A Multicenter Retrospective Study on Clinical Characteristics,
Treatment Patterns, and Outcome in Elderly Patients with
OLGA N. KOZYREVA,aDORCAS CHI,aJEFFREY W. CLARK,bHEJING WANG,cKATHY P. THEALL,a
DAVID P. RYAN,bANDREW X. ZHUb
aTufts Medical Center Cancer Center, Tufts Medical School, Boston, Massachusetts, USA;bMassachusetts
General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA;cUniversity of
California Los Angeles, Los Angeles, California, USA
Key Words. Hepatocellular carcinoma • Epidemiology • Elderly • Treatment pattern • Survival
Disclosures: Olga N. Kozyreva: None; Dorcas Chi: None; Jeffrey W. Clark: None; Hejing Wang: None; Kathy P. Theall:
None; David P. Ryan: Consultant/advisory role: Threshold Pharmaceuticals, Array Bioscience, Millennium Pharmaceuticals;
Andrew X. Zhu: Consultant/advisory role: Onyx, ImClone, Novartis, Pfizer, Sanofi; Research funding/contracted research: Bayer.
The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from
commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer
ical presentation and outcome of elderly hepatocellular
carcinoma (HCC) patients. We performed a multicenter
on potential differences in clinical characteristics, treat-
ment patterns, and outcome in HCC patients.
Methods. We retrospectively analyzed HCC patients
treated at two U.S. tertiary institutions from 1998 to
2008. Demographics, tumor parameters, etiology and
severity of cirrhosis, treatment, and survival from diag-
nosis were collected and analyzed. After exclusion of
transplanted patients, survival analyses were per-
formed using the Kaplan-Meier method with log-rank
tests and Cox proportional hazards models.
Results. Three hundred thirty-five HCC patients were
divided into two groups: “elderly” (95 patients, age >70
years) and “younger” (240 patients, aged <70 years). The
and elderly groups, respectively (p < .0001). Hepatitis C
virus (HCV) infection rate was 48.3% in younger and
21.1%in elderly patients (p <.0001); Child class B and C
derly patients (p ? .063). Compared with younger pa-
tients, the elderly received transplant less frequently
(19.6% versus 5.3%, p ? .0002) and were more likely to
receive supportive care only (22.9% versus 36.8%, p ?
were seen in tumor parameters or other treatments re-
ceived. Overall (p ? .47) and HCC-specific survival rates
(p ? .38) were similar in both age groups.
Conclusions. Characteristics that distinguish elderly
from younger HCC patients include lower M/F ratio,
worse performance status, lower rate of HCV infection,
and less advanced underlying cirrhosis. Elderly patients
receive supportive care only. However, overall and HCC-
Correspondence: Andrew X. Zhu, M.D., Massachusetts General Hospital Cancer Center, 55 Fruit Street, LH/POB 232, Boston, Massa-
chusetts 02114, USA. Telephone: 617-643-3415; Fax: 617-724-3166; e-mail: email@example.com
through the open access option. ©AlphaMed Press 1083-7159/2011/$30.00/0 doi: 10.1634/theoncologist.2010-0223
Received July 6, 2010; accepted for
The incidence and mortality of hepatocellular carcinoma
(HCC) have been dramatically increasing in the United
States . Age is a known risk factor for HCC [2–4]. In the
. The incidence rate of HCC among the elderly is pro-
utable to screening, improved management of chronic
liver disease, the rising incidence of nonalcoholic steato-
hepatitis-related cirrhosis, and an epidemic of hepatitis C
virus (HCV) infection in the late 1970s . As the pop-
ulation ages, it is becoming increasingly important to
recognize age-specific cancer epidemiologic trends and
differences in cancer outcomes to aid in prevention strat-
egies, diagnostic approaches, and treatment decisions.
Historically, the elderly represent an important popula-
tion particularly vulnerable to disparities in cancer treat-
ment [8, 9]. There is a paucity of information on the
possible differences in the clinical presentation, treatment
patterns, and outcomes of HCC based on age. The limited
available data are mainly from Asia, where HCC has a dis-
tinct underlying etiology and different treatment pattern
[10–17]. Additional studies from Europe reflect disease
trends inherent to a less demographically diverse popula-
it difficult to extrapolate to U.S. patients [18, 19].
The increasing HCC incidence, aging population, de-
velopment of new HCC treatment modalities, and limited
age-related data available prompted the current study. By
using a multi-institutional database, we designed the pres-
ent study to examine the clinical characteristics, treatment
patterns, and outcomes in elderly patients with HCC.
