Table 1.
Clinical trials showing abscopal effect in tumor subtypes.
| Trial | Tumor type (n) | Best abscopal CR/PR RECIST responses | Radiation | Sequence | Systemic agent | Median overall survival (months) | Unirradiated sites assessed | ARR (%) |
|---|---|---|---|---|---|---|---|---|
| Local radiotherapy and granulocyte-macrophage colony-stimulating factor to generate abscopal responses in patients with metastatic solid tumors: a proof-of-principle trial (26) | Non–small cell lung cancer (n = 13) | 2 PR; 2 CR | Conventional 35 Gy/10 fx | Sequential GM-CSF and concurrent chemotherapy | Chemotherapy + GM-CSF | 20.98 | Lung, liver, lymph nodes | 27 |
| Breast cancer (n = 11) | 4 PR | |||||||
| Thymic cancer (n = 2) | 2 PR | |||||||
| Nivolumab and hypofractionated radiotherapy in patients with advanced lung cancer: ABSCOPAL-1 clinical trial (75) | Non–small cell lung cancer (n = 23) | 3 CR | SBRT | Sequential | Nivolumab | NR | Unknown | 45.2 |
| 6 PR | 40–50 Gy/5 fx and hypofractionated brachytherapy (30 Gy/1 fx) | |||||||
| Potentiation of the abscopal effect by modulated electro-hyperthermia in locally advanced cervical cancer patients (76) | Cervical cancer (n = 108) | 13 CMR | Conventional | Concurrent | Cisplatin | Not assessed | Lymph nodes | 24.1a |
| 50 Gy/25 fx and HDR (24 Gy/3 fx) ± electro hypothermia | ||||||||
| Phase II trial of ipilimumab with stereotactic radiation therapy for metastatic disease: outcomes, toxicities, and low-dose radiation -related abscopal responses (77) | Multiple tumor types (n = 106) | NSCLC: 1 CR; | SBRT | Concurrent vs. sequential | Ipilimumab | NR | Liver, lung, adrenal glands | 26 |
| 3 PR | 50–60 Gy/4–10 fx | |||||||
| Cervical adenocarcinoma: 1 CR | ||||||||
| RCC: 1 PR | ||||||||
| NET: 1 PR | ||||||||
| Phase II trial of combined durvalumab plus tremelimumab with proton therapy to boost the abscopal effect for recurrent or metastatic head and neck squamous cell carcinoma (78) | Head and neck squamous cell carcinoma (n = 31) | 1 CR | Proton therapy | Concurrent | Durvalumab and tremelimumab | 6.4 | Unknown | 27.3 |
| 5 PR | 25 Gy/5 fx | |||||||
| ARRs after salvage radiation in patients with progressive disease on immunotherapy (79) | Non–small cell lung cancer (n = 17) Melanoma (n = 5) | Unknown | Conventional or SBRT | Concurrent | Immunotherapy | Not assessed | Liver, lung, adrenal glands | 11 |
| Intratumoral tavokinogene telseplasmid induces abscopal clinical responses in metastatic melanoma patients (80) | Melanoma (n = 28) | 5 CR | Electroporation | Sequential | Intratumorally with IL-12 | NR | Subcutaneous satellite nodules | 29.2 |
| 6 PR | D1,5,8 Q90D | |||||||
| Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials (18) | Lung cancer (n = 148) | 30 CR+PR | Conventional or SBRT | Concurrent vs. sequential | Pembrolizumab | 19.2 | Lung, liver, lymph nodes, adrenal glands | 41.7 |
| 24Gy/3 fx; 50Gy/4 fx; 45Gy/15 fx | ||||||||
| Phase 1/2 study of intratumoral G100 (TLR4 agonist) with or without pembrolizumab in follicular lymphoma (81) | Follicular lymphoma (n = 51) | 6 CR+PR | Low-dose radiation (4Gy/2 fx) | Sequential | Intratumoral G100 (TLR4 agonist) ± pembrolizumab | NR | Lymph nodes | 16.2 |
| Nivolumab in Combination with Stereotactic Body Radiotherapy in Pretreated Patients with Metastatic Renal Cell Carcinoma. Results of the Phase II NIVES study (82) | Renal cell carcinoma (n = 69) | 2 CR | SBRT 30Gy/3 fx | Sequential | Nivolumab | 20 | Lungs, liver, lymph nodes, bones | 12 |
| 6 PR | ||||||||
| A stratified phase I dose escalation trial of hypofractionated radiotherapy followed by ipilimumab in metastatic melanoma: long-term follow-up and final outcomes (83) | Melanoma (n = 22) | 5 PR | SBRT 6 or 8 Gy (2–3 fx) | Sequential | Ipilimumab | 10.7 | Lung, liver, subcutaneous nodules | 22.7 |
| A prospective trial evaluating the safety and systemic response from the concurrent use of radiation therapy with checkpoint inhibitor immunotherapy in metastatic non–small cell lung cancer (84) | Non–small cell lung cancer (n = 34) | 2 CR | SBRT | Concurrent | PD-1/PD-L1 inhibitor ± chemotherapy | 15 | Lungs, liver, lymph nodes, bones, adrenal glands | 53 |
| 16 PR | 48Gy/3–5 fx | |||||||
| Phase II single-arm study of durvalumab and tremelimumab with concurrent radiotherapy in patients with mismatch repair–proficient metastatic colorectal cancer (85) | Colorectal cancer | 2 PR | Conventional or SBRT | Sequential | Durvalumab and tremelimumab | 11.4 | Liver, lung, bone, soft tissue, peritoneum, spleen, lymph nodes | 8.3 |
| (n = 24) | 27–70Gy/3–25 fx | |||||||
| Radiotherapy enhances immunotherapy response in microsatellite stable colorectal and pancreatic adenocarcinoma in a phase II trial (86) | Colorectal cancer (n = 40) | 1 CR | SBRT | Concurrent | Ipilimumab + nivolumab | 7.1 | Unknown | 10 |
| 3 PR | 24Gy/3 fx | |||||||
| Pancreatic cancer (n = 25) | 1 CR | 4.2 | 12 | |||||
| 2 PR |
Abbreviations: CMR, complete metabolic resolution (SUV <2.5) on 18F-FDG PET/CT; CR, complete response; HDR, high-dose brachytherapy; PR, partial response.
aARR in this study includes resolution of tumor within and outside the radiation field.