Clinical management of uveal melanoma: a comprehensive review with a treatment algorithm

Uveal melanoma (UM), the most frequently occurring non-cutaneous melanoma and most common primary intraocular malignancy in adults, arises from the melanocytes of the choroid in approximately 95% of cases. Prompt diagnosis and treatment is vital as primary tumor size is one of the key factors associated with survival. Despite recent advances in management, more than half of the patients develop metastatic disease which portends poor survival. Currently, treatment options for UM include local resection, enucleation, plaque brachytherapy, and/or particle beam radiotherapy (RT). Enucleation was initially the standard of care in the management of UM, but a shift towards eye-preserving therapeutic choices such as RT and local resection has been noted in recent decades. Plaque brachytherapy, a form of localized RT, is the most popular option and is now the preferred treatment modality for UM. In this review we discuss the etiopathogenesis, clinical presentation and diagnosis of UM and place a special emphasis on therapeutic options. Furthermore, we review the current literature on UM management and propose a functional treatment algorithm for non-metastatic disease.

Management of symptomatic radiation necrosis after stereotactic radiosurgery and clinical factors for treatment response

Purpose@#Approximately 10% of patients who received brain stereotactic radiosurgery (SRS) develop symptomatic radiation necrosis (RN). We sought to determine the effectiveness of treatment options for symptomatic RN, based on patient-reported outcomes. @*Materials and Methods@#We conducted a retrospective review of 217 patients with 414 brain metastases treated with SRS from 2009 to 2018 at our institution. Symptomatic RN was determined by appearance on serial magnetic resonance images (MRIs), MR spectroscopy, requirement of therapy, and development of new neurological complaints without evidence of disease progression. Therapeutic interventions for symptomatic RN included corticosteroids, bevacizumab and/or surgical resection. Patient-reported therapeutic outcomes were graded as complete response (CR), partial response (PR), and no response. @*Results@#Twenty-six patients experienced symptomatic RN after treatment of 50 separate lesions. The mean prescription dose was 22 Gy (range, 15 to 30 Gy) in 1 to 5 fractions (median, 1 fraction). Of the 12 patients managed with corticosteroids, 6 patients (50%) reported CR and 4 patients (33%) PR. Of the 6 patients managed with bevacizumab, 3 patients (50%) reported CR and 1 patient (18%) PR. Of the 8 patients treated with surgical resection, all reported CR (100%). Other than surgical resection, age ≥54 years (median, 54 years; range, 35 to 81 years) was associated with CR (odds ratio = 8.40; 95% confidence interval, 1.27–15.39; p = 0.027). @*Conclusion@#Corticosteroids and bevacizumab are commonly utilized treatment modalities with excellent response rate. Our results suggest that patient’s age is associated with response rate and could help guide treatment decisions for unresectable symptomatic RN.

Daily localization of partial breast irradiation patients with three-dimensional ultrasound imaging

PURPOSE: Accurate localization of the lumpectomy cavity during accelerated partial breast radiation (APBR) is essential for daily setup to ensure the prescribed dose encompasses the target and avoids unnecessary irradiation to surrounding normal tissues. Three-dimensional ultrasound (3D-US) allows direct visualization of the lumpectomy cavity without additional radiation exposure. The purpose of this study was to evaluate the feasibility of 3D-US in daily target localization for APBR.MATERIALS AND METHODS: Forty-seven patients with stage I breast cancer who underwent breast conserving surgery were treated with a 2-week course of APBR. Patients with visible lumpectomy cavities on high quality 3D-US images were included in this analysis. Prior to each treatment, X-ray and 3D-US images were acquired and compared to images from simulation to confirm accurate position and determine shifts. Volume change of the lumpectomy cavity was determined daily with 3D-US.RESULTS: A total of 118 images of each modality from 12 eligible patients were analyzed. The average change in cavity volume was 7.8% (range, -24.1% to 14.4%) on 3D-US from simulation to the end-of-treatment. Based on 3D-US, significantly larger shifts were necessary compared to portal films in all three dimensions: anterior/posterior (p = 7E-11), left/right (p = 0.002), and superior/inferior (p = 0.004).CONCLUSION: Given that the lumpectomy cavity is not directly visible via X-ray images, accurate positioning may not be fully achieved by X-ray images. Therefore, when the lumpectomy cavity is visible on US, 3D-US can be considered as an alternative to X-ray imaging during daily positioning for selected patients treated with APBR, thus avoiding additional exposure to ionizing radiation.

