108 - Evaluating Short Course Radiation and ctDNA for Organ Preservation: The Nonoperative Management and Early Response Assessment in Rectal Cancer (NOM-ERA) Trial
Presenter(s)
H. Kim1, C. J. Anker2, J. R. Olsen3, C. L. Hallemeier4, M. Silviera5, J. Moore6, M. M. Barry7, Z. Jin8, K. L. Mathis9, D. Shonebarger10, J. Hamner11, A. Tin12, H. Calkins13, Y. Xu14, E. Lu14, M. Mutch15, A. Mo1, D. Denardo1, K. Pedersen8, and S. Hunt5; 1WashU Medicine, Department of Radiation Oncology, St. Louis, MO, 2University of Vermont, Department of Radiation Oncology, Burlington, VT, 3UCHealth Memorial Hospital Central, Department of Radiation Oncology, Colorado Springs, CO, 4Department of Radiation Oncology, Mayo Clinic, Rochester, MN, 5Washington University School of Medicine, Department of Surgery, St. Louis, MO, 6University of Vermont, Department of Surgery, Burlington, VT, 7University of Vermont, Department of Medicine, Burlington, VT, 8Mayo Clinic Rochester, Department of Medicine, Rochester, MN, 9Mayo Clinic Rochester, Department of Surgery, Rochester, MN, 10UCHealth Memorial Hospital, Department of Medicine, Colorado Springs, CO, 11UCHealth Memorial Hospital Central, Department of Surgery, Colorado Springs, CO, 12Natera, Inc., Austin, TX, 13Natera, Inc, Hugo, MN, 14Washington University School of Medicine, Department of Surgery, Division of Public Health Sciences, St. Louis, MO, 15WashU Medicine, St. Louis, MO
Purpose/Objective(s):
In patients treated for rectal cancer there are limited prospective data evaluating nonoperative management (NOM) after short course radiation therapy (SCRT). The role of ctDNA in rectal cancer NOM is not well defined. Materials/Methods: NOM-ERA is a prospective, multi-institution, single arm, phase II trial in which 63 patients with stage I-III rectal adenocarcinoma were treated with SCRT followed by consolidative chemotherapy. Treatment entailed 25 Gy in 5 fractions, 4 months of FOLFOX or CAPOX, then watch-and-wait surveillance for clinical complete response (cCR) or recommended total mesorectal excision (TME) for partial response (cPR). Radiation boost to rectal primary (30 Gy) was permitted. The primary endpoint was cCR rate at first assessment after SCRT and chemotherapy (post-treatment). Secondary endpoints included progression-free survival (PFS) and TME-free survival. Tumor-informed ctDNA analysis was performed (Signatera, Natera, Inc) in relation to event-free survival (EFS) for patients consenting to pre-treatment research biopsy. Comparisons utilized log-rank (PFS) and Fisher’s exact (cCR rate) tests.Results:
Most patients had T3 (66%) or N+ (61%) disease. Of 61 patients evaluable for primary endpoint, 37 (61%) demonstrated cCR at first assessment and eventually 44 (72%) achieved cCR. 2-year PFS and TME-free survival were 84% [70-92] and 57% [43-69], respectively, with median follow-up of 21 months. 2-year local control and distant metastasis-free survival was 98% [84-100] and 88% [74-94], respectively. 27 (45%) patients received primary tumor boost, with no difference in cCR rate (p=0.57) or TME-free survival (p=0.91) compared to patients without boost. For patients with pre-treatment samples available (N=20), 19/20 tested ctDNA-positive. 134 plasma samples were assessed. ctDNA positivity post-treatment was prognostic for EFS (HR 5.2 [0.92-30]; p=0.038). Notably, post-treatment ctDNA-positive cPR patients had significantly shorter median EFS (7 months) compared to ctDNA-negative cPR patients (22 months). Patients with ctDNA-positive cCR had numerically decreased EFS compared to patients with ctDNA-negative cCR (HR 9.3 [0.95-91]; p=0.056).Conclusion:
Organ preservation is achievable in more than half of rectal cancer patients treated with SCRT and consolidative chemotherapy. Post-treatment ctDNA positivity is predictive of recurrence and may help determine patient suitability for NOM.