Optimizing neoadjuvant chemoradiation in resectable and borderline resectable pancreatic cancer: Evidence-based insights

Table 1 An overview of borderline resectable pancreatic cancer definitions

Criteria	NCCN version 2.2024[19]	MDSCC version 6 (2019)[18]	AHPBA-SSO-SSAT[21]	ASCO[20]	JPS[24]		IAP[23]
					BR-PV	BR-A	BR-PV	BR-A
CA	Solid-tumor contact ≤ 180° or contact > 180° without involvement of the aorta or GDA	No involvement	No involvement	No interface	No tumor contact/invasion	Tumor contact/invasion of less than 180 without showing stenosis/deformity	No tumor contact/invasion	Tumor contact of less than 180 without showing deformity/stenosis
CHA	Solid-tumor contact without extension to CA or hepatic artery bifurcation	Short-segment encasement or abutment of CHA or GDA	GDA encasement up to hepatic artery with either short-segment encasement or direct no tumor contact/invasion abutment of hepatic artery	No interface	No tumor contact/invasion	Tumor contact/invasion without showing tumor contact/invasion of the PHA and/or CA.	No tumor contact/invasion	Tumor contact without showing tumor contact of the PHA and/or CA
SMA	Solid-tumor contact ≤ 180° or solid-tumor contact with variant arterial anatomy	Tumor abutment of ≤ 180°	Tumor contact is not to exceed > 180°	No interface	No tumor contact/invasion	Tumor contact/invasion of less than 180 without showing stenosis/deformity	No tumor contact/invasion	Tumor contact of less than 180 without showing deformity/stenosis
SMV or PV	Solid-tumor contact > 180° or ≤ 180° with contour abnormality or thrombosis of the vein, provided there is a suitable proximal and distal vessel to allow venous resection and reconstruction	Short-segment occlusion with patent vessels above and below the occlusion	Tumor abutment with or without impingement and narrowing of the lumen; encasement without encasement of the nearby arteries; short-segment occlusion with the suitable proximal and distal vessel, allowing safe resection and reconstruction	No interface	Tumor contact/invasion of 180 or more/occlusion, not exceeding the inferior border of the duodenum	No tumor contact/invasion	Tumor contact 180 or greater or bilateral narrowing/occlusion, not exceeding the inferior border of the duodenum	-

NCCN: National Comprehensive Cancer Network; MDSCC: MD-Anderson Cancer Centre; AHPBA-SSO-SSAT: Americas Hepato Pancreatic Biliary Association-Society of Surgical Oncology-Society of the Alimentary Tract; ASCO: American Society of Clinical Oncology; JPS: Japan Pancreas Society; IAP: International Association of Pancreatology; BR: Borderline resectable; GDA: Gastroduodenal artery; CHA: Common hepatic artery; SMA: Superior mesenteric artery; SMV: Superior mesenteric vein; PV: Portal vein; PHA: Proper hepatic artery; CA: Celiac artery.

Table 2 Studies including neoadjuvant chemoradiation in resectable and borderline resectable pancreatic cancer

