Split-Course Adaptive Radioimmunotherapy for Oligometastatic Non-Small Cell Lung Cancer (SiCARIO): A Case Report

Abstract

Current treatment paradigms for oligometastatic non-small cell lung cancer (NSCLC) utilize systemic chemotherapy alone or in combination with immune checkpoint inhibitors (ICIs). The addition of ICIs in NSCLC has led to significant improvements in survival; however, recurrence remains common. New methods are needed to enhance anti-tumor immune responses and improve patient outcomes. Here, we present the first case of utilization of the Ethos OART platform to deliver multi-site pulsed hypofractionated radiotherapy in a patient with oligometastatic disease on the single arm prospective clinical trial SiCARIO (Split-Course Adaptive Radioimmunotherapy in Oligometastatic NSCLC, NCT05501665). A 67-year-old man with stage IV NSCLC with metastases to bilateral adrenal glands, retroperitoneum, and mesentery was prescribed treatment of 40 Gy in 5 fractions on SiCARIO in combination with SOC chemoimmunotherapy. A multi-target single isocenter approach was utilized to treat nine distinct targets in five total isocenters. Treatment plans were generated using an isotopic approach prioritizing organ at risk (OAR) constraints with the goal of minimum coverage of at least 30 Gy in 5 fractions. CBCT was acquired with each fraction to generate new targets and OAR contours based on anatomic changes with the patient on the treatment table. A comparison of an adapted plan to a base plan was performed online with a selection of superior plans based on target coverage and OAR constraints. The adapted plan was deemed superior for all but 1 fraction of a single isocenter for this patient. The discussion will focus primarily on the bilateral adrenal isocenter, where bulk tumor shrinkage of greater than 80% was observed in this patient with corresponding significant dosimetric benefits. This case demonstrates a potential clinical benefit of OART in multi-metastasis RT. Further data is needed to confirm the safety and efficacy of this approach. Enrollment is ongoing.

Keywords: ct-guided adaptive radiotherapy; metastatic non-small cell lung cancer; online adaptive radiotherapy (art); radioimmunotherapy; sbrt (stereotactic body radiotherapy).

Figure 1. Initial staging PET-CT demonstrated multiple sites of FDG-avid disease.

(A) Skull base to mid-thigh PET-CT images with arrows indicating thoracic and bilateral adrenal disease; (B) axial slice demonstrating lung mass and mediastinal disease; (C) axial slice demonstrating bulky bilateral adrenal metastases.

Figure 2. SiCARIO study schema.

FDG PET: fluorodeoxyglucose positron emission tomography, MRI: magnetic resonance imaging, FSPG PET: (S)-4-(3-18F-fluoropropyl)-L-glutamic acid positron emission tomography, ICI: immune checkpoint inhibitor, ChT: chemotherapy, ctDNA: circulating tumor DNA, SOC: standard of care

Figure 3. Representative images of multi-site target contours.

(A) Representative coronal image, (B) Representative sagittal image, (C) Representative axial image demonstrating lung mass and mediastinal disease, (D) Representative axial image demonstrating bilateral adrenal disease.

Figure 4. Base and adapted radiotherapy plans demonstrating interval response in bilateral adrenals.

(A) Representative coronal image of the base radiotherapy plan for the multi-target plan. (B) Representative axial slices of bilateral adrenals demonstrating interval tumor shrinkage at fractions 3 and 5 from baseline. (C) Representative axial PET images demonstrating resolution of the FDG PET (fluorodeoxyglucose positron emission tomography) signal from baseline to prior to fraction 3.

Figure 5. Dose volume histogram for fraction 3 and fraction 5 of bilateral adrenal RT plans.

Comparison of reference (base) plan and adapted plan for bilateral adrenal isocenter. (A) Fraction 3 of treatment, demonstrating reduced Dmax to small bowel (peach) and stomach (yellow), solid: adapted plan, dashed: reference plan, (B) Fraction 5 of treatment, demonstrating reduced Dmax to small bowel (peach) and stomach (yellow); solid: adapted plan; dashed: reference plan. These fractions are representative of dosimetric benefits observed across all fractions, with approximately 20-25% reductions in Dmax to adjacent critical organs.