| Literature DB >> 28886106 |
Hui Guo1,2, Tao Wu2, Qiang Lu1,3, Jian Dong1,3, Yi-Fan Ren1,3, Ke-Jun Nan2, Yi Lv1,3, Xu-Feng Zhang1,3.
Abstract
The number of elderly patients diagnosed with hepatocellular carcinoma (HCC) is expected to increase. The present study aims to evaluate the role of age on treatments and outcome of HCC patients. 1530 patients firstly diagnosed with HCC were retrospectively included and classified as older (≥65 years, n = 318, 21%) and younger patients (<65 years, n = 1212, 79%). The two groups were compared with clinical characteristics, tumor burden, Barcelona Clinics Liver Cancer (BCLC) stage, treatments and long-term prognosis. Elderly patients were more HCV infected, had more diabetes, poorer performance status, and were less aggressively treated. The proportion of HCC within BCLC stage 0-A, B or C was similar between the two groups, but elderly patients were more presented with BCLC stage D. The overall survival of older patients was poorer compared to younger patients before and after propensity score matching. However, elderly patients were less often effectively treated with surgery and loco-regional therapies across different BCLC stages. After stratified by BCLC stages or treatments, older patients showed comparable long-term outcome to younger patients. Performance status, BCLC stages and effective treatments, rather than age, was independent factors determining prognosis in the whole cohort and only elderly patients by multivariate analysis. In conclusion, older could have comparable survival to younger patients within the same tumor stage or after similar treatments. Thus, equally active treatments should be encouraged to elderly patients.Entities:
Mesh:
Year: 2017 PMID: 28886106 PMCID: PMC5590882 DOI: 10.1371/journal.pone.0184160
Source DB: PubMed Journal: PLoS One ISSN: 1932-6203 Impact factor: 3.240
Demographic, clinical and tumor characteristics, and treatments of young and elderly patients with HCC.
| Variables | Young (<65 y) (n = 1212) | Elderly (≥65 y) (n = 318) | P value |
|---|---|---|---|
| Gender (male/female) | 988/224 | 250/68 | 0.262 |
| Child-Pugh class | 0.048 | ||
| A | 1072 (88.4%) | 265 (83.3%) | |
| B | 126 (10.4%) | 47 (14.8%) | |
| C | 14 (1.2%) | 6 (1.9%) | |
| Smoking history | 535 (44.1%) | 120 (37.7%) | 0.040 |
| Alcohol abuse | 310 (25.6%) | 60 (18.9%) | 0.012 |
| Diabetes | 95 (7.8%) | 43 (13.5%) | 0.003 |
| ECOG score | <0.001 | ||
| 0 | 962 (79.4%) | 209 (65.7%) | |
| 1 | 213 (17.6%) | 68 (21.4%) | |
| ≥2 | 37 (3.1%) | 41 (12.9%) | |
| Hepatitis status | <0.001 | ||
| Hepatitis B | 966 (79.7%) | 157 (49.4%) | |
| Hepatitis C | 39 (3.2%) | 48 (15.1%) | |
| Hepatitis B + C | 5 (0.4%) | 2 (0.6%) | |
| None | 202 (16.7%) | 111 (34.9%) | |
| Routine HCC screening | 647 (53.4%) | 139 (43.7%) | 0.009 |
| Liver cirrhosis | 847 (69.9%) | 168 (52.8%) | <0.001 |
| First Dept. admitted | 0.013 | ||
| Surgery | 999 (82.4%) | 239 (75.2%) | |
| Internal Medical Dept. | 191 (15.8%) | 70 (22.0%) | |
| Other Dept. | 22 (1.8%) | 9 (2.8%) | |
| Tumor size (>5 cm) | 707 (58.3%) | 196 (61.6%) | 0.306 |
| Multinodular tumor | 692 (57.1%) | 153 (48.1%) | 0.004 |
| Macrovascular invasion | 213 (17.6%) | 48 (15.1%) | 0.316 |
| BCLC stages | <0.001 | ||
| 0-A | 362 (29.9%) | 86 (27.0%) | |
| B | 603 (49.8%) | 144 (45.3%) | |
| C | 197 (16.3%) | 43 (13.5%) | |
| D | 50 (4.1%) | 45 (14.2%) | |
| Primary treatments | <0.001 | ||
| Liver transplant | 34 (2.8%) | 0 | |
| Surgical resection | 383 (31.6%) | 78 (24.5%) | |
| Radiofrequency ablation | 86 (7.1%) | 32 (10.1%) | |
| Loco-regional therapies | 444 (36.6%) | 101 (31.8%) | |
| Supportive treatments | 265 (21.9%) | 107 (33.6%) | |
| 30-day mortality | 59 (4.9%) | 16 (5.0%) | 0.884 |
| 90-day mortality | 114 (9.4%) | 42 (13.2%) | 0.048 |
| Median survival (months) | 33 (0–108) | 27 (0–104) | 0.002 |
†Only for HCC within BCLC stage 0-A.
