SOFT Preop
ForResectable, borderline or LA type A PDAC, ECOG 0-2, post >1 mo neoadj chemo
41% vs 38%
SBRT vs Chemo-RT, p = 0.754, ns; chemo-RT superiority hypothesis not met
TL;DRPath node positivity 41% SBRT vs 38% chemo-RT (p = 0.754) preop in PDAC; mOS 26.04 vs 42.96 mo (p= 0.639); QOL favored SBRT.
Local/regional recurrence split 6 SBRT vs 2 chemo-RT (8 events, 7.8%) at median follow-up 3.4 years, with elective nodes at 25 Gy/5 and primary at 33-40 Gy in 5, mostly on 1.5 T adaptive MR guidance. The preop fractionation choice moves toward SBRT on QOL only where that nodal volume and platform are reproduced.
In resectable, borderline, or LA type A PDAC already through >1 month of neoadjuvant chemo and planned for preop RT, this informs choosing 5-fraction SBRT over 28-fraction chemo-RT on QOL grounds; it does not address whether preop RT adds to chemo alone.
Local/regional recurrence split 6 SBRT vs 2 chemo-RT (8 events, 7.8%) at median follow-up 3.4 years, with elective nodes at 25 Gy/5 and primary at 33-40 Gy in 5, mostly on 1.5 T adaptive MR guidance. The fractionation choice moves toward SBRT on QOL only where that nodal volume and platform are reproduced.
83/98 (84.7%) reached resection, 41 SBRT and 42 chemo-RT, with no difference in surgical complications, so the 5-fraction course did not cost operability. Node positivity was 41% vs 38%; margin negativity and pathologic response are called equal but no figures appear in the abstract.
11 details 1 trial watching
Prospective, randomized phase II, 1:1 allocation after neoadjuvant chemo. 102 pts targeted and enrolled, anticipating a 15% drop out before surgery; 4 withdrew after enrollment. Median follow-up among all enrolled pts 3.4 [2.6, 5.1] years.
Resectable, borderline, or locally advanced (LA) type A PDAC, ECOG 0-2, > 1 month of neoadjuvant chemo. Median age 65 (34-82); 38%/42%/20% resectable, borderline, and LA type A. Prior chemo was FOLFIRINOX (79%), gemcitabine/nab-paclitaxel (12%), or other (9%), with 92% receiving more than 2 months.
Chemo-RT: 50.4 Gy/28 fractions with weekly gemcitabine or capecitabine. SBRT: 25 Gy/5 to elective nodes and 33-40 Gy in 5 to the primary, without concurrent chemo. Most SBRT pts were treated using 1.5 T adaptive MRI guidance.
Primary: pathologic node positivity, hypothesizing lower rates with chemo-RT. Secondary: PFS, OS, patient-reported QOL (PROMIS), physician-reported toxicity, surgical complications, translational endpoints.
Arm-level figures are in the table. 83/98 (84.7%) completed all intended therapy including surgical resection, equal in both arms.
| Endpoint | SBRT | Chemo-RT | p |
|---|---|---|---|
| Path node positivity | 41% | 38% | p = 0.754 |
| Median OS | 26.04 mo (95% CI 17.9 to 59.28) | 42.96 mo (95% CI 18.72 to 54.72) | p= 0.639 |
| Alive at 3 years | 42.6% | 57.5% | p = 0.198 |
| PFS | 14.28 mo (95% CI 9-29.64) | 21.6 mo (95% CI 10.56-38.04) | p = 0.96 |
| Local/regional recurrence (events) | 6 | 2 | not reported |
| Completed all therapy incl. resection | 41 | 42 | not reported |
No difference in surgical complications; no rates given. Physician-reported toxicity was a secondary endpoint but is not reported in the abstract. PROMIS physical function, global physical health, and fatigue were better preserved with SBRT (p = < 0.05).
Alliance A021501 tested preop SBRT or hypofractionated RT against chemotherapy alone, and PREOPANC established gemcitabine-based preop chemo-RT against upfront surgery. Neither compared one RT schedule with another. The authors describe this as the first randomized trial comparing SBRT with chemo-RT in the neoadjuvant setting for PDAC.
