Table 1.
Summary of studies reporting solid tumors with DR associated with immunotherapy.
| Authors | Year | Tumor type | Design of study | Treatment of ICIs | Radiological evaluation | Definition of DR | Frequency of DR (%; n/N) | Prognosis of patients with DR | Treatment of patients with DR |
|---|---|---|---|---|---|---|---|---|---|
| Sato et al. 15 | 2021 | NSCLC | Retro | Nivolumab | CT and MRI | (1) Having both CR/PR in organs and PD (2) having all CR/PR but with the appearance of new lesions or apparent deterioration of unmeasurable lesions |
4.7 (5/107) | OS for DR and concordant PD: 46.9 versus 8.2 months; p = 0.038 | All patients continued nivolumab |
| Wong et al. 13 | 2021 | RCC | Retro | Nivolumab, pembrolizumab, ipilimumab-nivolumab | CT, MRI, and PET/CT | (1) Mixed response with new lesions (2) Mixed stable and progressing or regressing lesions |
47.8 (22/46) | OS for RECIST PD with DR and RECIST PD without DR: HR: 0.40; p = 0.186 | Concurrent surgery, SBRT or GKS for nonresponding lesions without changing their ICI treatment regime |
| Tozuka et al. 12 | 2020 | NSCLC | Retro | Nivolumab, pembrolizumab, atezolizumab | CT | A disease with some shrinking lesions as well as growing or emerging new lesions | 9.2 (11/120) | OS for DR and true PD: 14.0 versus 6.5 months; p = 0.022 | Five patients with continuation of ICIs, and others with chemotherapy or local radiotherapy |
| Bernard‑Tessier et al. 14 | 2020 | Solid tumors | Retro | CTLA-4 and PD-1 inhibitors | CT | A concomitant relative decrease greater than 30% in some tumor lesions and relative increase greater than 20% in others (significant increase ⩾5 mm in the sum of measures) | 3.3 (12/360) | PFS for atypical response and PD: 23.8 versus 1.8 months OS for atypical response and PD: not reached versus 5.1 months |
Among the 203 patients who experienced an initial progression in the 12 weeks of drug exposure, 81 (39.4%) patients were treated beyond progression |
| Zhou et al. 19 | 2020 | NSCLC | Retro | PD-1/PD-L1 inhibitors | CT | DR was defined as a reduction at baseline or increase <20% in target lesions compared with the nadir in the presence of new lesions | 22.1 (52/235) | OS for DR and RECIST 1.1 defined PD without new lesions: 11.70 versus 5.25 months; p = 0.019 | Among the 52 patients who had DR, 32 (61.54%) continued ICIs, 20 (38.46%) instead received subsequent antitumor therapy |
| Humbert et al. 17 | 2019 | NSCLC | Pro | Nivolumab, pembrolizumab | PET/CT | Concomitant decrease in certain hypermetabolic lesions associated with an increase in other lesions. | 10.0 (5/50) | Increased clinical benefit | In all patients showing DR, the treatment was continued (due to an improved, or at least stable, clinical status according to the tumor board) |
| Vaflard et al. 18 | 2019 | Solid tumors | Retro | PD-1/PD-L1 inhibitors | CT | (1) One TL in CR/PR and one progressive TL (DR1) (2) One stable TL and one progressive TL (DR2) 3) One TL in CR/PR and one stable TL (DR3) |
DR1: 8.0 (8/100) DR2: 44.0 (44/100) DR3: 10.0 (10/100) |
NR | NR |
| Tazdait et al. 16 | 2018 | NSCLC | Retro | PD-1/PD-L1 inhibitors | CT | Concomitant decrease in certain tumoral elements and increase in other elements | 7.5 (20/160) | OS for atypical responses (PsPD and DR) and PD: 9.8 versus 6.1 months; p < 0.0001 | The proportion of patients treated beyond RECIST PD was around 90% |
CR, complete response; CT, computed tomography; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; DR, dissociated response; GKS, gamma knife surgery; ICIs, immune checkpoint inhibitors; MRI, magnetic resonance imaging; NR, not reported; NSCLC, non-small cell lung cancer; OS, overall survival; PD-1, programmed cell death protein-1; PD-L1, programmed death ligand-1; PET/CT, positron emission tomography/computed tomography; PFS, progression-free survival; PR, partial response; Pro, prospective; PsPD, pseudoprogressive disease; RCC, renal cell carcinoma; RECIST, response evaluation criteria in solid tumors; Retro, retrospective; SBRT, stereotactic body radiation therapy; TL, target lesion.