Table 3.

Proposed ISABR studies

Patient population	SABR dose (Gy)/number of fractions	SABR target	Type of immunotherapy	Sequence	Readout
Stage I NSCLC	50–60/3–5 60–70/8–10	Primary tumor	Vaccine-MAGE* PD-L1	Immunotherapy followed by SABR Concurrent ISABR	PET/CT scan, PD-L1, TIL, Treg, CD8/CD4, Exome micro-RNA, cytokine production, CEA-specific T cells
Early stage hepatocellular carcinoma	40–60/3–5 50–70/8–10	Primary tumor	PD-L1	Concurrent ISABR	MRI scan, PD-L1, TIL, Treg, CD8/CD4, Exome micro-RNA, cytokine production
Stage IV CRC	50–60/3–5 60–70/8–10	Dominant Liver or lung metastasis	Vaccine-CEA PD-1	Immunotherapy followed by SABR Concurrent ISABR	CT scan, MRI of the abdomen, cytokine production, CEA-specific T cells, TILs in treated and off-target metastases, inflammatory cytokine production, PD-L1, Treg, CD8/CD4, Exome micro-RNA
Stage IV NSCLC with spinal/brain metastases	12–25/1 15–24/1	Spinal metastases Brain metastases	PD-L1 PD-1 + ipilumumab	Immunotherapy then SABR Concurrent ISABR	PET/CT, brain MRI, tumour-specific T cells, PD-L1 expression levels, inflammatory cytokine production, TIL, Treg, CD8/CD4, Exome micro-RNA
Stage IV NSCLC	Organ-dependent dose regimen	Oligometastasis	PD-L1 PD-1 + ipilumumab	SABR then immunotherapy Concurrent ISABR	PET/CT scan to monitor regression at distant metastatic sites, PD-L1 expression levels, TILs in treated primary and untreated metastases, Treg, CD8/4, Exome micro-RNA

CEA, carcinoembryonic antigen; CRC, colorectal cancer; ISABR; Immunotherapy combined and stereotactic ablative radiotherapy; MAGE, melanoma antigen E; NSCLC, non-small-cell lung cancer; SABR, stereotactic ablative radiotherapy; TILs, tumour-infiltrating lymphocytes; T-reg, regulatory T-cells; RNA, ribonucleic acid.

^*MAGE-tumor-associated antigen is expressed in 50% of patients with NSCLC⁶⁸, with no immunohistochemical staining of this antigen observed in normal lung tissue samples⁶⁹.