Predictor Of Radiation Response Research Articles

The Relevance of Regenerating Gene 1a Polymorphisms to Radiation Sensitivity and Survival of Nasopharyngeal Carcinoma Receiving Radiotherapy in a Southern Chinese Population.

ObjectiveGene polymorphism is closely related to tumor development, therapeutic response and prognosis. The relationship between regenerating gene 1A (Reg1A) polymorphism and nasopharyngeal carcinoma (NPC) is unclear. This retrospective study aimed to analyze the association between Reg1a polymorphisms and metastasis, radiation sensitivity and survivals in patients with NPC.MethodsA total of 308 patients who had received radiotherapy at the Affiliated Xinhua Hospital, Hainan Medical College, between January 2010 and December 2018 with NPC, were enrolled for assessment of Reg1a polymorphisms through direct DNA sequencing.ResultsIn the polymorphism of gene REG1A, patients with rs10165462 20CC genotype had later T stages (OR = 4.051, 95% CI: 1.775–9.244, P = 0.001), whereas carriers with rs12072 2922CC genotype had earlier T stages (OR = 1.891, 95% CI: 1.018–3.514, P = 0.044) after adjustments for age and gender, respectively. Among rs10165462 20 C/T polymorphism, 20TT wild-type was associated with better radiation response (P = 0.0019), and multivariate analysis showed that it was the only genotype of polymorphism that was significantly associated with better radiation response (OR = 0.265, 95% CI: 0.096–0.727, P = 0.01). Patients with the 20TT wild-type had a better five-year overall survival (60.9%) rate and five-year progression-free survival (60.8%) than those with the 20CC genotype (41.8% and 39.4%, P = 0.01 and P = 0.004, respectively). Patients with variant alleles (CC + CT) had significantly poorer OS (45.2%) and PFS (41.8%) compared with wild-type (TT) carriers (60.9% and 60.8%; P = 0.037 and P = 0.015, respectively). As for rs12072, patients with variant alleles (TT + TC) had significantly adverse OS and PFS compared with wild-type (CC) carriers (62.5% vs 44.8% and 62.5% vs 42.9%; P = 0.024 and P = 0.027, respectively). Cox regression showed that rs10165462 20CT was the only prognostic factor for OS (HR = 1.642, 95% CI 1.038–2.598, P = 0.034) and PFS (HR = 1.705, 95% CI 1.080–2.692, P = 0.022).ConclusionReg1a polymorphisms may be a predictor of radiation response, local invasion, OS and PFS in patients with NPC who undergo radiotherapy treatment.

Development and validation of genomic predictors of radiation sensitivity using preclinical data

BackgroundRadiation therapy is among the most effective and commonly used therapeutic modalities of cancer treatments in current clinical practice. The fundamental paradigm that has guided radiotherapeutic regimens are ‘one-size-fits-all’, which are not in line with the dogma of precision medicine. While there were efforts to build radioresponse signatures using OMICS data, their ability to accurately predict in patients is still limited.MethodsWe proposed to integrate two large-scale radiogenomics datasets consisting of 511 with 23 tissues and 60 cancer cell lines with 9 tissues to build and validate radiation response biomarkers. We used intrinsic radiation sensitivity, i.e., surviving fraction of cells (SF2) as the radiation response indicator. Gene set enrichment analysis was used to examine the biological determinants driving SF2. Using SF2 as a continuous variable, we used five different approaches, univariate, rank gene ensemble, rank gene multivariate, mRMR and elasticNet to build genomic predictors of radiation response through a cross-validation framework.ResultsThrough the pathway analysis, we found 159 pathways to be statistically significant, out of which 54 and 105 were positively and negatively enriched with SF2. More importantly, we found cell cycle and repair pathways to be enriched with SF2, which are inline with the fundamental aspects of radiation biology. With regards to the radiation response gene signature, we found that all multivariate models outperformed the univariate model with a ranking based approach performing well compared to other models, indicating complex biological processes underpinning radiation response.ConclusionTo summarize, we found biological processes underpinning SF2 and systematically compared different machine learning approaches to develop and validate predictors of radiation response. With more patient data available in the future, the clinical value of these biomarkers can be assessed that would allow for personalization of radiotherapy.

