Table 2.
Published clinical series including patients treated with SBRT for oligometastatic cancer (at any site, including lymph nodes).
| Authors, year of publication | No. of LN treated/(the whole series) | Nature of study | SBRT technique | Primary site/histology | Systemic therapy | Fiducial markers | Treated volumes |
|---|---|---|---|---|---|---|---|
| Kang et al., 201013 a | 41 (78): pelvic (29 ln) Para-aortic (11 ln, 7 pts) Mediastinal (1 ln, 1 pt) | Retrospective | CBK | Colorectal cancer | CHT before SBRT in 49/59 pts | Not reported | Cumulative CTV median volume for LN: 24 cm3 |
| Bae et al., 201214 b | 19 (50); no. of pts treated on LN: 18 (41) | Retrospective | CBK | Colorectal cancer | Adj CHT in all pts; adj CHT after SBRT in 33 pts; neoadj CHT before SBRT in 21 pts | Not reported | Cumulative GTV volume for LN: median 18 cm3; total cumulative GTV volume: median 13 cm3 |
| Jereczek-Fossa et al., 201215 c | 18 (38) total number of pts: 34 | Retrospective | CBK | Prostate cancer | ADT in 18 pts/21 lesions (12/18 LN mts lesions), estramustine in 1 pt | Yes in 26 lesions (68%), of which 9 LN mts (9/18) | Not reported |
| Jereczek-Fossa et al., 201316 | 11 (118) | Prospective | CBK | Miscellaneous (excluded prostate cancer; mostly breast, lung, head/neck cancer) | Concomitant in 47/118 treatments (40%): CHT 32, HT 3, both 12 | Yes in 8/118 total lesions (6.8%) | Not reported |
| Berkovic et al., 201317 | 22(49), (11/24 pts) | Prospective (single arm study) | LINAC | Prostate cancer | Yes: single short acting LH-RH analog + antiandrogen 1 month before SBRT | Not reported | Not reported |
| Ahmed et al., 201318 | 1/21 | Prospective | IMRT and 3D-CRT | Prostate cancer | In 15 pts (88%) ADT after completion of SBRT | Not reported | Not reported |
| Hoyer et al., 200619 | 3 pts/64 pts (5%) | Prospective phase II trial | LINAC | Colorectal cancer | Neoadj CT before SBRT in 33/64 pts (52%) | Not reported | GTV median diameter 35 mm |
| Kodany et al., 201120 | 6 (34), 17% of total sites (cervical LNs) | Retrospective | CBK | Miscellaneous, mostly squamous cell carcinoma | No concomitant | Not reported | GTV median volume 11.6 cm3 |
| Roh et al., 200921 | 11 (44): 8 neck LN and 3 retropharyngeal LN | Retrospective | CBK | Miscellaneous | In 21 pts (58.3%) previous CHT in 6 pts CHT after SBRT | Yes in pts with lesion below C4 level | Median GTV volume 22.6 cm3 |
| Greco et al., 201122 | 14 (124) | Prospective, phase I | LINAC, single-dose IGRT, 6–15 MV photons, 7–9 coplanar fields | Miscellaneous (mostly prostate, renal cell, colorectal) | Not reported | Yes, if deemed necessary | PTV median volume 54.9 cm3 |
| Wersall et al.200523 | 6 (162) | Retrospective | LINAC | Renal cell carcinoma | Prior systemic treatment in 15 pts | Not reported | Not reported |
| Salama et al., 201224 | 22(113) | Prospective dose escalation study | LINAC (non overlapping axial and non coplanar fields), RPM when needed | Miscellaneous (mostly lung, breast, renal, squamous K of head and neck) | CHT not allowed, only HT allowed. Prior systemic therapy in 49 pts (80.3%) | Not reported | Median lesion size 2.5 cm |
| Kawaguchi et al., 201025 | 8 of the 22 pts had LN mts (1 limited recurrence with LN) | Prospective | CBK | Squamous cell carcinoma of head&neck | Low dose oral 5-FU from 1 mo after SBRT | Not reported | GTV median volume 24.5 cm3 |
