Multi-Institutional Comparison of Ablative 5-Fraction Magnetic Resonance-Guided Online Adaptive Versus 15/25-Fraction Computed Tomography-Guided Moderately Hypofractionated Offline Adapted Radiation Therapy for Locally Advanced Pancreatic Cancer
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design and Participants
2.2. Five-Fraction SMART
2.3. Fifteen/Twenty-Five-Fraction HART
2.4. Additional Therapy After SMART/HART
2.5. Response Assessment After SMART/HART
2.6. Toxicity
2.7. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
A-RT | Ablative radiation therapy |
BED | Biological effective dose |
BH | Breath hold |
CA | Celiac artery |
CBCT | Cone beam computed tomography |
CI | Confidence interval |
CT | Computed tomography |
CTCAE | Common terminology criteria for adverse events |
CTV | Clinical tumor volume |
DF | Distant failure |
GI | Gastrointestinal |
GTV | Gross tumor volume |
HART | Hypofractionated ablative radiation therapy |
HR | Hazard ratio |
IDLs | Isodose lines |
IRB | Institutional review board |
kV | Kilovoltage |
LAPC | Locally advanced pancreatic cancer |
LF | Local failure |
MCI | Miami Cancer Institute |
MR | Magnetic resonance |
MSKCC | Memorial Sloan Kettering Cancer Center |
MVA | Multivariate analysis |
OARs | Organs at risk |
OS | Overall survival |
PDAC | Pancreatic ductal adenocarcinoma |
PET | Position emission tomography |
PFS | Progression-free survival |
PPIs | Prophylactic proton pump inhibitors |
PRV | Planning OAR volume |
RECIST | Response evaluation criteria in solid tumors |
RT | Radiation therapy |
SMA | Superior mesenteric artery |
SMART | Stereotactic magnetic resonance-guided adaptive radiation therapy |
T | Tesla |
UVA | Univariate analysis |
VMAT | Volumetric modulated arc therapy |
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SMART (n = 91) | HART (n = 120) | Total (n = 211) | p Value | |
---|---|---|---|---|
Age (year), median | 72.0 (47–94) | 68.0 (42–91) | 70.0 (42–94) | 0.004 |
Gender Male Female | 49 (53.8%) 42 (46.2%) | 59 (49.2%) 61 (50.8%) | 108 (51.2%) 103 (48.8%) | 0.501 |
ECOG PS 0–1 2 | 85 (93.4%) 6 (6.6%) | 108 (90.0%) 12 (10.0%) | 193 (91.5%) 18 (8.5%) | 0.380 |
Tumor location Head Body/tail | 73 (80.2%) 18 (19.8%) | 75 (62.5%) 45 (37.5%) | 148 (70.1%) 63 (29.9%) | 0.005 |
T stage 1–2 3–4 | 23 (25.3%) 68 (74.7%) | 20 (16.7%) 100 (83.3%) | 43 (20.4%) 168 (79.6%) | 0.124 |
N stage Positive Negative Unknown | 23 (25.3%) 68 (74.7%) 0 (0.0%) | 51 (42.5%) 54 (45.0%) 15 (12.5%) | 74 (35.1%) 122 (57.8%) 15 (7.1%) | < 0.001 |
Tumor size (cm), median | 3.7 (1.5–6.9) | 3.8 (1.4–7.4) | 3.8 (1.4–7.4) | 0.583 |
Overlap w/GI OARs (cc), median GTV + 3 mm GTV + 5 mm | 1.4 (0–19.6) 3.9 (0–32.4) | 1.0 (0–12.5) 2.8 (0–24.0) | 1.2 (0–19.6) 3.2 (0–32.4) | 0.036 0.028 |
CA19-9 baseline (U/mL), median | 156.4 (1.0–19,000) | 166.0 (0–2766) | 165.0 (0–19,000) | 0.780 |
CA19-9 pre-RT (U/mL), median | 55.0 (1.2–11,534) | 79.0 (0–3507) | 70.0 (0–11,534) | 0.909 |
Induction chemotherapy duration (month), median | 3.9 (0–9.1) | 3.7 (0–13) | 3.8 (0–13) | 0.531 |
Induction chemotherapy regimen FOLFIRINOX Gemcitabine/nab-paclitaxel Gemcitabine/cisplatin Other 5-fluorouracil-based Other gemcitabine-based Other None | 49 (53.8%) 26 (28.6%) 6 (6.6%) 0 (0.0%) 1 (1.1%) 0 (0.0%) 9 (9.9%) | 66 (55.0%) 37 (30.8%) 4 (3.3%) 4 (3.3%) 5 (4.2%) 1 (0.8%) 3 (2.5%) | 115 (54.5%) 63 (29.9%) 10 (4.7%) 4 (1.9%) 6 (2.8%) 1 (0.5%) 12 (5.7%) | 0.068 |
