Multimodality therapy is recommended for limited-stage combined small cell esophageal carcinoma

Figures & data

Table 1 Patient characteristics

	n (%)
Sex (72 available)
Male	56 (78)
Female	16 (22)
Age (years) (72 available)
≤60	25 (35)
>60	47 (65)
Tumor location (55 available)
Upper 1/3	4 (7)
Middle 1/3	42 (76)
Lower 1/3	9 (17)
Tumor size (42 available)
≤5 cm	29 (69)
>5 cm	13 (31)
Combined additional components (72 available)+
Squamous cell carcinoma	53 (74)
Adenocarcinoma	6 (8)
Squamous cell carcinoma and adenocarcinoma	1 (1)
Others‡	10 (14)
Unknown	2 (3)
The number of additional components (72 available)
1	64 (89)
≥2	6 (8)
Unknown	2 (3)
T classification (72 available)§
cT1	12 (17)
cT2	13 (18)
cT3	23 (32)
cT4	1 (1)
Unknown	23 (32)
N status (72 available)§
cN0	34 (47)
cN1	25 (35)
Unknown	13 (18)
TNM stage (72 available)§
cI	8 (11)
cIIa	15 (21)
cIIb	11 (15)
cIII	17 (24)
Unknown	21 (29)
Treatment types (72 available)
S	13 (18)
CT	2 (3)
RT	2 (3)
CT+RT	13 (18)
S+CT	29 (40)
S+RT	1 (1)
S+CT+RT	12 (17)
CT regimen (72 available)
Platinum-based*	49 (68)
EP	15 (21)
CE	20 (28)
IP	4 (6)
PF	10 (13)
Non-platinum-based	7 (10)
None	16 (22)
# of CT cycles (38 available)
<4	21 (55)
≥4	17 (45)

Notes:

+ Pathological diagnosis according to endoscopic biopsy or postoperative biopsy.

‡ The other combined components included sarcomatoid, Rosette, and Paget’s disease.

§ The AJCC (6th edition) was used for staging.

* Platinum-based CT regimens included cisplatin, carboplatin, or oxaliplatin.

Abbreviations: AJCC, American Joint Committee on Cancer; c, clinical; CE, carboplatin + etoposide; CT, chemotherapy; EP, etoposide + cisplatin; IP, irinotecan + cisplatin; PF, cisplatin + 5-fluorouracil; RT, radiotherapy; S, surgery; TNM, tumor/nodes/metastasis.

Table 2 Patient characteristics, for study patients treated at our hospital

Patient number	Age	Sex	Location	TNM stage+	Pathology	Treatment course	Dose of RT	CT regimen	PFS (months)	PD site	Treatment after recurrence	Survival time and status
1	40	M	Middle	T3N1M0 (III)	SC+Sq	S+CT	–	COME	10.7	Right supraclavicular LN	CT	12.7 (DOD)
2	54	M	Upper	T3N1M0 (III)	SC+Sq	S+CT+RT	60 Gy	EP+COME	7.0	Right upper mediastinal LN	RT	23.0 (DOD)
3	45	M	Middle	T2N1M0 (IIB)	SC+Sq	S+CT	–	EC	20.0	Primary tumor site	–	27.0 (DOD)
4	54	M	Middle	T3N1M0 (III)	SC+Pa	S+CT	–	EC	6.0	Multiple mediastinal LN	–	10.7 (DOD)
5	70	M	Middle	T3N1M0 (III)	SC+Pa	S+CT	–	EC	6.3	Liver and abdominal LN	–	10.0 (DOD)
6	70	M	Lower	T2N1M0 (IIB)	SC+Pa	S+CT	–	EC	24.0	None	–	24.0 (DOD)
7	65	F	Middle	T2N0M0 (IIA)	SC+Sq	S+CT	–	COME	80.3	None	–	80.3 (DOD)
8	63	M	Middle	T3N1M0 (III)	SC+Sq	S	–	–	9.3	None	–	9.3 (DOD)
9	70	M	Upper	T2N0M0 (IIA)	SC+Sq	CT+RT	60 Gy	CAP	21.4	Liver and mediastinal LN	CT	86.0 (DOD)
10	73	M	Middle	T3N1M0 (III)	SC+Pa	CT+RT	50 Gy	EC	3.4	Bone and lung	CT+RT	9.0 (DOD)
11	42	M	Upper	T3N1M0 (III)	N/A	S+CT+RT	65 Gy	EC	10.7	None	–	10.7 (DOD)
12	62	M	Middle	T2N1M0 (IIB)	SC+Sq	S+CT	–	EP	22.8	None	–	22.8 (DOD)
13	77	F	Middle	T1N0M0 (I)	SC+Sq	S+CT+RT	50.4 Gy	EC	4.0	The neck and hilar LN	CT+RT	46.2 (DOD)
14	64	M	Lower	T2N0M0 (IIA)	SC+Sq	CT	–	EC	26.5	None	–	26.5 (DOD)
15	73	M	Lower	T3N1M0 (III)	SC+Sq	CT+RT	47.4 Gy	EC	5.4	None	–	5.4 (DOD)
16	62	M	Middle	T2N1M0 (IIB)	SC+Sq	CT+RT	60 Gy	EC	6.0	Brain	RT	25.2 (DOD)
17	61	M	Middle	T3N0M0 (IIA)	N/A	S+CT	–	EC	7.8	None	–	7.8 (DOD)
18	58	F	Middle	T2N1M0 (IIB)	SC+Sq	S	–	–	32.5	None	–	32.5 (Alive)
19	67	M	Middle	T3N0M0 (IIA)	SC+Ad	S+CT	–	EP	35.4	None	–	35.4 (Alive)
20	54	M	Middle	T3N1M0 (III)	SC+Ad	S+CT	–	EP	2.0	Multiple metastases	–	4.6 (DOD)
21	52	M	Lower	T2N0M0 (IIA)	SC+Sq	S+CT	–	PF	11.7	Liver and lung	CT	15.5 (DOD)
22	55	M	Middle	T3N0M0 (IIA)	SC+Sq	S+CT+RT	50 Gy	EP	24.0	Bone and LN	RT+CT	30.3 (DOD)
23	71	M	Middle	T2N0M0 (IIA)	SC+Sq	S+CT+RT	54 Gy	PF	13.7	None	–	13.7 (DOD)
24	62	F	Upper	T3N1M0 (III)	SC+Sq	S+CT	–	EC	4.8	None	–	4.8 (Alive)

