Safety and Efficacy of Concurrent or Sequential Radiotherapy Plus (PD-1) Inhibitors in Oligometastatic Esophageal Cancer

Figures & data

Figure 1 The patient screening process: screening EC patients received PD-1 inhibitors in our center, 800 patients received PD-1 inhibitors were screed, excluded 576 patients without OMEC. 224 patients with OMEC received PD-1 inhibitors were screed, 11 patients with other active synchronous carcinomas were excluded. Subsequently, 213 patients with OMEC received PD-1 inhibitors were screed, 127 patients who only received systemic therapy were excluded. Eventually, 86 patients with OMEC who received radiotherapy plus PD-1 inhibitors were included in this study.

Table 1 Baseline Characteristics (n=86)

Characteristic		No. (%)
Age, y	Median (IQR)	61.2(57.8–66.7)
Sex	Male	77(90)
	Female	9(10)
KPS	≥80	75(87)
	70	11(13)
Drinking status	Current or former	43(50)
	Never	43(50)
Primary histology	SCC	84(98)
	Other	2(2)
Location of primary tumor	Cervical	2(2)
	Upper	10(12)
	Middle	30(35)
	Lower	26(30)
	Multiple primary	18(21)
T stage	T1–2	15(17)
	T3–4	71(83)
Classification of OMEC	SO	54(64)
	MO	32(36)
No. of metastatic lesions	1–2	42(49)
	3–5	44(51)
Site of metastases	Extra-regional lymph node	61(71)
	Distant organ	17(20)
	Both	8(9)
Radiation dose	≥50.4Gy	62(72)
	<50.4Gy	24(28)
Radiation site	Primary tumor	15(17)
	Metastasis	30(35)
	Both	41(48)
Sequence of PD-1 and RT	RT concurrent with PD-1	44(51)
	RT sequential with PD-1	42(49)
Type of PD-1 inhibitors	Camrelizumab	38(44)
	Sintilimab	29(34)
	Pembrolizumab	9(10)
	Tislelizumab	8(9)
	Multiple	2(3)
Chemotherapy regimen	TP	67
	PF	4
	Other	15
Treatment line	1	55(64)
	2	25(29)
	≥3	6(7)

Note: Multiple: treatment with 2 or greater different PD-1 inhibitors during the treatment.

Abbreviations: SO, synchronous OMEC; MO, metachronous OMEC.

Table 2 Details of Distant Metastatic Sites (n=228)

Sites of Metastases	No. (%)
Lung	13(5.7)
Liver	11(4.8)
Adrenal glands	1(0.4)
Brain	8(3.5)
Bone	6(2.6)
Soft tissue	3(1.3)
Pleura	3(1.3)
Extraregional lymph nodes	183(80.3%)

Table 3 Response to Treatment

Best Overall Response
Complete response	1(1.2%)
Partial response	39(45.3%)
Stable disease	39(45.3%)
Progressive disease	4(4.7%)
Could not be evaluated	3(3.5%)
Objective response rate (95% CI)	46.5% (36.9–58.4%)
Disease control rate (95% CI)	91.8% (87.5–98.5%)
Duration of response (months)	13.5 (95% CI,11.2–16.0)

Figure 2 (A) The median PFS of all patients was 15.2m (95% CI, 12.1–18.2), 1-year and 2-year PFS rate were 61.4% and 26.7%; (B) The median PFS of SO (15.1m, 11.7–18.5) and MO (16.3m, 12.0–20.6) patients (p=0.63).

Abbreviations: SO, synchronous OMEC patients; MO, metachronous OMEC patients.

Table 4 Failure Patterns in Full-Analysis Population

	N (%)
Any failure	46(53.5%)
Locoregional failure only	14(16.3%)
Distant metastasis only	20(23.3%)
Both LRF and DM	6(7.0%)
Unable to confirm due to death	6(7.0%)
Alive with failure	27(31.4%)
Death from EC	17(20.0%)
Treatment-related death	1(1.2%)
Any death	19(10.5%)

Abbreviations: LRF, Locoregional failure; DM, distant metastasis.

Table 5 Treatment-Related Adverse Events

	No. (%) of Patients
	Total of Patients (n=86)		RT Sequential with PD-1 (n=39)		RT Concurrent with PD-1 (n=47)
	Any Grade	≥Grade 3	Any Grade	≥Grade 3	Any Grade	≥Grade 3
Treatment-related adverse events	86(100)	42(48.8)	39(45.3)	13(15.1)	47(54.7)	29(33.7)
Reactive cutaneous capillary endothelial Proliferation	9(9.3)	1(1.2)	4(4.7)	0	5(5.8)	1(1.2)
Anemia	46(53.4)	2(2.3)	18(20.9)	1(1.2)	28(32.6)	1(1.2)
Leukopenia	69(80.2)	26(30.2)	27(31.4)	6(7.0)	42(48.8)	20(23.3)
Neutropenia	50(58.1)	16(18.6)	16(18.6)	3(3.5)	34(39.5)	13(15.1)
Platelet count decreased	19(22.1)	3(3.5)	8(9.3)	0	11(12.8)	3(3.5)
Lymphocyte count decreased	37(43.0)	7(8.1)	10(11.6)	1(1.2)	27(31.4)	6(7.0)
Nausea	37(43.0)	1(1.2)	17(19.8)	0	20(23.3)	1(1.2)
Fatigue	26(30.2)	1(1.2)	11(12.8)	0	15(17.4)	1(1.2)
Decreased appetite	35(40.7)	0	14(16.3)	0	21(24.4)	0
Constipation	11(12.8)	0	5(5.8)	0	6(7.0)	0
Fever	22(25.6)	2(2.3)	9(10.5)	0	13(15.1)	2(2.3)
Radioactive esophagitis	42(48.8)	1(1.2)	9(10.5)	0	33(38.4)	1(1.2)
Radioactive dermatitis	16(18.6)	1(1.2)	3(3.5)	0	13(15.1)	1(1.2)
Esophageal fistula	3(3.5)	1(1.2)	1(1.2)	1(1.2)	2(2.3)	0
Lung infection	10(11.6)	3(3.4)	4(4.7)	2(2.3)	6(7.0)	1
Hypokalemia	1(1.2)	0	0	0	1(1.2)	0
Pneumonitis	14(16.3)	4(4.7)	3(3.5)	1(1.2)	11(12.8)	3(3.5)
Immune-related adverse events	65(75.6)	7(8.1)	27(31.4)	4(4.7)	38(44.2)	3(3.5)
Hypothyroidism	38(44.2)	1(1.2)	17(19.8)	1(1.2)	21(24.4)	0
Hyperthyroidism	9(10.5)	0	2(2.3)	0	7(8.1)	0
Cardiotoxicity	22(25.6)	2(2.3)	12(14.0)	2(2.3)	10(11.6)	0
Capillary hemangioma	9(10.4)	0	4(4.7)	0	5(5.8)	0
Pruritus	5(5.8)	0	1(1.2)	0	4(4.7)	0
Rash	6(7.0)	1(1.2)	1(1.2)	0	5(5.8)	1(1.2)
Pneumonitis	9(10.5)	1(1.2)	4(4.7)	1(1.2)	5(5.8)	4(4.7)
Allergy	2(2.3)	1	0	0	2(2.3)	1(1.2)
Hypokalemia	1(1.2)	0	0	0	1(1.2)	0
Hypophysitis	1(1.2)	0	0	0	1(1.2)	0