| Scorsetti et al., 201126 | 4(70), isolated abdominal LN | Prospective | VMAT (RapidArc) with FFF beams | Not reported | Not reported | Not reported | PTV volume in abdominal lesions: 115 ± 82 cm3 |
| Scorsetti et al., 201127 | 12 (37) retroperitoneal LN | Retrospective | VMAT RapidArc | Miscellaneous (mostly colorectal, pancreatic) | No | Not reported | Max axial diameter: median 35 mm, for abdominal LN: median 23.5 mm |
| Milano et al., 200828 | 28 pts (121) (24 pts thoracic LN, 4 pts pelvic/abdominal LN) | Prospective | LINAC conformal arcs or multiple fixed coplanar beams | Miscellaneous (mostly breast, colorectal) | No | Not reported | Median sum of GTVs 28 cm3 mean 52 cm3 |
| Milano et al., 200829 d | 39 (293) (33 thoracic, 6 abdomino-pelvic LN) | Retrospective | LINAC conformal arcs or multiple fixed coplanar beams | Miscellaneous (mostly breast, colorectal) | Not reported | Not reported | Thoracic LN: median 19 cm3 abdomino/pelvic LN: median 7.2 cm3 |
| Milano et al., 200930 e | 21 (155) 32 pts (of 121 total pts) undergoing ≥2 SBRT courses/total of 155 lesions |
Retrospective | Conformal arcs or multiple fixed coplanar beams | Miscellaneous | Not reported | Not reported | GTV median volume 6 cm3, mean 4 cm3 |
| Authors, year of publication | Re-irradiation | SBRT dose | Median follow-up | Toxicity | Overall survival | Local control/pattern of failure |
|---|---|---|---|---|---|---|
| Kang et al., 201013 a | Not reported | SBRT alone (26 pts): 36–51 Gy in 3 fr, NTD 66–115 Gy. SBRT as boost (5 pts): 16 Gy in single fr, NTD 35 Gy (+40–45 Gy EBRT) | 32 mo | Pelvic LN: G1–G2: 9/23 pts; G4: 1/23 ptsa Para-aortic LN: G1–G2: 2/7 pts; G4: 1/7 ptsa |
3-year OS 49% | 3-year LC 66% 3 year PFS 25% Failure pattern NED 21 pts PD 35 pts (local 8, distant 11, regional 8) |
| Bae et al., 201214 b | In 1 case, after previous SBRT | For LN mts: median 48 Gy, (45–51 Gy) in 3 fr | 28 mo | Acute G1–G2: 17 pts (39%) Late ≥G3 in 3 pts (7%): liver, pelvic LN, paraortic LNb |
3-year and 5-year OS: 60% and 38% | 3-year and 5-year LC: 64% and 57% PD in 23/41 pts (56%): 14 local, 15 regional, 14 distant, 9 local + regional + distant |
| Jereczek-Fossa et al., 201215 c | In 27/38 lesions (71%), of which 8 LN mts (8/18) | Median 30 Gy in 4.5 fr (for LNs: 33 Gy/3 fr) | 16.9 mo | None in 68% of pts. Acute: 1 G3 LN SBRT (1/16 = 6%) Late G3: 2 (6%) |
At the time of analysis: 19 pts NED, 15 pts AWD | PFS at 12 mo 68.1% at 18 and 30 mo. 42.6% (63.5% in LN group) PFS longer in case of LN recurrence (median PFS > 30 mo) than for other sites (11–14 mo) In-field PD only in 3 cases (not LN or M), 8% |
| Jereczek-Fossa et al., 201316 | Yes in 47/118 total lesions (40%) | Median 24 Gy in 3 fr | 12 mo | Acute: none in 85% of treatments. G1–G2: 14 G3: 4 Late: G1–G2: 3 G3: 5 |
3-year OS 31.2% 3-year CSS 39.6% |
3-year LC: 67.6% 3-year PFS: 18.4% |
| Berkovic et al., 201317 | Not reported | Median 50 Gy in 10 fr BED: 80 (if α/β = 3); 92 (if α/β = 1.5) |
24 mo | Acute: G2: 14% No ≥G3 Late: G2 9% No ≥G3 |
12 pts AWD at last FU, 1-year ADT-FS 82%, 54% at 2 years; median deferment of ADT: 38 mo |
LC 100%, no in-field PD Pattern of recurrence: 11 pts oligometastatic, 6 pts multiple metastasis, 3 pts only biochemical 2-year PFS: 42% |