HCC, hepatocellular carcinoma; ECOG, the Eastern Cooperative Oncology Group; BCLC, Barcelona Liver Cancer; Dept., Department.
Fig 1Overall survival of older and younger patients with hepatocellular carcinoma before (A) and after (B) propensity score matching.
Demographic and clinical characteristics of the younger and elderly patients with HCC in propensity model.
| Variables | Young (<65 y) (n = 305) | Elderly (≥65 y) (n = 305) | P value |
|---|---|---|---|
| Male gender | 239 (78.4%) | 239 (78.4%) | 1.000 |
| ECOG score ≥1 | 96 (31.5%) | 96 (31.5%) | 1.000 |
| Child-Pugh Class B/C | 46 (15.1%) | 46 (15.1%) | 1.000 |
| Smoking history | 127 (41.6%) | 114 (37.4%) | 0.282 |
| Alcohol abuse | 66 (21.6%) | 57 (18.7%) | 0.364 |
| Diabetes | 33 (10.8%) | 41 (13.4%) | 0.321 |
| Liver cirrhosis | 168 (55.1%) | 168 (55.1%) | 1.000 |
| Tumor size (>5 cm) | 180 (59.0%) | 190 (62.3%) | 0.407 |
| Multinodular tumor | 155 (50.8%) | 141 (46.2%) | 0.257 |
| Macrovascular invasion | 51 (16.7%) | 46 (15.1%) | 0.580 |
| BCLC stages | 1.000 | ||
| 0-A | 82 (26.9%) | 82 (26.9%) | |
| B | 144 (47.2%) | 144 (47.2%) | |
| C | 43 (14.1%) | 43 (14.1%) | |
| D | 36 (11.8%) | 36 (11.8%) | |
| Primary treatments | <0.001 | ||
| Liver transplant | 10 (3.3%) | 0 | |
| Surgical resection | 88 (28.9%) | 75 (24.6%) | |
| Radiofrequency ablation | 30 (9.8%) | 18 (5.9%) | |
| Loco-regional therapies | 117 (38.4%) | 110 (36.1%) | |
| Supportive treatments | 60 (19.7%) | 102 (33.4%) | |
| 30-day mortality | 16 (5.2%) | 16 (5.2%) | 1.000 |
| 90-day mortality | 34 (11.1%) | 39 (12.8%) | 0.533 |
| Median survival (months) | 33 (0–106) | 27 (0–104) | 0.022 |
†only for HCC within BCLC stage 0-A.
ECOG, the Eastern Cooperative Oncology Group; BCLC, Barcelona Liver Cancer; Dept., Department.
Fig 2Treatments (A) and overall survival (B-E) of older and younger patients according to different Barcelona Clinics Liver Cancer (BCLC) stages of hepatocellular carcinoma.
RFA, radiofrequency ablation; LRT, loco-regional therapies; BST, best supportive treatments.
Fig 3Overall survival of older and younger patients after surgical resection (A), loco-regional therapies (LRT, B) and best supportive treatments (BST, C).
Analysis of factors affecting survival of 1530 HCC patients using proportional hazards regression model.
| Factors | comparison | Univariate analysis | Multivariate analysis | ||
|---|---|---|---|---|---|
| HR (95% CI) | P value | HR (95% CI) | P value | ||
| Sex | Male vs. female | 1.0 (0.8–1.2) | 0.935 | ||
| Age (years) | ≥65 vs. <65 | 1.3 (1.1–1.5) | 0.002 | 1.1 (0.9–1.3) | 0.281 |
| Child-Pugh | B-C vs. A | 1.7 (1.4–2.0) | <0.001 | 1.2 (0.9–1.4) | 0.156 |
| Smoking | Yes vs. no | 1.1 (0.9–1.2) | 0.374 | ||
| Alcohol | Yes vs. no | 1.0 (0.9–1.2) | 0.715 | ||
| Diabetes | Yes vs. no | 0.9 (0.7–1.2) | 0.448 | ||
| ECOG | ≥1 vs. 0 | 1.6 (1.3–1.8) | <0.001 | 1.4 (1.2–1.6) | <0.001 |
| Hepatitis | None | 1 | |||
| B | 1.1 (0.8–1.5) | 0.571 | |||
| C | 0.9 (0.7–1.2) | 0.456 | |||
| Liver cirrhosis | Yes vs. no | 1.1 (0.9–1.2) | 0.243 | ||
| BCLC stage | 0-A | 1 | 1 | ||
| B | 1.3 (1.1–1.6) | <0.001 | 1.3 (1.1–1.5) | <0.001 | |
| C-D | 2.8 (2.4–3.4) | <0.001 | 2.4 (2.0–2.8) | <0.001 | |
| Treatments | BST | 1 | |||
| Curative treatments | 0.4 (0.4–0.5) | <0.001 | 0.5 (0.4–0.6) | <0.001 | |
| LRT | 0.7 (0.6–0.8) | <0.001 | 0.8 (0.7–0.9) | <0.001 | |
HCC, hepatocellular carcinoma; ECOG, the Eastern Cooperative Oncology Group; BCLC, Barcelona Clinic Liver Cancer; BST, best supportive treatment; LRT, loco-regional therapies.
