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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

3458 - Circulating tumour DNA (ctDNA) as a tool to assess response and guide therapy adaptation in rectal cancer

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Shelize Khakoo

Citation

Annals of Oncology (2018) 29 (suppl_8): viii649-viii669. 10.1093/annonc/mdy303

Authors

S. Khakoo1, P. Carter2, N. Valeri3, R. Shaikh2, T. Jones2, R. Begum1, I. Rana1, S. Picchia4, M. Bali4, G. Brown4, A. Wotherspoon5, M. Terlizzo5, K. von Loga6, I. Ahmed5, D. Watkins1, I. Chau1, N. Starling1, D. Tait1, M. Hubank2, D. Cunningham1

Author affiliations

  • 1 Medicine, Royal Marsden Hospital NHS Foundation Trust  , SM2 5PT - Sutton/GB
  • 2 Clinical Genomics, Royal Marsden Hospital NHS Foundation Trust  , SM2 5PT - Sutton/GB
  • 3 Molecular Pathology, The Institute of Cancer Research/Royal Marsden NHS Foundation Trust, SM2 5PT - Sutton/GB
  • 4 Radiology, Royal Marsden Hospital NHS Foundation Trust  , SM2 5PT - Sutton/GB
  • 5 Histopathology, Royal Marsden Hospital NHS Foundation Trust  , SW3 6JJ - London/GB
  • 6 Histopathology, Royal Marsden Hospital NHS Foundation Trust  , SM2 5PT - Sutton/GB
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Resources

Abstract 3458

Background

Neo-adjuvant chemoradiation (CRT) is associated with varied response in patients (pts) with localised rectal cancer. Early identification of poor responders and pts at risk of developing systemic disease using ctDNA would allow tailoring of treatment.

Methods

Tissue and serial plasma was collected from 47 pts with localised rectal cancer scheduled to undergo long course CRT. Cell-free DNA (cfDNA) was purified from a mean of 3.6 ml plasma per time-point. Somatic variants were identified in tissue by sequencing using a targeted capture panel. Up to 3 variants per patient in genes of interest were tracked in plasma using custom TaqMan assays on a droplet digital PCR platform. Tumour response assessments were conducted according to RECIST. Statistical analysis included Fisher’s exact test and Spearman’s correlation.

Results

62% of pts were male, median age 59, range 30-83. On baseline MRI, circumferential resection margin was involved or threatened in 75% and EMVI positive in 81%. Plasma was collected at a median of: 6 days (d) prior to CRT (baseline), 21 d from the start of CRT (mid) and 37 d after completion of CRT (end). The frequency (%) of mutation detection in tissue was: TP53 (85), APC (74), KRAS (36), PIK3CA (15), NRAS (4) and BRAF (2). ctDNA was detectable in 74% of pts at baseline and in 21% at mid and end of CRT. ctDNA detection increased with stage at baseline: stage 1 (n = 0/1), stage 2 (n = 3/5, 60%) and stage 3 (n = 32/41, 78%). Stage had no impact on detection at mid or end of CRT. At baseline, ctDNA was detectable in all 15 CEA secretors (≥5 ug/l) compared to 63% in 30 non-secretors (P = 0.008). Baseline ctDNA levels were not associated with ki67 tumour assessment. MRI response assessment of the primary tumour was not associated with ctDNA detection at any timepoint. 11 patients developed metastases of which 3 occurred after surgery. End of CRT ctDNA detection was higher in pts that developed metastases (64%) compared to those that did not (8.3% P = 0.0005). Detection of ctDNA at baseline that persisted at mid CRT was also higher in pts that developed metastases (36% vs 11%, p = 0.07).

Conclusions

ctDNA detection can help identify rectal cancer pts with localised disease at risk of developing metastases. These pts could benefit from earlier intervention with systemic therapy.

Clinical trial identification

CCR 3085, NCT00825110.

Legal entity responsible for the study

Royal Marsden Hospital NHS Foundation Trust.

Funding

Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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