Chemotherapy and intensity-modulated radiation therapy for locally advanced pancreatic cancer achieves a high rate of R0 resection*

Figures & data

Table 1. Patient characteristics.

Characteristic	Whole population (n, %) n = 134
Age (years)
Mean ± SD	64.1 ± 9.9
Median	64.5
Range	36.7–84.1
Gender
Male	71 (53)
Female	63 (47)
Karnofsky performance status
100–90%	52 (39)
80–70%	(59)
<70%	(2)
Location
Head	83 (62)
Body or tail	51 (38)
Tumor size (cm)
Mean ± SD	3.8 ± 1.4
Median	3.5
Range	1.2–8.9
Exploratory laparotomy
No	101 (75)
Yes	33 (25)
Level of CA19-9 at diagnosis
Mean ± SD	564 ± 1066.5
Median	185
Range	0–6806
Not evaluated	25

Figure 1. (a) Kaplan-Meier overall survival curve for all patients. (b) Kaplan-Meier overall survival curves stratified by response to IMRT.

CR + PR: complete response + partial response; PD: progressive disease; SD, stable disease.

Table 2. Univariate and multivariate analysis of overall survival.

	Univariate analysis		Multivariate analysis
Factor	Number of death/censored, n	p-Value^1		p-Value^1
Radiographic arterial involvement		.30
No	36/6
Yes	62/30
Response to ICT		.0009
PR	33/18
SD	47/16
PD	8/1
Response to IMRT^1		<.0001
CR + PR	23/18		1.00
SD	57/17		1.37 (0.82–2.28)	.23
PD	13/0		4.42 (1.96–9.98)	.0004
Maintenance chemotherapy		.58
No	29/21
Yes	66/15
Duration of induction chemotherapy		.47
<3.2 months	46/19
≥3.2 months	51/17
Surgery^a		.004^1
Yes	13/13		1.00
No	69/23		1.84 (0.99–3.39)	.052

^aTime to overall survival (OS) was calculated from 4.1 months post-radiotherapy (RT) end date for response to intensity-modulated radiation therapy and surgery on univariate analysis (UVA), and for stepwise multivariate analysis; time to OS was calculated from RT end date for other factors on UVA.

Figure 2. Cumulative incidence of local failure for all patients.

Table 3. Acute treatment-related toxicity according to NCI CTCAE version 3.0.

Toxicity (CTCAE)	Grade 2n (%)	Grade 3n (%)	Grade 4n (%)
Hematologic toxicity
Anemia	47 (35)	12 (9)	0
Neutropenia	13 (10)	4 (3)	1 (1)
Thrombocytopenia	20 (15)	22 (16)	4 (3)
Non-hematologic toxicity
Fatigue	55 (41)	3 (2)	0
Nausea	18 (13)	1 (1)	0
Vomiting	3 (2)	0	1 (1)
Diarrhea	8 (6)	3 (2)	0
Rash	1 (1)	0	0
Mucositis	2 (1)	0	0

Table 4. Summary of intensity-modulated radiation therapy studies in locally advanced pancreatic adenocarcinoma.

Author	Year	N	Treatment	Grade 3-4 GIAcute Toxicity (%)	Median OS(months)	1-yearOS (%)	Rate ofresection (%)
Current study	2016	134	56 Gy 5-FU or Gem	4.5	23	85	19
Krishnan	2016	200	50–67.5 Gy Capecitabine or 5-FU or Gem	2	15.3	60	–
Ke	2014	32	54 Gy S-1	25	15.2	75	–
Esnaola	2014	37 (24 LA)	54 Gy Capecitabine	9.5	9.3	50	8
Badiyan	2013	32 (25 LA)	55 Gy Gem	22	23.1	–	24
Abelson	2012	47 (18 LA)	50.4–54 Gy 5-FU or capecitabine	9	7.7	24	–
Tunceroglu	2012	20	50.4–54 Gy 5-FU or Gem	20	11.6	55	–
Ben-Josef	2012	50	50–60 Gy Gem	24	14.8	73	24
Yovino	2010	46 (15 LA)	50.4–59.4 Gy 5-FU or capecitabine	4	9.7	–	–
Fuss	2007	41 (24 LA)	54 Gy Concurrent CT	7	10	33	–
Ben-Josef	2004	15 (8 LA)	45–55 Gy Capecitabine or Gem	7	–	69	25
Milano	2004	20 (14 LA)	50.4–59.4 Gy 5-FU	20	9.3	–	32
Bai	2003	16	30 Gy then 21–30 Gy 5-FU or Gem	–	–	35	–
Crane	2001	5	33 Gy Gem	50	–	–	20

Gem: gemcitabine; GI: gastrointestinal; LA: locally advanced; OS: overall survival; 5-FU: 5-fluorouracil.