Congress Report
By the ESTRO lower GI focus group

In all, 22 cutting-edge abstracts were presented across mini-oral, poster discussion, and proffered paper formats, offering fresh insight into the evolving landscape of rectal and anal cancer care.
 

Key Themes in Rectal Cancer

• Total neoadjuvant therapy (TNT): refinement of strategies to enhance compliance and reduce toxicity.
• Organ preservation: promising outcomes from selective treatment approaches and normal tissue complication probability (NTCP) modelling.
• Quality of life: new data emphasise the need for metrics to measure this outcome long-term in TNT-treated patients.
   

Advances in anal cancer

• De-escalation of radiotherapy: the ACT4 trial shows reduced toxicity with no compromise in disease control.
• Patient-reported outcomes: longitudinal data highlight persistent sexual dysfunction, which is driving a need for targeted survivorship support.
• Sex-based prognostic factors: novel findings suggest that T4 classification in women may overstate risk.
   

Rectal cancer

A phase II trial was presented by Huiying Ma (Beijing, China) [A1] (NCT04543695), in which three neoadjuvant approaches were compared for locally advanced rectal cancer: TNT with consolidation chemotherapy using six cycles of XELOX after consolidation chemoradiotherapy (CNCT), TNT with induction chemotherapy before chemoradiotherapy (INCT), and chemoradiotherapy alone as control. Both TNT groups demonstrated superior tumour downstaging (75.6% CNCT, 74.1% INCT) and complete response (CR) rates (43.0%, 38.8%) compared with the controls. Although toxicity was higher in the TNT arms, most patients tolerated treatment well, and surgical complications were not increased. These findings supported the use of TNT as an effective intensified approach.

Yanqi Huang (Maastricht, Netherlands) had developed an MRI-based radiomics framework that used habitat imaging to predict rates of disease-free survival (DFS) after neoadjuvant chemoradiotherapy. Through analysis of patients’ pre-treatment MRIs, the patients were classified into imaging subtypes with distinct DFS outcomes. This model provided independent prognostic information beyond clinical factors, suggesting it could be used to personalise treatment by identifying patients at higher risk of recurrence.

Haoyue Li (Beijing, China), in a phase II study, compared simultaneous integrated boost (SIB) intensity-modulated radiation therapy (IMRT) with standard 3D conformal radiotherapy (CRT) for stage II/III rectal adenocarcinoma. While pathological CR rates were similar, SIB-IMRT significantly improved rates of nine-year DFS (70.8% vs. 47.2%) and overall survival (74.3% vs. 48.9%) without increasing late toxicity, indicating long-term benefits of dose escalation in CRT.

A multicentre study by Georg W Wurschi (Jena, Germany) compared short-course radiotherapy (SCRT) and CRT within TNT. The use of CRT led to higher CR rates (56.1% vs. 37.6%) and more patients undergoing non-operative management, but it caused more toxicity. Recurrence and mortality rates were similar. Longer TNT duration improved CR rates; this finding highlighted the importance of treatment sequencing.

Barbara Salas (Las Palmas de Gran Canaria, Spain), in a phase II trial, added locoregional deep hyperthermia (HT) to SCRT with TNT chemotherapy in 61 patients. The use of HT increased pathological CR by 10 percentage points (39.5% vs. 29.5%) without increasing toxicity or postoperative complications. HT was well tolerated, so this showed promise to enhance radiotherapy efficacy safely.

The THUNDER 2 phase II trial (Giuditta Chiloiro,Rome, Italy) used the early tumour regression index (ERI) to identify non-responders to standard therapy and applied MRI-guided dose escalation. Overall, the CR rate was 37.1%, and dose escalation doubled CR rates in non-responders (22.6%). This adaptive approach, with application of the early tumour index, improved outcomes by tailoring treatment intensity.

Rebecca Muirhead presented (Oxford, UK) a 2023 UK audit that showed improved adoption of IMRT/volumetric modulated arc therapy techniques and peer review in line with national radiotherapy guidelines, but the continuation of considerable variation in neoadjuvant treatment approaches and SIB use indicates a need for further standardisation.

The multicentre “TNTox” study of the toxicity of TNT (Georg W Wurschi, Jena, Germany) found that higher cumulative chemotherapy doses during TNT were correlated with increased CR rates but also with more severe toxicity, especially in older patients. These results underscore the need to balance efficacy and toxicity in TNT.

