The role of cesium-131 brachytherapy in brain tumors: a scoping review of the literature and ongoing clinical trials.

PURPOSE: Cesium-131 radioactive isotope has favored the resurgence of intracavitary brachytherapy in neuro-oncology, minimizing radiation-induced complications and maximizing logistical and clinical outcomes. We reviewed the literature on cesium-131 brachytherapy for brain tumors. METHODS: PubMed, Web-of-Science, Scopus, Clinicaltrial.gov, and Cochrane were searched following the PRISMA extension for scoping reviews to include published studies and ongoing trials reporting cesium-131 brachytherapy for brain tumors. RESULTS: We included 27 published studies comprising 279 patients with 293 lesions, and 3 ongoing trials. Most patients had brain metastases (63.1%), followed by high-grade gliomas (23.3%), of WHO Grade III (15.2%) and Grade IV (84.8%), and meningiomas (13.6%), mostly of WHO Grade II (62.8%) and Grade III (27.9%). Most brain metastases were newly diagnosed (72.3%), while most gliomas and meningiomas were recurrent (95.4% and 88.4%). Patients underwent gross-total (91.1%) or subtotal (8.9%) resection, with median postoperative cavity size of 3.5 cm (range 1-5.8 cm). A median of 20, 28, and 16 seeds were implanted in gliomas, meningiomas, and brain metastases, with median seed activity of 3.8 mCi (range 2.4-5 mCi). Median follow-up was 16.2 months (range 0.6-72 months). 1-year freedom from progression rates were local 94% (range 57-100%), regional 85.1% (range 55.6-93.8%), and distant 53.5% (range 26.3-67.4%). Post-treatment radiation necrosis, seizure, and surgical wound infection occurred in 3.4%, 4.7%, and 4.3% patients. CONCLUSION: Initial data suggest that cesium-131 brachytherapy is safe and effective in primary or metastatic malignant brain tumors. Ongoing trials are evaluating long-term locoregional tumor control and future studies should analyze its role in multimodal systemic tumor management.

Analysis of Outcomes in Patients With BRCA1/2 Breast Cancer Mutations Treated With Accelerated Partial Breast Irradiation (APBI).

OBJECTIVE: To analyze outcomes and survival for BRCA1/2+ patients treated with accelerated partial breast irradiation (APBI). MATERIALS AND METHODS: Retrospective review was performed on 341 women treated with intracavitary APBI (Mammosite or Contura) postlumpectomy from 2002 to 2013. Patients were treated to 34.0 Gy in 10 BID fractions. Of 341 treated patients, 11 (3.2%) had BRCA1/2 mutations, 5 of whom had an oophorectomy. Ipsilateral breast tumor recurrence (IBTR), contralateral breast tumor recurrence (CBTR), and breast tumor recurrence progression-free survival were analyzed using SPSS-17. BRCA1/2+ patient outcomes were compared with a general population treated cohort. RESULTS: Median age at diagnosis was 66 years, for BRCA1/2+ women it was 61 years. Median follow-up was 8.4 years and for BRCA1/2+ patients it was 8.8 years. IBTR for the entire cohort was 3.5%, while CBTR was 1.2%. Both IBTR and CBTR for the BRCA1/2+ group were 0%. The 5-year IBTR-free survival was 97.3% (95% confidence interval [CI]=94.9%, 98.6%), and the CBTR-free survival was 99.4% (95% CI=97.6%, 99.9%). The 5-year breast tumor recurrence-free survival was 96.7% (95% CI=94.1%, 98.2%). As no patients with BRCA1/2+ mutation died of metastatic breast cancer or recurrence during follow-up and review, overall survival could not be evaluated. CONCLUSIONS: To date, BRCA1/2+ patients treated with APBI sustained no recurrences, or second cancers. Most patients had an ER+ status and underwent oophorectomy, which may be a protective mechanism for recurrence. This is the first outcomes report in the literature of BRCA1/2 mutations treated with APBI technique.

Prostate-specific membrane antigen expression in tumor-associated vasculature of breast cancers.

