Factors Associated with Hemorrhage of Melanoma Brain Metastases after Stereotactic Radiosurgery in the Era of Targeted/Immune Checkpoint Inhibitor Therapies

We aimed to evaluate the factors associated with hemorrhage (HA) of melanoma brain metastases (MBM) after Cyberknife stereotactic radiosurgery (SRS) in the modern era of systemic therapy. A total of 55 patients with 279 MBM were treated in 93 fractions. The median age, SRS dose, radiological follow-up, and time to HA were 60.4 years, 20 Gy, 17.7 months, and 10.7 months, respectively. Radiologically evident HA was documented in 47 (16.8%) metastases. Of the 55 patients, 25 (45.4%) suffered an HA. Among those, HA caused grade 3 toxicity in 10 patients (40%) and grade 1 symptoms in 5 patients (20%). Ten patients (40%) with HA experienced no toxicity. Logistic regression revealed the use of anticoagulants and the administration of systemic therapy within 7/15 days from SRS to be predictive for HA. When considering the HA causing grade 3 symptomatology, only the use of anticoagulants was significant, with the delivery of whole brain radiation therapy (WBRT) before the HA narrowly missing statistical significance. Our retrospective analysis showed that the administration of modern systemic therapy within 7/15 days from SRS may contribute to HA of MBM, though it appears safe, at least concerning grade 3 toxicity. The use of anticoagulants by the time of SRS significantly increased the risk of HA

High-dose-rate brachytherapy as monotherapy for low- and intermediate-risk prostate cancer. Oncological outcomes after a median 15-year follow-up

Introduction: To evaluate the oncological outcome of high dose rate (HDR) brachytherapy (BRT) as monotherapy for clinically localised prostate cancer (PCA). Material and Methods: Between January 2002 and February 2004, 141 consecutive patients with clinically localised PCA were treated with HDR-BRT monotherapy. The cohort comprised 103 (73%) low-, 32 (22.7%) intermediate- and 6 (4.3%) high risk patients according to D’Amico classification or 104 (73.8%) low-, 24 (17.0%) intermediate favourable-, 12 (8.5%) intermediate unfavourable- and one (0.7%) very high risk patient according to National Comprehensive Cancer Network (NCCN) one. Patients received four fractions of 9.5 Gy delivered within a single implant up to a total physical dose of 38 Gy. Catheter-implantation was transrectal ultrasound-based whereas treatment planning CT-based. Thirty-three patients (23.4%) received ADT neoadjuvantly and continued concurrently with BRT. Biochemical relapse-free survival (BRFS) was defined according to the Phoenix Consensus Criteria and genitourinary (GU)/gastrointestinal (GI) toxicity evaluated using the Common Toxicity Criteria for Adverse Events version 5.0. Results: Median age at treatment and median follow-up time was 67.2 and 15.2 years, respectively. Twenty-three (16.3%) patients experienced a biochemical relapse and 5 (3.5%) developed distant metastases, with only one patient dying of PCA. The BRFS was 85.1% at 15 years and 78.7% at 18 years. The corresponding overall survival, metastases-free survival, and prostate cancer specific mortality at 15- and 18-years was 73.9%/59.1%, 98.3%/90.6%, and 100%/98.5% respectively. Late grade 3 GI and GU toxicity was 4.2% and 5.6% respectively. Erectile dysfunction grade 3 was reported by 27 (19%) patients. From the prognostic factors evaluated, tumor stage (≤T2b compared to ≥T2c) along with the risk group (low-intermediate vs. high) when using the D’Amico classification but not when the NCCN one was taken into account, correlated significantly with BRFS. Conclusion: Our long-term results confirm HDR-BRT to be a safe and effective monotherapeutic treatment modality for low- and intermediate risk PCA

CT-Guided Interstitial HDR-Brachytherapy for Recurrent Glioblastoma Multiforme: A 20-Year Single-Institute Experience

PURPOSE: To report our results of computed tomography-guided interstitial high-dose-rate (HDR) brachytherapy (BRT) in the treatment of patients with recurrent inoperable glioblastoma multiforme (GBM). PATIENTS AND METHODS: Between 1995 and 2014, 135 patients were treated with interstitial HDR BRT for inoperable recurrent GBM located within previously irradiated volumes. Patient\u27s median age was 57.1 years (14-82 years). All patients were pretreated with surgery, postoperative external beam radiation therapy (EBRT) and systemic chemotherapy (ChT). The median recurrent tumor volume was 42cm(3) (2-207cm(3)). The prescribed HDR dose was median 40Gy (30-50Gy) delivered in twice-daily fractions of 5.0Gy over consecutive days. No repeat surgery or ChT was administered in conjunction with BRT. Survival from BRT, progression-free survival (PFS), toxicity as well as the impact of several prognostic factors were evaluated. RESULTS: At a median follow-up of 9.2 months, the median overall survival following BRT and the median PFS were 9.2 and 4.6 months, respectively. Of the prognostic variables evaluated in univariate analysis, extent of surgery at initial diagnosis, tumor volume at recurrence, as well as time from EBRT to BRT reached statistical significance, retained also in multivariate analysis. Eight patients (5.9%) developed treatment-associated complications including intracerebral bleeding in 4 patients (2.9%), symptomatic focal radionecrosis in 3 patients (2.2%), and severe convulsion in 1 patient (0.7%). CONCLUSIONS: For patients with recurrent GBM, interstitial HDR BRT is an effective re-irradiation method for even larger tumors providing palliation without excessive toxicity

Serum oxidized low-density lipoprotein is inversely correlated to telomerase activity in peripheral blood mononuclear cells of haemodialysis patients

Background. Telomerase preserves telomeres’ function and structure preventing cellular senescence. Its activity is reduced in peripheral blood mononuclear cells (PBMC) of haemodialysis (HD) patients. The purpose of this study is to investigate the potential correlation between increased oxidative stress/inflammation and telomerase activity in PBMC of HD patients. Methods: Telomerase activity was measured by PCR-ELISA in PBMC isolated from a group of 42 HD patients and 39 subjects with estimated glomerular filtration rate >= 80 mL/min (control group). Serum oxidized low-density lipoprotein (ox-LDL), tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) were also measured in both groups by ELISA. Results: Ox-LDL was negatively correlated to percentage telomerase activity in PBMC (r = -0.506, P = 0.000 in the whole group of 81 HD and normal subjects and r = -0.559, P < 0.001 in HD patients). TNF was also inversely associated with percentage telomerase activity in the whole group studied (r= -0.492, P= 0.000) while IL-10 was not. In stepwise multiple linear regression, taking into consideration the most important characteristics of the HD patients and control group, the only significant predictors for percentage telomerase activity in PBMC were ox-LDL and TNF (beta = -0.421, t= -4.083, P= 0.000 and beta= -0.381, t= -3.691, P= 0.000, respectively) while examining separately HD patients, the predictors for the same parameter were ox-LDL and HD duration (beta = -0.671, t = -4.709, P = 0.000 and beta= -0.349, t = -2.447, P = 0.023, respectively). Conclusion: Ox-LDL serum level is inversely correlated to telomerase activity in PBMC of HD patients. Our study proposes a new consequence of increased oxidative stress in HD patients: the premature cellular senescence potentially related to atherosclerosis through LDL oxidation