Neoadjuvant strategies for pancreatic cancer

doi:10.3748/wjg.v20.i28.9374

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World Journal of Gastroenterology

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World J Gastroenterol. Jul 28, 2014; 20(28): 9374-9383
Published online Jul 28, 2014. doi: 10.3748/wjg.v20.i28.9374

Table 1 Definition of borderline resectable and locally advanced according to the MD Anderson Cancer Center and the American Hepatopancreatobiliary Association/Society of Surgical Oncology/Society for Surgery of the Alimentary Tract/National Comprehensive Cancer Network classification systems of stage III pancreatic cancer

Definition system	Vessel	BRPC	LAPC
MDACC	SMV	Short segment occlusion	No reconstruction feasible
	PV	Short segment occlusion	No reconstruction feasible
	SMA	Abutment	Encasement
	CHA	Abutment, short encasement	Long encasement
	CT	Abutment¹	Encasement¹
	Metastases	Absent	Absent
AHPBA/SSO/SSAT/NCCN	SMV	Abutment, Encasement, Occlusion	No reconstruction feasible
	PV	Abutment, Encasement, Occlusion	No reconstruction feasible
	SMA	Abutment	Encasement
	CHA	Abutment, Short encasement	Long encasement
	CT	Nor encasement or abutment¹	Abutment¹
	Metastases	Nor visceral nor extra-regional nodal	Nor visceral nor extra-regional nodal

¹Differences. SMV: Superior mesenteric vein; PV: Portal vein; SMA: Superior mesenteric artery; CHA: Common hepatic artery; CT: Celiac trunk; BRPC: Borderline resectable; LAPC: Locally advanced; MDACC: MD Anderson Cancer Center; AHPBA: American Hepatopancreatobiliary Association; SSO: Society of Surgical Oncology; SSAT: Society for Surgery of the Alimentary Tract; NCCN: National Comprehensive Cancer Network.

Table 2 Studies on chemotherapy for advanced pancreatic cancer

Ref.	CT regimen	Study	LAPC (n)	ORR (%)	OS median	Res rate (%)	Metastatic	ORR (%)	OS median
Conroy et al[33]	FOLFIRINOX vs Gem	Multicentric phase II trial	0	NA	NA	NA	342	31.6 vs 9.4	11.1 vs 6.4
Louvet et al[45]	GEMOX vs GEM alone	phase III	98	14.9 vs 27.3	10.3 vs 10.3	NA	215	18.3 vs 26.4	6.7 vs 8.5
Rocha Lima et al[46]	Irinotecan + GEM vs GEM alone	Multicenter, open label, phase III	51	25.9 vs 4.2	9.8 vs 11.7	NA	293	14.9 vs 4.8	5.4 vs 5.9
Poplin et al[47]	GEM vs GEM FDR vs GEMOX	phase II, multicentric	86	36	9.2	NA	737	NR	4.9 vs 6.2 vs 5.7
Kindler et al[49]	GEM + Bevacizumab vs GEM + placebo	Double blind, placebo controlled, phase III	31	NA	NA	NA	189	NR	5.8 vs 5.9
Gunturu et al[53]	FOLFIRINOX	Single centre, retrospective	16	50	NA	NA	19	47	NA
Peddi et al[55]	FOLFIRINOX	Registry	18	34	NA	NA	22	18	NA

CT: Chemotherapy; LAPC: Locally advanced pancreatic cancer; ORR: Overall response rate; OS: Overall survival; Res: Resection; NA: Not available; NR: Not reported; FOLFIRINOX: 5-fluorouracil + leucovorin + oxaliplatin + irinotecan; GEM: Gemcitabine; GEM FDR: Gemcitabine fixed dose ratio.

Table 3 Studies on neoadjuvant chemotherapy for locally advanced pancreatic cancer

Ref.	Study type	CT regimen	Staging system	LAPC (n)	Res rate (%)	R0 resections/total resections	ORR	OS median
Lee et al[51]	Prospective non-randomized	Gemcitabine + capecitabine	NCCNAPBCC	18 BR 25 UR33 BR 10 UR	61 BR 24 UR46 BR 20 UR	9/11 BR 5/6 UR13/15 BR 1/2 UR	NRNR	23.1 mo (cumulative)
Sahora et al[52]	Prospective phase II	NeoGEMTAX	NR	12 BR 13 UR	32	7/8	NR	16 mo (resected patients)
FARIS¹ et al[54]	Single centre, retrospective	FOLFIRINOX	NCNN	22	NR	22.7	27.3% (CT alone)	NR
Hosein¹ et al[39]	Prospective phase II	FOLFIRINOX	NR	14 BR 4UR	55.5	7/8	NR	16 mo (resected patients)

¹Some patients had CRT. ORR: Overall response rate; OS: Overall survival; NR: Not reported; NeoGEMTAX: Gemcitabine + docetaxel; FOLFIRINOX: 5-Fluorouracil + leucovorin + oxaliplatin + irinotecan; GEM: Gemcitabine; GEM FDR: Gemcitabine fixed dose ratio; NCCN: National comprehensive cancer network; APBCC: Asan pancreaticobiliary cancer center.

