Is concomitant radiotherapy necessary with gemcitabine-based chemotherapy in pancreatic cancer?

Table 1 Patient demographics and characteristics of the included studies

Study	Groups	Chemo regimens	RT regimens	No. of patients	Male	Age (yr)	MS (M)	Follow-up (M)	Clinical stage
Chauffert et al[16]	GEM-CRT	5-FU infusion, 300 mg /m2 per day, days 1-5 for 6 wk; cisplatin, 20 mg /m2 per day, days 1-5 during wk 1 and 5. Then, GEM 1000 mg/m2 weekly, 3/4 wk	Induction: 60 Gy, 2 Gy/fraction	59	31	60 (41-79)	8.6	31	Locally advanced unresectable PC
	GEM alone	GEM 1000 mg/m2 weekly for 7 wk. Then, GEM 1000 mg/m2 weekly, 3/4 wk	None	60	34	62 (38-80)	13	33	Locally advanced PC
Loehrer et al[18]	GEM+RT	600 mg/m2 per week for wk 1 to 5, then 4 wk later, 1000 mg/m2 for 3 of 4 wk	Starting on day 1, 1.8 Gy/Fx for a total of 50.4 Gy	34	19	66 (46.9-83.5)	11.1	NG
	GEM alone	1000 mg/m2 per week for wk 1 to 6, followed by 1 wk rest, then for 3 of 4 wk	None	37	18	69 (49.7-83.7)	9.2	NG
Van Laethem et al[19]	GEM-CRT	2 cycles of GEM (1000 mg/m2 on days 1, 8, 15, followed by 1 wk rest-a cycle), then GEM 300 mg/m2 once per wk for 5 to 6 wk	50.4 Gy in 28 fractions, 1.8 Gy per fraction for 5 to 6 wk	45	24	61 (44-75)	24.3	30.7	Curatively resected PC
	GEM alone	4 cycles of GEM (1000 mg/m2 on days 1, 8, 15, followed by 1 wk rest-a cycle)	None	45	27	58 (32-77)	24.4	33.3
Wang et al[17]	GEM-RT	2 cycles of GEM (1000 mg/m2 on radiation 1, 8, 15, 21-d a cycle)	50.4 Gy in 28 fractions on Monday through Friday over 5.5 wk	35	17	61 (44-71)	13	8-24	Locally advanced PC
	GEM alone	4-6 cycles of GEM (1000 mg/m2 on days 1, 8, and 15, 28 d a cycle)	None	21	13	61 (39-71)	8	8-24

GEM: Gemcitabine; RT: Radiotherapy; CRT: Chemoradiotherapy; PC: Pancreatic cancer; MS: Median survival; NG: Not given.

Table 2 Quality assessment of the studies included

Study	AC	Blinding	ITT	Withdrawals	Score
Chauffert et al[16]	Unclear	Open-label	No	4.0%	1
Loehrer et al[18]	Unclear	Open-label	Yes	21.0%	2
Van Laethem et al[19]	Adequate	Open-label	Yes	0.8%	4
Wang et al[17]	Unclear	Open-label	No	NG	0

AC: Allocation concealment; ITT: Intention-to-treat; NG: Not given.

Table 3 Meta-analysis of adverse events

Outcome	Studies	Participants	Statistical method	Effect size	95%CI	P	I2(%)
Anemia	3	240	RR, Fixed	5.32	(2.23-12.66)	0.0002	0
Leukocytopenia	3	240	RR, Random	2.31	(1.08-4.97)	0.03	49
Neutropenia	3	240	RR, Random	1.37	(0.60-3.16)	0.46	78
Thrombocytopenia	3	240	RR, Fixed	2.34	(1.04-5.29)	0.04	0
Anorexia	2	154	RR, Fixed	5.74	(1.05-31.39)	0.04	0
Diarrhea	3	240	RR, Fixed	2.58	(0.51-13.01)	0.25	0
Nausea/vomiting	3	240	RR, Fixed	3.58	(1.32-9.69)	0.01	0
SGPT abnormality	2	154	RR, Fixed	0.99	(0.34-2.88)	0.98	0
Asthenia/Fatigue	2	154	RR, Fixed	3.54	(1.23-10.18)	0.02	29
Weight Loss	2	154	RR, Fixed	4.02	(0.46-35.04)	0.21	0

RR: Relative risk.