Maintenance chemotherapy Yes No | 6 (6.6%) 85 (93.4%) | 19 (15.8%) 101 (84.2%) | 25 (11.8%) 186 (88.2%) | 0.039 |
SMART (n = 91) | HART (n = 120) | Total (n = 211) | p Value | |
---|---|---|---|---|
Prescribed BED10 (Gy) 85.5 97.5 97.9 100 | 4 (4.4%) 0 (0.0%) 0 (0.0%) 87 (95.6%) | 0 (0.0%) 97 (80.8%) 23 (19.2%) 0 (0.0%) | 4 (1.9%) 97 (46.0%) 23 (10.9%) 87 (41.2%) | <0.001 |
GTV (cc), median | 34.4 (5.6–155.6) | 31.2 (2.2–206.7) | 32.0 (2.2–206.7) | 0.466 |
GTV D95% scaled (%), median | 91.5 (64.9–119.9) | 76.6 (42.9–108.3) | 82.7 (42.9–119.9) | <0.001 |
GTV D90% scaled (%), median | 101.1 (74.2–122.2) | 84.5 (44.6–111.7) | 91.2 (44.6–122.2) | <0.001 |
GTV D80% scaled (%), median | 106.7 (83.3–128.3) | 95.2 (47.8–121.3) | 101.0 (47.8–128.3) | <0.001 |
GTV V130% (cc), median | 2.8 (0–34.9) | 0 (0–27.4) | 0 (0–34.9) | <0.001 |
GTV V120% (cc), median | 14.5 (0–79.5) | 0 (0–45.8) | 0 (0–79.5) | <0.001 |
GTV V100% (cc), median | 29.4 (5.6–124.8) | 20.5 (0–153.6) | 25.4 (0–153.6) | <0.001 |
GTV min dose scaled (%), median | 66.7 | 60.5 | 62.8 | <0.001 |
Median (Months) | 1-Year (95% CI) | 2-Year (95% CI) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
SMART | HART | p Value | SMART | HART | p Value | SMART | HART | p Value | |||
LF | Not reached | 36.8 (29.0–.) | --- | 3.1% (1.9–6.3%) | 11.8% (9.5–15.4% | 0.001 | 6.5% (2.5–14.6%) | 32.9% (26.3–41.1%) | <0.001 | ||
DF | 6.0 (5.0–10.0) | 7.0 (6.0–14.0) | 0.423 | 57.1% (51.2–62.2%) | 59.1% (52.9–61.1%) | 0.837 | 68.3% (61.2–74.1%) | 71.5% (64.7–78.6%) | 0.576 | ||
PFS | 7.0 (5.0–8.0) | 5.0 (4.0–7.0) | 0.792 | 29.1% (19.4–38.7%) | 29.8% (21.5–38.0%) | 0.525 | 15.9% (7.8–24.0%) | 14.1% (7.8–20.5%) | 0.991 | ||
OS | 14.0 (11.0–16.0) | 17.0 (14.0–20.0) | 0.217 | 52.0% (41.0–63.0%) | 62.3% (53.5–71.1%) | 0.272 | 31.0% (20.2–41.9%) | 35.3% (26.5–44.2%) | 0.056 |
No Local Failure (n = 171) | Local Failure (n = 36) | p Value | |
---|---|---|---|
GTV (cc), median | 32 | 27.5 | 0.177 |
GI OAR overlap (cc), median GTV + 3 mm isotropic expansion GTV + 5 mm isotropic expansion | 1.2 3.4 | 1 2.9 | 0.274 0.280 |
GTV D95% scaled (%), median | 83.9 | 77.7 | 0.103 |
GTV D90% scaled (%), median | 91.7 | 84.3 | 0.042 |
GTV D80% scaled (%), median | 101.7 | 84.8 | 0.003 |
GTV V130% (cc), median | 0.1 | 0 | <0.001 |
GTV V120% (cc), median | 4.9 | 0 | <0.001 |
GTV V100% (cc), median | 26.5 | 18.1 | 0.036 |
GTV min dose scaled (%), median | 42 | 46.5 | <0.001 |
LF | OS | |||||||
---|---|---|---|---|---|---|---|---|
Variables | Univariate | Multivariate | Univariate | Multivariate | ||||
HR (95% CI) | p Value | HR (95% CI) | p Value | HR (95% CI) | p Value | HR (95% CI) | p Value | |
Age (year) | ||||||||
>Median | Reference | Reference | ||||||
≤Median | 1.012 (0.525–1.902) | 0.958 | 1.141 (0.836–1.556) | 0.406 | ||||
Gender | ||||||||
Male | Reference | Reference | ||||||
Female | 1.085 (0.573–2.049) | 0.826 | 1.068 (0.783–1.457) | 0.678 | ||||
ECOG performance status | ||||||||
0–1 | Reference | Reference | ||||||
2 | 1.152 (0.537–1.983) | 0.624 | 1.238 (0.726–2.109) | 0.433 | ||||
Tumor location | ||||||||
Body/tail | Reference | Reference | ||||||
Head | 0.982 (0.512–1.874) | 0.915 | 1.228 (0.874–1.725) | 0.238 | ||||
T stage | ||||||||
1–2 | Reference | Reference | ||||||
3–4 | 1.150 (0.518–2.532) | 0.751 | 0.977 (0.672–1.422) | 0.905 | ||||
N stage | ||||||||
N− | Reference | Reference | ||||||
N+ | 1.048 (0.535–2.049) | 0.905 | 0.951 (0.683–1.324) | 0.766 | ||||
N/A | 1.345 (0.395–4.590) | 0.645 | 1.020 (0.558–1.863) | 0.949 | ||||
