Stereotactic Body Radiotherapy for Oligometastases From Colorectal Cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer,Colorectal Neoplasms
PROVIDER: 2225646 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Purpose: Stereotactic body radiotherapy (SBRT) is an emerging treatment modality for pancreatic ductal adenocarcinoma (PDAC) that can effectively prime cytotoxic T cells by inducing immunogenic tumor cell death in preclinical models. SBRT effects on human PDAC have yet to be thoroughly investigated, therefore, this study aimed to characterize immunomodulation in the human PDAC tumor microenvironment following therapy. Experimental Design: Tumor samples were obtained from patients with resectable PDAC. Radiotherapy was delivered a median of seven days prior to surgical resection, and sections were analyzed by multiplex IHC (mIHC), RNA-Seq, and T cell receptor sequencing (TCR-Seq). Results: Analysis of SBRT-treated tumor tissue indicated reduced tumor cell density and increased immunogenic cell death relative to untreated controls. Radiotherapy promoted collagen deposition, however, vasculature was unaffected and spatial analyses lacked evidence of T cell sequestration. Conversely, SBRT resulted in fewer tertiary lymphoid structures and failed to lessen or reprogram abundant immune suppressor populations. Higher percentages of PD-1+ T cells were observed following SBRT, and a subset of tumors displayed more clonal T cell repertoires. Conclusions: These findings suggest that SBRT augmentation of antitumor immunogenicity may be dampened by an overabundance of refractory immunosuppressive populations, and support the continued development of SBRT/immunotherapy combination for human PDAC.
2021-10-08 | GSE185311 | GEO
Project description:AimsTo evaluate the efficacy and toxicity of extracranial stereotactic body radiotherapy (SBRT) in the treatment of oligometastatic lymph node involvement in the mediastinum, retroperitoneum, or pelvis, in a consecutive group of patients from real clinical practice outside clinical trials.MethodsA retrospective analysis of 90 patients with a maximum of four oligometastases and various primary tumors (the most common being colorectal cancers). The endpoints were local control of treated metastases (LC), freedom from widespread dissemination (FFWD), progression-free survival (PFS), overall survival (OS), and freedom from systemic treatment (FFST). Acute and delayed toxicities were also evaluated.ResultsThe median follow-up after SBRT was 34.9 months. The LC rate at three and five years was 68.4 and 56.3%, respectively. The observed median FFWD was 14.6 months, with a five-year FFWD rate of 33.7%. The median PFS was 9.4 months; the three-year PFS rate was 19.8%. The median FFST was 14.0 months; the five-year FFST rate was 23.5%. The OS rate at three and five years was 61.8 and 39.3%, respectively. Median OS was 53.1 months. The initial dissemination significantly shortened the time to relapse, death, or activation of systemic treatment-LC (HR 4.8, p < 0.001), FFWD (HR 2.8, p = 0.001), PFS (HR 2.1, p = 0.011), FFST (HR 2.4, p = 0.005), OS (HR 2.2, p = 0.034). Patients classified as having radioresistant tumors noticed significantly higher risk in terms of LC (HR 13.8, p = 0.010), FFWD (HR 3.1, p = 0.006), PFS (HR 3.5, p < 0.001), FFST (HR 3.2, p = 0.003). The multivariable analysis detected statistically significantly worse survival outcomes for initially disseminated patients as well as separately in groups divided according to radiosensitivity. No grade III or IV toxicity was reported.ConclusionOur study shows that targeted SBRT is a very effective and low toxic treatment for oligometastatic lymph node involvement. It can delay the indication of cytotoxic chemotherapy and thus improve and maintain patient quality of life. The aim of further studies should focus on identifying patients who benefit most from SBRT, as well as the correct timing and dosage of SBRT in treatment strategy.
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Project description:Background and purpose: To directly reveal the change in genome mutation, RNA transcript of tumor cells, and tumor microenvironment (TME) after stereotactic body radiotherapy (SBRT) in paired human lung tumor specimens.
2020-12-10 | GSE162945 | GEO
Project description:Background and purpose: To directly reveal the change in genome mutation, RNA transcript of tumor cells, and tumor microenvironment (TME) after stereotactic body radiotherapy (SBRT) in paired human lung tumor specimens.
2020-12-10 | GSE162944 | GEO
Project description:This is a single-centre, single-arm open-label proof-of-concept study to analyze the imaging (DCE-CT,CEUS and Quantitative US) effects of neoadjuvant bevacizumab and SBRT on colorectal metastases to the liver. Patients will receive 2 doses of bevacizumab 5mg/kg IV prior to SBRT. The second dose of bevacizumab will be given 2 weeks after the first dose of bevacizumab and within 48 hours of starting the first dose of SBRT. The SBRT prescription dose will be up to 60 Gy in 6 fractions, delivered on alternating weekdays for 2 weeks. Total SBRT dose will be determined by size of target lesion, liver sparing and organs-at-risk dose constraints. DCE-CT, CEUS and Quantitative US will be performed within 7 days prior to the first dose of bevacizumab, after the second dose of bevacizumab and within 7 days of completing SBRT.
| 2123176 | ecrin-mdr-crc
Project description:This is a randomized open-label multicentre Phase III superiority study of the effect of adding SBRT to the standard of care treatment on overall survival in patients with rare oligometastatic cancers.
Patients will be randomized in a 1:1 ratio between current standard of care treatment vs. standard of care treatment + SBRT to all sites of known metastatic disease.
