ESTRO 2023

Session Item

Monday

May 15

11:40 - 12:40

Plenary Hall

Highlights of Proffered Papers - Latest clinical trials

Chair: , United Kingdom;

Chair: , Switzerland

Session Code: 3290

Session Type: Proffered Papers

Track: Interdisciplinary

12:10 - 12:20

Standard vs dose reduced chemoradiotherapy in anal cancer: short-term results of the PLATO-ACT4 RCT

, United Kingdom

Presentation Number: OC-0831

Abstract

Abstract Title:

Standard vs dose reduced chemoradiotherapy in anal cancer: short-term results of the PLATO-ACT4 RCT

Authors:

Alexandra Gilbert¹, Joanne Webster², Sarah Brown², Joanna Copeland², Sharon Ruddock², Duncan Gilbert³, Maria Hawkins⁴, Rebecca Muirhead⁵, Andrew Renehan⁶, Richard Adams⁷, Mark Harrison⁸, David Sebag-Montefiore¹

¹University of Leeds, Leeds Cancer Centre, Leeds, United Kingdom; ²University of Leeds, Leeds Institute of Clinical Trials Research, Leeds, United Kingdom; ³Royal Sussex County Hospital, Sussex Cancer Centre, Brighton, United Kingdom; ⁴University College London, Dept of Medical Physics & Biomedical Engineering, London, United Kingdom; ⁵Oxford University Hospitals NHS Trust, Department of Oncology, Churchill Hospital, Oxford, United Kingdom; ⁶Manchester Cancer Research Centre, NIHR Manchester Biomedical Research Centre, Manchester, United Kingdom; ⁷Cardiff University, Centre for Trials Research, Cardiff, United Kingdom; ⁸Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, London, United Kingdom

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Purpose or Objective

Localised squamous cell carcinoma of the anus is treated with radical chemoradiotherapy. Cure rates are high but treatment can result in significant long-term morbidity.

Material and Methods

ACT 4 is a phase II prospective, multi-centre, 2-arm RCT, embedded within the PLATO platform; investigating dose reduced intensity modulated radiotherapy (dr-IMRT) with chemotherapy in patients (pts) with T1-2(≤4cm)N0 anal cancer. The primary outcome is 3-year locoregional control; with the aim of reducing acute and late toxicity. We report on the planned 6-month endpoint analysis – radiological complete clinical response rates (cRR), acute toxicity (CTCAEv5), treatment compliance, and patient reported outcomes (PROs; EORTC-QLQ C30 and ANL27).

Pts with T1-2(≤4cm)N0M0 squamous cancer of the anus were randomised 1:2 to standard dose IMRT (sd-IMRT; 50.4Gy in 28F; elective nodal irradiation 40Gy in 28F) or dr-IMRT (41.4Gy in 23F; elective nodal irradiation 34.5Gy in 23F) with concurrent mitomycin 12mg/m2 day (D)1 and capecitabine (CAP) 825mg/m2 twice daily on days of RT. 123 pts were required to demonstrate dr-IMRT does not produce efficacy rates <80% and reaches efficacy rates of ≥90%. The sample was inflated to 162 for analysis of p16+ genotype outcomes.

Results

160 pts were recruited from 28 UK sites (sd-IMRT n=55; dr-IMRT n=105) between Jan 2017 and Dec 2020. 3 pts randomised to reduced dose IMRT were excluded for the modified intention to treat analysis. See Table 1 for pt characteristics.

For pts with MRI at 6 months, 90.0% sd-IMRT (n=45/50) and 92.4% dr-IMRT (n=85/92) had a TRG grade 1 or 2 (complete or fibrosis only) (see Table 2).

99% received planned RT; 1 pt (sd-IMRT) withdrew due to toxicity and 1 pt (dr-IMRT) withdrew consent from the trial at D17. One pt (dr-IMRT) received 50.4Gy after stopping CAP on D2 due to toxicity. 25.5% (sd-IMRT; n=14) and 15.2% (dr-IMRT; n=16) experienced at least one RT interruption; 32% due to toxicity, 68% logistical. Chemotherapy modifications (sd-IMRT n=32, 58.2%; dr-IMRT n=50, 47.6%) were in the majority of cases due to toxicity (65-80%).

≥G3 acute toxicity was reported in 45.5% sd-IMRT (n=25) versus 35.2% dr-IMRT (n=37; see Table 1). Overall for PROs, there was a large to moderate deterioration in pain, fatigue, overall bowel function, quality of life, physical, role and social function at the end of CRT which resolved to baseline by either 6 weeks or 6 months in both arms. Sexual function improved to baseline levels by 6 weeks for men and 6 months for women in dr-IMRT, but poorer sexual function was maintained to 6 months in sd-IMRT for both men and women.

Conclusion

High 6 month cRR were seen in both arms. sd-IMRT had more RT interruptions and chemotherapy modifications than dr-IMRT. Fewer patients reported overall ≥G3 acute toxicity with dr-IMRT. Most PRO symptoms and function changes had improved to baseline by 6 months, while sexual function had improved for men and women receiving dr-IMRT, it remained poor following sd-IMRT.