Gastroenterol Res

Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access

Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc

Journal website https://gr.elmerpub.com/

Original Article

Volume 17, Number 5-6, December 2024, pages 195-204

Risk Factors Predicting Outcomes in Advanced Upper Gastrointestinal Cancers Treated With Immune Checkpoint Inhibitors

**Table 1.** Baseline Characteristics of the Study Population
Baseline characteristics	Distribution
AA: African American; ICI: immune checkpoint inhibitor; HER2: human epidermal growth factor receptor 2; FOLFOX: combination of 5-flurouracil and oxaliplatin.
Age of diagnosis	62 years (33 - 87)
Gender (male)	84%
Race	Caucasian: 88%, AA: 5%, Asian: 1%, other: 6%
Primary tumor type, esophageal vs. gastric	Esophageal: 61% (n = 39), gastric: 39% (n = 25)
Agent	Nivolumab: 42%, pembrolizumab: 58%
Line of ICI, > 2 lines vs. 1 - 2 lines	1 - 2: 73%, > 2: 27%
History of surgery	23%
History of radiation	41%
Chemotherapy combination	11% (FOLFOX: n = 4, and FOLFOX + trastuzumab: n = 2)
Lung metastasis-present	23%
Liver metastasis-present	44%
Bone metastasis-present	22%
Distant lymph node metastasis-present	50%
Other metastatic sites	33%
White blood cell count (baseline)	7.46
Red blood cell count	3.75
Hemoglobin (baseline)	10.73
Platelet count (baseline)	225.79
Neutrophil count (baseline)	6.71
Lymphocyte count (baseline)	0.93
Platelet to lymphocyte ratio	336.55
Neutrophil to lymphocyte ratio	12.14
Total bilirubin (baseline)	0.68
Albumin (baseline)	3.40
Alkaline phosphatase (baseline)	162.74
Aspartate transferase (baseline)	24.00
Thyroid stimulating hormone (baseline)	24.77
T4 (baseline)	30.60
HER2 status	4.37
Immune-related adverse event	Positive: 14%, negative: 69%, not available: 17%
Programmed cell death ligand 1(PD-L1) status	Yes: 8%
	Negative: 8%, 1 - 5: 28%, > 5: 25%, not available: 39%
Microsatellite instability-high	11%

Table 1. Baseline Characteristics of the Study Population

Baseline characteristics

Distribution

AA: African American; ICI: immune checkpoint inhibitor; HER2: human epidermal growth factor receptor 2; FOLFOX: combination of 5-flurouracil and oxaliplatin.

Age of diagnosis

62 years (33 - 87)

Gender (male)

84%

Race

Caucasian: 88%, AA: 5%, Asian: 1%, other: 6%

Primary tumor type, esophageal vs. gastric

Esophageal: 61% (n = 39), gastric: 39% (n = 25)

Agent

Nivolumab: 42%, pembrolizumab: 58%

Line of ICI, > 2 lines vs. 1 - 2 lines

1 - 2: 73%, > 2: 27%

History of surgery

23%

History of radiation

41%

Chemotherapy combination

11% (FOLFOX: n = 4, and FOLFOX + trastuzumab: n = 2)

Lung metastasis-present

23%

Liver metastasis-present

44%

Bone metastasis-present

22%

Distant lymph node metastasis-present

50%

Other metastatic sites

33%

White blood cell count (baseline)

7.46

Red blood cell count

3.75

Hemoglobin (baseline)

10.73

Platelet count (baseline)

225.79

Neutrophil count (baseline)

6.71

Lymphocyte count (baseline)

0.93

Platelet to lymphocyte ratio

336.55

Neutrophil to lymphocyte ratio

12.14

Total bilirubin (baseline)

0.68

Albumin (baseline)

3.40

Alkaline phosphatase (baseline)

162.74

Aspartate transferase (baseline)

24.00

Thyroid stimulating hormone (baseline)

24.77

T4 (baseline)

