Open Access
Review
Table 1
Studies investigating the combination of radiotherapy and chemotherapy.
| First author | Year | Country | Type | No. of patients (All, each groups) | Inclusion criteria | Enrollment time | Treatment strategy | Local treatment | Radiation dose | Systemic treatment | Treatment regimens | Primary endpoints | Secondary endpoints | Efficacy (same order as “Treatment Strategy”) | Toxicity |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Qi Liu (ESO-Shanghai 10, NCT 03000816) | 2021 | China | Prospective, Single-arm, Phase II | 34 | Oligometastasis (1–3 metastatic lesions. 1–2 anatomical sites, longest diameter ≤ 5 cm), Primary tumor treated definitively without progression > 3 months, SCC | 2015–2018 | CCRT | SBRT | Metastases: 48 Gy/6f (BED > 80 Gy, except for bone metastases) | C | First-line: cisplatin + fluorouracil, paclitaxel + cisplatin, paclitaxel + carboplatin, or fluorouracil + oxaliplatin; Second-line: paclitaxel/docetaxel/irinotecan alone | PFS | OS, LCR, Toxicity | mPFS: 13.3 mm; OS: 24.6 m; 1y-LCR: 92.1%; 2y-LCR: 92.1% | Leukocytopenia/neutropenia: 65%, G3 18%, G4 18%; G3 related to SBRT: 3% (Abdominal pain) |
| Zhenguo Shi | 2022 | China | Retrospective, Controlled, Double-centered | 532 (240/292) | Synchronous Oligometastasis (1–5 metastatic lesions), SCC | 2012–2018 | CCRT vs. C | R | Primary tumor: 50 Gy/25f; Metastases: 45 Gy/18f | C | cisplatin + 5-fluorouracil/docetaxel | PFS, OS | ORR, DCR, Toxicity | mPFS: 9.7 m vs. 7.6 m, p < 0.001 (before PSM); 9.4 m vs. 7.8 m, p = 0.001 (after PSM); mOS: 18.5 m vs. 15.2 m, p < 0.001 (before PSM); 18.4 m vs. 15.3 m, p = 0.012 (after PSM); ORR: 57.9% vs. 42.1%, p < 0.001; DCR: 84.2% vs. 65.8%, p < 0.001 | Leukocytopenia: G3 21.3% vs. 16.1%, G4 9.6% vs. 6.2%, p = 0.025; Radiation pneumonitis: G3 5.4%, G4 1.3%; Radiation esophagitis: G3 6.3%, G4 0.8% |
| Tiuri E. Kroese | 2022 | The Netherlands | Retrospective, single-centered, controlled | 85 (49/12/24) | Synchronous or Metachronous oligometastasis (1 organ or extraregional lymph node station, 1–3 metastatic lesions), Controlled primary tumor after S or definitive CRT, without loco-regional recurrence | 2010–2021 | Local vs. Local + Systemic vs. Systemic | SBRT/RT/S | Metastases: ≥ 10 Gy per fraction with ≥ 1 fraction (s); ≥7 Gy per fraction with ≥ 5 fractions; ≥5 Gy per fraction with ≥ 12 fractions or total ≥ 50 Gy | C ± T | NA | OS | Prognostic factors for OS and PFS | Primary tumor controlled: 86% vs. 75% vs. 29%; mPFS: 10 m vs. Not Reached vs. 15 m; mOS: 17 m vs. 35 m vs. 16 m | NA |
| Independent prognostic factor for OS: Local plus Systemic: Reference; Local treatment: HR = 2.11, 95% CI 1.05–5.07; Systemic therapy: HR = 2.28, 95% CI 1.04–6.07 | |||||||||||||||
| Yue Shao | 2021 | China | Retrospective, SEER database, controlled | 2862 (1431/1431) | Metastasis | 2010–2016 | CRT vs. C | RT | NA | C | NA | OS, CSS | 1y-OS%: 37.24% vs. 40.66%; 2y-OS%: 16.13% vs. 18.35%; OS: p = 0.28 (before PSM), p = 0.34 (after PSM); 1y-CSS%: 37.66% vs. 41.28%; 2y-CSS%: 16.60% vs. 19.01%; CSS: p = 0.25 (before PSM), p = 0.28 (after PSM) | NA | |
| Guanghao Qiu | 2021 | China | Retrospective, SEER database, controlled | 537 (153/109/91/184) | Age ≥ 65 y, Metastasis, SCC | 2010–2016 | Local + Systemic vs. Systemic vs. Local vs. None | R/S | NA | C | NA | OS, CSS | OS: Local + Systemic: Reference; Systemic: HR = 0.917, 95% CI 0.695–1.212, p = 0.544; Local: HR = 2.146, 95% CI 1.619–2.845, p < 0.001; No treatment: HR = 3.564, 95% CI 2.787–4.558, p < 0.001; CSS: Local + Systemic: Reference; Systemic: HR = 0.898, 95% CI 0.676–1.192, p = 0.456; Local: HR = 2.136, 95% CI 1.604–2.845, p < 0.001; No treatment: HR = 3.453, 95% CI 2.684–4.444, p < 0.001 | NA | |
