Radiogenomics in the Era of Advanced Radiotherapy

Brothwell, Morag; West, Catharine M L; Dunning, Alison M.; Burnet, N.G.; Barnett, Gillian C.

doi:10.1016/j.clon.2019.02.006

Cited by 22 publications

(20 citation statements)

References 33 publications

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“…There is a high need for biomarkers that can predict responders and select those patients that will only suffer from side effects. In patients individual radiation sensitivity is a quantitative and tissue-specific trait and large patient numbers and standardized outcome measures are essential as well as independent validation cohorts to identify QT-loci and the inclusion of ‘real world' data (205). While such studies provide hypothesis for future mechanistic investigation it is not yet evident how this can be translated into radiotherapy practice.…”

Section: Discussionmentioning

confidence: 99%

Radiation-Induced Lung Injury (RILI)

et al. 2019

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Radiation pneumonitis (RP) and radiation fibrosis (RF) are two dose-limiting toxicities of radiotherapy (RT), especially for lung, and esophageal cancer. It occurs in 5–20% of patients and limits the maximum dose that can be delivered, reducing tumor control probability (TCP) and may lead to dyspnea, lung fibrosis, and impaired quality of life. Both physical and biological factors determine the normal tissue complication probability (NTCP) by Radiotherapy. A better understanding of the pathophysiological sequence of radiation-induced lung injury (RILI) and the intrinsic, environmental and treatment-related factors may aid in the prevention, and better management of radiation-induced lung damage. In this review, we summarize our current understanding of the pathological and molecular consequences of lung exposure to ionizing radiation, and pharmaceutical interventions that may be beneficial in the prevention or curtailment of RILI, and therefore enable a more durable therapeutic tumor response.

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Section: Discussionmentioning

confidence: 99%

Radiation-Induced Lung Injury (RILI)

et al. 2019

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“…In patients considered to have low risk of RT toxicity, dose escalation, more extensive volumes (eg, the addition of an elective nodal volume), and reirradiation strategies could be considered whereas alternative treatments (eg, surgery) may be more appropriate for those considered high-risk. 91…”

Section: Elective Nodal Rt Volumesmentioning

confidence: 99%

Patterns of Lymph Node Failure in Patients With Recurrent Prostate Cancer Postradical Prostatectomy and Implications for Salvage Therapies

Slevin

Beasley

Cross

et al. 2020

Advances in Radiation Oncology

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Purpose There is increasing use of radical prostatectomy to treat patients with high-risk prostate cancer. This has contributed toward a pathologic stage migration, and a greater number of patients are subsequently being diagnosed with biochemical failure. There is increasing use of advanced imaging techniques in the setting of biochemical failure, including positron emission tomography-computed tomography (PET-CT). Methods and Materials This critical literature review highlights the evidence for PET-CT in postprostatectomy biochemical failure and identifies sites of pelvic lymph node relapse in the setting of biochemical failure and the potential implications that the locations of these relapses may have for salvage therapies. Potential future directions are then considered. Results The optimal PET-CT tracer remains uncertain but there is increasing use of prostate-specific membrane antigen PET-CT for investigating sites of nodal metastasis at low prostate-specific antigen levels, and this is leading to a blurring of the biochemical and radiologic recurrence phases. The optimal therapeutic approach remains undefined, with current trials investigating postoperative radiation therapy to the whole pelvis in addition to the prostatic fossa, the use of PET-CT in the setting of biochemical recurrence to guide delivery of salvage radiation therapy, and, for patients with node-only relapsed prostate cancer, the addition of whole pelvis radiation therapy to metastasis-directed therapies such as stereotactic ablative radiotherapy. Conclusions The most appropriate target volume for salvage radiation therapy remains uncertain, and the findings of studies using PET-CT to map nodal recurrences suggest that there could be a role for extending whole pelvis radiation therapy volumes to increase coverage of superior nodal regions. The emerging fields of radiomics and radiogenomics could provide important prognostic information and aid decision making for patients with relapsed prostate cancer.