The primary objective of this trial is to assess if the addition of stereotactic body radiotherapy (SBRT) to standard of care treatment improves overall survival (OS) as compared to standard of care treatment alone in patients with rare oligometastatic cancers.
| 2347710 | ecrin-mdr-crc
Project description:PurposeIn pulmonary oligometastases from colorectal cancer (POM-CRC), the primarily recommended local therapy is metastasectomy. Stereotactic body radiotherapy (SBRT) is another local therapy modality that is considered as an alternative option in patients who cannot undergo surgery. The purpose of this meta-analysis is to demonstrate the effects of SBRT on POM-CRC by integrating the relevant studies.Materials and methodsThe authors explored MEDLINE, EMBASE, Cochrane Library, Web of Science, and SCOPUS, and selected studies including patients treated with SBRT for POM-CRC and availability of local control (LC) or overall survival (OS) rate. In this meta-analysis, the effect of SBRT was presented in the form of the LC and OS rates for 1, 2, 3, and 5 years after SBRT as pooled estimates, and the frequency of pulmonary toxicity of grade 3 or higher after SBRT (PTG3-SBRT).ResultsFourteen full texts among the searched 4,984 studies were the objects of this meta-analysis. The overall number of POM-CRC patients was 495 as per the integration of 14 studies. The pooled estimate LC rate at 1, 2, 3, and 5 years after SBRT was 81.0%, 71.5%, 56.0%, and 61.8%, and the OS rate was 86.9%, 70.1%, 57.9%, and 43.0%, respectively. The LC and OS rates gradually declined until 3 years after SBRT in a similar pattern. Among the 14 studies, only two studies reported PTG3-SBRT as 2.2% and 10.8%, respectively.ConclusionFor POM-CRC, SBRT is an ablative therapy with a benefit on LC and OS rates and less adverse effects on the lung.
| S-EPMC7577807 | biostudies-literature
Project description:AimTo evaluate the clinical outcomes of metastatic colorectal cancer (mCRC) patients with oligometastases, oligoprogression, or local control of dominant tumors after stereotactic body radiotherapy (SBRT) and establish a nomogram model to predict the prognosis for these patients.Methods and materialsA cohort of 94 patients with 162 mCRC metastases was treated with SBRT at a single institution. Treatment indications were oligometastases, oligoprogression, and local control of dominant tumors. End points of this study were the outcome in terms of progression-free survival (PFS), overall survival (OS), local progression (LP), and cumulative incidence of starting or changing systemic therapy (SCST). In addition, univariate and multivariable analyses to assess variable associations were performed. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve.ResultsMedian PFS were 12.6 months, 6.8 months, and 3.7 months for oligometastases, oligoprogression, and local control of dominant tumors, respectively. 0-1 performance status, < 10 ug/L pre-SBRT CEA, and ≤ 2 metastases were significant predictors of higher PFS on multivariate analysis. Median OS were 40.0 months, 26.1 months, and 6.5 months for oligometastases, oligoprogression, and local control of dominant tumors, respectively. In the multivariate analysis of the cohort, the independent factors for survival were indication, performance status, pre-SBRT CEA, and PTV, all of which were selected into the nomogram. The calibration curve for probability of survival showed the good agreement between prediction by nomogram and actual observation. The C-index of the nomogram for predicting survival was 0.848.ConclusionsSBRT for metastases derived from colorectal cancer offered favorable survival and symptom palliation without significant complications. The proposed nomogram could provide individual prediction of OS for patients with mCRC after SBRT.
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Project description:Background and purposeMagnetic resonance (MR)-linac delivery is expected to improve organ at risk (OAR) sparing. In this study, OAR doses were compared for online adaptive MR-linac treatments and conventional cone beam computed tomography (CBCT)-linac radiotherapy, taking into account differences in clinical workflows, especially longer session times for MR-linac delivery.Materials and methodsFor 25 patients with pelvic/abdominal lymph node oligometastases, OAR doses were calculated for clinical pre-treatment and daily optimized 1.5 T MR-linac treatment plans (5 × 7 Gy) and compared with simulated CBCT-linac plans for the pre-treatment and online anatomical situation. Bowelbag and duodenum were re-contoured on MR-imaging acquired before, during and after each treatment session. OAR hard constraint violations, D0.5cc and D10cc values were evaluated, focusing on bowelbag and duodenum.ResultsOverall, hard constraints for all OAR were violated less often in daily online MR-linac treatment plans compared with CBCT-linac: in 5% versus 22% of fractions, respectively. D0.5cc and D10cc values did not differ significantly. When taking treatment duration and intrafraction motion into account, estimated delivered doses to bowelbag and duodenum were lower with CBCT-linac if identical planning target volume (PTV) margins were used for both modalities. When reduced PTV margins were achievable with MR-linac treatment, bowelbag doses were lower compared with CBCT-linac.ConclusionsCompared with CBCT-linac treatments, the online adaptive MR-linac approach resulted in fewer hard planning constraint violations compared with single-plan CBCT-linac delivery. With respect to other bowelbag/duodenum dose-volume parameters, the longer duration of MR-linac treatment sessions negatively impacts the potential dosimetric benefit of daily adaptive treatment planning.
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Project description:In patients with proven distant metastases from solid tumors, it has been a notion that the condition is incurable, warranting palliative care only. The term "oligometastases" was coined to refer to isolated sites of metastasis, whereby the entire burden of disease can be recognized as a finite number of discrete lesions that can be potentially cured with local therapies. Stereotactic body radiation therapy (SBRT) is a novel treatment modality in radiation oncology that delivers a very high dose of radiation to the tumor target with high precision using single or a small number of fractions. SBRT is the result of technological advances in patient and tumor immobilization, image guidance, and treatment planning and delivery. A number of studies, both retrospective and prospective, showed promising results in terms of local tumor control and, in a limited subset of patients, of survival. This article reviews the radiobiologic, technical, and clinical aspects of SBRT for various anatomical sites.
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