Table 2.
Review of stereotactic body radiation therapy (SBRT) pancreatic cancer clinical studies (2000–current).
| Author | Disease | Sample Size | Study Design | Chemotherapy | Total Dose (Gy) and Fractionation | Acute Side Effects Criteria for Adverse Events Version |
Late Side Effects | MST Months (Range) |
1-year OS Rate | 2-year OS Rate | PFS | FFLP | Median FU Period Months (Range) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chang, et al. [22] Φ * | Unresectable LAPC | 77 | Retrospective, single institute, combination of phase I and phase II studies. | Variety of gemcitabine-based regimens | 25 in 1 | Grade ≥ 2 = 5% NR |
Grade ≥ 2 = 4% Grade ≥ 3 = 9% |
11.8 | 21% | NR | 1-year = 9% | 1-year = 84% | 6 (3–31) |
| Schellenberg, et al. [48] * | LAPC | 20 | Prospective, phase II trial, single institute. | Gemcitabine 1000 mg/m2 weekly (days 1, 8, and 15) | 25 in 1 | Grade ≥ 2 = 15% Grade 3 = 0% V3 [90] |
Grade ≥ 2 = 15% Grade ≥ 3 = 5% |
11.8 | 50% | 20% | Median time to progression was 9.2 months | 1-year = 94% | 2 patients remaining alive = 25.1–36.4 months |
| Schellenberg, et al. [41] * | LAPC | 16 | Prospective, phase II, single institute. | Gemcitabine 1000 mg/m2 weekly (days 1, 8, and 15) | 25 in 1 | Grade 2 = 13% Grade 3 = 6% V3 [90] |
Grade ≥ 2 = 33% Grade ≥ 3 = 13% |
11.4 | 50% | Estimate 18% | Median time to progression was 9.7 months. | 1-year = 100% | 9.1 (22.3 for living patients) |
| Hoyer, et al. [47] * | Unresectable LAPC | 22 | Prospective, phase II, single institute. | NR | 45 in 3 | Grade ≥ 2 = 100% NR |
Grade ≥ 2 = 94% | 5.4 | 5% | NR | 1-year = 9% Median time to progression was 4.8 months. |
Local control rate = 57% | 14 days–18 months |
| Wild, et al. [91] * | Recurrent | 18 | Reirradiation, retrospective, single institute. | 5-fluorouracil-based regimen for 10 patients Gemcitabine- based regimen for 7 patients |
25, 20 or 27 in 5 After chemoradiation of 50.4 Gy in 27 |
Grade 2 = 28% Grade 3 = 0% NR |
Grade 3 = 6% | 8.8 | NR | NR | Median = 3.7 months | 1-year = 62% | 34.3 (6.4–61.6) |
| Macchia, et al. [92] * | Unresectable disease or recurrent | 16 | Prospective, phase I, single institute. | Variety of chemotherapy regimens | 20–35 in 4–7 | Grade 1 = 50% Grade 2 = 0% NR |
Grade 3 = 6.3% | NR Overall response rate =56.2% |
NR | 50% | 2-year distant progression free = 58.7% | 2-year local progression free = 85.7% | 24 (10–85) |
| Didolkar, et al. [39] * | Unresectable LAPC | 85 | Retrospective, single institute. | Variety of gemcitabine-based regimens post-SBRT | 15–30 in 1–4 | NR acute compared to late Grade ≥ 3 = 22.3% V2 [93] |
18.6 | 50% Median 1-year = 13.4 months |
NR | NR | Local control = 91.7% | NR (25.8 months at last follow up) |
|
| Mahadevan, et al. [54] † | LAPC | 36 | Retrospective, single institute. | Gemcitabine 1000 mg/m2 weekly (for 6 months) | 24, 30 or 36 in 3 | Grade 1 = 42% Grade 2 = 25% Grade 3 = 8% NR |
Grade ≥ 3 = 6% | 14.3 | NR | NR | Median = 9.6 months | Local control = 78% | 24 (12–33) |
