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Radiobiology of stereotactic ablative radiotherapy (SABR): perspectives of clinical oncologists.

ABSTRACT: Stereotactic ablative radiotherapy (SABR) is a novel radiation treatment method that delivers an intense dose of radiation to the treatment targets with high accuracy. The excellent local control and tolerance profile of SABR have made it become an important modality in cancer treatment. The radiobiology of SABR is a key factor in understanding and further optimizing the benefits of SABR. In this review, we have addressed several issues in the radiobiology of SABR from the perspective of clinical oncologists. The appropriateness of the linear-quadratic (LQ) model for SABR is controversial based on preclinical data, but it is a reliable tool from the perspective of clinical application because the biological effective dose (BED) calculated with it can represent the tumor control probability (TCP). Hypoxia is a common phenomenon in SABR in spite of the relatively small tumor size and has a negative effect on the efficacy of SABR. Preliminary studies indicate that a hypoxic radiosensitizer combined with SABR may be a feasible strategy, but so far there is not adequate evidence to support its application in routine practice. The vascular change of endothelial apoptosis and blood perfusion reduction in SABR may enhance the response of tumor cells to radiation. Combination of SABR with anti-angiogenesis therapy has shown promising efficacy and good tolerance in advanced cancers. SABR is more powerful in enhancing antitumor immunity and works better with immune checkpoint inhibitors (ICIs) than conventional fractionation radiotherapy. Combination of SABR with ICIs has become a practical option for cancer patients with metastases.

SUBMITTER: Li S

PROVIDER: S-EPMC7378931 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Radiobiology of stereotactic ablative radiotherapy (SABR): perspectives of clinical oncologists.

Li Shan S Shen Liangfang L

Journal of Cancer 20200627 17

Stereotactic ablative radiotherapy (SABR) is a novel radiation treatment method that delivers an intense dose of radiation to the treatment targets with high accuracy. The excellent local control and tolerance profile of SABR have made it become an important modality in cancer treatment. The radiobiology of SABR is a key factor in understanding and further optimizing the benefits of SABR. In this review, we have addressed several issues in the radiobiology of SABR from the perspective of clinica ...[more]

PMID: 32742453

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Project description:BackgroundResearch in treatment of non-small cell lung cancer (NSCLC) has shown promising results with stereotactic ablative radiotherapy (SABR) of oligometastatic disease, wherein distant disease may be limited to one or a few distant organs by host factors. Traditionally, PET/CT has been used in detecting metastatic disease and avoiding futile surgical intervention, however, sensitivity and specificity is limited to only 81 and 79%, respectively. Mediastinal staging still identifies occult nodal disease in up to 20% of NSCLC patients initially thought to be operative candidates. Endobronchial ultrasound and transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive tool for the staging and diagnosis of thoracic malignancy. When EBUS is combined with endoscopic ultrasound using the same bronchoscope (EUS-B), the diagnostic sensitivity and negative predictive value increase to 84 and 97%, respectively. Endoscopic staging in patients with advanced disease has never been studied, but may inform treatment if a curative SABR approach is being taken.MethodsThis is a multi-centre, prospective, cohort study with two-stage design. In the first stage, 10 patients with oligometastatic NSCLC (lung tumour ± hilar/mediastinal lymphadenopathy) with up to 5 synchronous metastases will be enrolled An additional 19 patients will be enrolled in the second stage if rate of treatment change is greater than 10% in the first stage. Patients will be subject to EBUS or combined modality EBUS/EUS-B to assess bilateral lymph node stations using a N3 to N2 to N1 progression. Primary endpoint is defined as the rate of change to treatment plan including change from SABR to conventional dose radiation, change in mediastinal radiation field, and change from curative to palliative intent treatment.DiscussionIf a curative approach with SABR for oligometastatic disease is being explored, invasive mediastinal staging may guide treatment and prognosis. This study will provide insight into the use of endoscopic mediastinal staging in determining changes in treatment plan of NSCLC. Results will inform the design of future phase II trials.Trial registrationClinicaltrials.gov identifier NCT04852588. Date of registration: April 19, 2021.Protocol version1.1 on December 9, 2021.

Project description:PURPOSE:To explore the utility of diffusion and perfusion changes in primary renal cell carcinoma (RCC) after stereotactic ablative body radiotherapy (SABR) as an early biomarker of treatment response, using diffusion weighted (DWI) and dynamic contrast enhanced (DCE) MRI. METHODS:Patients enrolled in a prospective pilot clinical trial received SABR for primary RCC, and had DWI and DCE MRI scheduled at baseline, 14 days and 70 days after SABR. Tumours <5cm diameter received a single fraction of 26 Gy and larger tumours received three fractions of 14 Gy. Apparent diffusion coefficient (ADC) maps were computed from DWI data and parametric and pharmacokinetic maps were fitted to the DCE data. Tumour volumes were contoured and statistics extracted. Spearman's rank correlation coefficients were computed between MRI parameter changes versus the percentage tumour volume change from CT at 6, 12 and 24 months and the last follow-up relative to baseline CT. RESULTS:Twelve patients were eligible for DWI analysis, and a subset of ten patients for DCE MRI analysis. DCE MRI from the second follow-up MRI scan showed correlations between the change in percentage voxels with washout contrast enhancement behaviour and the change in tumour volume (? = 0.84, p = 0.004 at 12 month CT, ? = 0.81, p = 0.02 at 24 month CT, and ? = 0.89, p = 0.001 at last follow-up CT). The change in mean initial rate of enhancement and mean Ktrans at the second follow-up MRI scan were positively correlated with percent tumour volume change at the 12 month CT onwards (? = 0.65, p = 0.05 and ? = 0.66, p = 0.04 at 12 month CT respectively). Changes in ADC kurtosis from histogram analysis at the first follow-up MRI scan also showed positive correlations with the percentage tumour volume change (? = 0.66, p = 0.02 at 12 month CT, ? = 0.69, p = 0.02 at last follow-up CT), but these results are possibly confounded by inflammation. CONCLUSION:DWI and DCE MRI parameters show potential as early response biomarkers after SABR for primary RCC. Further prospective validation using larger patient cohorts is warranted.

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Radiobiology of stereotactic ablative radiotherapy (SABR): perspectives of clinical oncologists.

Publications

Radiobiology of stereotactic ablative radiotherapy (SABR): perspectives of clinical oncologists.

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