5.3. 결과
5.3.3. 혈중 비타민 B 12 수준과 종양 진행 기간
험도의 유의미한 차이를 보이지는 않았다(adjusted HR: 1.9; 95% CI: 0.8-4.2,
p
=0.132) (표 5-4).No. at risk
<691.4 23 22 8 6 2 0
≥691.4 23 21 3 0 0 0
Figure 5-8A. Kaplan-Meier curve for cancer progression according to serum vitamin B12 levels in all patients
Median time to progressions in patients with vitamin B12 <691.4 pg/mL and in patients with vitamin B12 ≥691.4 pg/mL were 3.4 months (95% confidence interval [CI]: 1.8-5.0) and 2.1 months (95% CI: 1.9-2.3), respectively (p=0.011); p values by log-rank test.
No. at risk
<691.4 13 13 7 6 1 1
≥691.4 6 6 1 0 0 0
Figure 5-8B. Kaplan-Meier curve for cancer progression according to serum vitamin B12 levels in patients without liver lesion
Median time to progressions in patients with vitamin B12 <691.4 pg/mL and in patients with vitamin B12 ≥691.4 pg/mL were 6.3 months (95% confidence interval [CI]: 2.9-9.7) and 1.6 months (95% CI: 0.0-3.5), respectively (p=0.021); p values by log-rank test;
Liver lesion included hepatocellular carcinoma and liver metastasis.
No. at risk
<691.4 10 8 5 1 0 0 0
≥691.4 17 16 11 3 1 0 0
Figure 5-8C. Kaplan-Meier curve for cancer progression according to serum vitamin B12 levels in patients with liver lesion
Median time to progressions in patients with vitamin B12 <691.4 pg/mL and in patients with vitamin B12 ≥691.4 pg/mL were 1.8 months (95% confidence interval [CI]: 1.0-2.6) and 2.1 months (95% CI: 2.0-2.3), respectively (p=0.816); Liver lesion included hepatocellular carcinoma and liver metastasis; p values by log-rank test.
No. at risk
<691.4 15 15 6 4 0 0
≥691.4 16 16 2 0 0 0
Figure 5-8D. Kaplan-Meier curve for cancer progression according to serum vitamin B12 levels in patients without receiving chemotherapy
Median time to progressions in patients with vitamin B12 <691.4 pg/mL and in patients with vitamin B12 ≥691.4 pg/mL were 2.1 months (95% confidence interval [CI]: 2.0-2.3), 1.8 months (95% CI: 1.0-2.6), respectively (p=0.816); p values by log-rank test.
No. at risk
<691.4 8 8 2 2 1 0
≥691.4 7 6 0 0 0 0
Figure 5-8E. Kaplan-Meier curve for cancer progression according to serum vitamin B12 levels in patients with receiving chemotherapy
Median time to progressions in patients with vitamin B12 <691.4 pg/mL and in patients with vitamin B12 ≥691.4 pg/mL were 2.3 months (95% confidence interval [CI]: 0.3-4.4) and 1.6 months (95% CI: 1.5-1.7), respectively (p=0.061); p values by log-rank test.
Vitamin B12 levels
(pg/mL)
No. of deaths
No. of subjects
Person- months
Age-and sex- adjusted
Multivariable- adjusted1) HR
(95%CI)
p value
HR (95%CI)
p value
<691.4 17 21 332.5 1 (Ref) 1 (Ref)
≥691.4 25 25 84.2 2.2 (1.1-4.4) 0.029 2.3 (1.1-4.7) 0.021 Table 5-3. Risk for cancer progression according to serum vitamin B12
levels
HR, hazard ratio; CI, confidence interval; p values by Cox proportional hazard model.
1)multivariable-adjusted for age (continuous variable, years), sex (female or male), Eastern Cooperative Oncology Group Performance Status (>2 or ≤2), and concurrent chemotherapy (yes or no).
Vitamin B12 levels
(pg/mL)
No. of deaths
No. of subjects
Person- months
Age-and sex- adjusted
Multivariable- adjusted1) HR
(95%CI)
p value
HR (95%CI)
p value Stage IV
<691.4 16 16 69.4 1 (Ref) 1 (Ref)
≥691.4 21 21 53.7 1.8 (0.9-3.7) 0.12 2.2 (1.0-4.8) 0.05 Chemotherapy
Yes
<691.4 14 17 246.1 1 (Ref) 1 (Ref)
≥691.4 16 16 50.4 2.4 (1.0-5.9) 0.057 2.4 (1.0-6.1) 0.06 No
<691.4 7 8 107.5 1 (Ref) 1 (Ref)
≥691.4 7 7 12.9 2.6
(0.7-10.2)
0.164 6.2
(0.6-64.6)
0.129 Liver lesion
Yes
<691.4 17 18 45.4 1 (Ref) 1 (Ref)
≥691.4 10 11 34.9 1.1 (0.5-2.6) 0.76 1.0 (0.4-2.5) 0.969 No
<691.4 9 13 318.6 1 (Ref) 1 (Ref)
≥691.4 6 6 17.87 2.8 (0.8-9.4) 0.103 4.0
(1.0-16.0)
0.053 Peritoneal metastasis
No
<691.4 16 20 345.6 1 (Ref) 1 (Ref)
≥691.4 16 16 49.3 1.8 (0.8-4.1) 0.132 1.9 (0.8-4.2) 0.132 Table 5-4. Risk for cancer progression according to serum vitamin B12
levels stratified by stage (stage IV), concurrent chemotherapy, liver lesion and peritoneal metastasis (those without metastasis)
HR, hazard ratio; CI, confidence interval; p values by Cox proportional hazard model.