Prostate-specific membrane antigen (PSMA) has been found to be expressed in the tumor-associated neovasculature of multiple solid tumor types including breast cancers. However, thus far, the number of cases studied from some tumor types has been limited. In this study, we set out to assess PSMA expression in the tumor-associated vasculature associated with invasive breast carcinomas in a sizable cohort of patients. One hundred and six patients with AJCC stage 0-IV breast cancer were identified. Ninety-two of these patients had primary breast cancer [invasive breast carcinoma with or without co-existing ductal carcinoma in situ (DCIS) (74) or DCIS alone (18)]. In addition, 14 patients with breast cancer metastases to the brain were identified. Immunohistochemical staining for PSMA and CD31 was performed on parallel representative tumor sections in each case. Tumor-associated vascular endothelial cell PSMA immunoreactivity was semi-quantitatively assessed based on two parameters: overall percent of endothelial positivity and staining intensity. PSMA expression for tumor-associated vascular endothelial cells was scored 0 if there was no detectable PSMA expression, 1 if PSMA staining was detectable in 5-50%, and 2 if PSMA expression was positive in >50% of microvessels. CD 31 staining was concurrently reviewed to confirm the presence of vasculature in each case. Tumor-associated vasculature was PSMA-positive in 68/92 (74%) of primary breast cancers and in 14/14 (100%) of breast cancers metastatic to brain. PSMA was not detected in normal breast tissue or carcinoma cells. All but 2 cases (98%) showed absence of PSMA expression in normal breast tissue-associated vasculature. The 10-year overall survival was 88.7% (95% CI = 80.0%, 93.8%) in patients without brain metastases. When overall survival (OS) was stratified based on PSMA score group, patients with PSMA scores of 0, 1, and 2 had 10-year OS of 95.8%, 96.0%, and 79.7%, respectively (p = 0.12). When PSMA scores of 0 and 1 were compared with 2, there was a statistically significant difference in OS (96.0% vs 79.7%, respectively, p = 0.05). Patients with a PSMA score of 2 had a significantly higher median tumor size compared with patients in the lower PSMA score groups (p = 0.04). Patients with higher nuclear grade were more likely to have a PSMA score of 2 compared with patients with lower nuclear grade (p < 0.0001). Patients with a PSMA score of 2 had a significantly higher median Ki-67 proliferation index compared with patients in the lower PSMA score groups (p < 0.0001). Patients with estrogen receptor (ER)-negative tumors were more likely to have a PSMA score of 2 compared with patients with ER-positive tumors (p < 0.0001). Patients with progesterone receptor (PR)-negative tumors were more likely to have a PSMA score of 2 compared with patients with PR-positive tumors (p = 0.03). No significant association was observed between PSMA score group status and lymph node involvement (p = 0.95). Too little variability was present in Human epidermal growth factor receptor-2 (Her2/neu) amplified tumors to correlate with PSMA score group status. To date, this is the first detailed assessment of PSMA expression in the tumor-associated vasculature of primary and metastatic breast carcinomas. Further studies are needed to evaluate whether PSMA has diagnostic and/or potential therapeutic value.

Assessment of pain as a sequela in patients treated with intracavitary brachytherapy accelerated partial breast irradiation (IBAPBI): preliminary results of a prospective study.

To assess pain rates and relationship to radiation-induced fibrosis (RIF) in patients treated with intracavitary brachytherapy accelerated partial breast irradiation (IBAPBI). Thirty-nine patients treated with IBAPBI were assessed prospectively for development of pain pretreatment, 1 month post-IBAPBI, and every 6 months thereafter. A qualitative subjective Late Effects of Normal Tissue-Subjective Objective Management Analytical (LENT-SOMA) questionnaire assessed pain. Use of pain medications was assessed as "no", "sometimes", or "regularly". A quantitative objective validated pressure threshold (PTH) measured pain in the site of IBAPBI breast (index) and its mirror-image in the nonirradiated breast (control). A validated tissue compliance meter (TCM) quantitatively assessed RIF in the index and control breasts at all time points. Mean ΔPTH(kg) and ΔTCM(mm) values reflected mean difference between the index and control breasts. Median follow-up is 44 months (range 5-59 months). According to LENT-SOMA, pain occurred in 89% at 1 and 24 months, 67% at 30 months, 30% at 36 months, 29% at 40 months, and 20% at 48 months. No patient used pain medication "regularly" but the use "sometimes" decreased over time: 61% at 1 month, 42% at 18 and 24 months, 13% at 36 months, and 10% at 40 months. Mean ΔPTH values, compared to Δ0 kg at baseline, peaked in absolute value by 1 month to -1.36 kg (p < 0.0001), persisted after 18 months at -0.99 kg (p < 0.0001) and 24 months at -0.73 kg (p < 0.0001), and returned to nearly baseline by 40 months at -0.11 kg (p < 0.57). Mean ΔPTH and ΔTCM correlated significantly with subjective patient reports of pain at each time point (p < 0.0001). To date, this is the first report to prospectively assess pain employing quantitative and qualitative inventories in patients treated with IBAPBI. Pain is experienced in the majority of patients experienced pain within the first 2 years, sometimes requiring a medication, and though subsides, it may persist 4 years after IBAPBI.