Developments and challenges in neoadjuvant therapy for locally advanced pancreatic cancer

Table 1 Definitions of locally advanced pancreatic cancer by different groups

Group	Definition
	Arterial	Venous
NCCN[14]	Head/uncinate process:	Unreconstructible SMV/PV due to tumor involvement or occlusion (can be due to tumor or bland thrombus)
	Solid tumor contact > 180° with the SMA or CA
	Body and tail
	Solid tumor contact of > 180° with the SMA or CA
	Solid tumor contact with the CA and aortic involvement
IAP[15]	Tumor contact/invasion of 180 or more degree CHA	Bilateral narrowing/occlusion, exceeding the inferior border of the duodenum
	Tumor contact/invasion showing tumor contact/invasion of the PHA and/or CA
CMA[5]	Head	Unreconstructible SMV/PV due to tumor involvement or occlusion (can be due to tumor or bland thrombus). The tumor extensively involves the distal jejunal drainage branch of the superior mesenteric vein
	Solid tumor contact of > 180° with the SMA or CA
	Body and tail
	Solid tumor contact of > 180° with the SMA or CA
	Solid tumor contact with the CA and aortic involvement

CA: Celiac axis; CHA: Common hepatic artery; CMA: Chinese Medical Association; IAP: International Association of Pancreatology; NCCN: National Comprehensive Cancer Network; PHA: Proper hepatic artery; PV: Portal vein; SMA: Superior mesenteric artery; SMV: Superior mesenteric vein.

Table 2 Summary of trials evaluating neoadjuvant therapy for locally advanced pancreatic cancer

Ref.	Type of study	Years of accrual	No. of patients	Primary endpoint	Arms	Key findings
NCT03652428[19]	Phase 1; Phase 2	2019-2023	24	12 mo after registration or until death	Proton therapy with concurrent GEM + Nab-paclitaxel	Ongoing
NCT02578732[22]	Phase 2	2016-2024	28	Until progression, up to 5 yr	FOLFOX	Ongoing
NCT04247165[23]	Phase 1; Phase 2	2020-2024	20	12 mo	Drug: GEM; Nab-paclitaxel; Nivolumab; Ipilimumab	Ongoing
NCT02873598[24]	Phase 1	2016-2021	15	Up to 5 yr	FOLFIRINOX or GEM/abraxane followed by SBRT	Not yet publicly available
NCT02704143[25]	Phase 2	2016-2020	63	3 yr	Combination of Cyberknife with S-1	Promising efficacy

FOLFOX: Folinic acid, fluorouracil, and oxaliplatin; FOLFIRINOX: Folinic acid, fluorouracil, irinotecan hydrochloride, and oxaliplatin; GEM: Gemcitabine; S-1: Tegafur, gimeracil, and oteracil; SBRT: Stereotactic body radiation therapy.

Table 3 Monoclonal antibody-based therapies targeting non-immune cells for pancreatic ductal adenocarcinoma

Ref.	Type of study	Years of accrual	Target	mAb
NCT01521325[44]	Phase 1	2011-2013	Mesothelin	MORAb-009
Patel et al[45]	Preclinical study	2013	MUC-5AC	NPC-1C
NCT03376659[46]	Phase 1/Phase 2	2018-2023	VEGF	Bevacizumab
NCT00614653[47]	Phase 1	2008-2016	VEGF	Bevacizumab
O'Sullivan et al[48]	Preclinical study	2017	AnxA6	9E1
Smith et al[49]	Phase 1	2008-2011	DLL4	Demcizumab
NCT02722954[50]	Phase 1	2016-2017	DLL4	Demcizumab

AnxA6: Annexin A6; DLL4: Delta-like ligand 4; mAb: Monoclonal antibody; MUC: Mucin; VEGF: Vascular endothelial growth factor.