Targeted next-generation DNA sequencing identifies Notch signaling pathway mutation as a predictor of radiation response

Purpose: Identifying the association between somatic mutations and the radiation response of tumor is essential for understanding the mechanisms and practicing personalized radiotherapy. The present study aimed to discover specific genes or pathways that are associated with radiation response using targeted next-generation DNA sequencing.Material and methods: Fifty-five patients with various solid tumors whose specimen were sequenced using institutional panel which includes 148 cancer-related genes and received radiotherapy for a measurable tumor were analyzed. Patients with irradiated tumors in complete or partial remission for more than 6 months were defined as responders. Association between mutations including pathogenic single nucleotide variants and insertions/deletions in the 148 genes and 39 molecular pathways and radiation response was investigated.Results: Analyzing 17 responders and 38 non-responders, biologically effective dose (BED), but not concurrent chemotherapy, was associated with radiation response. No single gene correlated with radiation response. Mutations in Notch signaling pathway were associated with radiosensitivity after correction for multiple comparison (adjusted p = .094). When BED and Notch signaling pathway mutation were tested with logistic regression, both variables were associated with radiation response.Conclusions: Our results suggest that somatic mutations in Notch signaling pathway may be related to sensitivity to radiation, although these results should be validated in a larger and more homogeneous cohort.

A prospective biomarker trial of microbiome, immune, and genomic markers as predictors of radiation response in anal squamous cell carcinoma.

TPS869 Background: Preclinical evidence suggests that the microbiome plays a significant role in carcinogenesis and in response to immunotherapy and chemotherapy, but little is known about the role of the microbiome in response to radiation. Our group previously demonstrated that in patients with cervical squamous cell carcinoma (SCC), radiation response and immune response to radiation are improved with increased rectal microbial diversity. Methods: We are currently enrolling patients with local anal SCC undergoing definitive chemoradiation on a prospective biomarker trial evaluating changes in the gastrointestinal microbiome, immune microenvironment, and whole genome sequencing using a novel, non-invasive swab biopsy technique in addition to serial blood collections. This biopsy technique allows novel evaluation of dynamic changes throughout the course of chemoradiation. Microbiome sequencing is performed using 16s rRNA sequencing. Immune profiling is done using multiparametric flow cytometry for T-cell activation and exhaustion phenotypes and T-cell receptor sequencing. Inclusion criteria are biopsy proven HPV-related SCC of the anus, with no evidence of metastatic disease, and undergoing definitive chemoradiation. Our population is uniquely treated with cisplatin/5-FU based chemotherapy, rather than lymphotoxic mitomycin-C, allowing unique evaluation of immune populations. The primary endpoint of this study is complete tumor response based on pelvic MRI and digital rectal exam at three weeks. Secondary endpoints include FDG-avid diseases at 3 months and disease recurrence. To date we have accrued 10 patients out a planned 30 patient pilot cohort. We expect the remainder of these patients to be accrued by December 2017.

C36. Can nitric oxide be used as a predictor of radiation response?

C36. Can nitric oxide be used as a predictor of radiation response?

Dynamic contrast-enhanced MRI as a predictor of tumour response to radiotherapy

A predictive technique in the management of patients with cancer could improve the therapeutic index by allowing better individualisation of treatment. The standard risk factors that are currently used do not adequately account for the unpredictable and substantial variation seen in the treatment response of patients with a similar risk profile. Dynamic contrast-enhanced (DCE) MRI is a non-invasive technique that can provide anatomical and physiological information on the tumour. The DCE-MRI data reflects the tumour microenvironment variables that are known to influence radiation response. The aim of this review is to describe the potential clinical application of DCE-MRI as a predictor of radiation response. We have reviewed the literature and identified 29 studies (total of 1194 patients) that correlate DCE-MRI with histopathological or clinical outcome data relevant to radiotherapy.

255 Correlating dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) with changes in tumour volume, as a predictor of radiation response in cervix cancer

255 Correlating dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) with changes in tumour volume, as a predictor of radiation response in cervix cancer

Can serum Glutathione-S-transferase levels in carcinoma cervix be a predictor of radiation response?

We conducted a pilot study wherein serum Glutathione-S-transferase levels were measured before and after radiotherapy in carcinoma cervix patients and correlated with response to treatment during a two-year follow-up period. Out of 17 patients who received radiotherapy, 9 showed a significant decrease (p<0.005) while 8 showed significant increase (p<0.004) in post radiotherapy glutathione-S-transferase values as compared to pre treatment values respectively. These patients were followed up for two years and we observed that 71% who had significant increase in post radiotherapy values had relapse of cancer within 2 years where as 66% of those who had significant decrease in post radiotherapy values had no evidence of relapse. This shows that alterations in serum Glutathione-S-transferase levels may help us to predict radiation response.

Measurement of serum squamous cell carcinoma antigen levels as a predictor of radiation response in patients with carcinoma of the uterine cervix.

