Project description:BACKGROUND:In an oligometastatic setting, metastasis-directed treatment could render patients disease free, possibly for a protracted interval. Stereotactic ablative radiotherapy (SABR) is one of the treatment modalities that can be offered to these patients. In addition, the radiobiological qualities of SABR are promising for the use in perceived radioresistant tumours. There is also emerging evidence that SABR can stimulate the immune response, and a specific therapeutic window may exist for the optimal use of radiotherapy as an immune adjuvant. However, when SABR is considered for non-spine bone or lymph node metastases, the optimal fractionation schedule is not yet known. METHODS:The DESTROY-trial is a non-randomized prospective phase I trial determining a regimen of choice for patients with non-spine bone and lymph node metastases. A total of 90 patients will be included in three different treatment regimens. They will be offered stereotactic ablative radiotherapy in 5, 3 or 1 fractions. Dose-limiting toxicity will be recorded as primary endpoint. Acute and late toxicity, local response and local recurrence, and progression-free survival are secondary endpoints. Liquid biopsies will be collected throughout the course of this study from the second fractionation schedule on. DISCUSSION:Despite its almost universal use in (oligo-)metastatic patients, the level of evidence supporting radical local treatment in general, and stereotactic radiotherapy in particular, is low. This prospective phase I trial will evaluate different SABR regimens for metastases and the differences in immune-stimulatory effects. TRIAL REGISTRATION:The Ethics committee of the GZA Hospitals (B099201732915) approved this study on 05/07/2017. Amendment for translational research was approved on 06/02/2018. Trial registered on Clinicaltrials.gov ( NCT03486431 ) on 03/04/2018 - Retrospectively registered.
Project description:BackgroundDose escalation with brachytherapy after pelvic irradiation is standard for treating cervical cancer. Its application can be impossible for some patients. Dose escalation with SBRT is widely used with high local control and acceptable toxicity rates in different body parts. The study enrolled patients who underwent SBRT treatment for dose escalation in the cervix.MethodsPatients who were pathologically diagnosed and treated with cervical SBRT after definitive CRT were included in the study. A total of 30 Gy in 5 fractions for the high-risk volume was prescribed. The first response evaluation was performed three months after the completion of treatment. Treatment toxicity was documented according to the RTOG-EORTC scale. Oncological outcomes and toxicity were assessed.ResultsBetween 02.2019 and 05.2023, 40 patients were treated with an SBRT boost after pelvic irradiation. The median follow-up time was 16 months (7-44 months). The median HR CTV was 47 cc (8,3-168,2 cc). There were 39 patients who achieved a complete response and one who achieved a partial response in the third month after treatment. There were two local or two regional recurrences. The 1-year metastasis-free survival was 88%, and the 1-year progression-free survival was 88%. During the follow-up period, one grade 3 gastrointestinal side effect was observed.ConclusionsSBRT which has low toxicity and reasonable locoregional control rates in a short follow-up period, may be an option for dose escalation in brachytherapy-ineligible cervical cancer patients.
Project description:Patients treated with surgery for lung cancer are at risk of second primary lung cancers (SPLCs), which when localized, may be amenable to radical treatment. Treatment options, however, are limited due to reduced cardiopulmonary reserve and competing mortality risks. The aim of this study was to perform a systematic review of publications examining treatment planning considerations, clinical outcomes, and toxicity rates of stereotactic ablative radiotherapy (SABR) in patients who have previously undergone pneumonectomy. A systematic review of the literature was conducted in accordance with PRISMA guidelines using PubMed and EMBASE from inception to July 2018. Articles were limited to those published in the English language. Non-review articles with patients who received exclusively lung SABR post-pneumonectomy were included. Two reviewers independently performed abstract and full-text review, with discrepancies settled by a third reviewer. Of the 215 articles identified by the initial search, 6 articles comprising 53 patients who received lung SABR post-pneumonectomy met inclusion criteria. The mean age was 68, and most patients were male (73.7%). The mean time to pneumonectomy was 6.5 years. The mean biologically effective dose was 115 Gy, and the most common dose fractionation schemes were 54 Gy in 3 fractions, 48 Gy in 4 fractions, and 50 Gy in 5 fractions. The mean follow-up was 25.4 months. The mean 1-year overall survival and 2-year local control rates were 80.6% and 89.4%. Grade 3 or higher toxicity was reported in 13.2% of patients. SABR appears to be a safe and feasible option for SPLCs in patients with prior pneumonectomy. Multi-institutional and/or prospective studies would be helpful to determine the true risk and appropriateness of SABR in this high-risk patient population.
