Table 2.
Studies supporting the clinical evidence behind ICD-based effects of treatment modalities in GBM.
| Main ICD-based treatment modality | Clinical evidence in GBM | Oxford level of evidence | Number of patients receiving the therapy | Articles supporting this evidence (ref) | ICD/immune response measured?* |
|---|---|---|---|---|---|
| 5-aminolevulinic acid (PDT) | RCT | 1b | 13 | Ejmael et al. (2007) [143] | No |
| Cohort study | 2b | 10 | Beck et al. (2007) [144] | No | |
| Cohort study | 2b | 5 | Johansson et al. (2013) [145] | No | |
| ‘‘Outcomes’’ research | 2c | 15 | Schwartz et al. (2015) [146] | No | |
| Radiotherapy | Only preclinical studies available [95, 96] | ||||
|
Chemotherapy Temozolomide (in combination with a peptide-based vaccine) |
RCT | 1b | 22 | Sampson et al. (2010) [147] | No |
| Tumor treating fields | RCT | 1b | 120 | Stupp et al. (2012) [123] | No |
| ‘Outcomes’ research | 2c | 457 | Mrugala et al. (2014) [148] | No | |
| RCT | 1b | 466 | Stupp et al. (2017) [124] | No | |
| RCT | 1b | 475 | TRIDENT (ongoing) | No | |
| DC-vaccination | Cohort study | 2b | 7 | Yu et al. 2001 [149] | T-cell infiltration |
| Cohort study | 2b | 7 | Yamanaka et al. (2003) [150] | T-cell infiltration | |
| Cohort study | 2b | 9 | Yu et al. (2004) [151] | T-cell infiltration | |
| Cohort study | 2b | 12 | Liau et al. (2005) [152] | TGF-β2 expression | |
| Cohort study | 2b | 56 | De Vleeschouwer et al. (2008) [153] | Immune response | |
| Cohort study | 2b | 32 | Wheeler et al. (2008) [154] | IFN & immune response | |
| Cohort study | 2b | 10 | Chang et al. (2011) [155] | T-cell infiltration | |
| Cohort study | 2b | 16 | Fadul et al. (2011) [156] | IFN & T-cell response | |
| Cohort study | 2b | 77 | Ardon et al. (2012) [157] | Immune response | |
| Cohort study | 2b | 18 | Cho et al. (2012) [158] | No | |
| Cohort study | 2b | 7 | Akiyama et al. (2012) [159] | Immune response | |
| Cohort study | 2b | 13 | Jie et al. (2012) [160] | Immune response | |
| Cohort study | 2b | 20 | Shah et al. (2013) [161] | TGF-β2 expression | |
| Cohort study | 2b | 21 | Phuphanich et al. (2013) [162] | Tumor-associated antigens; immune response | |
| Cohort study | 2b | 7 | Vik-Mo et al. (2013) [163] | Immune response | |
| Cohort study | 2b | 6 | Sakai et al. (2015) [164] | T-cell response | |
| Cohort study | 2b | 14 | Hunn et al. (2015) [165] | IFN & immune response | |
| Cohort study | 2b | 11 | Akasaki et al. (2016) [166] | Immune response | |
| Cohort study | 2b | 22 | Batich et al. (2017) [167] | IFN & T-cell response | |
| RCT | 1b | 32 | Inognés et al. (2017) [168] | IFN & immune response | |
| RCT | 1b | 232 | Liau et al. (2018) [169] | No | |
| RCT | 1b | 22 | Yao et al. (2018) [170] | IFN & immune response | |
| RCT | 1b | 17 | Reap et al. (2018) [171] | IFN & immune response | |
| RCT | 1b | 81 | Wen et al. (2019) [172] | IFN & immune response | |
| Cohort study | 2b | 5 | Wang et al. (2020) [173] | IFN & immune response | |
| RCT | 1b | 15 | Mitsuya et al. (2020) [174] | IFN & immune response |
*While some studies measured immune (macrophages, T-cells,…) - or ICD-associated features (DAMPS) others only described the clinical effect (outcome, quality of life,…) of ICD-inducing therapies.