A retrospective study evaluating the pretreatment tumor volume (PTV) in non-small cell lung cancer (NSCLC) as a predictor of response to program death-1 (PD-1) inhibitors

Figures & data

Figure 1 Example PTV measurement using the Philips Intellispace Multi-Modality Tumor Tracking (MMTT) application.

Table 1 Demographic and clinical characteristics

	N=116
Sex
Male	67 (58%)
Female	49 (42%)
Age
Median (IQR)	63 (57, 70)
Primary
Lung adeno	77 (66%)
Lung squam	33 (28%)
Lung poorly diff	6 (5%)
Mets category
M0	1 (1%)
M1a	44 (38%)
M1b	12 (10%)
M1c	59 (51%)
Number of lines of previous tx
0	24 (21%)
1	64 (55%)
2	23 (20%)
3	2 (2%)
4	2 (2%)
5	1 (1%)
Agent
Pembro	21 (18%)
Pembro plus chemo	15 (13%)
Pembro plus investigational	7 (6%)
Pembro plus ipi	8 (7%)
Nivo	65 (56%)
Protocol
No	71 (61%)
Yes	45 (39%)
Best response^a
PR	26 (26%)
SD	39 (39%)
PD	34 (34%)
Not recorded	4 (4%)
Reason for discontinuation
Progression	37 (32%)
PD-1 Adverse events	16 (14%)
PS Decline, hospital admit, hospice	43 (37%)
Completed therapy	11 (10%)
Unknown, lost	6 (5%)
Long vacation	1 (1%)
No response	2 (2%)
Hospitalization within 6 weeks of first dose^a
No	78 (76%)
Yes	25 (24%)
Total volume, median (IQR)
Median (IQR)	53.7 (13.3, 107.9)
Lung volume
Median (IQR)	15.1 (0.0, 65.4)
Unmeasurable lung
No	27 (23.3%)
Yes	89 (76.7%)
LN volume
Median (IQR)	5.1 (0.0, 18.1)
Unmeasurable LN
No	43 (37.1%)
Yes	73 (62.9%)
Liver volume
Median (IQR)	0.0 (0.0, 0.0)
Unmeasurable liver
No	93 (80%)
Yes	23 (20%)
Soft tissue volume
Median (IQR)	0.0 (0.0, 0.0)
Unmeasurable soft tissue
No	85 (73%)
Yes	31 (27%)

Notes: ^aFor those followed for at least weeks.

Abbreviations: SD, stable disease; PD-1, program death-1; PR, partial response; LN, lymph node; PS, performance status; PD, progression of disease.

Table 2 Associations of total volume with demographic and clinical characteristics

	N	Median total vol	IQR	P-value
Sex				0.21^b
Male	67	66	14, 116
Female	49	37	13, 79
Age				0.73^c
≤59 yrs	41	49	15, 99
60–69 yrs	42	57	11, 111
≥70 yrs	33	58	15, 103
Primary				0.56^b
Lung adeno	77	53	13, 105
Lung squam	33	63	28, 111
Lung poorly diff	6	28	10, 72
Best response^a				0.61^c
PR	26	43	13, 88
SD	39	37	13, 79
PD	34	60	18, 84
Mets category				0.07^c
M0/M1a	45	35	13, 72
M1b	12	59	22, 116
M1c	59	56	21, 128
Lines of previous Tx				0.70^a
0	24	35	13, 115
1	64	60	15, 105
2 or more	28	71	13, 108
Agent				0.29^b
Pembro	21	36	11, 70
Pembro + other	30	43	14, 132
Nivo	65	65	18, 116
On protocol				0.76^b
No	71	51	13, 101
Yes	45	63	15, 123
Hospitalizations w/i 6 wks^a				0.91^b
No	78	47	13, 88
Yes	25	55	15, 80
Reason discontinuation				0.14^b
PD, decline, PD-1 AE	96	56	15, 113
Completed therapy	11	36	7, 71
Other	7	193	2, 462
Unmeasurable lung				0.04^b
No	27	71	36, 132
Yes	89	44	13, 92
Unmeasurable LN				0.33^b
No	43	36	13, 84
Yes	73	61	14, 116
Unmeasurable liver				0.64^b
No	93	55	13, 103
Yes	23	37	18, 138
Unmeasurable soft tissue				0.56^b
No	85	63	13, 126
Yes	31	50	20, 79

Notes: ^aFor those followed for at least weeks; ^bKruskal–Wallis Test; ^cSpearman’s rank correlation.

Abbreviations: AE, adverse events; SD, stable disease; PD-1, program death-1; PR, partial response; LN, lymph node; PD, progression of disease.

