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Predictive Role of Biopsy Based Biomarkers for Radiotherapy Treatment in Rectal Cancer.

ABSTRACT: Radiation therapy has long been contemplated as an important mode in the treatment of rectal cancer. However, there are few ideal tools available for clinicians to make a radiotherapy decision at the time of diagnosis for rectal cancer. The purpose of this study was to assess whether biomarkers expressed in the biopsy could help to choose the suitable therapy and provide predictive and/or prognostic information. In total, 30 biomarkers were analyzed in 219 biopsy samples before treatment to discover the possibility of using them as an indicator for radiotherapy selection, diagnosis, survival and recurrence. Twenty-two biomarkers (COX2-RT, COX2-NonRT, etc.; 36.67%) had diagnostic value. For survival, four biomarkers (NFKBP65, p130, PINCH and PPAR) were significant in regulating gene promoter activity and overall survival, while four had a trend (AEG1, LOX, SATB1 and SIRT6). Three biomarkers (COX2, PINCH and WRAP53) correlated with disease-free survival, while eight had a trend (AEG1, COX2, Ki67, LOX, NFKBP65, PPAR and SATB1). Four biomarkers (COX2-RT, NFKBP65cyto-RT, P130cyto-NonRT and PPARcyto-RT) were independent prognostic factors for recurrence. NFKBP65 and SIRT6 were significantly correlated with lymph node metastasis regardless of radiation. Patients with high AEG1, LOX, NFKBP65, PPAR and SATB1 had or showed a positive trend for better survival after radiotherapy, while those with positive PINCH and WRAP53 expression would not benefit from radiotherapy. AEG1, LOX, NFKBP65cyto, PPAR and SATB1 could be used as indicators for choosing radiotherapy. COX2-RT, COX2-NonRT and some other biomarkers may provide additional help for diagnosis.

SUBMITTER: Wen Y

PROVIDER: S-EPMC7712120 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Predictive Role of Biopsy Based Biomarkers for Radiotherapy Treatment in Rectal Cancer.

Wen Yugang Y Zhao Senlin S Holmqvist Annica A Hahn-Stromberg Victoria V Adell Gunnar G Holmlund Birgitta B Pathak Surajit S Peng Zhihai Z Sun Xiao-Feng XF

Journal of personalized medicine 20201013 4

<h4>Background and purpose</h4>Radiation therapy has long been contemplated as an important mode in the treatment of rectal cancer. However, there are few ideal tools available for clinicians to make a radiotherapy decision at the time of diagnosis for rectal cancer. The purpose of this study was to assess whether biomarkers expressed in the biopsy could help to choose the suitable therapy and provide predictive and/or prognostic information.<h4>Experimental design</h4>In total, 30 biomarkers we ...[more]

PMID: 33066317

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Project description:BackgroundOnline adaptive radiotherapy has the potential to reduce toxicity for patients treated for rectal cancer because smaller planning target volumes (PTV) margins around the entire clinical target volume (CTV) are required. The aim of this study is to describe the first clinical experience of a Conebeam CT (CBCT)-based online adaptive workflow for rectal cancer, evaluating timing of different steps in the workflow, plan quality, target coverage and patient compliance.MethodsTwelve consecutive patients eligible for 5 × 5 Gy pre-operative radiotherapy were treated on a ring-based linear accelerator with a multidisciplinary team present at the treatment machine for each fraction. The accelerator is operated using an integrated software platform for both treatment planning and delivery. In all directions for all CTVs a PTV margin of 5 mm was used, except for the cranial/caudal borders of the total CTV where a margin of 8 mm was applied. A reference plan was generated based on a single planning CT. After aligning the patient the online adaptive procedure started with acquisition of a CBCT. The planning CT scan was registered to the CBCT using deformable registration and a synthetic CT scan was generated. With the support of artificial intelligence, structure guided deformation and the synthetic CT scan contours were adapted by the system to match the anatomy on the CBCT. If necessary, these contours were adjusted before a new plan was generated. A second and third CBCT were acquired to validate the new plan with respect to CTV coverage just before and after treatment delivery, respectively. Treatment was delivered using volumetric modulated arc treatment (VMAT). All steps in this process were defined and timed.ResultsOn average the timeslot needed at the treatment machine was 34 min. The process of acquiring a CBCT, evaluating and adjusting the contours, creating the new plan and verifying the CTV on the CBCT scan took on average 20 min. Including delivery and post treatment verification this was 26 min. Manual adjustments of the target volumes were necessary in 50% of fractions. Plan quality, target coverage and patient compliance were excellent.ConclusionsFirst clinical experience with CBCT-based online adaptive radiotherapy shows it is feasible for rectal cancer. Trial registration Medical Research Involving Human Subjects Act (WMO) does not apply to this study and was retrospectively approved by the Medical Ethics review Committee of the Academic Medical Center (W21_087 # 21.097; Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, The Netherlands).

Dataset Information

Predictive Role of Biopsy Based Biomarkers for Radiotherapy Treatment in Rectal Cancer.

Publications

Predictive Role of Biopsy Based Biomarkers for Radiotherapy Treatment in Rectal Cancer.

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