Ref.	Period of study	Type of study	Number of patients (n)	Intervention	Resection rate	Category	R0	N0 resection	Survival (months)	Post-surgical complications
Combination of chemotherapy and radiotherapy in resectable pancreatic cancer
Golcher et al[41]	2003-2009	Phase II RCT, multicentre, randomized	n = 66; 2 arms	Neoadj. Gemcitabine/cisplatin	57.5% vs 70% (P = 0.31)	RPC	48% vs 52% (P = 0.81)	30% vs 39% (P = 0.44)	Median OS-14.4 vs 17.4 (P = 0.96)	97% vs 66%
			Sur (n = 33)	Based CRT (50.4-55.8 Gy)-Sur-adj. Gemcitabine
			Neoadj-Sur (n = 33)
Casadei et al[52]	2007-2014	RCT, single centre, randomized	n = 38; 2 arms	Neoadj. Gemcitabine-based CRT	75.0% vs 61.1%	RPC	25.0% vs 39% (P = 0.489)	10% vs 28%	Median OS-19.5 vs 22.4 (P = 0.973)	45.0% vs 55.6%, P = 0.746
			Sur (n = 20)	(54 Gy)-Sur-adj. Gemcitabine
			Neoadj-Sur (n = 18)
Combination of chemotherapy and radiotherapy in both resectable and borderline resectable pancreatic cancer
Versteijne et al[55]	2013-2017	Phase III RCT, multicentre, randomized	n = 246; 2 arms	Neoadj. Gemcitabine-based CRT	72% vs 61% (P = 0.058)	RPC and BRPC	40% vs 71% (P < 0.001)	78% vs 33% P < 0.001	Median OS: 14 vs 16 months (P = 0.07)	36% vs 41% (P = 0.44)
			Sur (n = 127)	(36 Gy)-Sur-adj. Gemcitabine
			Neoadj-sur (n = 119)
Combination of chemotherapy and radiotherapy in borderline resectable pancreatic cancer
Jang et al[42]	2012-2014	Phase 2/3 RCT, multicentre, randomized	n = 50; 2 arms	Neoadj. Gemcitabine-based CRT	63% vs 78%	BRPC	26.1% vs 52% (P = 0.004)	70.6% vs 16.7%	Median OS: 12 vs 21 (P = 0.028)	23.6% vs 16.8%
			Sur (n = 23)	(54 Gy)-Sur-adj. Gemcitabine					2-YR OS: 26% vs 41%
			Neoadj-sur (n = 27)
Ghaneh et al[63]	2014-2018	Phase II RCT, multicentre, randomized	n = 90	Neoadj. Gemcitabine + capecitabine	(Combined neoadjuvant group vs Sur)	BRPC	(Combined neoadjuvant group vs Sur)	NR	(Combined neoadjuvant group vs Sur)	50% vs 38% (P = 0.54)
			Sur (n = 33)	Neoadj. mFOLFIRINOX	68% vs 55% (P = 0.33)		14% vs 23% (P = 0.49)		1-year OS = 39% vs 78% vs 84% vs 60%, 1-year DFS = 33% and 59% (P = 0.016)
			Neoadj. Gemcitabine/capecitabine (n = 20)	Neoadj. Capecitabine-based CRT (50.4 Gy)
			Neoadj. mFOLFIRINOX (n = 20)	All of them received adj. Gemcitabine or adj. 5-FU/FA after Sur
			Neoadj capacibine-based CRT (n = 17)
Katz et al[57]	2013-2014	Phase II, multicentre, single-arm	n = 22	Neoadj. mFOLFIRINOX)-capecitabine-based	68%	BRPC	93%	NR	Median OS: 22 months	53%
				CRT (50.4 Gy)-Sur-adj. Gemcitabine
Murphy et al[60]	2012-2016	Phase II, single centre single-arm	n = 48	FOLFIRINOX-short-course (25Gy/5 fractions) or long-course (50.4 Gy-58.8 Gy)	65%	BRPC	97%	NR	Median OS: 38 months	NR
				Capecitabine-based CRT-Sur
Takahashi et al[64]	2019	Phase II single-arm, multicentre	n = 52	Neoadj. S1 (a prodrug of 5-fluorouracil)-based	-	BRPC	52%	NR	Median OS: 30.8 months	7.5%
				CRT (50.4 Gy)

RCT: Randomized controlled trial; Sur: Surgery; Neoadj: Neoadjuvant; Adj: Adjuvant; NR: Not reported; CRT: Chemoradiotherapy; BRPC: Borderline resectable pancreatic cancer; RPC: Resectable pancreatic cancer; DFS: Disease-free survival; OS: Overall survival; YR: Year survival; 5-FU/FA: Fluorouracil with folinic acid; mFOLFIRINOX: modified Fluorouracil with folinic acid, irinotecan, oxaliplatin.