12-month follow-up (or until treatment failure). Local tumour control was compared among study groups based on methods for measuring DTR: Group 1 (TI alone), Group 2A (postoperative US alone) and Group 2B (combination). RESULTS: Fifty-four eyes (54 patients) with uveal melanomas were included: Group 1 (22 eyes, 41%), Group 2A (11 eyes, 20%) and Group 2B (21 eyes, 39%). Mean age at diagnosis was 64 years [median 66 years, range 23-86 years]. Fifty tumours (93%) involved the choroid, while four involved the ciliary body (7%). In Group 2B, PBT treatment was based on the DTR obtained using US; DTR differed between TI and US by ≥1 mm for 25 rings in 16 eyes and ≥2 mm for 12 rings in 7 eyes. Five-year Kaplan-Meier estimate revealed a difference in local treatment success between Groups 1 and 2, (0.82 vs. 1.0, p = 0.02) with no difference in overall survival estimate, (0.85 vs. 0.83, p = 0.8). CONCLUSIONS: US can be used to measure DTR in PBT planning for uveal melanoma. This may improve accuracy of tumour localisation and improve local treatment success.

Technical Note: Feasibility study of titanium markers in choroidal melanoma localization for proton beam radiation therapy.

PURPOSE: The purpose of this study is to explore the feasibility of the use of titanium fiducial markers to minimize the metallic artifact seen with tantalum markers which causes significant distortion on postoperative orbital CT scans. METHOD: We designed and constructed the titanium markers in the shop of Crocker Nuclear Laboratory, UC Davis, CA. The markers were placed on an eyeball phantom. The eyeball was inserted into the Rando phantom in the orbital space. The Rando phantom was imaged with coplanar x rays on Nucletron simulator at UCSF, on digital panel on the eye beam line at CNL eye treatment facility and on CT scanner at UCSF. RESULTS: The titanium markers can be clearly seen on the hard copy of x rays and on digital panel. The CT scan of an orbit using tantalum markers on the right eye and titanium markers on the left eye shows the metal artifact from tantalum markers. Titanium markers show very little distortion on CT images. CONCLUSION: The present study describes these markers and their relative benefit in comparison with tantalum marker, which has been used for localizing ocular tumor for decades.

Phase I/II Randomized Study of Proton Beam with Anti-Vascular Endothelial Growth Factor for Exudative Age-Related Macular Degeneration: One-Year Results.

OBJECTIVE: To assess the safety and efficacy of proton beam therapy (PBT) as an adjunct to intravitreal anti-vascular endothelial growth factor (VEGF) for the treatment of exudative age-related macular degeneration. DESIGN: Phase I/II, interventional, prospective, randomized, sham-controlled double-blinded study. PARTICIPANTS: Eyes with newly diagnosed exudative age-related macular degeneration with vision between 20/40 and 20/400 were included. Exclusion criteria included diabetes or other ocular comorbidities affecting vision. METHODS: Eyes were randomized to receive either 16 GyE, 24 GyE, or sham PBT. All eyes had 3 monthly intravitreal anti-VEGF treatments, followed by monthly visits with treatments as needed. MAIN OUTCOME MEASURES: Mean change in best-corrected visual acuity (BCVA), mean number of anti-VEGF injections, proportion of eyes with >15 letters BCVA decrease, proportion of eyes developing radiation retinopathy or papillopathy, proportion of eyes with cataract progression, and mean changes central retinal thickness on OCT and lesion size on angiography at 1 year. RESULTS: Of 30 enrolled eyes, 22 completed follow-up monthly for 12 months for analysis. The BCVA improved by a mean of 8 letters (0.48±0.36 logarithm of the minimum angle of resolution) overall from baseline. Overall, central retinal thickness decreased from 340±155 to 246±48 (P = 0.008) at 12 months. The mean change in BCVA and central retinal thickness was not different among the 3 study groups. The mean number of anti-VEGF injections at 12 months was 6.13 for sham irradiation arm, 5.52 in the 16 GyE arm, and 3.83 for the 24 GyE arm (P = 0.004 between sham and 24 GyE). No eye had severe visual loss, radiation retinopathy, or papillopathy. CONCLUSIONS: No safety issue was noted associated with combining 16 GyE or 24 GyE PBT with intravitreal anti-VEGF therapy in eyes with exudative age-related macular degeneration. Overall improvements in BCVA and imaging parameters were not affected by the addition of PBT, but the number of anti-VEGF treatments needed was significantly lower with the addition of 24 GyE PBT.

