Search

Purpose: SBRT-Spanish Group-05 (ClinicalTrials.gov.Identifier: NCT02192788) is a collaborative (SBRT-SG, Grupo de Investigación Clínica en Oncología Radioterápica, and Sociedad Española de Oncología Radioterápica) prospective multicenter phase II trial testing stereotactic body radiation therapy (SBRT) and androgen deprivation therapy (ADT) in patients with oligorecurrent prostate cancer., Methods and Materials: Two cohorts of patients with prostate cancer in an oligorecurrent stage (hormone-sensitive in the principal cohort and castration-resistant in the exploratory cohort) were assigned to receive ADT and SBRT for at least 24 months from the time of the enrollment. Concomitant treatment with chemotherapy, abiraterone, or enzalutamide was not allowed. Oncologic outcomes were assessed in both cohorts. Toxicity was prospectively analyzed., Results: From 2014 to 2019, 81 patients with a total of 126 lesions from 14 centers met the inclusion criteria, 14 of whom were castration-resistant. With a median follow-up of 40 months (12-58 months), 3-year local recurrence-free survival was 92.5% (95% CI, 79.9%-96.3%) and 85.7% (95% CI, 48.2%-95.6%) in the principal and exploratory cohorts, respectively. In the principal cohort, biochemical relapse-free survival and metastasis progression-free survival at 1, 2, and 3 years were 91% (95% CI, 81%-95.8%), 73.7% (95% CI, 61.1%-82.8%), 50.6% (95% CI, 36.2%-63.3%), and 92% (95% CI, 83%-97%), 81% (95% CI, 70%-89%), and 67% (95% CI, 53%-77%), respectively. In the exploratory cohort, metastasis progression-free survival at 1, 2, and 3 years was 64% (95% CI, 34%-83%), 43% (95% CI, 18%-66%), and 26% (95% CI, 7%-51%), respectively. None of the patients developed grade III or higher toxicity or symptoms related to local progression, and only 2 (2.4%) patients developed grade II toxicity., Conclusions: The combination of SBRT and ADT is safe and shows favorable clinical outcomes in patients with hormone-sensitive and castration-resistant prostate cancer. Validation studies are needed in patients with castration-resistant prostate cancer., (Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: Most monotherapies available against glioblastoma multiforme (GBM) target individual hallmarks of this aggressive brain tumor with minimal success. In this article, we propose a therapeutic strategy using coenzyme Q 10  (CoQ 10 ) as a pleiotropic factor that crosses the blood-brain barrier and accumulates in cell membranes acting as an antioxidant, and in mitochondrial membranes as a regulator of cell bioenergetics and gene expression., Methods: Xenografts of U251 cells in nu/nu mice were used to assay tumor growth, hypoxia, angiogenesis, and inflammation. An orthotopic model was used to explore microglial infiltration, tumor growth, and invasion into the brain parenchyma. Cell proliferation, migration, invasion, proteome remodeling, and secretome were assayed in vitro. Conditioned media were used to assay angiogenesis, monocyte chemoattraction, and differentiation into macrophages in vitro., Results: CoQ 10  treatment decreased tumor volume in xenografts and orthotopic models, although its effect on tumor cell proliferation was not direct. Tumors from mice treated with CoQ 10  were less hypoxic and vascularized, having less infiltration from inflammatory cells. Treatment-induced downregulation of HIF-1α and NF-kB led to a complete remodeling of the tumor cells proteome and secretome, impacting angiogenesis, monocyte infiltration, and their differentiation into macrophages. Besides, tumor cell migration and invasion were drastically restricted by mechanisms involving modulation of the actin cytoskeleton and downregulation of matrix metalloproteases (MMPs)., Conclusions: CoQ 10  has a pleiotropic effect on GBM growth, targeting several hallmarks simultaneously. Thus, its integration into current treatments of this fatal disease should be considered., (© 2022. The Author(s).)

