K Wakeham1, L Murray2, R Muirhead3, M A Hawkins4, D Sebag-Montefiore2, S Brown5, L Murphy6, G Thomas7, S Bell8, M Whibley9, C Morgan9, K Sleigh9, D C Gilbert10. 1. Sussex Cancer Centre, Royal Sussex County Hospital, Brighton, UK; Institute of Cancer Sciences, University of Glasgow, Glasgow, UK. 2. Leeds Institute of Medical Research, University of Leeds, Leeds Cancer Centre, Leeds, UK. 3. Oxford University Hospitals NHS Trust, Department of Oncology, Churchill Hospital, Oxford, UK. 4. University College London, Medical Physics and Biomedical Engineering, London, UK. 5. Clinical Trials Research Unit, University of Leeds, Leeds, UK. 6. MRC Clinical Trials Unit at UCL, London, UK. 7. Department of Cellular Pathology, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Cancer Sciences Unit, University of Southampton, Southampton, UK. 8. Institute of Cancer Sciences, University of Glasgow, Glasgow, UK. 9. Sussex Cancer Centre, Royal Sussex County Hospital, Brighton, UK. 10. MRC Clinical Trials Unit at UCL, London, UK. Electronic address: duncan.gilbert2@nhs.net.
Abstract
AIMS: Anal squamous cell carcinomas (ASCC) are strongly associated with human papillomaviruses. Standard of care is chemoradiotherapy at uniform doses with no treatment stratification. Immunohistochemical staining for p16INK4A (p16), a surrogate for human papillomaviruses, is prognostic for outcomes. We investigated this alongside clinical-pathological factors, including tumour infiltrating lymphocyte (TIL) scores. MATERIALS AND METHODS: Using an independent, multicentre cohort of 257 ASCC treated with chemoradiotherapy, pretreatment biopsies were stained and scored for p16 and TIL. Kaplan-Meier curves were derived for outcomes (disease-free survival [DFS], overall survival and cancer-specific survival), by stage, p16 and TIL scores and Log-rank tests were carried out to investigate prognostic effect. A multivariate analysis was carried out using Cox regression. RESULTS: Stage, sex, p16 and TILs were independently prognostic. Hazard ratios for death (overall survival) were 2.51 (95% confidence interval 1.36-4.63) for p16 negative versus p16 positive, 2.17 (1.34-3.5) for T3/4 versus T1/2, 2.42 (1.52-3.8) for males versus females and 3.30 (1.52-7.14) for TIL1 versus TIL3 (all P < 0.05). CONCLUSIONS: We have refined prognostic factors in ASCC. p16 adds to stratification by stage with respect to DFS in early disease and overall survival/DFS in locally advanced cancers. Our data support the role of the host immune response in mediating outcomes. These factors will be prospectively evaluated in PLATO (ISRCTN88455282).
AIMS: Anal squamous cell carcinomas (ASCC) are strongly associated with human papillomaviruses. Standard of care is chemoradiotherapy at uniform doses with no treatment stratification. Immunohistochemical staining for p16INK4A (p16), a surrogate for human papillomaviruses, is prognostic for outcomes. We investigated this alongside clinical-pathological factors, including tumour infiltrating lymphocyte (TIL) scores. MATERIALS AND METHODS: Using an independent, multicentre cohort of 257 ASCC treated with chemoradiotherapy, pretreatment biopsies were stained and scored for p16 and TIL. Kaplan-Meier curves were derived for outcomes (disease-free survival [DFS], overall survival and cancer-specific survival), by stage, p16 and TIL scores and Log-rank tests were carried out to investigate prognostic effect. A multivariate analysis was carried out using Cox regression. RESULTS: Stage, sex, p16 and TILs were independently prognostic. Hazard ratios for death (overall survival) were 2.51 (95% confidence interval 1.36-4.63) for p16 negative versus p16 positive, 2.17 (1.34-3.5) for T3/4 versus T1/2, 2.42 (1.52-3.8) for males versus females and 3.30 (1.52-7.14) for TIL1 versus TIL3 (all P < 0.05). CONCLUSIONS: We have refined prognostic factors in ASCC. p16 adds to stratification by stage with respect to DFS in early disease and overall survival/DFS in locally advanced cancers. Our data support the role of the host immune response in mediating outcomes. These factors will be prospectively evaluated in PLATO (ISRCTN88455282).
Authors: Brian De; Ethan B Ludmir; Craig A Messick; Matthew C Cagley; Van K Morris; Prajnan Das; Bruce D Minsky; Cullen M Taniguchi; Grace L Smith; Eugene J Koay; Albert C Koong; Radhe Mohan; Emma B Holliday Journal: J Gastrointest Oncol Date: 2021-10