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“…Single nucleotide polymorphisms (SNPs) are DNA sequence variations that arise when a single nucleotide within a gene is altered. SNPs constitute more than 99% of all genetic variations that can affect mRNA stability, rates of transcription, protein translation and/or regulation of gene methylation resulting in dysregulated function and varying degrees of clinical radiosensitivity (14,17). After a thorough literature search for identifying candidate genetic polymorphisms, we selected 7 genes related to DNA repair and one from the pro-fibrotic pathway for their presumed or demonstrated role in radiosensitivity.…”

Section: Introductionmentioning

confidence: 99%

Genetic Variants of DNA Repair Genes as Predictors of Radiation-Induced Subcutaneous Fibrosis in Oropharyngeal Carcinoma

et al. 2021

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PurposeTo investigate the impact of genetic variants of DNA repair and pro-fibrotic pathway genes on the severity of radiation-induced subcutaneous fibrosis in patients of oropharyngeal carcinoma treated with radical radiotherapy.Materials and MethodsPatients of newly diagnosed squamous cell carcinoma of oropharynx being treated with two-dimensional radical radiotherapy were enrolled in the study. Patients who had undergone surgery or were receiving concurrent chemotherapy were excluded. Patients were followed up at 6 weeks post completion of radiotherapy and every 3 months thereafter for a median of 16 months. Subcutaneous fibrosis was graded according to the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) grading system and the maximum grade was recorded over the length of the patient’s follow-up. Patients with severe fibrosis (≥G3), were compared to patients with minor (≤G2) fibrotic reactions. Eight single nucleotide polymorphisms of 7 DNA repair genes and 2 polymorphisms of a single pro-fibrotic pathway gene were analyzed by Polymerase Chain Reaction and Restriction Fragment Length Polymorphism and were correlated with the severity of subcutaneous fibrosis.Results179 patients were included in the analysis. Subcutaneous fibrosis was seen in 168 (93.9%) patients. 36 (20.1%) patients had severe (grade 3) fibrosis. On multivariate logistic regression analysis, Homozygous CC genotype of XRCC3 (722C>T, rs861539) (p=0.013*, OR 2.350, 95% CI 1.089-5.382), Homozygous AA genotype of ERCC4 Ex8 (1244G>A, rs1800067) (p=0.001**, OR 11.626, 95% CI 2.490-275.901) and Homozygous TT genotype of XRCC5 (1401G>T, rs828907) (p=0.020*, OR 2.188, 95% CI 1.652-7.334) were found to be predictive of severe subcutaneous fibrosis. On haplotype analysis, the cumulative risk of developing severe fibrosis was observed in patients carrying both haplotypes of variant Homozygous AA genotype of ERCC4 Ex8 (1244G>A, rs1800067) and Homozygous TT genotype of XRCC5 (1401 G>T, rs828907) (p=0.010*, OR 26.340, 95% CI 4.014-76.568).ConclusionWe demonstrated significant associations between single nucleotide polymorphisms of DNA repair genes and radiation-induced subcutaneous fibrosis in patients of oropharyngeal carcinoma treated with radiotherapy. We propose to incorporate these genetic markers into predictive models for identifying patients genetically predisposed to the development of radiation-induced fibrosis, thus guiding personalized treatment protocols.

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Radiogenomics in the Era of Advanced Radiotherapy

Cited by 22 publications

References 33 publications

Radiation-Induced Lung Injury (RILI)

Radiation-Induced Lung Injury (RILI)

Patterns of Lymph Node Failure in Patients With Recurrent Prostate Cancer Postradical Prostatectomy and Implications for Salvage Therapies

Genetic Variants of DNA Repair Genes as Predictors of Radiation-Induced Subcutaneous Fibrosis in Oropharyngeal Carcinoma

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