Project description:BackgroundStereotactic ablative radiotherapy (SABR) shows a remarkable local control of non-small cell lung cancer (NSCLC) metastases, partially as a result of host immune status. However, the predictors of immune cells for tumor response after SABR are unknown. To that effect, we investigated the ability of pre-SABR immune cells in peripheral blood to predict early tumor response to SABR in patients with lung metastases from NSCLC.MethodsThis study included 70 patients with lung metastases from NSCLC who were undergoing SABR. We evaluated the early tumor response 1 month and 6 months after SABR in these patients following RECIST 1.1 guidelines. Pre-SABR peripheral CD8+ T cell count, CD8+CD28+ T-cell count, CD8+CD28- T-cell count, CD4+ T-cell count, and Treg-cell count were measured using flow cytometry.ResultsIncreased CD8+CD28+ T-cell counts (14.43 ± 0.65 vs. 10.21 ± 0.66; P = 0.001) and CD4/Treg ratio (16.96 ± 1.76 vs. 11.91 ± 0.74; P = 0.011) were noted in 1-month responsive patients, compared with non-responsive patients. In univariate logistic analyses, high CD8+CD28+ T-cell counts (OR 0.12, 95% CI 0.03-0.48; P = 0.003), CD4/Treg ratio (OR 0.24, 95% CI 0.06-0.90; P = 0.035), and BED10 (OR 0.91, 95% CI 0.84-0.99; P = 0.032) predicted a 1-month tumor response to SABR. According to multivariate logistic analyses, the CD8+CD28+ T-cell count predicted a 1-month tumor response to SABR (OR 0.19, 95% CI 0.04-0.90; P = 0.037) independently. Furthermore, we confirmed the independent predictive value of the CD8+CD28+ T-cell count in predicting tumor response to SABR in 41 patients 6 months after treatment (OR 0.08, 95% CI 0.01-0.85; P = 0.039).ConclusionsA pre-SABR CD8+CD28+ T-cell count could predict early tumor response to SABR in patients with lung metastases from NSCLC. Larger, independently prospective analyses are warranted to verify our findings.
Project description:Prostate cancer (PCa) is the most common noncutaneous solid organ malignancy among men worldwide. Radiation therapy is a standard of care treatment option that has historically been delivered in the form of small daily doses of radiation over the span of multiple weeks. PCa appears to have a unique sensitivity to higher doses of radiation per fraction, rendering it susceptible to abbreviated forms of treatment. Stereotactic body radiation therapy (SBRT) and high-dose-rate brachytherapy (HDRBT) are both modern radiation modalities that allow the precise delivery of ablative doses of radiation to the prostate while maximally sparing sensitive surrounding normal structures. In this review, we highlight the evidence regarding the radiobiology, oncological outcomes, toxicity and dose/fractionation schemes of SBRT and HDRBT monotherapy in men with low-and intermediate-risk PCa.
Project description:BackgroundCytoreductive nephrectomy is thought to improve survival in metastatic renal cell carcinoma (mRCC). As many patients are ineligible for major surgery, we hypothesized that SABR could be a safe alternative.MethodsIn this dose-escalation trial, inoperable mRCC patients underwent SABR targeting the entire affected kidney. Toxicity (CTCAE v3.0), quality of life (QoL), renal function, and tumour response (RECIST v1.0) were assessed.ResultsTwelve patients of mostly intermediate (67%) or poor (25%) International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic class, median KPS of 70%, and median tumour size of 8.7 cm (range: 4.8-13.8) were enrolled in successive dose cohorts of 25 (n = 3), 30 (n = 6), and 35 Gy (n = 3) in 5 fractions. SABR was well tolerated with 3 grade 3 events: fatigue (2) and bone pain (1). QoL decreased for physical well-being (p = 0.016), but remained unchanged in other domains. SABR achieved a median tumour size reduction of - 17.3% (range: + 5.3 to - 54.4) at 5.3 months. All patients progressed systemically and median OS was 6.7 months. Crude median follow-up was 5.8 months.ConclusionsIn non-operable mRCC patients, renal-ablative SABR to 35 Gy in 5 fractions yielded acceptable toxicity, renal function preservation, and stable QoL. SABR merits further prospective investigation as an alternative to cytoreductive nephrectomy.Trial registrationClinicalTrials.gov NCT02264548. Registered July 22 2014 - Retrospectively registered: https://clinicaltrials.gov/ct2/show/NCT02264548.
