Stereotactic radiotherapy and the potential role of magnetic resonance-guided adaptive techniques for pancreatic cancer

Table 1 Studies of stereotactic body radiotherapy in locally advanced pancreatic cancer

Ref.	Participants	Dosimetry	Outcome	Toxicity	Resectability post-treatment
Herman et al[15], 2015, Phase 2 Trial	49 LAPC	33 Gy/5 fractions	(1) Median OS 13.9 mo; (2) 59% 1-yr OS; and (3) 18% 2-yr OS	(1) 1 patient acute grade 4 duodenal ulcer; (2) 10% acute grade ≥ 3; (3) 11% late grade ≥ 2; and (4) 6% serious late GI toxicity	10% resectable after treatment
Comito et al[2], 2017, Phase 2 trial	43 LAPC	45 Gy/6 fractions	Median OS 13 mo	(1) 49% acute grade 1 or 2; (2) 0 acute grade ≥ 3; (3) 2 patients late G2 gastritis; and (4) 0 late grade ≥ 3	7% resectable after treatment
Dohopolski et al[3], 2017, Retrospective	696 LAPC	24-40 Gy/3-5 fractions	Median OS 12.6 mo (compared to 11.2 mo for CFRT)	Not recorded	Not recorded
Park et al[4], 2017, Retrospective	44 unresectable	30-33 Gy/5 fractions	(1) 56% 1-yr OS; (2) 26% 2-yr OS; and (3) Median OS 15.7 mo (no significant difference from IMRT)	(1) 7% acute grade ≥ 2 GI toxicity (24% for IMRT); (2) 5% grade ≥ 3 haematological toxicity (26% for IMRT); and (3) 9% late GI bleed	7% resectable after treatment (no significant difference from IMRT)
Yechieli et al[10], 2017, Retrospective	18 unresectable	30-36 Gy/3-5 fractions	(1) Median recurrence-free survival 6.8 mo; and (2) Median OS 6.4 mo	(1) 50% no toxicity; (2) 15% grade ≥ 3; and (3) 10% GI bleed	Not recorded
Zhong et al[13], 2017, Retrospective	631 LAPC	Median 40 Gy/5 fractions	(1) 22% 2-yr OS (17% for CFRT); and (2) Median OS 13.9 mo (11.6 mo for CFRT)	0 grade ≥ 3	11% resectable after treatment (9% for CFRT)
Mazzola et al[14], 2018, Retrospective	33 LAPC	36-45 Gy/6 fractions	(1) 81% 1-yr LC; and (2) 75% 1-yr OS	(1) 15% acute grade 1; (2) 9% acute grade 2; (3) 0 acute grade ≥ 3; and (4) No late toxicity	18% resectable after treatment
Jung et al[16], 2019, Retrospective	95 LAPC	24-36 Gy/4-5 fractions	(1) Median OS 16.7 mo; and (2) 67% 1-yr OS	(1) 3% acute grade 3 GI; and (2) 3% late grade 3	7% resectable after treatment
Shaib et al[19], 2020, Retrospective	6950 LAPC (64 received SBRT)	Median 30 Gy	(1) Median OS 8.6 mo (6.7 mo for IMRT, 3.4 mo for no RT); (2) 32% 1-yr OS (22% for IMRT, 15% for no RT); and (3) 9% 2-yr OS (7% for IMRT, 5% for no RT)	Not recorded	Not recorded
Toesca et al[17], 2020, Retrospective	149 unresectable	20-45 Gy/3-6 fractions (high-dose group ≥ 40 Gy, standard-dose group < 40 Gy)	(1) Median OS 16 mo both groups; (2) Median OS 23 mo for high-dose group (14 mo for standard-dose group); and (3) 82% 1-yr OS for high-dose group (57% for standard-dose group)	(1) 10% grade ≥ 2 for high-dose group (15% for low-dose group); and (2) 6% grade ≥ 3 for high-dose group (7% for low-dose group)	5% resectable after treatment

LAPC: Locally advanced pancreatic cancer; OS: Overall survival; GI: Gastrointestinal; CFRT: Conventionally fractionated radiotherapy; IMRT: Intensity modulated radiotherapy; LC: Local control; SBRT: Stereotactic body radiotherapy; RT: Radiotherapy.

Table 2 Studies of magnetic resonance-guided radiotherapy in locally advanced pancreatic cancer

Ref.	Participants	Dosimetry	Outcome	Toxicity
Heerkens et al[25], 2018, Trial	20 (18 LAPC, 2 unresectable)	24 Gy/3 fractions	(1) Median OS 8.5 mo; (2) 69% improved QOL compared to baseline at 1 mo; and (3) 33% improved QOL compared to baseline at 12 mo	No grade ≥ 3 acute or late toxicity
Luterstein et al[8], 2018, Case Report	1 LAPC	40 Gy/5 fractions	LC at 16 mo	None
Rudra et al[31], 2019, Retrospective	44 unresectable (22 received SBRT)	30-35 Gy/5 fractions (standard-dose group, n = 6); 40-52 Gy/5 fractions (high-dose group, n = 16)	(1) 49% 2-yr OS (high-dose group); (2) 30% 2-yr OS (standard-dose group); (3) 77% 2-yr FFDF (high-dose group); and (4) 57% 2-yr FFDF (standard-dose group)	Acute: (1) 7% grade ≥ 3 GI (all in standard-dose group); and (2) 2% grade 4

LAPC: Locally advanced pancreatic Cancer; OS: Overall survival; QOL: Quality of life; LC: Local control; SBRT: Stereotactic body radiotherapy; FFDF: Freedom from distant failure; GI: Gastrointestinal.