NOAC9 - Circulating Tumor DNA Guided Follow-Up in Anal Cancer

NOAC9 - A Phase II Randomised Nordic Anal Cancer Group Study on Circulating Tumor DNA Guided Follow-Up

This study investigates if circulating tumor DNA can improve the detection of early treatment failure or recurrence in localized squamous cell carcinoma of the anus (SCCA) after curative chemoradiotherapy thereby increasing the potential for cure. This will be done by comparing the standard follow-up program with ctDNA guided imaging follow-up. Secondly, the aim is to establish early interventions against late morbidities.

Squamous cell carcinoma of the anus (SCCA) is a rare disease with less than 200 new cases in Denmark and Sweden each year and approximately 100 new cases in Norway and Finland but with increasing incidence. Primary treatment is chemo-radiotherapy (CRT) comprising high dose IMRT based radiation therapy with combination chemotherapy of 5-FU and Cisplatin. Overall treatment response is good in small tumors, but less pronounced for high-risk tumors. In absence of complete pathological response after CRT or local recurrence, patients are evaluated for. salvage surgery. The importance of R0 resection on overall survival has been described in several studies. It is suggested that early detection of treatment failure and recurrences increases the chance of possible curative surgery (R0-resection) and thereby overall survival. A follow-up program has 3 purposes To detect lack of complete response to primary treatment Early detection of local or distant recurrences Describing and managing late morbidity Purpose: The main purpose of this follow-up study is to investigate if circulating tumor tDNA can improve detection of early treatment failure or recurrences thereby assisting in increasing the potential for cure. Secondly, to provide evidence for use of imaging and third objective is to establish early intervention against late morbidities.

The national follow-up program + collection of blood samples for retrospective translational research

The national follow-up program + ctDNA guided additional imaging + collection of blood samples for retrospective translational research

Patients with HPV negative disease will be included in an observational arm (ARM O) ARM O: The national follow-up program + collection of blood samples for retrospective translational research

Blood samples in follow-up positive for ctDNA leads to an extra PET-CT scan to detect early treatment failure

Pattern of failure defined as ln-field failures (within GTV-T, GTV-N, CTV or irradiated areas) or out-of-field failures

Inclusion Criteria: Patients with SCCA eligible for definitive (chemo)radiotherapy ≥ 18 of years Written and oral consent Exclusion Criteria: Conditions that will contraindicate blood samples Conditions that will contraindicate a PET-CT scan. Potential lack of compliance to standard FU program and study participation.