Optimal timing of the measurement of serum squamous cell carcinoma (SCC) antigen during radiation therapy (RT) and its significance for predicting the response of cervical carcinoma patients as early as possible remain unknown. Sixty-three patients with SCC of the uterine cervix who received RT only were studied. Patients were treated with a combination of external beam irradiation and high-dose rate intracavitary irradiation. The serum SCC antigen level was measured before, every 2 or 3 weeks during, and 1 or 2 months after RT. Clinical outcome was divided into complete response and incomplete response. Forty-seven patients (74.6%) had serum SCC antigen levels 1.5 ng/mL (the reference value) before RT. Normalization of serum SCC antigen levels at the end of RT were found to be significantly correlated with complete response in the SCC-positive patients. It was especially noted that in patients with serum SCC levels between 5-30 ng/mL before RT, a > 70% decrease in the serum SCC antigen level at 4 weeks was correlated significantly with complete response. In this group, a significant correlation also was found between a > 70% decrease in serum SCC level at 4 weeks and the normalization of SCC at the end of RT. The current study data suggest that the serum SCC antigen level not only before, but also during and at the end of RT can predict the response of patients with cervical carcinoma and help in identifying those patients who are at high risk of local recurrence and/or distant metastasis.

Genome-wide screening for radiation response factors in head and neck cancer.

Radiation therapy is an integral part of the treatment of head and neck cancer. Factors predicting radiation response are ill defined. The aim of this study was to identify genetic aberrations associated with radiation response in cell lines derived from head and neck squamous cell carcinomas (HNSCC) using comparative genomic hybridization (CGH) for genome-wide screening. Five cell lines derived from HNSCC were subjected to a single course of radiation (400 cGy) in parallel with a similarly handled, untreated control. Cellular response to radiation was determined on posttreatment days 1, 2, 3, 4, and 5 using a cell viability assay (MTT assay). Radiation response was defined as 35% or greater decrease in cell survival relative to control. Tumor doubling time was determined by cell counts performed at day 0 and 1 for each cell line. All experiments were done in quadruplicate. CGH analysis was performed by differentially labeling DNA from tumor and normal tissue with fluorescent agents. The labeled DNAs were simultaneously hybridized to normal metaphase chromosomes. Image analysis for fluorescence intensity along the entire length of each metaphase chromosome allowed generation of a color ratio, which was used to detect copy number changes. Radioresistance was identified in two of five cell lines. The tumor doubling time was not a predictor of radiation response. CGH identified a complex pattern of aberrations, with gain of 3q common to all cell lines. The number of genetic aberration was higher in radiation-sensitive cell lines than in radiation-resistant ones. No recurrent aberrations were unique to the radiation-resistant cell lines. Recurrent gains at 7p and 17q and losses at 5q, 7q, and 18q were unique to the radiation-sensitive cell lines. The number of aberrations identified by CGH analysis may be a predictor of radiation response. A large study of primary tumors is warranted to confirm this association and identify specific genetic aberrations associated with radiation response.

The relevance of tumor size and cell kinetics as predictors of radiation response in head and neck cancer.A randomized study on the effect of intraarterial chemotherapy followed by radiotherapy

The relevance of tumor size and cell kinetics as predictors of radiation response in head and neck cancer.A randomized study on the effect of intraarterial chemotherapy followed by radiotherapy

Predictors of radiation response in lung cancer. A clinico-pathobiological analysis.

From February 1972 to July 1975, 200 lung cancer patients were seen at the University of Rochester Cancer Center's Division of Radiation Oncology; 40% had squamous cell tumors and 87.5% had advanced disease localized to the thorax. Of the 160 patients who completed treatment, 101 were treated with continuous therapy schedules, and 59 were treated with split-course schedules, and 59 were treated with split-course schedules; 40 patients did not complete treatment because of early metastatic disease or death. Radiation therapy was very effective in local tumor ablation. To assess local tumor response, doubling times were obtained in measurable lesions prior to treatment. The doubling times (DT) were 25 days for small cell cancers and 192 days for adenocarcinoma. More than 50% tumor shadow regression was a good prognosticator of local tumor response; this increased as the mean DT decreased. The order of kinetic increase in tumor ablation per histology was the opposite of the one-year survival results because of the metastatic spread patterns of the different tumors. Survival rates in lung cancer emerge as simplistic and inadequate to explain local radiation effectiveness. Survival is conditioned by stage, histology, and modality of treatment, total dose delivered, and local tumor response. Although the most effective treatment dose seems to be over 6000 rads, the most efficient schedules were split-course delivering lower tumor doses. This modality of treatment is proposed as the optimal schedule to be combined with other forms of therapy with the goal of achieving better survival.