30.60

HER2 status

4.37

Immune-related adverse event

Positive: 14%, negative: 69%, not available: 17%

Programmed cell death ligand 1(PD-L1) status

Yes: 8%

Negative: 8%, 1 - 5: 28%, > 5: 25%, not available: 39%

Microsatellite instability-high

11%

**Table 2.** Multivariate Analysis of the Study Population
Source	Survival^a
^aHazard ratios of the factors with insignificant (P > 0.05) were not mentioned. HR: hazard ratio; ICI: immune checkpoint inhibitor; HER2: human epidermal growth factor receptor 2; PD-L1: programmed cell death ligand 1; PFS: progression-free survival; OS: overall survival; OS-ICI: ICI-related overall survival.
Gender, male vs. female	0.0274	0.132327	0.1238		0.0072	0.043668
Race	0.6482		0.4371		0.4106
Primary tumor type, esophageal vs. gastric	0.499		0.8346		0.2608
Line of ICI, > 2 lines vs. 1 - 2 lines	0.0259	0.176569	0.0404	0.160335	0.0003	0.02733
History of surgery	0.9153		0.8765		0.006	0.119958
History of radiation	0.9914		0.5511		0.2714
Chemotherapy combination, yes vs. no	0.0071	0.08406	0.0514	0.706241	0.8084
Lung metastases, yes vs. no	0.0682	5.051652	0.2754		0.0613	0.971694
Liver metastases, yes vs. no	0.4401		0.8525		0.9595
Bone metastases, yes vs. no	0.3596		0.0305	3.633746	0.0009	10.98695
Distant lymph node metastases, yes vs. no	0.074	2.414344	0.3901		0.3246
Other organs with metastases, yes vs. no	0.562		0.6469		0.0848
White blood cell count (baseline)	0.6029		0.2715		0.1165
Red blood cell count (baseline)	0.0206	5.792107	0.0373	5.556215	0.0202	1.202369
Hemoglobin (baseline)	0.6823		0.2597		0.0332	6.718667
Platelet count (baseline)	0.1289		0.7293		0.4175
Neutrophil count (baseline)	0.1697		0.2122		0.7309
Lymphocyte count (baseline)	0.0285	0.273647	0.0817	0.374776	0.4688
Total bilirubin (baseline)	0.3151		0.6339		0.5006
Albumin (baseline)	0.1049		0.2023		0.7287
Alkaline phosphatase (baseline)	0.0224	1.00661	0.448		0.8361
Alanine transferase (baseline)	0.0072	1.123848	0.2477		0.4527
Aspartate transferase (baseline)	0.0289	0.897763	0.4947		0.5988
Thyroid stimulating hormone (baseline)	0.0443	1.124609	0.2159		0.013	1.179802
T4 (baseline)	0.6535		0.4648		0.8827
HER2	0.0061	0.563667	0.0525	0.096411	0.835
Immune-related adverse event, yes vs. no	0.1034		0.0813	0.192533	0.114
PD-L1, negative vs. > 1 vs. unavailable	0.0465	0.395261	0.3545		0.3955
Microsatellite instability-high, yes vs. no	0.5449		0.9917		0.5808

Table 2. Multivariate Analysis of the Study Population

Source

Survival^a

PFS

OS-ICI

P value

^aHazard ratios of the factors with insignificant (P > 0.05) were not mentioned. HR: hazard ratio; ICI: immune checkpoint inhibitor; HER2: human epidermal growth factor receptor 2; PD-L1: programmed cell death ligand 1; PFS: progression-free survival; OS: overall survival; OS-ICI: ICI-related overall survival.

Gender, male vs. female

0.0274

0.132327

0.1238

0.0072

0.043668

Race

0.6482

0.4371

0.4106

Primary tumor type, esophageal vs. gastric

0.499

0.8346

0.2608

Line of ICI, > 2 lines vs. 1 - 2 lines

0.0259

0.176569

0.0404

0.160335

0.0003

0.02733

History of surgery

0.9153

0.8765

0.006

0.119958

History of radiation

0.9914

0.5511

0.2714

Chemotherapy combination, yes vs. no

0.0071

0.08406

0.0514

0.706241

0.8084

Lung metastases, yes vs. no

0.0682

5.051652

0.2754

0.0613

0.971694

Liver metastases, yes vs. no

0.4401

0.8525

0.9595

Bone metastases, yes vs. no

0.3596

0.0305

3.633746

0.0009

10.98695

Distant lymph node metastases, yes vs. no

0.074

2.414344

0.3901

0.3246

Other organs with metastases, yes vs. no

0.562

0.6469

0.0848

White blood cell count (baseline)

0.6029

0.2715

0.1165

Red blood cell count (baseline)

0.0206

5.792107

0.0373

5.556215

0.0202

1.202369

Hemoglobin (baseline)

0.6823

0.2597

0.0332

6.718667

Platelet count (baseline)

0.1289

0.7293

0.4175

Neutrophil count (baseline)

0.1697

0.2122

0.7309

Lymphocyte count (baseline)

0.0285

0.273647

0.0817

0.374776

0.4688

Total bilirubin (baseline)

0.3151

0.6339

0.5006

Albumin (baseline)

0.1049

0.2023

0.7287

Alkaline phosphatase (baseline)

0.0224

1.00661

0.448

0.8361

Alanine transferase (baseline)

0.0072

1.123848

0.2477

0.4527

Aspartate transferase (baseline)

0.0289

0.897763

0.4947

0.5988

Thyroid stimulating hormone (baseline)