Evaluation of response to stereotactic radiosurgery in patients with radioresistant brain metastases

PURPOSE: Renal cell carcinoma (RCC) and melanoma have been considered ‘radioresistant’ due to the fact that they do not respond to conventionally fractionated radiation therapy. Stereotactic radiosurgery (SRS) provides high-dose radiation to a defined target volume and a limited number of studies have suggested the potential effectiveness of SRS in radioresistant histologies. We sought to determine the effectiveness of SRS for the treatment of patients with radioresistant brain metastases.MATERIALS AND METHODS: We performed a retrospective review of our institutional database to identify patients with RCC or melanoma brain metastases treated with SRS. Treatment response were determined in accordance with the Response Evaluation Criteria in Solid Tumors.RESULTS: We identified 53 radioresistant brain metastases (28% RCC and 72% melanoma) treated in 18 patients. The mean target volume and coverage was 6.2 ± 9.5 mL and 95.5% ± 2.9%, respectively. The mean prescription dose was 20 ± 4.9 Gy. Forty lesions (75%) demonstrated a complete/partial response and 13 lesions (24%) with progressive/stable disease. Smaller target volume (p < 0.001), larger SRS dose (p < 0.001), and coverage (p = 0.008) were found to be positive predictors of complete response to SRS.CONCLUSION: SRS is an effective management option with up to 75% response rate for radioresistant brain metastases. Tumor volume and radiation dose are predictors of response and can be used to guide the decision-making for patients with radioresistant brain metastases.

Long-term cosmesis following a novel schedule of accelerated partial breast radiation in selected early stage breast cancer: result of a prospective clinical trial

PURPOSE: There is controversy regarding the cosmetic outcome after accelerated partial breast radiation (APBR). We report the cosmetic outcome from a single-arm prospective clinical trial of APBR delivered using intensity-modulated radiation therapy (IMRT) in elderly patients with stage I breast cancer (BC), using a novel fractionation schedule. MATERIALS AND METHODS: Forty-two patients aged ≥65, with Stage I BC who underwent breast-conserving surgery were enrolled in a phase I/II study evaluating a 2-week course of APBR. Thirty eligible patients received 40 Gy in 4 Gy daily fractions. Cosmetic outcome was assessed subjectively by physician/patient and objectively by using a computer program (BCCT.core) before APBR, during, and after completion of the treatment. RESULTS: The median age was 72 years, the median tumor size was 0.8 cm, and the median follow-up was 50.5 months. The 5-year locoregional control in this cohort was 97% and overall survival 87%. At the last follow-up, patients and physicians rated cosmesis as ‘excellent’ or ‘good’ in 100% and 91 %, respectively. The BCCT.core program scored the cosmesis as ‘excellent’ or ‘good’ in 87% of the patients at baseline and 81% at the last follow-up. The median V50 (20 Gy) of the whole breast volume (WBV) was 37.2%, with the median WBV V100 (40 Gy) of 10.9%. CONCLUSION: An excellent rate of tumor control was observed in this prospective trial. By using multiple assessment techniques, we are showing acceptable cosmesis, supporting the use of IMRT planned APBR with daily schedule in elderly patients with early stage BC.

A novel schedule of accelerated partial breast radiation using intensity-modulated radiation therapy in elderly patients: survival and toxicity analysis of a prospective clinical trial

PURPOSE: Several accelerated partial breast radiation (APBR) techniques have been investigated in patients with early-stage breast cancer (BC); however, the optimal treatment delivery techniques remain unclear. We evaluated the feasibility and toxicity of APBR delivered using intensity-modulated radiation therapy (IMRT) in elderly patients with stage I BC, using a novel fractionation schedule. MATERIALS AND METHODS: Forty-two patients aged ≥65 years, with stage I BC who underwent breast conserving surgery were enrolled in a phase I/II study evaluating APBR using IMRT. Forty eligible patients received 40 Gy in 4 Gy daily fractions. Patients were assessed for treatment related toxicities, and cosmesis, before APBR, during, and after completion of the treatment. RESULTS: The median age was 73 years, median tumor size 0.8 cm and the median follow-up was 54 months. The 5-year locoregional control was 97.5% and overall survival 90%. Erythema and skin pigmentation was the most common acute adverse event, reported by 27 patients (69%). Twenty-six patients (65%) reported mild pain, rated 1-4/10. This improved at last follow-up to only 2 (15%). Overall the patient and physician reported worst late toxicities were lower than the baseline and at last follow-up, patients and physicians rated cosmesis as excellent/good in 93% and 86 %, respectively. CONCLUSION: In this prospective trial, we observed an excellent rate of tumor control with daily APBR. The acceptable toxicity profile and cosmetic results of this study support the use of IMRT planned APBR with daily schedule in elderly patients with early stage BC.