Table 4 Studies on neoadjuvant chemoradiotherapy for locally advanced pancreatic cancer

Ref.	Study type	CT regimen	RT	Staging System	LAPC (n)	Resection rate (%)	R0 resections/total resections	ORR (%)	OS median (mo)
Shinchi et al[57]	Prospective randomized trial	5-FU concurrent infusion	External beam RT (50.4 Gy/28 fractions) vs no RT	NR	31	NR	NR	31	13.2 vs 6.4
Tinkl et al[60]	Prospective study	Gemcitabine	Three dimensional conformal55.8 Gy tumor50.4 Gy nodes	NR	120	31.6	35/38	NR	25
Kim et al[61]	Phase I study	Gemcitabine + oxaliplatin	Concurrent external beam RT27 Gy/15 fractions	NCCN	38	28.9	7/11	15.7	12.5 (all patients)
Huguet et al[62]	Phase II and III trial	Upfront CT: FOLFUGEM, GEMOX, Gemcitabine vs GEMOX167 patients	External beam RT(55 Gy/30 fractions)72 patients	NR	167	NR	NR	NR	13.1
Krishnan et al[63]	Prospective non-randomized trial	Chemoradiation (247 patients)Upfront GEM CT followed by CRT5-FU, GEM, CAPE(76 patients)	30 Gy (220 patients) or55 Gy (27 patients) 30 Gy (64 patients) or55 Gy (12 patients)	MDACC	323	NR	NR	NR	9.1
Mukerjee et al[64]	Open label, randomized, phase II trial	Upfront CT GEM or CAPE CRT GEM or CAPE	58 Gy/30 fractions	NR	7438 GEM36 CAPE	NR	NR	20.2	15.2 (GEM) vs 13.4 (CAPE)
Leone et al[65]	Prospective non-randomized trial	Upfront CT GEMOX CRT GEM	50.4 Gy	NCCN	3915 BR24 UR	28.2	11/11	NR	16.7 27.8 BR 13.3 UR
Polistina et al[76]	Prospective non-randomized trial	Upfront GEM CTGEM CRT	SBRT30 Gy/3 fractions	MDACC	23 UR	8	2/3	69.5	10.6

NR: Not reported; RT: Radiotherapy; CT: Chemotherapy; CRT: Chemoradiotherapy; LAPC: Locally advanced pancreatic cancer; ORR: Overall response rate; OS: Overall Survival; GEM: Gemcitabine; CAPE: Capecitabine; FOLFUGEM: Leucovorin + gemcitabine + 5-fluorouracil; GEMOX: Gemcitabine + Oxaliplatin; NCCN: National comprehensive cancer network; MDACC: MD Anderson Cancer Center; BR: Borderline resectable; UR: Unresectable; SBRT: Stereotactic body radiotherapy.

Table 5 Studies on neoadjuvant chemotherapy for potentially resectable pancreatic cancer

Ref.	Study type	CT regimen	Patients (n)	Resection rate (%)	R0 resections rate (%)	OS median (mo)
Heinrich et al[66]	Prospective non-randomized phase II	Gemcitabine + cisplatin	28	93	80	26.5
Tajima et al[68]	Pilot study	S1 vs upfront surgery	34 (total) 13 (S1) vs 21 (upfront surgery)	100	84.6 vs 85.7	2 yr 55.6% vs 29.6%
Sho et al[69]	Single centre	GEM CRT (external beam 50 to 54 Gy)	61	97	92	NR
Van Buren et al[70]	Prospective phase II trial	FDR GEM + bevacizumab induction	59	72.8	38/43 (88.3%)	16. 8 (overall)
Van Buren et al[70]	Prospective phase II trial	GEM + bevacizumab Accelerated RT 30 Gy/10 fractions	59	72.8	38/43 (88.3%)	19.7 (resected patients)

CT: Chemotherapy; OS: Overall survival; NR: Not reported; GEM: Gemcitabine; CRT: Chemoradiotherapy.

Citation: Polistina F, Natale GD, Bonciarelli G, Ambrosino G, Frego M. Neoadjuvant strategies for pancreatic cancer. World J Gastroenterol 2014; 20(28): 9374-9383
URL: https://www.wjgnet.com/1007-9327/full/v20/i28/9374.htm
DOI: https://dx.doi.org/10.3748/wjg.v20.i28.9374