| Mahadevan, et al. [3] † | LAPC | 39 | Retrospective, single institute. | Gemcitabine 1000 mg/m2 weekly (for 6 months) | 24 or 30 in 3 | Grade 1 = 41% Grade 2 = 23% Grade 3 = 0% V3 [90] |
Grade 3 = 9% | 20 | NR | NR | Median = 15 months | Local control = 85% FFLP= 31% |
21 (6–33) |
| Lominska, et al. [94] † | LAPC | 28 | Reirradiation, retrospective, single institute. | Variety of chemotherapy regimens | 20–30 in 3–5 After 50.4 Gy XRT |
Grade 2 = 4% V3 [90] |
Grade 3 = 7% | 5.9 | 18% | NR | NR | 1-year = 70% | 5.9 (1–27) |
| Dagoglu, et al. [95] † | Recurrent | 30 | Reirradiation, retrospective, single institute. | Variety of chemotherapy regimens Gemcitabine for 14 patients FOLFOX for 6 patients Erlotinib for 12 patients None for 5 patients |
24–36 in 3–5 | Grade 3 = 11% NR |
Grade 3 = 7% | 14 | 50% | 5% | 78% | NR | 11 (4–24) |
| Tozzi, et al. [44] † | Unresectable LAPC = 21 Locally recurrent = 9 |
30 | Prospective, single institute (consecutive enrolment). | Variety of gemcitabine-based regimens | 36–45 in 6 | Grade 1 = 43% Grade 2 = 10% Grade 3= 0% V3 [90] |
Grade 3 = 0% | 11 | Median OS at 1-year = 47% | NR | Median PFS = 8 months | 1-year = 96% (for 45 Gy group) and 85% for others | 11.0 (2–28) |
| Gurka, et al. [96] † | LAPC (with elective nodes) | 10 | Prospective, single institute, pilot trial. | Concurrent gemcitabine with 1000 mg/m2 for 6 cycles | 25 in 5 | Grade 1 = 60% Grade 3 = 0% V3 [90] |
Grade 2 = 0% | 12.2 | NR | NR | 6.8 months | 1-year = 40% | Until death |
| Koong, et al. [42] * | LAPC | 15 | Prospective, single institute, phase I. | Prior to enrolment 2 patients received conventional 5-FU–based chemoradiation to a dose of 50 Gy and 1 patient received chemotherapy alone. | 15 (3 patients), 20 (5 patients), 25 (7 patients) in 1 | Grade 1 = 13% Grade 2 = 20% Grade 3 = 0% GI toxicities were scored according to the Radiation Therapy Oncology Group acute radiation morbidity criteria. |
NR | 11 | NR | NR | Median time to progression = 2 months | Local control = 75% | 5 |
| Koong, et al. [38] * | LAPC | 16 | Prospective, single institute, phase II. | Concurrent 5-fluorouracil | 45 in 25 (IMRT) and 25 in 1 (SBRT) | Grade 0= 18.7% Grade 1= 43.7% Grade 2= 25% Grade 3= 12.5% GI toxicities were scored according to the Radiation Therapy Oncology Group acute radiation morbidity criteria. |
NR | 8.3 | 15% | NR | Median time to progression = 4.38 months | 1-year = 8% Local control = 94% |
5.75 |
| Polistina, et al. [97] * | Unresectable LAPC | 33 | Prospective, single institute. | Gemcitabine 1000 mg/m2 weekly (for 6 weeks) | 30 in 3 | Grade 1 = 21.7% Grade 2 = 0% V3 [90] |
NR | 10.6 | 39.1% | 0% | Median time to progression = 7.3 months | 1-year = 82.6% | 9 |
| Rwigema, et al. [98] * | LAPC (mix of metastatic (11%), unresectable (56%) and recurrent disease (16%)) | 71 | Retrospective, single institute. | Variety of chemotherapy regimens | 18–25 in 1–3 | Grade 1 = 24% Grade 2 = 11.3% Grade 3 = 4.2% NR |