Project description:BackgroundUltra-central lung cancer (UCLC) is difficult to achieve surgical treatment. Over the past few years, stereotactic ablative radiotherapy (SABR) or stereotactic body radiotherapy (SBRT) obviously improved the clinical efficacy and survival of UCLC patients. However, the adapted scheme of radiation therapy is still controversial. For this, a single arm retrospective analysis was performed on UCLC patients treated with SBRT.Material and methodsWe retrospectively studied primary UCLC patients who were treated with SBRT of 56 Gy/6-8f between 2010 and 2018. UCLC was defined as planning target volume (PTV) touching or overlapping the proximal bronchial tree, trachea, esophagus, heart, pulmonary vein, or pulmonary artery within 2 cm around the bronchial tree in all directions.ResultsA total of 58 patients whose median age was 68 years (range, 46-85) were included in our study, 79.3% of whom did not undergo any previous therapy. The median dose of the PTV was 77.8 Gy (range, 43.3-91.8), and the median PTV of tumors was 6.2 cm3 (range, 12.9-265.0). With a median follow-up of 57 months (range, 6-90 months), the median cumulative overall survival (OS) rate was 58 months (range, 2-105). In addition, the 1-year, 2-year and 5-year OS rates were 94.7%, 75.0% and 45.0%, respectively. In our univariable analysis (p=0.020) and multivariate analysis (p=0.004), the OS rate was associated with the PTV. The 5-year OS rates for PTV <53.0 cm3 and PTV ≥53.0 cm3 were 61.6% and 37.4%, respectively. Regarding toxicity after SBRT, there were two cases (3.5%) with grade ≥3 adverse events, of which 1 case died of sudden severe unexplained hemoptysis.ConclusionsPatients with UCLC can benefit from SBRT at a dose of 56 Gy/6-8f. On the other hand, smaller PTV was associated with superior outcomes, and the cure difference needs to be validated by prospective comparative trials.
Project description:BackgroundLimited literature exists on the feasibility and effectiveness of integrating stereotactic ablative radiotherapy (SABR) techniques with hyperfractionated regimens for patients with lung cancer. This study aims to assess whether the SABR technique with hyperfractionation can potentially reduce lung toxicity.MethodsWe utilized the linear-quadratic model to find the optimal fraction to maximize the tumor biological equivalent dose (BED) to normal-tissue BED ratio. Validation was performed by comparing the SABR plans with 50 Gy/5 fractions and hyperfractionationed plans with 88.8 Gy/74 fractions with the same tumor BED and planning criteria for 10 patients with early-stage lung cancer. Mean lung BED, Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP), critical volume (CV) criteria (volume below BED of 22.92 and 25.65 Gy, and mean BED for lowest 1000 and 1500 cc) and the percentage of the lung receiving 20Gy or more (V20) were compared using the Wilcoxon signed-rank test.ResultsThe transition point occurs when the tumor-to-normal tissue ratio (TNR) of the physical dose equals the TNR of α/β in the BED dose-volume histogram of the lung. Compared with the hypofractionated regimen, the hyperfractionated regimen is superior in the dose range above but inferior below the transition point. The hyperfractionated regimen showed a lower mean lung BED (6.40 Gy vs. 7.73 Gy) and NTCP (3.50% vs. 4.21%), with inferior results concerning CV criteria and higher V20 (7.37% vs. 7.03%) in comparison with the hypofractionated regimen (p < 0.01 for all).ConclusionsThe hyperfractionated regimen has an advantage in the high-dose region of the lung but a disadvantage in the low-dose region. Further research is needed to determine the superiority between hypo- and hyperfractionation.
Project description:Background and purposeHypo-fractionated lung Stereotactic Ablative Body Radiotherapy (SABR) has often been avoided when tumours are close to the chest wall. Our strategic objective was the reduction of fraction number, while maintaining target biological effective dose coverage without increasing chest wall toxicity (CWT) predictors.Materials and methodsTwenty previously treated lung SABR patients were stratified into four cohorts according to distance from PTV to the chest wall, <1 cm, <0.5 cm, overlapping up to 0.5 cm and 1.0 cm. For each patient, four plans were created; a chest wall optimised plan for 54 Gy in 3 fractions, the clinical plan re-prescribed for 55 Gy in 5, 48 Gy in 3 and 45 Gy in 3 fractions.ResultsFor a PTV distance of 0.5-0.0 cm, a reduction of the median (range) Dmax from 55.7 (57.5-54.1) Gy to 40.0 (37.1-42.0 Gy) Gy was observed for the chest wall optimised plans. The median V30Gy decreased from 18.9 (9.7-25.6) cm3 to 3.1 (1.8-4.5) cm3. For a PTV overlap of up to 0.5 cm, the Dmax reduced from 66.5 (64.1-70) Gy to 53.2 (50.6-55.1) Gy. The V30Gy decreased from 21.5 (16.5-29.5) cm3 to 14.9 (11.3-20.2) cm3. For the cohort with up to 1.0 cm overlap, there was a reduction in Dmax values of 9.9 Gy. The V30Gy for clinical plans, at 66.8 (18.7-188.8) cm3, decreased to 55.3 (15.5-149) cm3.ConclusionWhen PTVs are within 0.5 cm of chest wall, lung SABR dose heterogeneity can be used to reduce fraction number without increasing CWT predictors.