Locally advanced esophageal adenocarcinoma: Response to neoadjuvant chemotherapy and survival predicted by ^[18F]FDG-PET/CT

Figures & data

Table I Patient characteristics (n = 66).

Factor	n (%)
Gender
Men	49 (74%)
Women	17 (26%)
Age
Median	66
Range	41–79
ASA score
1	18 (27)
2	29 (44)
3	19 (29)
Operation
IL	32 (49)
MIE	27 (41)
TH	1 (1.5)
EX	6 (9)
cTNM
T3N0	15 (23)
T3N1	43 (65)
T4N0	2 (3)
T4N1	6 (9)
ypTNM
Stage 0	9 (14)
Stage I	7 (11)
Stage IIA	15 (23)
Stage IIB	14(22)
Stage III	15 (23)
Stage IV	6 (9)
Tumor regression grade
I	48 (72)
II	4 (6)
III	6 (9)
IV (pCR)	8 (12)
Type of Neoadjuvant
EOX	53 (80)
DCF	9 (14)
ECF	4 (6)

cTNM, clinical TNM stage AJCC 2002 [13]; DCF, docetaxel-cisplatin-fluorouracil; ECF, epirubicin-cisplatinol-fluorouracil; EOX, epirubicin-oxaliplatin-cabecitabin; EX, exploration; IL, Ivor Lewis; MIE, minimally invasive esophagectomy; pCR, pathologic complete response; TH, transhiatal; ypTNM, pathologic TNM stage AJCC 2002 after neoadjuvant therapy and surgery [13].

Figure 1. Independent samples Median test-stem and leaf plot. Median change in SUVΔ% (maximum standardized uptake value percentage change after neoadjuvant therapy) in histopathologic responders and non-responders.

Table II ROC analysis of SUVΔ% and histopathologic response prediction.

CUTOFF	SE	SP	PPV	NPV	AUC (95%CI)	p
67%	79%	75%	46%	93%	0.810 (0.702–0.919)	< 0.0001
50%^a	93%	58%	37%	97%	NL	NL
35%^b	100%	33%	29%	100%	NL	NL

AUC, area under curve; NPV, negative predictive value; PPV, positive predictive value; ROC, receiver operating characteristics; SE, sensitivity; SP, specificity; SUVΔ%, percentage change in maximal SUV after neoadjuvant therapy. ^aauthor Port et al. [19]. ^bauthor Lordick et al. [11]

Figure 2. ROC curve analysis for prediction of histopathologic response by SUVΔ% (maximum standardized uptake value percentage change after neoadjuvant therapy). Arrow denotes optimal point of separation at 67% decrease in SUVΔ%. ROC, receiver operating characteristics.

Table III Cox regression univariate analysis of association of essential risk factors, long-term-, and disease-free survival among patients with locally advanced esophageal adenocarcinoma undergoing surgery after neoadjuvant chemotherapy.

	Overall survival		Disease-free survival
Variable	HR (95% Cl)	p	HR (95% Cl)	p
Age	0.969 (0.929–1.010)	0.139	0.971 (0.937–1.007)	0.116
Gender (M)	0.407 (0.166–0.999)	0.050	0.383 (0.173–0.849)	0.018
HPR+	0.030 (0.000–1.983)	0.101	0.208 (0.049–0.881)	0.033
ASA<3	0.356 (0.199–1.786)	0.131	0.415 (0.143–1.204)	0.106
ypStage < 2b	0.213 (0.070–0.643)	0.006	0.293 (0.122–0.704)	0.006
SUVΔ% > 67	0.249 (0.073–0.856)	0.027	0.383 (0.153–0.959)	0.040
SUVΔ% > 35	0.192 (0.077–0.476)	<0.0001	0.116 (0.075–0.370)	< 0.0001
SUVΔ% > 0	0.140 (0.052–0.379)	<0.0001	0.139 (0.049–0.376)	< 0.0001
SUVΔ%	0.973 (0.959–0.986)	<0.0001	0.974 (0.962–0.987)	< 0.0001
SUV1	0.935 (0.852–1.026)	0.157	0.966 (0.898–1.039)	0.352
SUV2	1.043 (0.970–1.122)	0.252	1.035 (0.969–1.108)	0.303

ASA, American Society of Anesthesiologists physical status classification [31]; CI, confidence interval; HPR, histopathologic response; HR, hazard ratio; SUV1 and SUV2, pre- and postneoadjuvant maximum standardized uptake values; SUVΔ%, Maximum standardized uptake value percentage change after neoadjuvant therapy; ypTNM, Tumor, node and metastasis staging according to AJCC 2002 after neoadjuvant therapy and surgery [13]

Figure 3. Cox regression proportional hazards univariate analysis of effect of HPR after neoadjuvant therapy on OS. OS, overall survival.