Objective: To investigate precision radiation therapy for metastatic spinal cord compression and compare it to conventional radiation therapy., Methods and Materials: In a multicenter phase 2 study, 40 patients received 5 Gy × 5 fractions of precision radiation therapy (38 volume modulated arc therapy, 2 intensity modulated radiation therapy) for metastatic spinal cord compression and were evaluated for local progression-free survival (LPFS), motor function, ambulatory status, sensory function, sphincter dysfunction, pain, distress, overall survival (OS), and toxicity. Maximum spinal cord dose was 101.5% (myelopathy risk, <0.03%) of the prescription dose. Patients were compared with a historical control group conventionally irradiated with 4 Gy × 5 fractions (propensity score analysis). The equivalent dose in 2 Gy-fractions of 5 Gy × 5 fractions is similar to 3 Gy × 10 fractions, which results in better LPFS than 4 Gy × 5 fractions. It was assumed that 5 Gy × 5 fractions is also superior to 4 Gy × 5 fractions for LPFS. (ClinicalTrials.gov-identifier: NCT03070431) RESULTS: Six-month rates of LPFS and OS were 95.0% and 42.6%, respectively. Improvement of motor function occurred in 24 patients (60%). Thirty-three patients (82.5%) were ambulatory after radiation therapy. Eight of 16 patients (50.0%) with sensory deficits improved. Pain and distress relief were reported by 61.9% and 54.2% of patients 1 month after radiation therapy. Grade 3 toxicities occurred in 1 patient and grade 2 toxicities in another 3 patients. Of the control group, 664 patients qualified for the propensity score analysis; 5 Gy × 5 fractions was significantly superior to 4 Gy × 5 fractions with regard to LPFS (P = .026) but not motor function (P = .51) or OS (P = .82)., Conclusions: Precision radiation therapy with 5 Gy × 5 fractions was well tolerated and effective and appeared superior to 4 Gy × 5 fractions in terms of LPFS. The retrospective nature of the historic control group, which might have led to a hidden selection bias, needs to be considered when interpreting the results., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Patients with metastatic spinal cord compression (MSCC) and favorable survival prognoses can benefit from radiation doses greater than 30Gy in 10 fractions in terms of improved local progression-free survival (LPFS) and overall survival (OS)., Methods/design: This prospective study mainly investigates LPFS after precision radiotherapy (volumetric modulated arc therapy or stereotactic body radiotherapy) with 18 × 2.33Gy in 3.5 weeks. LPFS is defined as freedom from progression of motor deficits during radiotherapy and an in-field recurrence of MSCC following radiotherapy. The maximum relative dose allowed to the spinal cord is 101.5% of the prescribed dose, resulting in an equivalent dose in 2Gy-fractions (EQD2) for radiation myelopathy is 45.5Gy, which is below the tolerance dose of 50Gy according to the Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC). The EQD2 of this regimen for tumor cell kill is 43.1Gy, which is 33% higher than for 30Gy in 10 fractions (EQD2 = 32.5Gy). Primary endpoint is LPFS at 12 months after radiotherapy. Secondary endpoints include the effect of 18 × 2.33Gy on motor function, ambulatory status, sensory function, sphincter dysfunction, LPFS at other follow-up times, overall survival, pain relief, relief of distress and toxicity. Follow-up visits for all endpoints will be performed directly and at 1, 3, 6, 9 and 12 months after radiotherapy. A total of 65 patients are required for the prospective part of the study. These patients will be compared to a historical control group of at least 235 patients receiving conventional radiotherapy with 10x3Gy in 2 weeks., Discussion: If precision radiotherapy with 18 × 2.33Gy results in significantly better LPFS than 10x3Gy of conventional radiotherapy, this regimen should be strongly considered for patients with MSCC and favorable survival prognoses., Trial Registration: Clinicaltrials.gov NCT04043156. Registered 30-07-2019.

Seven phase I-II studies fell within the inclusion criteria. Details on the radiotherapy technique, patient selection, fractionation scheme, exclusion criteria, treatment toxicity, quality-of-life, and tumor control were collected. The studies provide encouraging results of acute and late toxicity, with rare grade 3 events, that seem comparable to robotic SBRT. The biochemical disease-free survival rates look promising, but most patients belong to the low-risk group. The trials are limited by a short follow-up, small number of patients, and different approaches in prescribing dose and defining the acceptable dose heterogeneities. Currently, nonrobotic SBRT regimens should be used in the context of clinical trials.

Purpose: Single-institution single-arm prospective study. Endpoint: To assess whether there are more than 5 % of men having grade 3 GU or any grade 3 GI acute toxicity during stereotactic body radiation therapy (SBRT) for prostate cancer using helical tomotherapy., Methods: Since May 2012, 17 prostate cancer patients were treated with helical tomotherapy. The exclusion criteria used are the following: Gleason score ≥8, PSA >20 ng/ml, cT3b-4, IPSS ≥20 and history of acute urinary retention. CTV included the prostate gland and 1 cm of seminal vesicles in the low-risk group (LR) or the seminal vesicles completely in the intermediate (IR) and high-risk (HR) NCCN groups. CTV margins ranged from 2 to 8 mm, while PTV margins were 2 to 9 mm. Patients received eight fractions of 5.48 Gy (LR) or 5.65 Gy (IR, HR) on alternate days. Total equivalent doses at 2 Gy per fraction are 87.4 for LR and 92.3 Gy for IR-HR using an α/β value of 1.5. Correspondent figures for a α/β of 3 are 74.3 Gy and 78.2 Gy, respectively. Megavoltage CT (MVCT) for on-line correction was taken before every fraction., Results: The patient distribution by risk group is 29, 47 and 24 % for LR, IR and HR, respectively. 82 % received neoadjuvant-concomitant hormonal therapy. Acute GU toxicity grade 1, 2 and 3 was found in 70, 6 and 0 % of men. GI toxicity was observed in 50, 0 and 0. After 136 MVCT, the standard deviation of the mean individual corrections in the anterior-posterior direction was 2.5 mm., Conclusion: SBRT for prostate cancer using helical tomotherapy is feasible. Initial results show an early toxicity profile no worse than SBRT delivered with robotic radiosurgery or conventionally fractionated radiotherapy.

