Dataset Information

Stereotactic Body Radiotherapy Is Effective in Modifying the Tumor Genome and Tumor Immune Microenvironment in Non-Small Cell Lung Cancer or Lung Metastatic Carcinoma.

ABSTRACT:

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.

Materials and methods

Paired tumor samples were collected from 10 patients with non-small cell lung cancer (NSCLC) or lung metastatic carcinoma within a week before and after SBRT. DNA and RNA of tumor tissues was extracted from the paired samples. Whole-exome and RNA sequencing assays were performed by next-generation sequencing. Gene mutation, genomic expression, T-cell receptor (TCR) repertoire, and profiling of tumor-infiltrating immune cells were analyzed through bioinformatics analysis in paired tumor samples. CD8+ T-cell infiltration and PD-L1 expressions were detected by immunostaining in tumor tissues.

Results

The diversity of TCR repertoire and PD-L1 expression increased significantly in the TME, and the most enriched term of the gene ontology analysis was the immune response gene after receiving SBRT. SBRT induced neo-mutation of genes in tumor cells but did not increase tumor mutation burden in tumor tissues. TME displayed complex immune cell changes and infiltration and expression of immune-regulating factors such as C-X-C motif chemokine (CXCL) 10, CXCL16, interferons (IFNs), and IFN receptors. CD8+ T-cells in tumor tissues did not improve significantly after SBRT while the infiltrating TH1 and TH2 cells decreased remarkably.

Conclusion

SBRT improved the TCR repertoire diversity and PD-L1 expression in the TME and induced neo-mutation of genes in tumor cells but did not increase CD8+ T-cell infiltration and IFN expression in the tumor tissue within a week.

SUBMITTER: Zhou P

PROVIDER: S-EPMC7862546 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Stereotactic Body Radiotherapy Is Effective in Modifying the Tumor Genome and Tumor Immune Microenvironment in Non-Small Cell Lung Cancer or Lung Metastatic Carcinoma.

Zhou Pu P Chen Diangang D Zhu Bo B Chen Wei W Xie Qichao Q Wang Yali Y Tan Qiulin Q Yuan Bibo B Zuo Xuejiao X Huang Changlin C Zhu Hongfan H Li Guanghui G

Frontiers in immunology 20210122

<h4>Background and purpose</h4>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.<h4>Materials and methods</h4>Paired tumor samples were collected from 10 patients with non-small cell lung cancer (NSCLC) or lung metastatic carcinoma within a week before and after SBRT. DNA and RNA of tumor tissues was extracted from the paired samples. Whole-exome and R ...[more]

PMID: 33552051

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Project description:ObjectivesTo compare patterns of care and overall survival (OS) between stereotactic body radiotherapy (SBRT) and percutaneous local tumor ablation (LTA) for non-surgically managed early-stage non-small-cell lung cancer (NSCLC).Materials and methodsThe National Cancer Database (NCDB) was queried from 2004 to 2014 for adults with non-metastatic, node-negative invasive adenocarcinoma or squamous cell carcinoma of the lung with primary tumor size ≤5.0 cm who did not undergo surgery or chemotherapy and received SBRT or LTA. Patterns of care were assessed with multivariate logistic regression. After propensity-score weighting with generalized boosted regression, OS was assessed with univariate and doubly-robust multivariate Cox regression.ResultsOf 15,792 patients, 14,651 (93%) received SBRT and 1141 (7%) received LTA. Increasing age (OR 1.01, p = .035), treatment at an academic institution (OR 2.94, p < .001), increasing tumor size (OR 1.05, p < .001), and more recent year of diagnosis (OR 1.43, p < .001) were predictive of treatment with SBRT, whereas comorbidities (OR 0.74, p = .003) and treatment at a high-volume facility (OR 0.05, p < .001) were predictive for LTA. At a median follow-up of 26.2 months, SBRT was associated with improved OS relative to LTA within a propensity-score weighted doubly-robust multivariate analysis (HR 0.71, p < .001). On weighted subgroup analyses, improved OS was observed with SBRT for tumor sizes >2.0 cm (HR 0.72, p < .001) and for those treated at high-volume facilities (HR 0.71, p < .001). No OS difference was found with SBRT or LTA in tumor sizes ≤2.0 cm (HR 0.90, p = .227).ConclusionWithin the NCDB, SBRT was more commonly utilized and was associated with improved OS when compared to percutaneous LTA for patients with non-surgically managed early-stage NSCLC. Patients with small tumor volumes likely represent an appropriate population for future prospective randomized comparisons between SBRT and LTA.

Project description:IntroductionStereotactic body radiation therapy (SBRT) is increasingly utilized for patients with recurrent and metastatic sarcoma. SBRT affords the potential to overcome the relative radioresistance of sarcomas through delivery of a focused high biological effective dose (BED) as an alternative to invasive surgery. We report local control outcomes after metastatic sarcoma SBRT based on radiation dose and histology.MethodsFrom our IRB-approved single-institution registry, all patients treated with SBRT for metastatic sarcoma between 2014 and 2020 were identified. Kaplan-Meier analysis was used to estimate local control and overall survival at 1 and 2 years. A receiver operating characteristic (ROC) curve was generated to determine optimal BED using an α/β ratio of 3. Local control was compared by SBRT dose using the BED cut point and evaluated by histology.ResultsForty-two patients with a total of 138 lesions met inclusion criteria. Median imaging follow up was 7.73 months (range 0.5-35.0). Patients were heavily pre-treated with systemic therapy. Median SBRT prescription was 116.70 Gy BED (range 66.70-419.30). Desmoplastic small round cell tumor, Ewing sarcoma, rhabdomyosarcoma, and small round blue cell sarcomas were classified as radiosensitive (n = 63), and all other histologies were classified as radioresistant (n = 75). Local control for all lesions was 66.7% (95% CI, 56.6-78.5) at 1 year and 50.2% (95% CI, 38.2-66.1) at 2 years. Stratifying by histology, 1- and 2-year local control rates were 65.3% and 55.0%, respectively, for radiosensitive, and 68.6% and 44.5%, respectively, for radioresistant histologies (p = 0.49). The ROC cut point for BED was 95 Gy. Local control rates at 1- and 2-years were 75% and 61.6%, respectively, for lesions receiving >95 Gy BED, and 46.2% and 0%, respectively, for lesions receiving <95 Gy BED (p = 0.01). On subgroup analysis, local control by BED > 95 Gy was significant for radiosensitive histologies (p = 0.013), and trended toward significance for radioresistant histologies (p = 0.25).ConclusionThere is a significant local control benefit for sarcoma SBRT when a BED > 95 Gy is used. Further investigation into the dose-response relationship is warranted to maximize the therapeutic index.

Dataset Information

Stereotactic Body Radiotherapy Is Effective in Modifying the Tumor Genome and Tumor Immune Microenvironment in Non-Small Cell Lung Cancer or Lung Metastatic Carcinoma.

Background and purpose

Materials and methods

Results

Conclusion

Publications

Stereotactic Body Radiotherapy Is Effective in Modifying the Tumor Genome and Tumor Immune Microenvironment in Non-Small Cell Lung Cancer or Lung Metastatic Carcinoma.

Similar Datasets

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