Figure 4. Cox regression proportional hazards univariate analysis of effect of HPR after neoadjuvant therapy on DFS. DFS, disease-free survival; HPR, histopathologic response.

Figure 5. Cox regression proportional hazards univariate analysis of effect of percentage change >67% (SUVΔ%) of maximal SUV of the primary tumor after neoadjuvant therapy on OS. OS, overall survival.

Figure 6. Cox regression proportional hazards univariate analysis of the effect of percentual change >67% (SUVΔ%) of maximal SUV of the primary tumor after neoadjuvant therapy on DFS. DFS, disease-free survival.

Table IV Cox regression multivariate analysis of association of multiple risk factors and poor long-term overall survival among patients with locally advanced esophageal adenocarcinoma undergoing surgery after neoadjuvant chemotherapy.

	Overall survival
	Model 1.		Model 2.
Variable	HR (95% Cl)	p	HR (95% Cl)	p
Age	0.967 (0.919–0.10.17)	0.192	0.959 (0.911–1.011)	0.119
Sex (M)	0.301 (0.114–0.796)	0.016	0.168 (0.054–0.523)	0.002
HPR+	> 0.0001 (0–3.88E254)	0.966	> 0.0001 (0–9.06E179)	0.959
ASA<3	0.741 (0.240–2.289)	0.602	0.761 (0.252–2.300)	0.628
SUVΔ%>67%	0.313 (0.088–1.113)	0.073	NL
SUVΔ%>35%	NL		0.146 (0.049–0.436)	0.001
	Model 3.		Model 4.
Age	0.952 (0.903–1.004)	0.069	0.942 (0.889–0.998)	0.042
Sex (M)	0.208 (0.072–0.602)	0.004	0.156 (0.050–0.483)	0.001
HPR +	> 0.0001 (0–4.08E227)	0.963	> 0.0001 (0–1.65E274)	0.969
ASA<3	0.861 (0.269–2.754)	0.800	0.936 (0.300–2.920)	0.909
SUVΔ% > 0%	0.109 (0.034–0.349)	< 0.0001	NL
SUVΔ%	NL		0.966 (0.949–0.984)	< 0.0001

ASA, American Society of Anesthesiologists physical status classification [31]; CI, confidence interval; HPR, histopathologic response; HR, hazard ratio; SUVΔ%, Maximum standardized uptake value percentage change after neoadjuvant therapy; ypTNM, Tumor, node and metastasis staging according to AJCC 2002 after neoadjuvant therapy and surgery [13].

Table V Cox regression multivariate analysis of the association of multiple risk factors and poor long-term disease-free survival among patients with locally advanced esophageal adenocarcinoma operated on after neoadjuvant chemotherapy.

	Disease-free survival
	Model 1.		Model 2.
Variable	HR (95% Cl)	p	HR (95% Cl)	p
Age	0.975 (0.934–1.018)	0.211	0.985 (0.916–1.002)	0.063
Sex (M)	0.338 (0.143–0.801)	0.014	0.167 (0.062–0.451)	< 0.0001
HPR +	0.308 (0.069–1.384)	0.125	0.508 (0.106–2.420)	0.359
ASA<3	0.493 (0.163–1.493)	0.211	0.493 (0.166–1.469)	0.205
SUVΔ%>67%	0.498 (0.192–1.289)	0.151	NL
SUVΔ%>35%	NL		0.114 (0.043–0.300)	< 0.0001
	Model 3.		Model 4.
Age	0.953 (0.908–1.000)	0.049	0.958 (0.914–1.003)	0.069
Sex (M)	0.235 (0.090–0.613)	0.002	0.232 (0.092–0.585)	0.002
HPR+	0.340 (0.075–1.534)	0.160	0.501 (0.107–2.358)	0.382
ASA<3	0.756 (0.242–2.356)	0.629	0.605 (0.202–1.816)	0.370
SUVΔ% > 0	0.115 (0.037–0.357)	< 0.0001	NL
SUVΔ%	NL		0.973 (0.958–0.987)	< 0.0001

ASA, American Society of Anesthesiologists physical status classification [31]; CI, confidence interval; HPR, histopathologic response; HR, hazard ratio; SUVΔ%, Maximum standardized uptake value percentage change after neoadjuvant therapy; ypTNM, tumor, node and metastasis staging according to AJCC 2002 after neoadjuvant therapy and surgery [13].

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