| Ahmed et al., 201318 | Not reported | Dose to LN: 50 Gy in 5 fr | For LN: 4.4 mo | Acute: G1–G2: 3 cases (for LN no acute toxicity) No late toxicity |
12 mo CSS 100% | 2 pts died for distant PD at last FU 12 months FFDP 40% |
| Hoyer et al., 200619 | Yes in 1 pt | 45 Gy in 3 fr | 4.3 years, 1 pt lost to FU | (within 6 mo): G4: 1 pt G3: 3 pts |
3-year and 5-year OS: 22% and 13% | 2 year LC: 79% Local failure in 10/141 lesions progression pattern: 1 pt only local, 9 pts local + distant 2-year PFS 19% |
| Kodany et al., 201120 | Yes in 21/34 pts (65%). Median dose of previous RT 60 Gy, median interval 51 mo | Median 30 Gy in 5 fr | 16 mo | Acute: none Late: severe in 6 pts (18%), all in re-RT |
1-year OS 70.6%, 2-year OS 58.3% median survival 28 mo | Overall response rate 61.9% |
| Roh et al., 200921 | Yes (all 11 LN). Median dose of previous EBRT 70.2 Gy, median interval 24 mo | Median 30 Gy in 3–5 fr | 17.3 mo. 35 of the 44 sites followed at last assessment (80%) | Acute in 24 pts (G1-G3) Late in 3 pts 8.6% 1 treatment-related death (33 Gy in 3 fr to retropharyngeal LN) |
1-year OS and 2-year OS 52.1% and 30.9% | 1-year and 2-year LC: 61% and 52.2% Pattern of failure: local in 17 pts (in field 14.5%, out field 8.6%, marginal 5.7%), regional 2 pts (5.7%), distant 3 pts (8.6%) |
| Greco et al., 201122 | No | Median 24 Gy in single fr (starting from 18 to 20 Gy, than from 2006 22–24 Gy) | 18 mo, no pts lost to FU | Acute G3 in 2 cases Late ≥G3 in 11/103 pts, overall incidence of G3 late tox < 4% |
Not reported | 2 year LC 64% 29 local failures 2 year LC 82% for high doses (23–24 Gy), 25% for low doses (18–20 Gy), 69% for intermediate doses (21–22 Gy). 2 year LC for LN: 67% |
| Wersall et al.200523 | Not reported | Most frequent: 10 Gy × 3–4 (2–5 fr, with 5–16 Gy/fraction) | 37 mo for pts alive at censor date; 13 mo for uncensored pts |
In 23/58 pts 50% G1–G2; G4 in 1 pt |
Median survival time: 19- > 58 mo | LC rate: 98% Distant failure in 73% |
| Salama et al., 201224 | Not allowed | Starting dose: 24 Gy (8 Gy × 3); dose ceiling was 60 Gy (20 Gy × 3) for all cohorts | 20.9 months | Acute: G3: 2 Late: G3: 6 (1 GI bleeding for para-aortic LN treated with 24 Gy) |
1-year, 2-year OS: 81.5%, 56.7% | 1-year and 2-year LC: 67.2% and 52.7%; 1 year, 2 year PFS: 33.3%, 22% Patterns of failure: In 7 pts (11.7%) in field PD as first progression 33 pts (55%) only distant PD |
| Kawaguchi et al., 201025 | Yes in 14 pts; previous RT dose 40–65 Gy in 1.5–2 Gy daily fractions, median interval 11 mo | Median 33.73 Gy (range 20–42 Gy) in 2–5 fractions | 24 mo | Acute: G2: 17 pts (77.3%) G3: 5 pts (all in re-RT) Late: G1: 11 ptsG2: 3 pts |
2 year OS in pts without LN mts 78.6% vs 12.5% in pts with LN mts | CR maintained at a median 2-years follow-up in 10/22 pts (45.5%) |
| Scorsetti et al., 201126 | Not reported | 45 Gy in 6 fractions | Minimum follow-up 3 mo | Acute tox: 2 G2 in abdomen | Not reported | Early LC in 89% Outcome at 1st evaluation (55 pts evaluable of 70): CR 10, PR 26, SD 13, PD 6 |
| Scorsetti et al., 201127 | Not reported | 45 in 6 daily fractions (7.5 Gy/fr) for LN mts | 12 mo | Acute: G1 in 5 pts Late: G3 in 1 pt G1 in 1 pt |
Not reported | 6-mo crude LC rate: 79.2% |