Analysis of factors affecting survival of elderly HCC patients (≥65 years) using proportional hazards regression model.
| Factors | comparison | Univariate analysis | Multivariate analysis | ||
|---|---|---|---|---|---|
| HR (95% CI) | P value | HR (95% CI) | P value | ||
| Sex | Male vs. female | 1.4 (1.0–2.0) | 0.041 | 1.3 (0.9–1.0) | 0.137 |
| Child-Pugh | B-C vs. A | 1.9 (1.4–2.7) | <0.001 | 1.1 (0.7–1.6) | 0.688 |
| Smoking | Yes vs. no | 1.4 (1.1–1.8) | 0.015 | 1.3 (1.0–1.7) | 0.102 |
| Alcohol | Yes vs. no | 1.1 (0.8–1.6) | 0.445 | ||
| Diabetes | Yes vs. no | 1.1 (0.7–1.6) | 0.622 | ||
| ECOG | ≥1 vs. 0 | 2.1 (1.6–2.7) | <0.001 | 1.6 (1.2–2.2) | 0.002 |
| Hepatitis | None | 1 | |||
| B | 1.4 (0.9–2.1) | 0.108 | |||
| C | 1.0 (0.7–1.5) | 0.946 | |||
| Liver cirrhosis | Yes vs. no | 0.9 (0.7–1.2) | 0.480 | ||
| BCLC stage | 0-A | 1 | 1 | ||
| B | 1.3 (0.9–1.8) | 0.186 | 1.1 (0.8–1.6) | 0.518 | |
| C-D | 3.0 (2.1–4.3) | <0.001 | 2.3 (1.6–3.4) | <0.001 | |
| Treatments | BST | 1 | 1 | ||
| Curative treatments | 0.4 (0.3–0.6) | <0.001 | 0.5 (0.4–0.8) | 0.001 | |
| LRT | 0.6 (0.5–0.9) | 0.003 | 0.7 (0.5–1.0) | 0.068 | |
HCC, hepatocellular carcinoma; ECOG, the Eastern Cooperative Oncology Group; BCLC, Barcelona Clinic Liver Cancer; BST, best supportive treatment; LRT, loco-regional therapies.
Clinicopathological features and overall survival of younger and elderly patients from literatures.
| Study | Period | Country/region | Age groups | n/n | Older group compared with younger group | Overall survival |
|---|---|---|---|---|---|---|
| Cho et al. [ | 1987–2003 | Korea | <30, 30–60, ≥60 | 71/168/81 | More cirrhotic, earlier disease stage | Better ( |
| Mirici-Cappa et al. [ | 1987–2004 | Italy | <70, ≥70 | 1104/614 | More comorbidities, better liver function, higher CLIP score, more percutaneous but less surgical or TACE treatment | Similar ( |
| Chang et al. [ | 1988–1997 | Singapore | ≤40, >40 | 55/583 | Less HBV infection, worse liver function, less vascular invasion, earlier staged disease, but less surgically treated | Similar in all ( |
| Zhang et al. [ | 1988–2003 | China (SEER) | ≤45, >45 | 2102/25153 | More males and higher tumor burden | Worse ( |
| Poon et al. [ | 1989–1997 | China | <70, ≥70 | 1116/222 | More females, less HBV infected, more comorbidities, similar tumor stages, but less surgically treated | Similar ( |
| Lee et al. [ | 2003–2006 | Korea | <65, ≥65 | 149/113 | Less HBV infection, greater comorbidities, poorer performance status; similar tumor stages, but less surgically treated | Similar ( |
| Ozenne et al. [ | 2006–2008 | France | <75, ≥75 | 337/43 | More female, similar BCLC stages, less curatively treated | Similar ( |
| Borzio et al. [ | 2008–2015 | Italy | ≤70, >70 | 527/541 | More females, HCV infected, better liver function, similar BCLC stages, less curatively treated | Similar ( |
| Ours | 2008–2012 | China | <65, ≥65 | 1212/318 | More comorbidity, poorer performance status, more HCV infected, similar in BCLC stages 0-C, but less aggressively treated | Worse in all ( |
HBV, hepatitis B virus; HCV, hepatitis C virus; TACE, transarterial chemoembolization; SEER, Surveillance, Epidemiology, and End-Results; CLIP, the Cancer of the Liver Italian Programe; BCLC, Barcelona Clinics Liver Cancer