Table 3 Tumor volume in association with PFS

	HR (95% CI)	P-value
Total volume (per 100 cm^3)	1.1 (0.9, 1.3)	0.47
Sex		0.35
Male	1.0
Female	1.2 (0.8, 1.9)
Age		0.59
≤59 yrs	1.0
60–69 yrs	1.2 (0.7, 1.9)
≥70 yrs	0.9 (0.5, 1.5)
Primary		0.94
Lung adeno	1.0
Lung squam	1.0 (0.7, 1.6)
Lung poorly diff	0.9 (0.2, 2.4)
Best Response^a		<0.001
PR	1.0
SD	4.6 (2.3, 9.4)
PD	43.9 (17.9, 107.3)
Metastasizes		0.007
M0/M1a	1.0
M1b	1.0 (0.5. 2.3)
M1c	2.0 (1.3, 3.1)
Previous lines of Tx		0.005
0	1.0
1	2.4 (1.4, 4.3)
2 or more	2.1 (1.1, 4.2)
Agent		0.006
Pembro	1.0
Pembro + other	1.0 (0.5, 2.1)
Nivo	2.0 (1.1, 3.8)
On protocol		0.006
No	1.0
Yes	0.5 (0.3, 0.8)
Hospitalization w/i 6 wk^a		0.001
No	1.0
Yes	2.3 (1.4, 3.9)
Reason for discontinuation		<0.001
PD, decline, PD-1 AE	1.0
Completed Tx	0.1 ((0.05, 0.4)
Other	0.4 (0.1, 1.2)
Unmeasurable lung		0.03
No	1.0
Yes	1.8 (1.0, 3.0)
Unmeasurable LN		0.55
No	1.0
Yes	0.9 (0.6, 1.3)
Unmeasurable Liver		0.06
No	1.0
Yes	1.7 (1.0, 2.8)
Unmeasurable soft tissue		0.41
No	1.0
Yes	1.2 (0.8, 1.9)
Lung (per 100 cm^3) >2 cm	1.0 (0.8, 1.3)	0.99
LN (per 100 cm^3) >1.5 cm	0.8 (0.4, 1.7)	0.59
Liver (per 100 cm^3) >2 cm	2.6 (1.0, 7.0)	0.11
Soft tissue (per 100 cm^3) >2 cm	1.8 (1.1, 2.9)	0.02

Notes: ^aFor those followed for at least weeks.

Abbreviations: AE, adverse events; SD, stable disease; PD-1, program death-1; PR, partial response; PFS, progression free survival; LN, lymph node; PD, progression of disease.

Table 4 Tumor volume in association with OS

	HR (95% CI)	P-value
Total volume (per 100 cm^3)	1.2 (0.9, 1.5)	0.26
Sex		0.24
Male	1.0
Female	1.4 (0.8, 2.3)
Age		0.65
≤59 yrs	1.0
60–69 yrs	1.2 (0.6, 2.2)
≥70 yrs	0.9 (0.4, 1.7)
Primary		0.72
Lung adeno	1.0
Lung squam	0.8 (0.4, 1.5)
Lung poorly diff	1.2 (0.4, 4.0)
Best response^a		<0.001
PR	1.0
SD	5.6 (1.6, 19.1)
PD	17.4 (5.1, 59.3)
Metastasizes		0.008
M0/M1a	1.0
M1b	1.0 (0.3, 3.1)
M1c	2.2 (1.3, 4.4)
Previous lines of Tx		0.001
0	1.0
1	2.3 (1.0, 5.3)
2 or more	4.4 (1.9, 10.6)
Agent		0.19
Pembro	1.0
Pembro + other	0.9 (0.4, 2.3)
Nivo	1.6 (0.7, 3.5)
On protocol		0.10
No	1.0
Yes	0.6 (0.4, 1.1)
Hospitalization w/i 6 wk^a		<0.001
No	1.0
Yes	6.0 (3.2, 11.0)
Reason for discontinuation^b		–
PD, decline, PD-1 AE	1.0
Completed Tx	–
Other	–
Unmeasurable lung		0.02
No	1.0
Yes	2.2 (1.0, 4.7)
Unmeasurable LN		0.74
No	1.0
Yes	0.9 (0.5, 1.6)
Unmeasurable liver		0.09
No	1.0
Yes	1.7 (0.9, 3.3)
Unmeasurable soft tissue		0.46
No	1.0
Yes	1.3 (0.7, 2.3)
Lung (per 100 cm^3) 2 cm	1.1 (0.8, 1.4)	0.54
LN (per 100 cm^3) 1.5 cm	1.1 (0.5, 2.6)	0.77
Liver (per 100 cm^3) 2 cm	2.8 (1.0, 7.9)	0.05
Soft tissue (per 100 cm^3) 2 cm	1.3 (0.5, 3.3)	0.66

Notes: ^aFor those followed for at least weeks; ^bKruskal–Wallis Test.

Abbreviations: AE, adverse events; SD, stable disease; PD-1, program death-1; PR, partial response; OS, overall survival; LN, lymph node; PD, progression of disease.

Figure 2 Box plots illustrating the distribution of pretreatment tumor volume according to best response.

Figure 3 Boxplots illustrating the distribution of pretreatment tumor volume according to lung tumor histology.