| Milano et al., 200828 | In 6 pts | Preferred schedule 50 Gy in 5 Gy-fractions over 2 weeks | 41 mo | G1 in 1 pt G2 in 3 pts |
2-year and 4-year OS: 50% and 28% | 2-year and 4-year LC: 77% and 73% 2-year and 4-year PFS: 26% and 20% 15/121 pts only local failure 29/121 pts distant + local failure |
| Milano et al., 200829 d | 8 thoracic LNs received SBRT as a boost after mediastinal RT | For SBRT: 30–68 Gy (3–8 Gy/fr) BED 31–72 Gy (median 62.5 Gy, mean 57.5 Gy) |
41 mo | Alive at last follow-up: 89 pts Censored (death): 147 |
2-year and 4-year LC: 77% and 73% Local failure in 57/293 lesions No documented local failure in 236/293 lesions |
|
| Milano et al., 200930 e | 12 lesions undergoing salvage repeated SBRT | Not reported (see previous studies) | Not reported(see previous studies) | No ≥ G2 toxicity in the 9 pts reirradiated for a locally recurrent lesion | 2-year and 4-year OS: 65% and 33% | 2-year and 4-year LC: 88% and 82% 2-year and 4-year PFS: 54% and 28% 18/155 lesions failed locally 19/32 pts developed DM not amenable to curative-intent treatment |
Legend: Adj – adjuvant, ADT – androgen deprivation therapy, ADT-FS – androgen deprivation therapy free survival, AWD – alive with disease, BED – biologically equivalent dose, CBK – CyberKnife, CHT – chemotherapy, CR – complete response, CSS – cancer specific survival, CTV – clinical target volume, 3D-CRT – 3 dimensional conformal radiotherapy, DFS – disease free survival, DM – distant metastases, EBRT – external beam radiotherapy, FFF – flattening filter free, fr. – fractions, 5-FU – 5-fluorouracil, G1–G2–G3–G4 – grades 1, 2, 3, 4, GTV – gross tumor volume, HT – hormonal therapy, IG-IMRT – image guided intensity modulated radiotherapy, IGRT – image guided radiotherapy, IMRT – intensity modulated radiotherapy, LC – local control, LHRH – luteinizing hormone releasing hormone analogue, LN – lymph node, mo – months, mts – metastasis, NED – no evidence of disease, Neoadjuv – neoadjuvant, NTD – normalized total dose, OS – overall survival, PD – progressive disease, PFS – progression free survival, PR – partial response, pts – patients, PTV – planning target volume, RT – radiotherapy, SBRT – stereotactic body radiotherapy, SD – stable disease, tox – toxicity, VMAT – Volumetric modulated Arc Therapy.
a
It includes some patients considered in Kim et al., 200942 (the patient with G4 toxicity treated on para-aortic node is the same) and Kim et al. 200843 (the patient with G4 toxicity treated on pelvic node is the same).
b
It includes some patients considered in Kim et al., 200942 (the patient with G4 toxicity treated on paraortic node is the same), Kim et al., 200843 (the patient with G4 toxicity treated on pelvic node is the same), it evaluates the results of high doses > 45 Gy (escalation up to 60 Gy for liver and lung metastases, not for lymph nodes due to G4 toxicity at 48 and 51 Gy).
c
7 pts with lymph node recurrence included in the preliminary report, Jereczek-Fossa et al., 2009,38 have included in this series with updated follow-up.
d
Descriptive analysis of the 121 pts considered in the previous prospective study Milano et al., 2008.28
e
Analysis of oligometastatic patients undergoing 2 or more curative-intent SRT courses: about 32 of 121 pts considered in the prospective study Milano et al., 2008,28 those treated with 2 or more SBRT courses.