Temporal Evolution and Dose-Volume Histogram Predictors of Visual Acuity After Proton Beam Radiation Therapy of Uveal Melanoma.

PURPOSE: To perform an in-depth temporal analysis of visual acuity (VA) outcomes after proton beam radiation therapy (PBRT) in a large, uniformly treated cohort of uveal melanoma (UM) patients, to determine trends in VA evolution depending on pretreatment and temporally defined posttreatment VA measurements; and to investigate the relevance of specific patient, tumor and dose-volume parameters to posttreatment vision loss. METHODS AND MATERIALS: Uveal melanoma patients receiving PBRT were identified from a prospectively maintained database. Included patients (n=645) received 56 GyE in 4 fractions, had pretreatment best corrected VA (BCVA) in the affected eye of count fingers (CF) or better, with posttreatment VA assessment at specified post-PBRT time point(s). Patients were grouped according to the pretreatment BCVA into favorable (≥20/40) or unfavorable (20/50-20/400) and poor (CF) strata. Temporal analysis of BCVA changes was described, and univariate and forward stepwise multivariate logistic regression analyses were performed to identify predictors for VA loss. RESULTS: Median VA follow-up was 53 months (range, 3-213 months). At 60-month follow up, among evaluable treated eyes with favorable pretreatment BCVA, 45% retained BCVA ≥20/40, whereas among evaluable treated eyes with initially unfavorable/poor BCVA, 21% had vision ≥20/100. Among those with a favorable initial BCVA, attaining BCVA of ≥20/40 at any posttreatment time point was associated with subsequent maintenance of excellent BCVA. Multivariate analysis identified volume of the macula receiving 28GyE (P<.0001) and optic nerve (P=.0004) as independent dose-volume histogram predictors of 48-month post-PBRT vision loss among initially favorable treated eyes. CONCLUSIONS: Approximately half of PBRT-treated UM eyes with excellent pretreatment BCVA assessed at 5 years after treatment will retain excellent long-term vision. 28GyE macula and optic nerve dose-volume histogram parameters allow for rational treatment planning optimization that may lead to improved visual outcomes. The detailed temporal analysis with intermediate as well as long-term functional prognosis, and the relationship of outcomes with clinical and treatment planning parameters, is critical for informed care of UM patients before and after PBRT.

The role of up-front radiation therapy for incompletely resected pediatric WHO grade II low-grade gliomas.

The purpose of this study was to assess the impact of early radiation therapy and extent of surgical resection on progression-free survival (PFS) and overall survival (OS) in children with WHO grade II low-grade gliomas (LGGs). We conducted a historical cohort study of 90 patients, ages 21 or younger, diagnosed with WHO grade II LGGs between 1970 and 1995. Median follow-up for surviving patients was 9.4 years (range, 0.5-22.6 years). Tests for variables correlating with OS and PFS were conducted by using log-rank tests and Cox proportional hazards models. Eleven patients underwent gross total resections (GTRs), 43 had subtotal resections, and 34 underwent biopsy only at diagnosis. Two patients underwent biopsy at time of recurrence. Of the 90 patients, 52 received radiation as part of their initial therapy following diagnosis (early-RT group). The overall five-year PFS and OS rates +/- SE were 56% +/- 5% and 90% +/- 3%, respectively. Ten-year PFS and OS rates were 42% +/- 6% and 81% +/- 5%, respectively. For patients older than three years and without GTRs, administration of early radiation did not appear to influence PFS or OS (P = 0.98 and P = 0.40, respectively; log-rank test). This was confirmed by multivariate analyses (P = 0.95 and P = 0.33 for PFS and OS, respectively). Of the 11 patients with GTRs, disease progressed in only two, and all were alive with no evidence of disease at last follow-up. Patients who underwent GTRs had significantly longer PFS (P = 0.02), but did not have significantly improved OS. Excellent long-term survival rates were achieved for children with WHO grade II LGGs. We were unable to demonstrate a benefit for administering radiation as part of initial treatment. An outcome benefit was seen with greater extent of resection.

