Immune inflammation indicators in anal cancer patients treated with concurrent chemoradiation: training and validation cohort with online calculator (ARC: Anal Cancer Response Classifier)

Figures & data

Table 1 Patient characteristics

	Variable	Development set, n=161	Validation set, n=147	p-value
Age	Mean	62	68.8	0.098
	Range	36–83	42–91
Sex	Male	26 (16.2)	35 (23.8)	0.115
	Female	135 (83.8)	112 (82.2)
Pre-treatment Hb	Mean	13.1	13.2	0.339
	Range	7.6–16.8	8.8–17.2
T-stage	T1	14 (8.7)	7 (4.7)	0.067
	T2	90 (56.0)	71 (48.4)
	T3	40 (24.8)	35 (23.8)
	T4	15 (9.3)	27 (18.4)
	NA	2 (1.2)	7 (4.7)
N-stage	N0	91 (56.6)	74 (50.3)	0.012
	N1	26 (16.1)	31 (21.1)
	N2	34 (21.1)	19 (12.9)
	N3	10 (6.2)	23 (15.7)
Global stage	I	13 (8.1)	9 (6.1)	0.104
	II	72 (44.7)	47 (32)
	IIIA	29 (18.0)	39 (26.5)
	IIIB	46 (28.6)	45 (30.6)
	NA	1 (0.6)	7 (4.8)
Grade	G1	12 (7.5)	32 (21.8)	<0.01
	G2	86 (53.4)	52(35.3)
	G3	45 (27.9)	33 (22.5)
	NA	18 (11.2)	30 (20.4)

Figure 1 Univariate analysis of progression-free survival and overall survival.

Abbreviations: NLR, neutrophil-lymphocyte ratio; PLR, platelet-lymphocyte ratio; SII, systemic index of inflammation.

Figure 2 SII value for category of response.

Abbreviation: SII, systemic index of inflammation.

Figure 3 Progression-free survival (left) and overall survival (right) by pre-treatment SII.

Abbreviations: NLR, neutrophil-lymphocyte ratio; PLR, platelet-lymphocyte ratio; SII, systemic index of inflammation.

Figure 4 Nomogram with predictors of response to chemoradiotherapy.

Abbreviations: Hb, hemoglobin; SII, systemic index of inflammation.

Figure S1 Calibration plot of the external validation of the nomogram.

Figure S2 Progression-free survival and overall survival in the external validation.

Table S1 Treatment characteristics

Variable	N (%)
SIB	96 (59.6)
PTV dose-tumor (Gy)
54 Gy/30 fractions	58 (60.4)
50.4 Gy/28 fractions	38 (39.6)
PTV dose-positive nodes (Gy)
54 Gy/30 fractions	8 (21.6)
50.4 Gy/30 fractions	29 (78.4)
PTV dose-negative nodes (Gy)
45 Gy/30 fractions	58 (60.4)
42 Gy/30 fractions	38 (39.6)
Sequential boost	65 (40.4)
First-phase PTV
45 Gy/25 fractions	65 (100)
Sequential boost PTV
Yes	63 (96.9)
9 Gy	40 (61.5)
14.4 Gy	23 (35.4)
No	2 (3.1)
Chemotherapy
5-FU + MMC	158 (98.1)
No	3 (1.9)

Abbreviations: 5-FU, 5-fluorouracil; MMC, mitomycin; SIB, simultaneous integrated boost, PTV, planning target volume.

Table S2 Results of univariate analysis of the previous study

	PFS			OS
	HR	(95% CI)	P-value	HR	(95% CI)	P-value
SD+PD vs CR	41.8	40.9–42.7	<0.0001	53.3	52.1–54.3	<0.0001
PR vs CR	2.96	1.35–6.54	0.0071	2.45	0.82–7.31	0.1
Hb as a continuous variable	0.57	0.39–0.85	0.049	0.53	0.29–0.96	0.047

Abbreviations: CI, confidence interval; CR, complete response; Hb, hemoglobin; HR, hazard ratio; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease.

Table S3 Results of univariate and multivariate logistic model for prediction of nonresponse

Variable	Univariate model		Multivariate model
OR	95% CI	OR	95% CI
SII	3.03	2.24–3.84	2.99	2.04–3.94
N+ vs N–	13.73	11.64–15.82	5.88	3.37–8.40
Pre-treatment Hb (g/dL)	0.61	0.24–0.98	n.s.	n.s.
Pre-treatment NLR	1.24	1.01–1.47	n.s.	n.s.
Pre-treatment PLR	1.65	1.20–2.11	n.s.	n.s.

Abbreviations: SII, systemic index of inflammation; N, lymph node status; Hb, hemoglobin; NLR, neutrophils to lymphocyte ratio; n.s., not significant; PLR, platelets to lymphocyte ratio.