PATIENTS AND METHODS
Retrospective analysis of HCC patients treated at two U.S.
tertiary institutions from January 1998 to December 2008
was performed. A diagnosis of HCC was confirmed histo-
pathologically or according to the noninvasive European
Association for the Study of the Liver (EASL) diagnostic
criteria . The age of 70 years was chosen as the cutoff
point for the analysis because the 70 years of age landmark
the incidence of age-related organ dysfunction and the de-
age of 70 . Additionally, 70 years of age has been the
most frequently used cutoff age for comparisons between
tients, thus allowing for some comparability with these
other studies. The demographics, etiology of liver disease,
tumor parameters, comorbidities, performance status, body
mass index, detailed treatment information, length of sur-
vival from diagnosis, and cause of death were captured.
Race/ethnicity was categorized as White, Black, Asians,
and Hispanic. The etiology of the liver disease was catego-
rized as infection with hepatitis B (HBV), HCV, alcoholic
liver disease, nonalcoholic fatty liver disease, hemochro-
matosis, autoimmune hepatitis, and primary biliary cirrho-
sis. The etiology of cirrhosis was considered to be
cryptogenic if no cause for chronic liver disease was iden-
tified after exhaustive testing. No quantitative analysis of
alcohol consumption was performed; assessment of habit-
Underlying cirrhosis was confirmed histologically or
liver contour, presence of ascites, varices, enlargement of the
caudate lobe, splenomegaly, and collateral portal-venous
was made during evaluation for possible HCC based on pre-
senting signs or symptoms or as a result of surveillance.
Multimodality treatment was defined as therapy that
combines more than one method (e.g., combination of che-
motherapy and embolization) of treatment. Death was cat-
egorized as attributable to HCC based on review of death
certificate, discharge summary, or hospice documentation.
institution for this retrospective study.
The patient characteristics were summarized using mean ?
SD, median and interquartile range for continuous vari-
tests and Wilcoxon rank sum tests were used to compare
the patient characteristics between the two age groups.
Three types of survival analysis were performed to com-
pare the clinical outcome between the elderly and younger
patients: (a) Overall survival (OS) defined as the interval
HCC diagnosis to death from HCC (deaths from non-HCC
causes were treated as censoring); (c) HCC-specific survival,
but non-HCC death was treated as a competing risk. The Ka-
plan-Meier method was used to estimate survival distribution
for OS and HCC-specific survival. Cumulative incidence rate
for HCC death was estimated for the two age groups when
non-HCC death was treated as a competing risk.
and nonelderly groups while other prognostic factors were
controlled. All factors listed in Table 1, but not age, were
Kozyreva, Chi, Clark et al.
Table 1. Patient characteristics
Younger (age <70 years)
(n ? 240)
Elderly (age >70 years)
(n ? 95)
Mean ? SD
Presence of symptoms
Diagnosed by screening
Alcoholic liver disease
Child Pugh class
56.6 ? 7.5
75.6 ? 5.0
Clinical Features of Elderly HCC Patients
included in the original model, and a stepwise method was
used for variable selection. Eastern Cooperative Oncology
vein thrombosis (PVT), BMI, and HCV were identified as
the significant prognostic factors for OS and HCC-specific
survival and included in the final model. Analyses were
performed separately for patients with and without or-
thotopic liver transplantation (OLT) because trans-
planted HCC patients have substantial long-term
survival and the majority of transplanted patients were in
the younger group.
All statistical analyses were conducted using SAS 9.2 sta-
tistical software (SAS Institute, Cary, NC).
A total of 335 patients with HCC were included. Ninety-
five patients ?70 years old (median age of 74 years) at
diagnosis of HCC were defined as the elderly group. Two
hundred forty patients aged ?70 years (median age of
56) were regarded as the younger group. The patient
characteristics are summarized in Table 1. The male (M)-
to-female (F) ratio was 1.7:1 in the elderly and 5.8:1 in
the younger group, showing that there was a higher pro-
portion of women in the elderly group (p ? .0001). The
proportion of patients with HCV infection was signifi-
cantly lower in the elderly group (21.1% versus 48.3%,
p ? .0001). There were no significant differences in
HBV infection rates between younger and elderly pa-
tients (21.2% and 14.7%, respectively). Alcohol-induced
liver disease was found in 37.5% of younger patients and
29.5% of the elderly group; the difference was not statis-
tically significant (p ? .1657). There was a trend toward
more advanced CTP class in the younger group: CTP
class B and C cirrhosis 35.8% versus 25.3% (p ? .063).