Tumor size | ||||||||
>Median | Reference | Reference | ||||||
≤Median | 0.762 (0.401–1.435) | 0.361 | 0.904 (0.661–1.236) | 0.527 | ||||
GTV volume | ||||||||
>Median | Reference | Reference | ||||||
≤Median | 1.099 (0.578–2.102) | 0.790 | 1.279 (0.938–1.744) | 0.119 | ||||
Radiation technique | ||||||||
5-fraction SMART | Reference | Reference | ||||||
15/25-fraction HART | 6.510 (1.975–21.350) | 0.001 | 5.389 (1.298–21.975) | 0.021 | 0.823 (0.598–1.132) | 0.23 | ||
CA19-9 prior to RT | 1.000 (1.000–1.000) | 0.521 | 1.000 (1.000–1.000) | 0.204 | ||||
CA19-9 > 40% decrease prior to RT | ||||||||
No | Reference | Reference | ||||||
Yes | 1.105 (0.550–2.218) | 0.798 | 0.675 (0.481–0.947) | 0.023 | 0.703 (0.500–0.987) | 0.042 | ||
Induction chemo regimen | ||||||||
FOLFIRINOX | Reference | Reference | ||||||
Others | 2.104 (1.067–4.098) | 0.032 | 2.067 (1.038–4.052) | 0.047 | 1.136 (0.833–1.548) | 0.42 | ||
Induction chemo duration | ||||||||
>Median | Reference | Reference | ||||||
≤Median | 1.462 (0.735–2.901) | 0.289 | 0.787 (0.575–1.078) | 0.136 | ||||
GTV D80% scaled (%), median | 0.971 (0.948–0.996) | 0.031 | 0.971 (0.902–1.038) | 0.376 | 1.003 (0.991–1.014) | 0.625 | ||
GTV V120% (cc), median | 0.889 (0.815–0.978) | 0.019 | 0.992 (0.936–1.054) | 0.553 | 1.021 (1.009–1.034) | 0.001 | 1.021 (1.007–1.034) | 0.002 |
GTV minimum dose | 0.997 (0.976–1.020) | 0.710 | 0.995 (0.983–1.006) | 0.366 |
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Chuong, M.D.; O’Reilly, E.M.; Herrera, R.A.; Zinovoy, M.; Mittauer, K.E.; Rubens, M.; Kaiser, A.; Romesser, P.B.; Bassiri-Gharb, N.; Wu, A.J.; et al. Multi-Institutional Comparison of Ablative 5-Fraction Magnetic Resonance-Guided Online Adaptive Versus 15/25-Fraction Computed Tomography-Guided Moderately Hypofractionated Offline Adapted Radiation Therapy for Locally Advanced Pancreatic Cancer. Cancers 2025, 17, 2596. https://doi.org/10.3390/cancers17152596
Chuong MD, O’Reilly EM, Herrera RA, Zinovoy M, Mittauer KE, Rubens M, Kaiser A, Romesser PB, Bassiri-Gharb N, Wu AJ, et al. Multi-Institutional Comparison of Ablative 5-Fraction Magnetic Resonance-Guided Online Adaptive Versus 15/25-Fraction Computed Tomography-Guided Moderately Hypofractionated Offline Adapted Radiation Therapy for Locally Advanced Pancreatic Cancer. Cancers. 2025; 17(15):2596. https://doi.org/10.3390/cancers17152596
Chicago/Turabian StyleChuong, Michael D., Eileen M. O’Reilly, Robert A. Herrera, Melissa Zinovoy, Kathryn E. Mittauer, Muni Rubens, Adeel Kaiser, Paul B. Romesser, Nema Bassiri-Gharb, Abraham J. Wu, and et al. 2025. "Multi-Institutional Comparison of Ablative 5-Fraction Magnetic Resonance-Guided Online Adaptive Versus 15/25-Fraction Computed Tomography-Guided Moderately Hypofractionated Offline Adapted Radiation Therapy for Locally Advanced Pancreatic Cancer" Cancers 17, no. 15: 2596. https://doi.org/10.3390/cancers17152596
APA StyleChuong, M. D., O’Reilly, E. M., Herrera, R. A., Zinovoy, M., Mittauer, K. E., Rubens, M., Kaiser, A., Romesser, P. B., Bassiri-Gharb, N., Wu, A. J., Cuaron, J. J., Gutierrez, A. N., Hajj, C., Ucar, A., DeZarraga, F., Aparo, S., Crane, C. H., & Reyngold, M. (2025). Multi-Institutional Comparison of Ablative 5-Fraction Magnetic Resonance-Guided Online Adaptive Versus 15/25-Fraction Computed Tomography-Guided Moderately Hypofractionated Offline Adapted Radiation Therapy for Locally Advanced Pancreatic Cancer. Cancers, 17(15), 2596. https://doi.org/10.3390/cancers17152596