90P - Feasibility of using tumor-informed circulating tumor DNA (ctDNA)-based testing for patients with anal squamous cell carcinoma

Background

Anal squamous cell carcinoma (SCCA) is an uncommon malignancy with a rising incidence, that has a high cure rate in its early stages. However, there is an unmet need for a reliable, non-invasive method to monitor response to treatment and assist in surveillance. Standard-of-care surveillance primarily relies on radiological imaging and anoscopy with biopsy, which can potentially lead to false positive and negative results. Circulating tumor DNA (ctDNA) testing has shown great promise in other solid tumors for monitoring disease progression and detecting relapse in real time. This study aimed to determine the feasibility and clinical utility of personalized and tumor-informed ctDNA testing in SCCA.

Methods

We retrospectively analyzed real-world data from 251 patients with stage I-IV SCCA, collected between November 5, 2019 - May 31, 2022. The tumor genomic landscape and feasibility of ctDNA testing was examined for all patients. The prognostic value of longitudinal ctDNA testing was assessed in patients with clinical follow-up (N=37).

Results

Plasma samples (n=817) were collected from 251 SCCA patients (180 females, 71 males; median age 63.5 years; range: 27.9 - 89.4) at various time points. Analysis of whole exome sequencing revealed PIK3CA to be the most commonly mutated gene. No association with stage was observed with any of the genes. Anytime ctDNA positivity and higher ctDNA levels (MTM/ml) were more strongly associated with stage IV patients, compared to those with localized disease (p=0.004). For 37 patients with complete clinical data available, the median follow-up time was 21.0 months (range: 4.1-67.3) post-diagnosis. In this sub-cohort of patients with stage I-III disease anytime ctDNA-positivity after definitive treatment was found to be associated with a higher risk of recurrence (relapse-free survival HR: 18.7, P=0.018).

Conclusions

Our study demonstrates the feasibility of personalized and tumor-informed ctDNA testing in patients with SCCA as well as potential the clinical utility for detection of molecular/minimal residual disease, and relapse during surveillance. Prospective studies are needed to better evaluate the use of ctDNA testing in this indication.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Natera, Inc.

Disclosure

G. Azzi: Financial Interests, Personal, Stocks/Shares: Halozyme Therapeutics, Illumina, Guardant Health, TG Therapeutics, AptoseBiosciences, CytomxTherapeutics, Zymeworks, Global Blood, Invitae, SangamoTherapeutics, Cellectis, Cohbar, Fibrogen; Financial Interests, Personal, Advisory Board: Pfizer, Astellas/Seattle Genetics; Financial Interests, Personal, Speaker’s Bureau: Natera, Inc, Guardant Health. M. Tavallai, V. Aushev, A.E. Koyen Malashevich, S. Krinshpun, M. Malhotra, P. Olshan, A. Jurdi, A. Aleshin: Financial Interests, Personal, Stocks/Shares: Natera, Inc.; Financial Interests, Personal, Full or part-time Employment: Natera, Inc. G. Botta: Financial Interests, Personal, Advisory Board: Natera, Inc.; Financial Interests, Personal, Speaker’s Bureau: Natera, Inc.; Financial Interests, Personal, Training: Natera, Inc.; Financial Interests, Personal, Advisory Role, consultant: CEND Therapeutics; Financial Interests, Personal, Full or part-time Employment, employment of a family member: Applied Medical; Non-Financial Interests, Personal, Other, uncompensated relationship: SEngine Precision Medicine. P.M. Kasi: Financial Interests, Personal, Advisory Board: Natera, Inc., Foundation Medicine, MSD Oncology, Tempus, Bayer, Lilly, Delcath Systems, IPBA, QED Therapeutics, Boston Healthcare Associates, Servier, Taiho Oncology, Exact Sciences, Daiichi Sankyo/Astra Zeneca, Eisai, Seattle Genetics, Taiho Pharmaceutical, Ipsen; Financial Interests, Personal, Research Grant: Advanced Accelerator Applications, Tersera, Boston Scientific; Financial Interests, Personal, Other, travel/expenses: AstraZeneca. All other authors have declared no conflicts of interest.