Purpose: To prospectively study acute genitourinary (GU) and gastrointestinal (GI) toxicity during hypofractionated radiotherapy., Patients and Materials: One-hundred and seventy-one consecutive men with cT1-T3cN0cM0 prostate cancer were treated at 2.6 Gy/fraction to a total dose of 67.6 for low risk (EQD2 = 79 Gy) and 70.2 Gy for intermediate-high risk (EQD2 = 82 Gy) over 5.2-5.4 weeks (α/β 1.5). Acute toxicity was scored according to RTOG/EORTC toxicity extended criteria after completing a 22-item questionnaire (basal, weekly, at 6 months)., Results: Minimum and median follow-up were 36 and 54.2 months, respectively. GU toxicity grades 0, 1, 2 and 3 were found in 30.4, 37, 32 and 0.6 % of patients, respectively. The figures for grades 0, 1, 2 and 3 GI toxicity were 66, 24, 10 and 0 %. The highest degree of acute reactions was reached at 4-5 weeks. At 6 months, 15 % of patients had GU toxicity (11 % grade 1, 4 % grade 2) and 5.8 % GI toxicity (5.3 % grade 1, 0.5 % grade 2). Multivariate analysis shows that bladder volume receiving ≥65 Gy (V 65) is associated with an increased risk of GU complications (p = 0.017, HR = 1.143, 95 % CI = 1.025-1.276), while history of TURP is linked to lower risk (p = 0.002, HR = 0.310, 95 % CI 0.004-0.370). Mean rectal dose (p = 0.013, HR = 1.089, 95 % CI 1.018-1.116) and total dose (p = 0.019, HR = 0.734, 95 % CI 0.567-0.950) are significantly related to GI toxicity., Conclusions: This 5-week dose-escalation hypofractionated radiotherapy schedule that uses 3D-conformal radiotherapy without IGRT has resulted in <1 % grade 3 acute complications. Our study suggests that reducing the mean rectal dose and the bladder V 65 helps prevent acute toxicity. TURP before radiotherapy was associated with lower acute GU toxicity.

Purpose: There are several potential advantages of using 18-fluor-fluorodeoxiglucose (18F-FDG) PET for target volume contouring, but before PET-based gross tumor volumes (GTVs) can reliably and reproducibly be incorporated into high-precision radiotherapy planning, operator-independent segmentation tools have to be developed and validated. The purpose of the present work was to apply the adaptive to the signal/background ratio (R(S/B)) thresholding method for head and neck tumor delineation, and compare these GTV(PET) to reference GTV(CT) volumes in order to assess discrepancies., Materials and Methods: A cohort of 19 patients (39 lesions) with a histological diagnosis of head and neck cancer who would undergo definitive concurrent radiochemotherapy or radical radiotherapy with intensity-modulated radiotherapy technique (IMRT), were enrolled in this prospective study. Contouring on PET images was accomplished through standardized uptake value (SUV)-threshold definition. The threshold value was adapted to R(S/B). To determine the relationship between the threshold and the R(S/B), we performed a phantom study. A discrepancy index (DI) between both imaging modalities, overlap fraction (OF) and mismatch fraction (MF) were calculated for each lesion and imaging modality., Results: The median DI value for lymph nodes was 2.67 and 1.76 for primary lesions. The OF values were larger for CT volumes than for PET volumes (p < 0.001), for both types of lesions. The MF values were smaller for CT volumes than for PET volumes (p < 0.001), for both types of lesions. The GTV(PET) coverage (OF(PET)) was strongly correlated with the lesion volume (GTV(CT)) for metastatic lymph nodes (Pearson correlation = 0.665; p < 0.01). For smaller lesions, despite the GTV volumes were relatively larger on PET than in CT contours, the coverage was poorer. Accordingly, the MF(PET/CT) was negatively correlated with the lesion volume for metastatic lymph nodes., Conclusions: The present study highlights the considerable challenges involved in using FDG PET imaging for the delineation of GTV in head and neck neoplasms. The methods that rely mainly on SUV(max) for thresholding, as the RS/B method, are very sensitive to partial volume effects and may provide unreliable results when applied on small lesions.