From:  Non-targeted effects of stereotactic radiotherapy: a review of the evidence coming from the clinical field

Overview of studies included in the systematic review for thoracic primaries

Author, yearStudy typePrimaryPatients SRTSystemic therapyNon-target responseCriteria
Kim and Chang [46], 2023Retrospective monocentricBreast10/40 (25%)NRNone1-year PFS 70%No systemic treatment
Xu et al. [47], 2021Retrospective multicentricThymic1/12 (8%), MOn primaryNoneSD for 42 monthsResponse outside RT field
Siva et al. [48], 2013Case reportNSCLC78*, M26 Gy/single fx to lung primary after CF 60 GyNoneCR to bone and adrenal mtxs meanwhile progressedNo concomitant systemic treatment
Cong et al. [49], 2017Case reportNSCLC64*, F37.5 Gy/5 fx to paramediastinal NPrevious CHT and gefitinib; previous and concomitant 3rd line cytochine induced killer therapyCR of another pulmonary mtxPD under treatment
Britschgi et al. [50], 2018Case reportNSCLC47*, M18 Gy/3 fx to 2 nodesCHT; nivolumab started 14 weeks before RT, stopped 17 cycles after RT for severe G3 pancreatitisPF at 3.5 years FUP, 2 years after nivolumab stoppagePD under IT
Hamilton et al. [51], 2018Case reportNSCLC47*, MNoneCR a months after SRS of both BM and primary. PF at 7 months FUPNo systemic treatment
Tubin et al. [52], 2019Prospective monocentricNSCLC19/20 (95%)48 Gy/8 fxPrevious 6 cycles CHT, atezolizumab (neoadj, concomitant, after)BE and AE by SBRT-PATHY in 95% and 45% of patientsResponse outside RT field
Lin et al. [53], 2019Case reportNSCLC73*, M40–50 Gy/5 fxNivolumabNew brain PD requiring further SRSResponse outside RT field
Chen et al. [54], 2020Retrospective of 2 prospectiveNSCLC10/33 (30%)VariousAnti-CTLA-4 or Anti-PD-1Similar NTER rates between anti-PD-1 (37%) and anti-CTLA-4 (24%) groups (P = 0.054)Response outside RT field
Kareff et al. [55], 2020Case reportNSCLC69*, FVariousNivolumab/Pembrolizumab/AtezolizumabPR on treated lung nodule and another one, 3 months afterExclusion criteria, negligible dose outside the RT field
Ye et al. [56], 2021Prospective monocentricNSCLC0/14 (0%)30 Gy/5 fx to lumbar mtxPrevious unsuccessful 2 TKI, pneumococcal vaccine 3 months after SRTNoneResponse outside RT field
Wang et al. [57], 2022Retrospective monocentricNSCLC24/59 (41%)VariousAnti-PD-1NTER of IT plus RT group higher than in the IT alone group (41.3% versus 31.2%, P = 0.238). A trend toward greater clinical benefit from the addition of RT in the PD-L1-negative subgroupResponse outside RT field
Huang et al. [58], 2022Case reportNSCLC60*, M40 Gy/5 fx to an oligoprogressive lung mtxPrevious ocreotide acetate for 13 years, then everolimus, lutetium, lanreotide (neoadj, concomitant, adj)CR on primary 1 month after, pathologically confirmed, more than 27 months PFSResponse outside RT field
Ito et al. [45], 2024Prospective multicentricVarious4/10 (40%) (3 NSCLC)30 Gy/5 fx to N
35 Gy/7 fx
50 Gy/4 fx		Pembrolizumab
Pembrolizumab
Pembrolizumab		Patients in the AE group had a significantly better 1-year PFS≥ 30% decrease of ≥ 1 non-irradiated lesions before the next line of therapy
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* Age at time of SRT. fx: fraction(s); mtx: metastasis; mtxs: metastases; NR: not reported; CHT: chemotherapy; RT: radiation treatment; SD: stable disease; CR: complete response; PF: progression free; SRS: stereotactic radiosurgery; BM: brain metastases; AE: abscopal effect; PD: progression disease; BE: bystander effect; IT: immunotherapy; PR: partial response; SBRT: stereotactic body radiotherapy; SRT: stereotactic radiation techniques; FUP: follow-up; NSCLC: non-small cell lung cancer; M: male; F: female; N: node/nodal; TKI: tyrosine kinase inhibitor; PFS: progression free survival; NTER: non-targeted effects of treatment; adj: adjuvant; neoadj: neoadjuvant; CF: conventionally fractionated