3494 - Proton Beam Therapy for Tracheobronchial Adenoid Cystic Carcinoma: Outcomes and Genomic Insights into Recurrence
Presenter(s)
H. Hirata1, M. Nakamura1, J. Samejima2, H. Hojo1, A. Motegi1, S. I. Kageyama3, T. Taki4, M. Tsuboi2, T. Akimoto5, and S. Zenda1; 1Department of Radiation Oncology, National Cancer Center Hospital East, Kashiwa, Japan, 2Department of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Japan, 3Division of Translational Informatics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan, 4Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Japan, 5Department of Radiation Oncology, The Jikei University School of Medicine, Tokyo, Japan
Purpose/Objective(s): Tracheobronchial adenoid cystic carcinoma (TACC) is a rare cancer that obstructs the airway, making local therapy essential. Surgery is the preferred treatment; however, the high risk of airway invasion often results in positive resection margins. Proton beam therapy (PBT) has potential benefit for unresectable TACC or TACC with positive resection margins, as it can spare dose to normal tissues, but its efficacy is unclear. In this retrospective study, we evaluated the outcomes of TACC patients after PBT and explored recurrence-related gene alterations in serial plasma circulating tumor DNA (ctDNA) and tumor samples.
Materials/Methods: We retrospectively assessed consecutive patients with primary TACC who underwent either definitive PBT alone or postoperative PBT for TACC with positive margins at our institution during 2015–2022. As an exploratory objective, we performed ctDNA analysis in eight blood samples from three patients with recurrence after PBT. Three tumor samples (primary tumor pretreatment and liver/kidney metastases after PBT) obtained from one patient were subjected to whole-exome and RNA sequencing.
Results: Ten patients, with a median age of 47 (range: 22–79) years, were included. Six patients (all with cStage III, UICC 8th ed) received definitive PBT, and four (two each with pStage I and III) received postoperative PBT. All patients completed PBT at 60–70.4 Gy in 30–33 fractions. After a median follow-up from PBT initiation of 64 (range 21–114) months, the 5-year progression-free survival, overall survival, and local failure rates were 70% (95% Cl 47–100%), 90% (CI 73–100%), and 15% (CI 1–51%), respectively, for all patients; 67%, 83%, and 21%, respectively, for the patients who received definitive PBT; and 75%, 100%, and 0%, respectively, for the patients who received postoperative PBT. Four patients developed recurrence after PBT, and all initial recurrences were distant metastasis. No grade = 3 adverse events were observed. Serial ctDNA analysis revealed a TP53 mutation emerged more than 1 month before radiographic recurrence in a patient who developed multiple lung metastases after PBT, and the frequencies of this mutation reflected the clinical course. In contrast, no mutations were detected in the plasma of two patients with oligo-recurrence. Whole-exome and RNA sequencing showed that gene alterations, including MYBL1-NFIB fusion, detected pretreatment remained at the time of distant metastasis development. Gene set enrichment analysis showed significant downregulation of immune-related pathways in the distant metastases compared with the primary tumor (q < 0.05).
Conclusion: PBT for TACC achieved good 5-year outcomes, particularly in the postoperative setting. Certain gene alterations were detected at recurrence. Our findings warrant further studies to determine the long-term outcomes and impact of gene alterations on recurrence.