Ross K. McMahon’s study (Glasgow, UK) showed that serial proctoscopy biopsies during radiotherapy were acceptable to patients; few expressed regret that they had undertaken them, while there were perceived benefits, including anxiety reduction and research contribution. These findings support their use in clinical trials.

An analysis of the phase III RAPIDO trial presented by Ilaria Prata (Maastricht, Netherlands) revealed higher locoregional recurrence after TNT compared with CRT, particularly in sphincter-preserving surgery with ≤10mm distal margins. These findings suggest a need for wider margins in SCRT-based TNT for optimal control.

Max D. Tanaka (Amsterdam, Netherlands) presented a further RAPIDO trial analysis, in which the authors had developed NTCP models that predicted acute bowel toxicity and chemotherapy compliance. The results emphasised the requirement to limit bowel radiation dose during SCRT to reduce toxicity and maintain treatment adherence.

Finally, a study of the surveillance, epidemiology and end results (SEER) programme database by Xiaojun Liu (Lanzhou, China) on rectal neuroendocrine cancer patients showed that the use of radiotherapy significantly improved overall survival rates when combined with surgery and chemotherapy. Therefore, the use of radiotherapy is an important multimodal treatment component.
 

Anal cancer

Anne V. Jakobsen (Aarhus, Denmark) described a prospective study in 126 patients with squamous cell carcinoma of the anus (SCCA), in which she assessed the dynamics of circulating cell-free DNA (cfDNA) during chemoradiotherapy. Baseline cfDNA levels were linked with high-risk disease, but only a significant reduction in rates of cfDNA elimination (>−21.15%) was correlated with treatment failure and worse rates of DFS, suggesting that cfDNA decline could be a promising prognostic biomarker.

Hamish Sinclair (Brighton, UK) described UK retrospective evaluation of 338 frail or comorbid anal cancer patients who received de-escalated treatment. The analysis showed that despite variable regimens, over half of the patients achieved CR. However, the rate of overall survival was significantly lower than this CR rate, and these results emphasised the need for tailored clinical trials for this vulnerable group.

Charlotte L. Deijen’s Dutch nationwide cohort study (Amsterdam, Netherlands) of 462 anal cancer patients who had been treated with curative chemoradiotherapy reported a three-year locoregional recurrence-free survival of 79%, a CR rate of 82%, and a colostomy-free survival rate of 88%. These results confirmed current standards and provided a national benchmark.

Johanne H. Steffensen’s Danish prospective study (Aarhus, Denmark) documented persistent vaginal and sexual dysfunction after pelvic radiotherapy in women with anal cancer. Problems included vaginal dryness, pain, and reduced sexual enjoyment, and highlighted the urgent need for supportive interventions.

The ACT4 randomised trial compared reduced-dose (41.4Gy) with standard-dose (50.4Gy) chemoradiotherapy in early-stage anal cancer. Alexandra Gilbert (Leeds, UK) showed that the reduced dose led to reduced levels of acute toxicity and better recovery of bowel and sexual function with similar long-term outcomes, supporting the use of reduced-dose IMRT rather than standard.

Shefali P. Parikh’s study (Birmingham, UK) revealed that vaginal invasion in female anal cancer patients often resulted in T4 staging but was not a predictor of poorer survival outcomes compared with males; tumour size was a more relevant prognostic factor than the T-stage.

 

Metastatic setting

In the MIRACLE-2 study (Zhen Zhang, Shanghai, China), the application of radiotherapy combined with systemic therapy and tislelizumab was evaluated in microsatellite-stable, unresectable, metastatic rectal cancer. This treatment achieved an 84.2% early tumour shrinkage rate and 92.1% disease control rate with manageable toxicity, and hence showed promise in this immunotherapy-resistant group.

MIRACLE-1 showed that the same treatment combination, but in microsatellite-stable, locally advanced rectal cancer with resectable metastases, led to a partial response in 90% of cases and no evidence of disease in 65%.

The RIFLE trial results were presented by Fan Xia (Shanghai, China). She reported a 31.7% response rate with the combination treatment of stereotactic ablative body radiotherapy, fruquintinib, and tislelizumab in metastatic colorectal cancer.

Angela Romano (Rome, Italy) showed that MRI-guided stereotactic body radiotherapy offered high local control and safety for peritoneal oligometastases; the results were excellent for such a challenging setting.

Letizia Deantonio, MD
Department of Radiation Oncology, Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland
Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano Switzerland
Member of the ESTRO lower gastrointestinal focus group

e-mail: letizia.deantonio@eoc.ch