Note:

+ The AJCC (6th edition) was used for staging.

Abbreviations: Ad, adenocarcinoma; AJCC, American Joint Committee on Cancer; CAP, cyclophosphamide + doxorubicin + cisplatin; DOD, died of disease; CT, chemotherapy; COME, cyclophosphamide + vincristine + methotrexate + etoposide; EC, etoposide + carboplatin; EP, etoposide + cisplatin; F, female; LN, lymph node; M, male; NA, not available; Pa, Paget’s disease; PD, progressive disease; PF, cisplatin + 5-fluorouracil; PFS, progression-free survival; RT, radiotherapy; S, surgery; SC, small cell; Sq, squamous cell carcinoma; TNM, tumor/nodes/metastasis.

Figure 1 OS of patients with LS-C-SCEC.

Notes: (A) OS of all patients; (B) OS of patients with or without CT; (C) OS of patients who received monotherapy or multimodality therapy; and (D) OS of patients who received CT+RT, S+CT, or S+CT+RT.
Abbreviations: CI, confidence interval; CT, chemotherapy; LS-C-SCEC, limited-stage combined small cell esophageal carcinoma; OS, overall survival; RT, radiotherapy; S, surgery.

Table 3 Univariate analysis of the prognostic factors for survival in patients with LS-C-SCEC

Characteristics	MST (months)	1-year OS (%)	3-year OS (%)	χ^2	P-value
Sex (72 available)
Female	12.0	50	33	0.969	0.325
Male	13.7	57	23
Age (years) (72 available)
≤60	22.8	54	27	0.041	0.839
>60	12.7	58	25
Tumor location (55 available)
Upper 1/3	7.0	9	0	28.84	0.0001*
Middle 1/3	24.0	67	30
Lower 1/3	80.3	63	31
Tumor size (42 available)
≤5 cm	12.0	55	25	0.345	0.557
>5 cm	23.0	59	33
TNM stage (51 available)+
cI	15.0	63	38	2.325	0.508
cIIa	12.0	43	22
cIIb	15.0	64	27
cIII	11.0	45	12
Combined additional components (70 available)
Sq	12.7	55	21	1.054	0.788
Ad	10.7	33	17
Sq+Ad	27.0	–	–
Others‡	15.0	56	30
The number of additional components (70 available)
1	12.7	55	21	0.742	0.389
≥2	27.0	60	30
Type of treatment (72 available)
Monotherapy	8.0	23	0	30.83	0.0001*
Combination therapy	26.5	74	32
CT type (43 available)§
Platinum-based	12.7	57	27	1.133	0.287
Non-platinum-based	10.0	33	0

Notes:

+ The AJCC (6th edition) was used for staging.

‡ The other combined components included sarcomatoid, Rosette, and Paget’s disease.

§ Platinum-based CT regimens included cisplatin, carboplatin, or oxaliplatin.

* P-value <0.05.

Abbreviations: Ad, adenocarcinoma; AJCC, American Joint Committee on Cancer; CT, chemotherapy; LS-C-SCEC, limited-stage combined small cell esophageal carcinoma; MST, median survival time; OS, overall survival; Sq, squamous cell carcinoma; TNM, tumor/nodes/metastasis.

Table 4 Multivariate Cox regression analysis of predictors for OS in patients with LS-C-SCEC

Characteristics	HR	95% CI	P-values
Sex (male vs female)	0.576	0.141–2.354	0.443
Age (≤60 vs >60 years)	0.764	0.138–4.230	0.758
Tumor size (≤5 vs >5 cm)	0.757	0.188–3.052	0.696
Tumor location (upper 1/3 vs middle 1/3 vs lower 1/3)	0.210	0.057–0.770	0.019*
TNM stage (cI vs cIIa vs cIIb vs cIII)+	1.009	0.517–1.969	0.980
Combined additional components (Sq vs Ad vs Sq+Ad vs others)‡	1.094	0.549–2.180	0.798
The number of additional components (1 vs ≥2)	1.414	0.157–12.728	0.757
Type of treatment (multimodality vs monotherapy therapy)	0.063	0.005–0.731	0.027*
CT type (platinum-based vs non-platinum-based)§	1.469	0.332–6.510	0.613

Notes:

* P-value <0.05.

+ The AJCC (6th edition) was used for staging.

‡ The other combined components included sarcomatoid, Rosette, and Paget’s disease.

§ Platinum-based CT regimens included cisplatin, carboplatin, or oxaliplatin.

Abbreviations: Ad, adenocarcinoma; AJCC, American Joint Committee on Cancer; CI, confidence interval; CT, chemotherapy; HR, hazard ratio; LS-C-SCEC, limited-stage combined small cell esophageal carcinoma; OS, overall survival; Sq, squamous cell carcinoma; TNM, tumor/nodes/metastasis.