Abstract only: no per-arm allocation counts, no QOL magnitudes or timepoints, and no figures for pathologic response or margin negativity despite the conclusion citing them. QOL is patient-reported in an unblinded comparison. Concurrent agent varied in the chemo-RT arm and primary SBRT dose ranged 33-40 Gy.
The trial shows SBRT is deliverable preop with equal resection completion and better QOL, and it does not show nodal sterilization differs. It does not settle survival equivalence: median OS 26.04 vs 42.96 mo and LRR 6 vs 2 point the same direction in a sample too small to resolve them.
Randomised phase II, N=102, built to show chemo-RT superiority on nodal positivity and null. Not an equivalence design; survival and LRR lean numerically toward chemo-RT.
- Is preop SBRT non-inferior to chemo-RT for OS in PDAC?
- Does 25 Gy/5 elective nodal SBRT give adequate regional control?
- Does any preop RT add to neoadjuvant FOLFIRINOX alone? recruiting Preoperative mFOLFIRINOX (or Gem-Nab-P) +/- Isotoxic High-dose SBRT for Borderline Resectable Pancreatic Adenocarcinoma Phase 2n=256 · primary completion 2027-12 · preop mFOLFIRINOX +/- isotoxic high-dose SBRT in BRPC
📚 Sources · 📄 1 paper
Abstract
The longer read
The trial was built as a superiority test in the opposite direction to how it is being read. The hypothesis was that conventionally fractionated chemo-RT, with a longer course and a concurrent radiosensitizer, would sterilize nodes better than SBRT, and pathologic node positivity was the endpoint chosen to show it. It did not: 41% with SBRT vs 38% with chemo-RT, p = 0.754. A failed superiority test in 102 pts is not a demonstration of equivalence, and the conclusion that the data support SBRT rests on the absence of a detected difference, not on a prespecified non-inferiority margin. That distinction is the whole interpretive problem.
The secondary endpoints deserve a slower read than the abstract gives them. Median OS was 26.04 mo with SBRT and 42.96 mo with chemo-RT, 3-year survival 42.6% vs 57.5%, PFS 14.28 vs 21.6 mo, and local/regional recurrence 6 vs 2 events. None reaches statistical significance, and the OS intervals (17.9 to 59.28 vs 18.72 to 54.72) overlap almost entirely, so no single comparison carries weight. But every one leans the same way, toward chemo-RT, in a trial too small to exclude a clinically meaningful gap. "No difference" is a fair statistical summary and a weak clinical one. The honest position is that the trial cannot separate a modest chemo-RT advantage from noise.
Prior randomized evidence does not help resolve it. Alliance A021501 put preop SBRT or hypofractionated RT up against chemotherapy alone, and PREOPANC tested gemcitabine-based conventional chemo-RT against upfront surgery. Each asked whether preop RT belongs in the sequence; neither asked which schedule. This trial is the first to ask that, and it does so in a contemporary population, most of whom had received FOLFIRINOX for more than 2 months before enrollment. Whether RT of any kind adds to that backbone is a question the design cannot touch, since both arms were irradiated.
Technique gates transfer. The SBRT arm was a specific package: 25 Gy/5 to elective nodes, 33-40 Gy in 5 to the primary, and mostly 1.5 T adaptive MR guidance. A center delivering CT-guided SBRT to gross disease alone is not reproducing the tested arm, and whatever nodal parity exists here may depend on the elective volume. The 6 vs 2 local/regional split is too few events to interpret, yet it is the number an RT reader should carry forward, because it is where a real dose or volume deficit would show first. The chemo-RT arm was also not uniform, with either gemcitabine or capecitabine concurrent.
The positive finding is QOL: physical function, global physical health and fatigue were better preserved with SBRT. That is plausible for a five-fraction course without concurrent chemo, but it is patient-reported in an unblinded trial and the abstract gives no magnitudes or timepoints. What changes is narrow. Where preop RT is already planned, the tolerability argument for SBRT now has randomized support and no penalty in resection completion or surgical complications. What stays open is survival, and the reading would be wrong if a larger trial showed the OS lean to be real.