Proton therapy for the management of uveal melanoma and other ocular tumors.

Proton beam radiotherapy of uveal melanoma and other malignant and benign ocular tumors has shown tremendous development and success over the past four decades. Proton beam is associated with the lowest overall risk of local tumor recurrence in uveal melanoma, compared with other eye-conserving forms of primary treatment. Proton beam is also utilized for other malignant and benign tumors as primary, salvage, or adjuvant treatment with combined modality therapy. The physical characteristics of proton therapy allows for uniform dose distribution, minimal scatter, and sharp dose fall off making it an ideal therapy for ocular tumors in which critical structures lay in close proximity to the tumor. High radiation doses can be delivered to tumors with relative sparing of adjacent tissues from collateral damage. Proton beam therapy for ocular tumors has resulted in overall excellent chances for tumor control, ocular conservation, and visual preservation.

Practice Patterns Analysis of Ocular Proton Therapy Centers: The International OPTIC Survey.

PURPOSE: To assess the planning, treatment, and follow-up strategies worldwide in dedicated proton therapy ocular programs. METHODS AND MATERIALS: Ten centers from 7 countries completed a questionnaire survey with 109 queries on the eye treatment planning system (TPS), hardware/software equipment, image acquisition/registration, patient positioning, eye surveillance, beam delivery, quality assurance (QA), clinical management, and workflow. RESULTS: Worldwide, 28,891 eye patients were treated with protons at the 10 centers as of the end of 2014. Most centers treated a vast number of ocular patients (1729 to 6369). Three centers treated fewer than 200 ocular patients. Most commonly, the centers treated uveal melanoma (UM) and other primary ocular malignancies, benign ocular tumors, conjunctival lesions, choroidal metastases, and retinoblastomas. The UM dose fractionation was generally within a standard range, whereas dosing for other ocular conditions was not standardized. The majority (80%) of centers used in common a specific ocular TPS. Variability existed in imaging registration, with magnetic resonance imaging (MRI) rarely being used in routine planning (20%). Increased patient to full-time equivalent ratios were observed by higher accruing centers (P=.0161). Generally, ophthalmologists followed up the post-radiation therapy patients, though in 40% of centers radiation oncologists also followed up the patients. Seven centers had a prospective outcomes database. All centers used a cyclotron to accelerate protons with dedicated horizontal beam lines only. QA checks (range, modulation) varied substantially across centers. CONCLUSIONS: The first worldwide multi-institutional ophthalmic proton therapy survey of the clinical and technical approach shows areas of substantial overlap and areas of progress needed to achieve sustainable and systematic management. Future international efforts include research and development for imaging and planning software upgrades, increased use of MRI, development of clinical protocols, systematic patient-centered data acquisition, and publishing guidelines on QA, staffing, treatment, and follow-up parameters by dedicated ocular programs to ensure the highest level of care for ocular patients.

Long-term Results of the UCSF-LBNL Randomized Trial: Charged Particle With Helium Ion Versus Iodine-125 Plaque Therapy for Choroidal and Ciliary Body Melanoma.

