Table 12. Studies of IORT in the management of pancreatic cancers.
| Author/Year | Sample size | Study design | IORT type | IORT dose (Gy) | EBRT % | Median follow-up | LC 5 year (%) | OS 5 year (%) | Toxicity grade 3 or > |
|---|---|---|---|---|---|---|---|---|---|
| Mohiuddin et al. [178] 1995 | 49 UR-PC (Resected-0%) |
Retrospective | IOERT | 10–20 | 100 (Post-op) |
28 | 69 | 7 (4yr) | Acute toxicity-14% GI bleeding-2* Late toxicity-19% GI bleeding-3* Obstruction-2* |
| Nishimura et al. [179] 1997 | Resected-157 IORT- 55 No IORT-102 Unresectable-175 IORT-71 No IORT-104 |
Retrospective | IOERT | 12–33 Gy | Resected- 70 Unresectable-87 (Pre-op or post-op) |
NR | NR | Resected: IORT-16 No IORT-0 (2yr) Unresectable: IORT-14 No IORT-0 p < 0.05 (2yr) |
IORT: Late toxicity: gastric ulcer-18* Intestinal perforation-4* |
| Ma et al. [177] 2004 | 81 UR-PC (Resected-0%) IORT-18 IORT+EBRT-25 EBRT-16 Palliative Sx-22 |
Retrospective | IOERT | 15–25 | 80 (Post-op) |
NR | NR (60% complete pain relief with IORT) |
10.7 (M.S) 12.2 (M.S) 5.1 (M.S) 7 (M.S) |
IORT vs IORT+EBRT: Delayed gastric emptying: 3 vs 2* |
| Willet et al. [180] 2005 | 150 UR-PC (Resected-0%) |
Retrospective | IOERT | 15–20 Gy | 100 (Pre/post-op RT) | NR | NR | 7 (3Yr) | Post-operative complications- 20% Late toxicity- 15% Upper GI bleed-16* |
| Jingu et al. [176] 2012 | 322 Resected-83 Unresectable- 109 Metastatic-130 (exclude) |
Retrospective | IOERT | 20–30 | 29 (post-op RT) | 38 | 64 | 9 R2:HR-2.03, p < 0.001 |
Late toxicity GI-4* |
| Cai et al. [174] 2013 | 194 UR-PC (Resected-0%) |
Retrospective | IOERT | 10–25 | 97% (Pre-op CTRT) | 12 | 38 (3yr) | 6 (3yr) | Acute toxicity- 21% Late toxicity-14% Haemorrhage-23* |
| Chen et al. [175] 2016 |
247 UR-PC (Resected-0%) |
Retrospective | IOERT | 10–20 | 51% (Post-op CTRT) | 10 | 35 (3yr) Complete pain relief-70% |
7.2 (3yr) | Post-operative complications-14% Fistula-11* Haemorrhage- 7* |
| Keane et al. [181] 2016 |
68 UR-PC After NACTRT Resected-41 IORT-22 (R1-73%) No IORT-19 Unresectable-18 (IORT-17) |
Retrospective | IOERT |
8–13 15–17 |
100 % (NACTRT) | 21 | NR |
35.1 (M.S) 24.5 (M.S) 24.8 (M.S) |
No significant difference in post-operative complications |
| Kokubo et al. [172] 2000 | 138 R/BR-PC (Resected-100%, R1-29%) |
Retrospective | IOERT | 20–30 | 45 (Pre-op:13% Post op-47% Both-40%) |
NR | NR |
R0:19 R1:4 p < 0.005 (2-yr cause specific survival) |
Acute toxicity- none Late toxicity- GI ulcers-20% Perforation-2* |
| Alfieri et al. [165] 2001 | 46 R/BR-PC (Resected-100%) IORT-26 (R1-10%) No IORT-20 (R1-13%) |
NRC | IOERT | 10 |
100 0 (Post-op) |
82 |
IORT-58 No IORT-30 p < 0.001 |
IORT-16 No IORT-6 p = 0.06 |
IORT vs. No IORT Acute morbidity- 57% vs. 43% (p = 0.1) Perioperative mortality- 8% vs. 9% |
| Reni et al. [173] 2001 | 127 R/BR-PC (Resected-82%) IORT- 127 (R0-1:104, R2-23) No IORT- 76 (R0-1:62, R2-14) |
Retrospective | IOERT | 10–25 |
32 20 (Post-op) |
21 (in survivors) |
Stage I-II: IORT-73 No IORT-40 Stage III-IVA: IORT-50 No IORT-45 |
Stage I–II: IORT-22 No IORT-6 Stage III-IVA: IORT-3 No IORT-5 |
IORT vs. No IORT: Acute toxicity: N.S difference Chronic toxicity: Abdominal pain 15 vs. 22% Late GI bleed-6 vs. 3% Stenosis-3% vs. 0% |
| Messick et al. [169] 2008 | 49 R/BR-PC (Resected-100%, R1-74%) IORT-22 No IORT-27 |
NRC | IOERT | 10–12 |
76 64 |
10.1 13.3 |
IORT-82 No IORT-88 (N.S) |
IORT-20 (M.S) No IORT-13 (M.S) (N.S) |
IORT vs. No IORT: Delayed gastric emptying-6.7 vs. 4.2% Wound infection-4.5 vs. 22% Pancreatic fistula 10 vs. 4.8% (N.S) |
| Valentini et al. [171] 2008 | 26 R/BR-PC Resected-100%, R1-4% |
Retrospective | IOERT | 10 | 100 (Post-op: 65%) |
102 in survivors | 57 | 15 | Perioperative complications-11% |
| Showalter et al. [167] 2009 | R/BR-PC IORT-37 (R1-2:43%) No IORT-46 (R1-2: 30%) |
Retrospective | IOERT | 10–20 | 74 66 (Post-op RT) |
NR | IORT-79 No IORT-61 p = 0.19 |
IORT-21 (M.S) No IORT-19 (M.S) |
Perioperative complications-46% vs. 40% (N.S) |
| Valentini et al. [168] 2009 | 270 Resected-81% (R1-27%) |
ISIORT Pooled analysis | IOERT | 7.5–25 | 64 (pre-op:24 Post-op:40) |
96 | 23 Pre-op RT vs. post-op RT vs. IORT alone p < 0.0001 |
18 IORT + Pre-op RT vs. IORT + post-op RT vs. IORT alone p < 0.0001 |
Acute toxicity- None > G2 Late-NS |
| Ogawa et al. [170] 2010 | 210 R/BR-PC Resected-100%, R1-32% |
Retrospective | IOERT | 20–30 | 30 | 26 | 84 (2yr) | 42 (2yr) | Late toxicity GI-7* |
| Calvo et al. [166] 2013 |
60 R/BR-PC (Resected-83%, R1-43%) IORT-29 No IORT-31 |
Prospective | IOERT | 10–15 | 100% (Pre-op CTRT-32%) |
16 | 58 No IORT: HR-6.75, p = 0.01 |
20 |
Perioperative complications-43% (N.S) Chronic-17% Neuropathy-4* GI-3* |
RCT: randomised control trial, NRC: non-randomised comparison, Sx: surgery, LC: local control, OS: overall survival, DFS: disease-free survival, NR: not reported,
*
Number of patients,
# fractions, Pre-op: pre-operative, Post-op: post-operative, M.S: median survival in months, N.S: non-significant, R/BR-PC: resectable/borderline resectable pancreatic cancer, UR-PC: unresectable pancreatic cancer, NACTRT: neoadjuvant chemoradiotherapy, Resected: complete resections (R0/R1), Unresectable: R2/palliative resections.