younger patients were more frequently diagnosed as a re-
sult of HCC screening or surveillance (61.3% versus
32.6%, p ? .0001). More patients in the elderly group
had ECOG PS ? 1 than in the younger group (24.2% ver-
sus 7.9%, p ? .0001). There were no significant differ-
ences in the following: race distribution, stage, number
of lesions, symptomatic at presentation, PVT, alpha-
fetoprotein (AFP) level, Cancer of the Liver Italian Pro-
gram score, diabetes mellitus, or BMI.
The types of treatments received are summarized in
Table 2. Forty-seven (19.6%) of the younger patients un-
derwent liver transplant compared to 5.3% of the elderly
patients (p ? .0002). Conversely, a higher proportion of
elderly patients received only symptomatic treatment
(36.8% versus 22.9%, p ? .01). There was no difference
in the number of liver resections or liver directed treat-
ments, including radiofrequency ablation, transarterial
chemoembolization, radiation, and chemotherapy. The
rate of utilization of multimodality treatment was 28.3%
in the younger group and 23.2% in the elderly group; the
difference was not statistically significant.
Table 1. (Continued)
Younger (age <70 years)
(n ? 240)
Elderly (age >70 years)
(n ? 95)
Mean ? SD
Mean ? SD
Second primary cancer
1.72 ? 1.45
1.66 ? 1.48
27.6 ? 5.6
27.1 ? 5.6
Abbreviations: AFP, alpha-fetoprotein; CAD, coronary artery disease; CLIP, Cancer of the Liver Italian Program; COPD,
chronic obstructive pulmonary disease; DM, diabetes mellitus; ECOG, Eastern Cooperative Oncology Group; HBV,
hepatitis B virus; HCV, hepatitis C virus; HTN, hypertension; IQR, interquartile range.
Kozyreva, Chi, Clark et al.
Eighty nine of 95 patients (93%) in the elderly group had
comorbid conditions compared with 102 of 240 patients
(42.5%) in the younger group (p ? .0001). Cardiovascular
and cerebrovascular disease, chronic lung conditions, sec-
ond primary malignancies, chronic renal disease, or cogni-
tive disorders constituted the most common comorbid
conditions. The following statistically significant differ-
ences between the two groups were observed: 36.8% el-
derly patients had coronary artery disease compared to
10.4% in the younger group (p ? .0001); similar trends
were observed for hypertension (37.9% versus 24.2%, p ?
.0117) and second primary malignancy (21.1% versus
3.8%, p ? .0001).
Median follow-up was 15 months for the younger group
alive at the time of this analysis, the median follow-up time
was 27 months for the elderly and 31 months for the
52.9 ? 5.3%, 38.3 ? 5.2%, and 27.1 ? 5.2%, respectively,
for the elderly group and 63.1 ? 3.2%, 46.8 ? 3.4%, and
35.9 ? 3.4%, respectively, for the younger group. Figure
1A shows the overall survival curves for the elderly and
younger group. This difference was borderline significant
(log-rank test, p ? .06). One hundred forty-eight of the 190
elderly group died from all causes. Figure 1B shows the
group after exclusion of patients who underwent OLT. The
median survival time was 12.5 months (95% CI, 7.9–18.7
months) for the elderly group and 13.9 months (95% CI,
10.2–16.4 months) for the younger group. After exclusion
of transplanted patients, the 1-, 2-, and 3-year survival rates
were 51.4 ? 5.4%, 35.7 ? 5.3%, and 23.0 ? 5.2%, respec-
and 23.5 ? 3.5%, respectively, for the younger group. This
difference was not statistically significant (log-rank test,
p ? .47).
One hundred eighty-six HCC-related deaths were docu-
mented: 46 in the elderly group and 140 in younger group.
The median HCC specific survival time was 27.8 months
(95% CI, 13.4–36.9 months) for the elderly group and 24.5
For all patients, the 1-, 2-, and 3-year HCC-specific sur-
vival rates were 66.5 ? 5.3%, 52.3 ? 5.9%, and 39.1 ?