Grade 1 = 4.2% | 10.3 months overall median OS | 41% | NR | NR | Overall 1-year = 48.5% 1-year = 38% for unresectable 1-year = 18.8% for recurrent group 1-year = 40% for metastatic group |
12.7 (4–26) |
| Herman, et al. [55] * | Unresectable LAPC | 49 | Prospective single-arm, multi-institutional, phase II. | Gemcitabine 1000 mg/m2 (3 doses) followed by a week break prior to SBRT | 33 in 5 | Grade ≥ 2 = 2% V4 [99] |
Grade ≥ 2 = 11% | 13.9 (10.2–16.7) | 59% | 18% | Median PFS = 7.8 months 1-year = 32% 2-year = 10% |
1-year = 78% | 13.9 (3.9–45.2) |
| Chuong, et al. [37] † (and *) | Nonmetastatic LAPC (16 patients) and borderline resectable pancreatic cancer (57)) | 73 | Retrospective, single institute. | Induction gemcitabine-based regimens delivered over 3 cycles followed by SBRT |
35–50 in 5 | Grade ≥ 3 = 0 V4 [99] |
Grade ≥ 3 = 5.3% | 15 (LAPC) 16.4 (borderline) |
68.1% (LAPC) 72.2% borderline |
NR | Median PFS = 9.8 months 1-year PFS LAPC = 41% 1-year PFS borderline = 42.8% |
1-year LC for non-surgical patients= 81% | 10.5 (2.2–25.9) |
| Comito, et al. [40] * | Unresectable LAPC | 45 | Prospective, observational, single-arm, single institute, phase II. | 71% completed regimens 2 weeks prior to SBRT 19% received gemcitabine-based regimens |
45 in 6 | Grade 1–2 = 49% Grade ≥ 3 = 0% V3 [90] |
Grade 2 = 4% Grade ≥ 3 = 0% |
19 | 85% | 33% | Median PFS = 8 months | Median FFLP = 26 months 1-year = 87% 2-year = 87% |
13.5 months (6–48) |
| Gurka, et al. [36] * (and †) | Borderline resectable and inoperable LAPC | 38 | Retrospective, single institute. | Variety of gemcitabine-based regimens | 25–30 (one patient received 15) in 5 | Grade 2 = NR Grade 3 = 5.2% V3 [90] |
Grade 3 = 5.2% Grade 4 = 5.2% Grade 5 = 5.2% |
14.3 | NR | NR | 9.2 months | Local control rate = 79% | NR |
| Mellon, et al. [46] * | Borderline resectable and LAPC | 159 (110 BRPC and 49 LAPC) |
Retrospective, single institute. | Variety of induction chemotherapy regimens | 28–30 in 5 | Grade1-2 = 52% Grade 3 = 11% V4 [99] |
Grade 3 = 11% | 19.2 (borderline) 15 (LAPC) |
NR | NR | Event free survival = 11.9 months in borderline and 13.2 in LAPC |
1-year locoregional control = 78% | 5.6 (2.1–15.4) |
| Pollom, et al. [43] * | Unresectable (133), borderline resectable (11) pancreatic adenocarcinoma | 167 | Retrospective, single institute. | Variety of induction chemotherapy regimens (82% were gemcitabine-based) | 25 in 1 (76 patients) 25–45 in 5 (91 patients) |
Single-fraction: Grade ≥ 2 = 25% Multi-fraction: Grade ≥ 2 = 8.7% V4 [99] |
Single-fraction: Grade ≥ 3 = 12.3% Multi-fraction: Grade ≥ 3 = 5.6% |
13.6 | Single-fraction= 30.8% Multi- fraction= 34.9% |
NR | NR | NR | 7.9 (0.1–63.6) |
GI: gastrointestinal, MST: median survival time, OS: overall survival, XRT: photon radiation therapy, FU: follow up, NR: not reported, LAPC: locally advanced pancreatic cancer, IMRT: intensity modulated radiation therapy. Φ: Includes 40 patients from Schellenberg, et al. [41], Koong, et al. [42] and Koong, et al. [38]. *: OS measured from diagnosis †: OS measured from start of SBRT.