Early circulating tumour DNA kinetics measured by ultra-deep next-generation sequencing during radical radiotherapy for non-small cell lung cancer: a feasibility study.

BACKGROUND: The evaluation of circulating tumour DNA (ctDNA) from clinical blood samples, liquid biopsy, offers several diagnostic advantages compared with traditional tissue biopsy, such as shorter processing time, reduced patient risk and the opportunity to assess tumour heterogeneity. The historically poor sensitivity of ctDNA testing, has restricted its integration into routine clinical practice for non-metastatic disease. The early kinetics of ctDNA during radical radiotherapy for localised NSCLC have not been described with ultra-deep next generation sequencing previously. MATERIALS AND METHODS: Patients with CT/PET-staged locally advanced, NSCLC prospectively consented to undergo serial venepuncture during the first week of radical radiotherapy alone. All patients received 55Gy in 20 fractions. Plasma samples were processed using the commercially available Roche AVENIO Expanded kit (Roche Sequencing Solutions, Pleasanton, CA, US) which targets 77 genes. RESULTS: Tumour-specific mutations were found in all patients (1 in 3 patients; 2 in 1 patient, and 3 in 1 patient). The variant allele frequency of these mutations ranged from 0.05-3.35%. In 2 patients there was a transient increase in ctDNA levels at the 72 h timepoint compared to baseline. In all patients there was a non-significant decrease in ctDNA levels at the 7-day timepoint in comparison to baseline (p = 0.4627). CONCLUSION: This study demonstrates the feasibility of applying ctDNA-optimised NGS protocols through specified time-points in a small homogenous cohort of patients with localised lung cancer treated with radiotherapy. Studies are required to assess ctDNA kinetics as a predictive biomarker in radiotherapy. Priming tumours for liquid biopsy using radiation warrants further exploration.

PET-CT accurately predicts the pre-operative characteristics of colorectal hepatic metastases.

BACKGROUND: Since 2002, Positron Emission Tomography (PET-CT) has been considered to be an essential pre-operative investigation in the management of colorectal liver metastases (CRLM) in our institution. This study aimed to compare characteristics of hepatic metastases on PET-CT with post-operative histological findings and pathology of the primary tumour. METHODS: All patients with CRLM, who underwent surgical intervention from 2002 to 2008, were reviewed. PET-CT and pathology reports of hepatic resections and original colorectal resections were retrieved. Patient demographics, colorectal staging, number of metastases and their maximum diameter from both PET-CT and pathology reports were recorded. Values were expressed as mean (±SD). RESULTS: 141 patients were identified. The maximum diameter on PET-CT (4.2 ± 2.6) was similar to pathology (4.8 ± 3.6; p = 0.39), with significant correlation (r = 0.72, p < 0.0001). The number of lesions on PET-CT (1.6 ± 1.0) was similar to pathology (1.7 ± 1.3; p = 0.43) with significant correlation (r = 0.80, p < 0.0001). Mean SUV max was 9.22 (±4.39), with no correlation to lesion diameter (r = 0.25, p = 0.045), but significantly increased with decreasing differentiation (p = 0.01). CONCLUSIONS: PET-CT scanning accurately detected the number of lesions and their maximum diameter, with radiological evidence of poorer differentiation. Further studies of non-surgical patients are required to assess its overall accuracy.

Register of chromosomal abnormalities in Queensland.

The development and use of the computer-aided retrieval of karyotypes (CAROK), a register of chromosomal abnormalities in Queensland, is described. The six independent cytogenetic laboratories serving the population of 2.2 million contribute data to the register which provides total population information on the occurrence of chromosomal abnormalities, without selection. CAROK policy on confidentiality, security, access, and safety of data is described in detail. A cytogenetic register such as this ensures a reliable permanent file of results, facilitates research, and provides a data base which will enable questions of clustering or secular trends to be answered efficiently. The register is complete for the years 1976-1981, and contains information on 880 consecutive abnormal cases; in this sense, the data constitute an unselected six-year series of diagnosed chromosomal abnormalities in Queensland. These figures show an average incidence figure (over a six-year period) for newly diagnosed cases of chromosomal abnormality of 6.61/100 000 general population per year.