scholarly journals Cardiomyocyte-Specific Circulating Cell-Free Methylated DNA in Esophageal Cancer Patients Treated with Chemoradiation

2021 ◽  
Vol 3 (3) ◽  
pp. 100-112
Author(s):  
Sarah Martinez Roth ◽  
Eveline E. Vietsch ◽  
Megan E. Barefoot ◽  
Marcel O. Schmidt ◽  
Matthew D. Park ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cardiac Toxicity ◽  
Amplicon Sequencing ◽  
Neoadjuvant Chemoradiation ◽  
Patient Specific ◽  
High Dose ◽  
Specific Cell ◽  
Methylated Dna ◽  
Bisulfite Treatment ◽  
Dose Radiation

Thoracic high-dose radiation therapy (RT) for cancer has been associated with early and late cardiac toxicity. To assess altered rates of cardiomyocyte cell death due to RT we monitored changes in cardiomyocyte-specific, cell-free methylated DNA (cfDNA) shed into the circulation. Eleven patients with distal esophageal cancer treated with neoadjuvant chemoradiation to 50.4 Gy (RT) and concurrent carboplatin and paclitaxel were enrolled. Subjects underwent fasting blood draws prior to the initiation and after completion of RT as well as 4–6 months following RT. An island of six unmethylated CpGs in the FAM101A locus was used to identify cardiomyocyte-specific cfDNA in serum. After bisulfite treatment this specific cfDNA was quantified by amplicon sequencing at a depth of >35,000 reads/molecule. Cardiomyocyte-specific cfDNA was detectable before RT in the majority of patient samples and showed some distinct changes during the course of treatment and recovery. We propose that patient-specific cardiac damages in response to the treatment are indicated by these changes although co-morbidities may obscure treatment-specific events.

Low-Dose Versus High-Dose Radiation Therapy for the Palliation of Dysphagia From Esophageal Cancer: A Multicenter Retrospective Cohort Study

2020 ◽  
Vol 10 (4) ◽  
pp. e255-e263 ◽  
Author(s):  
Bram D. Vermeulen ◽  
Paul M. Jeene ◽  
Jasmijn Sijben ◽  
Robin Krol ◽  
Heidi Rütten ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Radiation Therapy ◽  
Cohort Study ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Low Dose ◽  
High Dose ◽  
Dose Radiation

INT 0123 (Radiation Therapy Oncology Group 94-05) Phase III Trial of Combined-Modality Therapy for Esophageal Cancer: High-Dose Versus Standard-Dose Radiation Therapy

2002 ◽  
Vol 20 (5) ◽  
pp. 1167-1174 ◽  
Author(s):  
Bruce D. Minsky ◽  
Thomas F. Pajak ◽  
Robert J. Ginsberg ◽  
Thomas M. Pisansky ◽  
James Martenson ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Radiation Therapy ◽  
Radiation Dose ◽  
Standard Dose ◽  
Combined Modality Therapy ◽  
High Dose ◽  
Regional Control ◽  
Combined Modality ◽  
Local Regional Control ◽  
Dose Radiation

PURPOSE: To compare the local/regional control, survival, and toxicity of combined-modality therapy using high-dose (64.8 Gy) versus standard-dose (50.4 Gy) radiation therapy for the treatment of patients with esophageal cancer. PATIENTS AND METHODS: A total of 236 patients with clinical stage T1 to T4, N0/1, M0 squamous cell carcinoma or adenocarcinoma selected for a nonsurgical approach, after stratification by weight loss, primary tumor size, and histology, were randomized to receive combined-modality therapy consisting of four monthly cycles of fluorouracil (5-FU) (1,000 mg/m2/24 hours for 4 days) and cisplatin (75 mg/m2 bolus day 1) with concurrent 64.8 Gy versus the same chemotherapy schedule but with concurrent 50.4 Gy. The trial was stopped after an interim analysis. The median follow-up was 16.4 months for all patients and 29.5 months for patients still alive. RESULTS: For the 218 eligible patients, there was no significant difference in median survival (13.0 v 18.1 months), 2-year survival (31% v 40%), or local/regional failure and local/regional persistence of disease (56% v 52%) between the high-dose and standard-dose arms. Although 11 treatment-related deaths occurred in the high-dose arm compared with two in the standard-dose arm, seven of the 11 deaths occurred in patients who had received 50.4 Gy or less. CONCLUSION: The higher radiation dose did not increase survival or local/regional control. Although there was a higher treatment-related mortality rate in the patients assigned to the high-dose radiation arm, it did not seem to be related to the higher radiation dose. The standard radiation dose for patients treated with concurrent 5-FU and cisplatin chemotherapy is 50.4 Gy.

Sequencing cell free DNA in patients receiving selective internal radiation therapy for colorectal liver metastases.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 646-646
Author(s):  
Helen Winter ◽  
P Kaisaki ◽  
Rebecca Carter ◽  
Anthony Cutts ◽  
Tessa Greenhalgh ◽  
...  
Keyword(s):  
Colorectal Liver Metastases ◽  
Somatic Mutations ◽  
Amplicon Sequencing ◽  
High Dose ◽  
Ion Torrent ◽  
Internal Radiation ◽  
Time Points ◽  
Mutational Status ◽  
High Concordance ◽  
Dose Radiation

646 Background: Tumour heterogeneity is a key determinants of cancer resistance. Serial sampling of cell free (cf)DNA may detect evolving somatic mutations. Monitoring cancers after therapies e.g. selective internal radiation therapy (SIRT) require new biomarkers as RECIST imaging was developed to assess response to chemotherapy and may not reflect tumour changes due to new therapeutic strategies. The utility of cfDNA to detect recurrence and predict response is emerging. The objective of this study was to sequence serial cfDNA samples from patients with liver predominant metastatic disease receiving SIRT, and explore the feasibility of using this method to detect evolution of somatic mutations after high dose radiation. Methods: A prospective imaging biomarker study was performed in patients with colorectal liver metastases (CRLM) receiving SIRT. Plasma was extracted and frozen within 4 hours at 3 time points: baseline, 4 and 10 weeks after SIRT. Ion Torrent Amplicon sequencing was performed using cancer hotspot panel v.2. Sequencing of primary tumours was obtained by pyrosequencing. Results: Twenty-four patients with CRLM were recruited from March – Dec 2015, and 18 had cfDNA extracted for sequencing at a minimum of two time points. Ion Torrent amplicon sequencing of baseline cfDNA showed high concordance with formalin-fixed paraffin-embedded (FFPE) tumour samples. Serial cfDNA sequencing in a patient with partial response by imaging, detected 22% KRAS G12C mutation at baseline, which decreased to 1.5% by 4 weeks, then was undetectable 10 weeks after SIRT. Sequencing of another patient’s cfDNA revealed persistence of KRAS G13D and a truncating APCmutation at both 4 and 10 weeks after SIRT, consistent with the patient’s progressive disease. Conclusions: Cell-free DNA is emerging as a biomarker in colorectal cancer. Our measurements of mutational status in baseline cfDNA and FFPE samples show high concordance. This study reports that serial cfDNA sequencing detects changes in mutational status and specific mutations following high dose radiation to the liver. This adds to the evidence of cfDNA as a tool to detect evolution of somatic mutations following therapy.

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