ESTRO 2024 Congress report

In this session were reported the latest updates in anal cancer treatment, exploring current and future directions with a special focus on the gross tumour volume (GTV) dose, as reported by David Sebag-Montefiore from the University of Leeds, UK.

‘Despite 30 years of trials, the optimal dose and fractionation for different target volumes, and the method for delivering the boost dose, remain unresolved’ said Professor Montefiore. Although first- and second-generation trials had confirmed the role of chemoradiation, and found no role for neoadjuvant and maintenance chemotherapy, no one had addressed the issue of radiotherapy dose.

Prof Montefiore said that ‘the questions we must address’ were avoiding overtreatment, optimising the GTV dose and understanding the disease’s biology.

The personalising anal cancer radiotherapy dose trial (PLATO) which is investigating doses of chemoradiotherapy for people with locally advanced anal cancer, now involves 709 patients and is focused on the GTV dose in different tumour presentations. The ACT 3 part of the trial is designed to show that it is feasible to avoid radiotherapy for clear-margin excised tumours. ACT 4 explores whether reduced doses for early tumours can reduce toxicity while maintaining control. Preliminary results suggest that lower doses (41Gy vs. 50Gy) result in similar tumour response with less toxicity.

ACT 5 examines GTV dose escalation in advanced cases to find the optimal dose among 53.2Gy, 58.8Gy and 61.6Gy.

A better understanding of tumour biology is a must to explain variations in behaviour. It is crucial to understand the biology of human papillomavirus (HPV) and its relationship with immune response, and this is achievable through the study of HPV biology, biomarkers, radiomics, the microbiome, immune response and radiosensitivity.

Luca Tagliaferri, from the Catholic University of Rome, Italy, illustrated the role of brachytherapy in the treatment of anal cancer. He showed how modern interventional radiotherapy could take full advantage of local boost. Brachytherapy is known to deliver high doses to the tumour while sparing surrounding tissues due to rapid dose fall-off and to show clinical advantages when delivered within 80 days of diagnosis. However, its application increases the risk of the development of radionecrosis and ulcers.

The advent of high-dose-rate, stepping sources and ultrasound/MR-guided brachytherapy has ushered in interventional radiotherapy, the use of which enables precise dose distribution and modulation. These advances enable the delivery of high doses to hypoxic, radioresistant areas and lower doses to healthy tissues, potential interaction with the microenvironment immune response and reduced movement issues.

Prof Tagliaferri said: ‘Although clinical results are scarce, inhomogeneous, and retrospective, the results of recent trials are promising. The recently published HIT-ART [high-tailored anal canal radiotherapy] trial, on more than 100 locally advanced anal cancer patients, reported a three-year colostomy-free survival of 84% and grade 3 toxicity under 5%, highlighting the benefits of modern techniques over older methods.’

 

The session closed with a presentation from Mariane Guren, from Oslo University Hospital, Norway, on patient-reported outcomes. Improvements in chemoradiation outcomes in the past 25 years had led to a growing number of anal cancer survivors.

Earlier studies that had used quick-response quality control 30 and 29 questionnaires had indicated that anal cancer patients experienced worse quality of life (QoL) compared with the general population, and poorer bowel and sexual function. To address the need for more specific assessments, a new questionnaire, the QoL anal-cancer-specific ANL27, has been developed and internationally validated for use in clinical trials.

Interestingly, patient-reported outcome measure studies had found no significant difference in bowel and sexual function before and one year after chemoradiation, highlighting the importance of minimising treatment side effects. Besides common side effects, pelvic insufficiency fractures represent a significant issue post-chemoradiation, with radiological detection rates as high as 50%, often at the sacral bone, from which pelvic pain is caused. A strong correlation with radiation dose has been found. Current trials adopt bone-sparing treatments to address this issue.

Preventive measures include the use of image-guided radiotherapy, dose reductions for early-stage tumours and risk-adapted cranial field clinical target volume modulation to decrease the dose to organs at risk. Management of these issues requires an interdisciplinary approach that addresses bowel, anorectal, endocrine, sexual and bone dysfunctions.

Maria Antonietta Gambacorta, MD, PhD

Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome

Università Cattolica del Sacro Cuore, Rome

Italy

ESTRO lower gastrointestinal focus group