PURPOSE: Relevant clinical data are needed given the increasing national interest in charged particle radiation therapy (CPT) programs. Here we report long-term outcomes from the only randomized, stratified trial comparing CPT with iodine-125 plaque therapy for choroidal and ciliary body melanoma. METHODS AND MATERIALS: From 1985 to 1991, 184 patients met eligibility criteria and were randomized to receive particle (86 patients) or plaque therapy (98 patients). Patients were stratified by tumor diameter, thickness, distance to disc/fovea, anterior extension, and visual acuity. Tumors close to the optic disc were included. Local tumor control, as well as eye preservation, metastases due to melanoma, and survival were evaluated. RESULTS: Median follow-up times for particle and plaque arm patients were 14.6 years and 12.3 years, respectively (P=.22), and for those alive at last follow-up, 18.5 and 16.5 years, respectively (P=.81). Local control (LC) for particle versus plaque treatment was 100% versus 84% at 5 years, and 98% versus 79% at 12 years, respectively (log rank: P=.0006). If patients with tumors close to the disc (<2 mm) were excluded, CPT still resulted in significantly improved LC: 100% versus 90% at 5 years and 98% versus 86% at 12 years, respectively (log rank: P=.048). Enucleation rate was lower after CPT: 11% versus 22% at 5 years and 17% versus 37% at 12 years, respectively (log rank: P=.01). Using Cox regression model, likelihood ratio test, treatment was the most important predictor of LC (P=.0002) and eye preservation (P=.01). CPT was a significant predictor of prolonged disease-free survival (log rank: P=.001). CONCLUSIONS: Particle therapy resulted in significantly improved local control, eye preservation, and disease-free survival as confirmed by long-term outcomes from the only randomized study available to date comparing radiation modalities in choroidal and ciliary body melanoma.

Uveal melanoma gene expression profile test result provided for uveal metastasis.

The DecisionDx-UM gene expression profiling test is an accurate, popular, and technically simple method for obtaining prognostic information from uveal melanoma tissue. However, this test does not provide diagnostic information and may errantly provide prognostication results for lesions other than uveal melanoma. A 73-year-old woman presented with a uveal metastasis from lung adenocarcinoma, which was misdiagnosed as uveal melanoma. DecisionDx-UM gene expression profiling was performed on tissue obtained from a needle biopsy. A test result was provided regarding the lesion's metastatic potential even though it was not a uveal melanoma.

Risk factors for neovascular glaucoma after proton beam therapy of uveal melanoma: a detailed analysis of tumor and dose-volume parameters.

PURPOSE: To determine neovascular glaucoma (NVG) incidence and identify contributing tumor and dosing factors in uveal melanoma patients treated with proton beam radiation therapy (PBRT). METHODS AND MATERIALS: A total of 704 PBRT patients treated by a single surgeon (DHC) for uveal melanoma (1996-2010) were reviewed for NVG in our prospectively maintained database. All patients received 56 GyE in 4 fractions. Median follow-up was 58.3 months. Analyses included the Kaplan-Meier method to estimate NVG distributions, univariate log-rank tests, and Cox's proportional hazards multivariate analysis using likelihood ratio tests to identify independent risk factors of NVG among patient, tumor, and dose-volume histogram parameters. RESULTS: The 5-year PBRT NVG rate was 12.7% (95% confidence interval [CI] 10.2%-15.9%). The 5-year rate of enucleation due to NVG was 4.9% (95% CI 3.4%-7.2%). Univariately, the NVG rate increased significantly with larger tumor diameter (P<.0001), greater height (P<.0001), higher T stage (P<.0001), and closer proximity to the disc (P=.002). Dose-volume histogram analysis revealed that if >30% of the lens or ciliary body received ≥50% dose (≥28 GyE), there was a higher probability of NVG (P<.0001 for both). Furthermore, if 100% of the disc or macula received ≥28 GyE, the NVG rate was higher (P<.0001 and P=.03, respectively). If both anterior and posterior doses were above specified cut points, NVG risk was highest (P<.0001). Multivariate analysis confirmed significant independent risk factors to include tumor height (P<.0001), age (P<.0001), %disc treated to ≥50% Dose (<100% vs 100%) (P=.0007), larger tumor diameter (P=.01), %lens treated to ≥90% Dose (0 vs >0%-30% vs >30%) (P=.01), and optic nerve length treated to ≥90% Dose (≤1 mm vs >1 mm) (P=.02). CONCLUSIONS: Our current PBRT patients experience a low rate of NVG and resultant enucleation compared with historical data. The present analysis shows that tumor height, diameter, and anterior as well as posterior critical structure dose-volume parameters may be used to predict NVG risk.