Dynamic ctDNA Assessment in Cervical and Anal Canal Tumors: Optimizing Follow-up and Clinical Outcomes

Summary

After definitive radiotherapy (RT) treatment (with or without chemotherapy), cervical and anal canal neoplasms frequently exhibit disease persistence or recurrence. Due to the local inflammatory process post-treatment, response assessment by imaging (current gold standard) is limited, often necessitating multiple follow-ups and repeated invasive biopsies. Conventional follow-up is complex and costly, requiring equipment from secondary and tertiary services, trained radiologists, and patient exposure to radiation and contrast. In this context of human papillomavirus(HPV)-related neoplasms, recent studies have demonstrated the role of ctDNA (circulating tumor DNA) in assessing the risk of recurrence or disease progression, providing a rationale for using the tool in two fronts: * Optimizing follow-up based on serial monitoring of ctDNA; * Selecting patients with positive ctDNA after RT, who are at high risk of recurrence, for treatment intensification. Monitoring with ctDNA as a standalone follow-up tool in cases evolving with negative ctDNA after RT has the potential to replace imaging exams, being a minimally invasive test performed on a peripheral blood sample. Currently, ctDNA testing has expensive methodologies not available in the Unified Health System (SUS). This project aims to develop a methodology for ctDNA evaluation focused on HPV ctDNA research that is low-cost and executable in SUS, as well to assess the accuracy of this test in the population with HPV-related tumors. Additionally, we will evaluate whether the early introduction of immunotherapy in patients with positive ctDNA after definitive treatment can increase cure rates. Immunotherapy already has a well-defined role in the treatment of metastatic HPV-related neoplasms. Recently, the use of anti-programmed death-1 (anti-PD1) has also shown benefits in patients with locally advanced cervical cancer with a high risk of recurrence who are candidates for chemoradiotherapy (CRT). Therefore, its use focused on HPV-related tumors, as well as a better understanding of which patients benefit from this strategy, warrants further investigation.

Timeline

Start

2025-03-14

Primary completion

2026-12

Completion

2027-01

Publications

• Background Bernard-Tessier A, Jeannot E, Guenat D, Debernardi A, Michel M, Proudhon C, Vincent-Salomon A, Bieche I, Pierga JY, Buecher B, Meurisse A, Francois E, Cohen R, Jary M, Vendrely V, Samalin E, El Hajbi F, Baba-Hamed N, Borg C, Bidard FC, Kim S. Clinical Validity of HPV Circulating Tumor DNA in Advanced Anal Carcinoma: An Ancillary Study to the Epitopes-HPV02 Trial. Clin Cancer Res. 2019 Apr 1;25(7):2109-2115. doi: 10.1158/1078-0432.CCR-18-2984. Epub 2018 Nov 30.
• Background Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, Bartlett BR, Wang H, Luber B, Alani RM, Antonarakis ES, Azad NS, Bardelli A, Brem H, Cameron JL, Lee CC, Fecher LA, Gallia GL, Gibbs P, Le D, Giuntoli RL, Goggins M, Hogarty MD, Holdhoff M, Hong SM, Jiao Y, Juhl HH, Kim JJ, Siravegna G, Laheru DA, Lauricella C, Lim M, Lipson EJ, Marie SK, Netto GJ, Oliner KS, Olivi A, Olsson L, Riggins GJ, Sartore-Bianchi A, Schmidt K, Shih lM, Oba-Shinjo SM, Siena S, Theodorescu D, Tie J, Harkins TT, Veronese S, Wang TL, Weingart JD, Wolfgang CL, Wood LD, Xing D, Hruban RH, Wu J, Allen PJ, Schmidt CM, Choti MA, Velculescu VE, Kinzler KW, Vogelstein B, Papadopoulos N, Diaz LA Jr. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014 Feb 19;6(224):224ra24. doi: 10.1126/scitranslmed.3007094.
• Background Cabel L, Bonneau C, Bernard-Tessier A, Hequet D, Tran-Perennou C, Bataillon G, Rouzier R, Feron JG, Fourchotte V, Le Brun JF, Benoit C, Rodrigues M, Scher N, Minsat M, Legrier ME, Bieche I, Proudhon C, Sastre-Garau X, Bidard FC, Jeannot E. HPV ctDNA detection of high-risk HPV types during chemoradiotherapy for locally advanced cervical cancer. ESMO Open. 2021 Jun;6(3):100154. doi: 10.1016/j.esmoop.2021.100154. Epub 2021 May 19.
• Background Jeannot E, Becette V, Campitelli M, Calmejane MA, Lappartient E, Ruff E, Saada S, Holmes A, Bellet D, Sastre-Garau X. Circulating human papillomavirus DNA detected using droplet digital PCR in the serum of patients diagnosed with early stage human papillomavirus-associated invasive carcinoma. J Pathol Clin Res. 2016 Jun 28;2(4):201-209. doi: 10.1002/cjp2.47. eCollection 2016 Oct.
• Background Jeannot E, Latouche A, Bonneau C, Calmejane MA, Beaufort C, Ruigrok-Ritstier K, Bataillon G, Larbi Cherif L, Dupain C, Lecerf C, Popovic M, de la Rochefordiere A, Lecuru F, Fourchotte V, Jordanova ES, von der Leyen H, Tran-Perennou C, Legrier ME, Dureau S, Raizonville L, Bello Roufai D, Le Tourneau C, Bieche I, Rouzier R, Berns EMJJ, Kamal M, Scholl S. Circulating HPV DNA as a Marker for Early Detection of Relapse in Patients with Cervical Cancer. Clin Cancer Res. 2021 Nov 1;27(21):5869-5877. doi: 10.1158/1078-0432.CCR-21-0625. Epub 2021 Jul 1.
• Background Lefevre AC, Pallisgaard N, Kronborg C, Wind KL, Krag SRP, Spindler KG. The Clinical Value of Measuring Circulating HPV DNA during Chemo-Radiotherapy in Squamous Cell Carcinoma of the Anus. Cancers (Basel). 2021 May 18;13(10):2451. doi: 10.3390/cancers13102451.

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