Five-fraction stereotactic magnetic resonance-guided adaptive radiotherapy targeting the primary tumor in metastatic pancreatic cancer

Table 4 Key studies investigating stereotactic body radiotherapy as primary-directed therapy in metastatic pancreatic ductal adenocarcinoma

Ref.	Study design	Patient population	Metastatic sites	Induction CTx	SBRT treatment	Dose	Overall survival	Local control	Toxicity
Su et al[24], 2015	Retrospective single-center analysis	16 mPDAC, 9 LAPC patients	NR	2/25 patients gemcitabine-based CTx	PDT	30-36 Gy/3 Fx; 40-48 Gy/4 Fx	Median: 9 months (mPDAC)	NR	Acute: 0% G ≥ 3; late: NR
Gkika et al[29], 2017	Retrospective single-center analysis	18 recurrent and omPDAC patients	Liver, lymph nodes	NR	PDT/MDT/combinations	PDT: Median BED10 67 Gy; MDT: NR	Median: 13 months, 6-/12-month: 87%/58%	6-/12-month freedom from local progression 93%/67%	Acute: 5% G ≥ 3; late 5% G ≥ 3
Lischalk et al[30], 2018	Retrospective single-center analysis	20 synchronous mPDAC patients	NR	Gemcitabine-based (20%), FOLFOX (15%), FOLFIRINOX (10%), FOLFIRI (5%), other (10%)	PDT	Median 30 Gy/5 Fx	Median: 14 months, 12-month: 53%	Median local control: 7 months; 12-month LC: 43%	Acute: NR; late: 0%
Koong et al[31], 2020	Retrospective single-center analysis	27 omPDAC patients (≤ 3 metastases, ≤ 2 organs)	Liver, lung, peritoneum, other	89% at least one cycle prior to SBRT, predominantly gemcitabine-based	PDT	Single Fx (63%) median 25 Gy; 5 Fx (37%): Median 33 Gy	Median: 7 months, 12-month: 53%	12-month local failure rate: 25%	Acute or late 7%
Ji et al[23], 2021	Retrospective single-center propensity score matched analysis	34 synchronous omPDAC patients (≤ 5 metastases) vs 59 patients treated with CTx alone	Liver	Predominantly gemcitabine-based (98%)	PDT	Median 42.5 Gy in 5-7 Fx	Median: 9 months (PDT + CTx) vs 8 months (CTx), 12-month: 40% vs 21%	12-month cumulative incidence of local progression: 22% (SBRT + CTx) vs 53% (CTx) (P = 0.016)	4% G3
Elamir et al[37], 2022	Retrospective single-center analysis	6 synchronous and 14 metachronous omPDAC patients (≤ 5 metastases) vs 21 patients treated with CTx alone	Liver, lung	90% (predominantly gemcitabine/nab-paclitaxel and FOLFIRINOX)	PDT (25%)/MDT (100%)	PDT: Median 40 Gy/5 Fx; MDT: Median 50 Gy/5 Fx	Median: 42 months (SBRT + CTx) vs 18 months (CTx) from omPDAC diagnosis	Median local control: Not reached; 12-/24-month local control: 92%/83%	NR
Webking et al[13], 2023	Retrospective bi-institutional analysis	22 synchronous or metachronous omPDAC patients (≤ 6 metastases)	Liver, lung, lymph nodes, bones	FOLFIRINOX (64%) gemcitabine/nab-paclitaxel (36%)	PDT (MRgRT) + MDT (41%)	PDT: Median 50 Gy/5 Fx; MDT: NR	Median from diagnosis: 24 months; median from SBRT: 12 months	FFLRF: Median 12 months	9% G3
Ludmir et al[38], 2024 (EXTEND)	Randomized phase 2 multicenter trial [CTx vs CTx + MDT (+ PDT)]	40 synchronous (35%), metachronous (65%) omPDAC patients (≤ 5 metastases)	Liver, lung, lymph node, bone, other sites	73% (predominantly FOLFIRINOX or nab-paclitaxel-based CTx)	SBRT to all active sites (11 Pat with PDT in experimental arm)	PDT: Median 40 Gy/5 Fx; MDT: Predominantly 50 Gy/4 Fx or 70 Gy/10 Fx	Median 12 months (CTx + SBRT) vs 10 months (CTx) (P = 0.24)	NR; median PFS 10 months vs 3 months (P = 0.03)	16% G3 (all classified as not related to SBRT)
Jiang et al[28], 2024	retrospective comparison PDT vs PDT + MDT	217 synchronous omPDAC patients (≤ 5 metastases)	Liver, lung, bone, other sites	100% adjuvant CTx (predominantly gemcitabine/nab-paclitaxel and FOLFIRINOX)	PDT (n = 158) vs PDT + MDT (n = 59)	PDT: Median BED 60 Gy (30-45 Gy/5-8 Fx); MDT: Median BED 93 Gy (40-64 Gy/5-8 Fx)	Median 11 months (PDT + MDT) vs 9 months (PDT) (P < 0.001); 12-month: 37% vs 3%	NR; median PFS: 7 months vs 4 months (P < 0.001)	G3/4: 24% vs 20%
Schumann et al (current study), 2026	Prospective single-center observational study	24 synchronous (54%) and metachronous (46%) mPDAC patients	Liver, lung, lymph nodes, peritoneal carcinomatosis	92% (predominantly FOLFIRINOX or nab-paclitaxel-based CTx)	PDT (MRgRT) + MDT (13%)	PDT: 33 Gy (54%) or 40 Gy (46%) in 5 Fx; MDT: Median BED 95 Gy	Median: 13 months; 12-month: 49%	12-/24-month local control: 76%/67%	Acute: 5% G ≥ 3; late 5% G ≥ 3

BED: Biologically effective dose; CTx: Chemotherapy; FFLRF: Freedom from locoregional failure; FOLFIRI: Folinic acid, fluorouracil, irinotecan; FOLFIRINOX: Folinic acid, fluorouracil, irinotecan, oxaliplatin; FOLFOX: Folinic acid, fluorouracil, oxaliplatin; Fx: Fraction; G3/4: Grade 3/4; Gy: Gray; LC: Local control; MDT: Metastasis-directed therapy; mPDAC: Metastatic pancreatic ductal adenocarcinoma; NR: Not reported; omPDAC: Oligometastatic pancreatic ductal adenocarcinoma; PDT: Primary-directed therapy; SBRT: Stereotactic body radiotherapy; LAPC: Locally advanced pancreatic cancer; SBRT: Stereotactic body radiotherapy; MRgRT: Magnetic resonance-guided radiotherapy; PFS: Progression-free survival.