0.0443

1.124609

0.2159

0.013

1.179802

T4 (baseline)

0.6535

0.4648

0.8827

HER2

0.0061

0.563667

0.0525

0.096411

0.835

Immune-related adverse event, yes vs. no

0.1034

0.0813

0.192533

0.114

PD-L1, negative vs. > 1 vs. unavailable

0.0465

0.395261

0.3545

0.3955

Microsatellite instability-high, yes vs. no

0.5449

0.9917

0.5808

**Table 3.** Summary of Multivariate Analysis of the Study Population
Outcome measured	Negative effect (hazard ratio > 1)	Positive affect (hazard ratio < 1)
RBC: red blood cell; ALP: alkaline phosphatase; ALT: alanine transferase; TSH: thyroid-stimulating hormone, PD-L1: programmed cell death ligand 1; AST: aspartate transferase; ICI: immune checkpoint inhibitor; HER2: human epidermal growth factor receptor 2.
Progression-free survival	HER2 positivity	Male gender
	Baseline RBC count, ALP, ALT, TSH	When used in the third line or more
		Used in combination with chemotherapy
		PD-L1 positive
		Baseline lymphocyte count and AST
ICI-related overall survival (OS-ICI)	Bone metastasis	When used in the third line or more
	Baseline RBC count	Baseline AST
Overall survival (OS)	Bone metastasis	Male gender
	Baseline RBC count, hemoglobin, and TSH levels	When used in the third line or more
		History of surgery

Table 3. Summary of Multivariate Analysis of the Study Population

Outcome measured

Negative effect (hazard ratio > 1)

Positive affect (hazard ratio < 1)

RBC: red blood cell; ALP: alkaline phosphatase; ALT: alanine transferase; TSH: thyroid-stimulating hormone, PD-L1: programmed cell death ligand 1; AST: aspartate transferase; ICI: immune checkpoint inhibitor; HER2: human epidermal growth factor receptor 2.

Progression-free survival

HER2 positivity

Male gender

Baseline RBC count, ALP, ALT, TSH

When used in the third line or more

Used in combination with chemotherapy

PD-L1 positive

Baseline lymphocyte count and AST

ICI-related overall survival (OS-ICI)

Bone metastasis

When used in the third line or more

Baseline RBC count

Baseline AST

Overall survival (OS)

Bone metastasis

Male gender

Baseline RBC count, hemoglobin, and TSH levels

When used in the third line or more

History of surgery

**Table 4.** Summary of Comparison of Various Groups in the Study Population
	Higher	Lower
ICI: immune checkpoint inhibitor; ALP: alkaline phosphatase; TSH: thyroid-stimulating hormone, PD-L1: programmed cell death ligand 1; AST: aspartate transferase; WBC: white blood cell.
Bad responders	Esophageal cancers	Chemotherapy combinations
	ICI use in the third line or more	Albumin
	History of radiation
	Baseline total bilirubin and ALP
Poor responders	ICI use in the third line or more
	Baseline WBC, total bilirubin, ALP, and TSH
Bad ICI-related overall survival (OS-ICI)	History of radiation	Chemotherapy combinations
	Baseline WBC count, total bilirubin, ALP, and TSH	Albumin
Poor ICI-related overall survival (OS-ICI)	History of radiation	Chemotherapy combinations
	Baseline WBC count, total bilirubin, ALP, AST, and TSH	Albumin
Bad overall survivors	Higher WBC count	History of surgery
Poor overall survivors	ICI use in the third line or more	History of surgery
	Liver metastasis	PD-L1 positive tumors
	Baseline WBC, platelet, and lymphocyte count

Table 4. Summary of Comparison of Various Groups in the Study Population

Higher

Lower

ICI: immune checkpoint inhibitor; ALP: alkaline phosphatase; TSH: thyroid-stimulating hormone, PD-L1: programmed cell death ligand 1; AST: aspartate transferase; WBC: white blood cell.

Bad responders

Esophageal cancers

Chemotherapy combinations

ICI use in the third line or more

Albumin

History of radiation

Baseline total bilirubin and ALP

Poor responders

ICI use in the third line or more

Baseline WBC, total bilirubin, ALP, and TSH

Bad ICI-related overall survival (OS-ICI)

History of radiation

Chemotherapy combinations

Baseline WBC count, total bilirubin, ALP, and TSH

Albumin

Poor ICI-related overall survival (OS-ICI)

History of radiation

Chemotherapy combinations

Baseline WBC count, total bilirubin, ALP, AST, and TSH

Albumin

Bad overall survivors

Higher WBC count

History of surgery

Poor overall survivors

ICI use in the third line or more

History of surgery

Liver metastasis

PD-L1 positive tumors

Baseline WBC, platelet, and lymphocyte count