Utilization of stereotactic body radiation therapy and circulating tumor DNA analysis to guide adjuvant systemic therapy in the setting of patients with oligometastatic disease

Purpose: Colorectal cancer is the fourth most common cancer and second in cancer-related death in the United States.1,3 There has been substantial improvement in therapeutic strategies and advances in molecular characterization of the tumor. Additionally, several studies have appreciated the utility of liquid biopsy to evaluate circulating tumor DNA (ctDNA) isolated from plasma which reliably monitors minimal residual disease (MRD) and can help identify patients at high risks of systemic recurrence.2,4 We aim to investigate systemic ctDNA as an important tool to strategize adjuvant systemic therapy after definitive stereotactic body radiation therapy (SBRT).

Methodology: A baseline ctDNA assay was obtained by personalized multiplex PCR next-generation sequencing assay (Natera Inc Signatera) with pretreatment CT imaging. This was repeated posttreatment of definitive Varian Truebeam SBRT 50Gy in 5 fractions to planning target volume with integrated boost to 60Gy internal target volume to all three lesions every other day.

Results: We present a case of an 80-year-old female patient status post resection of a pathologic T1 N0 rectal cancer in September 2020 and found to have biopsy-proven recurrent oligometastatic disease of the lung in April 2021. Pretreatment PET/CT scans between June – August 2021 revealed three nodules in the right upper lung. Systemic treatments were considered to prevent future metastatic disease; however, this was at an increased risk for toxicity. Longitudinal monitoring of ctDNA demonstrated a baseline ctDNA quantity of 0.15 mean tumor molecules per mL (MTM/mL). The patient was subsequently treated with definitive radiotherapy. During her posttreatment monitoring, she was found to have 0 MTM/mL indicating no disease burden by Signatera assay. A repeat CT CAP six weeks after treatment showed radiologic shrinkage of all three pulmonary nodules in the right upper lobe.

Conclusions: This case illustrates how an interval ctDNA clearance is personalized evidence to defer systemic therapy in favor of definitive local control of oligometastases. There is a prognostic value of ctDNA biomarker to facilitate treatment decisions and potentially mitigate toxicity from an intensified adjuvant treatment. Future prospective trials are being planned to study this lucrative use of a non-invasive ancillary tool for personalized management for patients with oligometastatic disease.

References: 1. American Cancer Society . Cancer Facts and Figures 2020. Atlanta, GA: American Cancer Society; 2020.
2. Loupakis F, Sharma S, Derouazi M, et al. Detection of Molecular Residual Disease Using Personalized Circulating Tumor DNA Assay in Patients With Colorectal Cancer Undergoing Resection of Metastases. JCO Precis Oncol. 2021;5:PO.21.00101. Published 2021 Jul 21. doi:10.1200/PO.21.00101
3. Siegel RL, Miller KD, Goding Sauer A, et al. Colorectal cancer statistics, 2020 CA Cancer J Clin 70145–1642020
4. Tang, Chad, et al. “Definitive Radiotherapy in Lieu of Systemic Therapy for Oligometastatic Renal Cell Carcinoma: a Single-Arm, Single-Centre, Feasibility, Phase 2 Trial.” The Lancet Oncology, Elsevier Ltd, 2021, https://doi.org/10.1016/S1470-2045(21)00528-3.