| Guanghao Qiu | 2021 | China | Retrospective, SEER database, controlled | 855 (189/246/113/307) | Age ≥ 70 y, Metastasis, AC | 2010–2015 | Local + Systemic vs. Systemic vs. Local vs. None | R/S | NA | C | NA | OS, CSS | OS: Local + Systemic: Reference; Systemic: HR = 1.014, 95% CI 0.810–1.268, p = 0.907; Local: HR = 2.232, 95% CI 1.730–2.880, p < 0.001; No treatment: HR = 4.782, 95% CI 3.821–5.984, p < 0.001; CSS: Local + Systemic: Reference; Systemic: HR = 1.036, 95% CI 0.821–1.306, p = 0.768; Local: HR = 2.345, 95% CI 1.803–3.050, p < 0.001; No treatment: HR = 4.750, 95% CI 3.762–5.998, p < 0.001 | NA | |
| Takeshi Morinaga | 2021 | Japan | Retrospective, single-centered, controlled | 97 (41/56) | Recurrence after curative esophagectomy, non-oligometastatic or oligometastatic (1 organ and lymph node, 1–5 recurrences), SCC | 2005–2019 | Local + Systemic vs. Local | R/S/RFA | NA | C | NA | OS | mOS: Oligometastatic recurrence: 39.2 m vs. 14.4 m, p = 0.038; Non-oligometastatic recurrence: 15.2 m vs. 11.0 m, p = 0.374 | NA | |
| Butuo Li | 2020 | China | Retrospective, single-centered, controlled | 273 | Oligometastasis (1–5 metastatic lesions) | 2013–2018 | Local + Systemic vs. Local vs. Systemic | R/S | NA | C | NA | PFS, OS | Local radiotherapy for primary tumor (Yes vs. No): mPFS 9.8 m vs. 4.5 m, p < 0.001; mOS 22.1 vs. 13.9, p < 0.001; Local radiotherapy for Metastases (All vs. Partial vs. No): mPFS 9.8 m vs. 8.6 m vs. 5.1 m, p<0.001 (Partial vs. No: p > 0.05) | NA | |
| Yongshun Chen | 2019 | China | Retrospective, double-centered, controlled | 461 (196/265) | Oligometastasis (1–3 metastatic lesions), PS 0–2 | 2012–2015 | CCRT vs. C | R | Primary tumor: 50 Gy/2 Gy/25f; Metastatic lesion: 45 Gy/3 Gy/15f | C | cisplatin + paclitaxel | DCR, PFS, OS, Dysphagia score, Toxicity | DCR: 83.2% vs. 75.5%, p = 0.045; mPFS: 8.7 m vs. 7.3 m, p = 0.002; mOS: 16.8 m vs. 14.8 m, p = 0.056; Improvement of dysphagia: 78.5% vs. 61.5%, p = 0.014 | Leukopenia: G3 19.4% vs. 17.4%, G4 10.2% vs. 6.4%, p = 0.560; Radiation pneumonitis: G3 6.1% vs. 1.9%, G4 1.5% vs. 0, p = 0.429; Esophagitis: G3 5.6% vs. 6.0%, G4 1.0% vs. 0, p = 0.335; Death within 30 days of completion of CCRT: 0.5% | |
| Jiahua Lyu | 2018 | China | Retrospective, single-centered, controlled | 141 (55/86) | Metastasis, SCC, KPS ≥ 70 | 2010–2015 | CCRT vs. C | R | Primary tumor: ≥ 50 Gy/1.8–2.0 Gy; Metastatic lesion: only with serious symptoms caused by metastatic lesions | C | cisplatin + 5-fluorouracil/paclitaxel | ORR, DCR, PFS, OS, Toxicity | ORR: 74.5% vs. 45.3%, p = 0.001; DCR: 94.5% vs. 80.2%, p = 0.024; mPFS: 8 m vs. 6 m, p = 0.005; mOS: 14 m vs. 11 m, p = 0.007 | Leucopenia: 96.4% vs. 96.5%, ≥G3 41.8% vs. 24.4%, p = 0.040; Treatment-related Pneumonitis: 54.5%, ≥G3 7.3%; Treatment-related Esophagitis: 87.3%, ≥G3 14.5% | |
| David M. Guttmann | 2017 | United States | Retrospective, NCDB, controlled | 12683 (2426/2983/7274) | Metastasis | 2004–2012 | R (≥50.4 Gy) +C vs. R (<50.4 Gy) +C vs. C | R | Primary tumor only: 20–72 Gy | C | NA | OS | mOS: 11.3 m vs. 7.5 m vs. 8.3 m, p < 0.001 | NA | |
| L. Depypere | 2017 | Belgium | Retrospective, single-centered, controlled | 167 (25/32/66/15/29) | Recurrence after curative esophagectomy, oligometastatic (1 organ or lymph node station) | 1990–2012 | S ± CRT vs. CRT vs. C vs. R vs. None | R/S | NA | C | NA | OS | OS: S ± CRT: Reference; CRT: HR = 1.46, 95% CI 0.75–2.85, p = 0.26; C: HR = 2.69, 95% CI 1.50–4.83, p = 0.001; R: HR = 6.50, 95% CI 2.98–14.15, p < 0.0001;None: HR = 7.03, 95% CI 3.68–13.44, p < 0.0001 | NA | |
y = year, m = month, SCC = Squamous Cell Carcinoma, AC = Adenocarcinoma, CCRT = Concurrent Chemoradiotherapy, R = Radiotherapy, S = Surgery, C = Chemotherapy, T = Targeted Therapy, RFA = Radiofrequency Ablation, PFS = Progression-Free Survival, OS = Overall Survival; CSS = Cancer-Specific Survival, LCR = Local Control Rate, ORR = Objective Response Rate, DCR = Disease Control Rate, CBR = clinical benefit rate, ARR = Abscopal response rate, ACR = abscopal control rate, NA = Not Available, PSM = Propensity Score Matching, HR = Hazard Ratio, CI = Confidence Interval.
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