1)multivariable-adjusted for age (continuous variable, years), sex (female or male), Eastern Cooperative Oncology Group Performance Status (>2 or ≤2), and concurrent chemotherapy (yes or no); Liver lesion included hepatocellular carcinoma and liver metastasis.
추가적으로 민감도 분석을 위해서 각각 무병상태의 환자군과 위절제술을 시행한 환자를 제외한 환자군을 대상으로 분석을 시행하였다. 전체 환자 중 총 7명의 환자 가 무병상태였고, 13명의 환자가 위절제술을 시행하였으며, 추적관찰에 실패한 환자 를 제외하고 각각 41명, 37명이 분석에 포함되었다.
무병상태의 환자를 제외한 분석에서는 총 41명의 환자 중 혈중 비타민 B12 수준이 임계값 이상인 군은 22명(53.7%), 미만인 군은 19명(46.3%)이었다. 첫 번째 검사일 을 기준으로 종양 진행이 나타나는데 걸리는 시간의 중앙값(median TTP)은 2.3개 월이었다. 종양의 진행에 영향을 끼칠 수 있는 성별, 나이, ECOG PS, 항암치료 여 부를 보정하고 시행한 Cox 비례 위험 모형에 의하면 혈중 비타민 B12 농도가 691.4 pg/mL 이상인 환자군은 그렇지 않은 환자군에 비교한 종양 진행에 대한 위험도가 유의미하게 높았다(adjusted HR: 2.3; 95% CI: 1.1-4.7,
p
=0.021) (표 5-4).위절제술을 시행한 환자를 제외한 분석에서는 총 37명의 환자 중 혈중 비타민 B12
수준이 임계값 이상인 군은 22명(59.5%), 미만인 군은 15명(40.5%)이었다. 첫 번째 검사일을 기준으로 종양 진행이 나타나는데 걸리는 시간의 중앙값(median TTP)은 2.2개월이었다. 종양의 진행에 영향을 끼칠 수 있는 성별, 나이, ECOG PS, 항암치 료 여부를 보정하고 시행한 Cox 비례 위험 모형에 의하면 혈중 비타민 B12 농도가 691.4 pg/mL 이상인 환자군은 그렇지 않은 환자군에 비교한 종양 진행에 대한 위 험도가 유의미하게 높았다(adjusted HR: 1.7; 95% CI: 0.8-3.6,
p
=0.146) (표 5-5).Vitamin B12 levels
(pg/mL)
No. of deaths
No. of subjects
Person- months
Age-and sex- adjusted
Multivariable- adjusted1) HR
(95%CI)
p value
HR (95%CI)
p value
<691.4 18 19 108.28 1 (Ref) 1 (Ref)
≥691.4 22 22 56.6 2.1 (1.0-4.3) 0.037 2.4 (1.2-4.8) 0.019 NED, No evidence of disease; HR, hazard ratio; CI, confidence interval; p values by Cox proportional hazard model; 1)multivariable-adjusted for age (continuous variable, years), sex (female or male), Eastern Cooperative Oncology Group Performance Status (>2 or ≤2), and concurrent chemotherapy (yes or no).
Table 5-5. Risk for cancer progression according to serum vitamin B12
levels excluding NED state patients
Vitamin B12 levels
(pg/mL)
No. of deaths
No. of subjects
Person- months
Age-and sex- adjusted
Multivariable- adjusted1) HR
(95%CI)
p value
HR (95%CI)
p value
<691.4 15 15 66.4 1 (Ref) 1 (Ref)
≥691.4 22 22 56.6 1.6 (0.8-3.4) 0.179 1.7 (0.8-3.6) 0.146 HR, hazard ratio; CI, confidence interval; p values by Cox proportional hazard model;
1)multivariable-adjusted for age (continuous variable, years), sex (female or male), Eastern Cooperative Oncology Group Performance Status (>2 or ≤2), and concurrent chemotherapy (yes or no).
Table 5-6. Risk for cancer progression according to serum vitamin B12
levels excluding patients who had gastrectomy