6.5%, respectively, for the elderly group and 66.7 ? 3.2%,
51.7 ? 3.5%, and 40.3 ? 3.6%, respectively, for the
curves for the elderly and younger group. This difference
was not statistically significant (log-rank test, p ? .89).
of the 90 elderly patients died from HCC, versus 131 pa-
tients (69%) of 190 patients in the younger group. The me-
dian disease-specific survival time was 24.9 months (95%
CI, 12.9–32.9 months) for the elderly group and 14.9
months (95% CI, 1–21.0 months) for the younger group.
The estimated 1-, 2-, and 3-year HCC-specific survival
rates were 65.9 ? 5.4%, 50.3 ? 6.2% and 34.9 ? 6.9%,
Table 2. Treatments received
(n ? 240)
(n ? 95)
Liver directed tx
p ? .0002
p ? .0095
p ? .2098
p ? .4134
p ? .1388
p ? .6053
(missing ? 9)
Figure 1. Kaplan-Meier overall survival curves. (A): Elderly
(n ? 95) and younger (n ?240) patients. (B): Overall survival
curves of elderly (n ? 90) and younger (n ? 193)
patients after exclusion of patients who underwent orthotic liver
transplantation. p values were calculated with the use of the log-
Clinical Features of Elderly HCC Patients
3.9%, and 27.6 ? 3.9%, respectively, for the younger
group. Figure 2B shows the HCC-specific survival curves
of the elderly group and the younger group after exclusion
of patients who underwent OLT. This difference was not
statistically significant (log-rank test, p ? .38).
HCC-Specific Survival Adjusted for
the elderly group and 20 in younger group. Although non-
HCC death was considered as a competing risk, there was
no statistically significant difference in the cumulative in-
cidence of the HCC-related death between the two patients
groups, hazard ratio of 1.02 (95% CI, 0.73–1.43, p ? .89).
There were a total of 38 non-HCC deaths after transplanted
younger group. The non-HCC-related deaths included in-
fections, myocardial infarction, stroke, renal failure, sui-
cide, and trauma.
Although non-HCC death was considered as a compet-
ing risk, there was no statistically significant difference in
the cumulative incidence of the HCC-related death among
1.21, p ? .39). However, comparing with younger patients,
elderly patients had a significantly worse survival for non-
HCC related deaths with a hazard ratio of 3.27 (95% CI,
1.76–6.05, p ? .0002).
Multivariate Analysis for Survival
Multivariate analysis did not show a significant difference
in clinical outcomes between the two age groups. When the
effects of the important prognostic factors were adjusted,
the estimated hazard ratio was 1.33 (95% CI, 0.97–1.82,
p ? .07) for OS; 0.98 (95% CI, 0.68–1.41, p ? .92) for
HCC-specific survival; and 0.98 (95% CI, 0.66–1.46, p ?
.92) for HCC-specific survival adjusted for competing risk.
The results of multivariate analysis for patients without
liver transplant are summarized in Table 3. No significant
difference between the two age groups was found. The es-
survival; and 0.90 (95% CI, 0.59–1.36, p ? .61) for HCC-
specific survival adjusted for competing risk.
In this retrospective multicenter study, we compared the
clinical characteristics, treatment modalities, and outcome
data for elderly (age ?70 years) compared to younger pa-
tients (age ?70 years) with HCC. Characteristics that dis-
tinguished the elderly group included lower M/F ratio,
fewer patients with HCV infections, and less advanced un-
derlying liver disease than the younger group. Several pre-
vious studies have shown differences in clinico-
pathological characteristics of elderly patients with HCC
including a lower rate of viral hepatitis positivity, lower
higher proportion of stage I-II patients in elderly group.
However, most of these studies were conducted in Asia
where HCC has a distinct epidemiologic pattern [22–24].
Additional data available from small-scale retrospective
European studies reflect a relatively homogenous patient
population and particular patterns of clinical practice, thus
making it difficult to extrapolate to U.S. patients. Both of
these studies found shorter survival in elderly patients with
HCC that could not be accounted for just by differences in
tumor extent or liver failure with the conclusion reached
tic intervention in elderly patients [18, 19].
A recent retrospective report from a U.S. institution il-
lustrated differences in clinicopathological characteristics
between young and elderly HCC patients. This cohort of
patients differed from ours in that they were selected for
transarterial embolization and therefore had relatively pre-
served hepatic function and less severe medical comorbidi-
ties. Similar to our findings, they found a lower M/F ratio
Figure 2. Kaplan-Meier HCC-specific survival curves. (A):
All elderly (n ? 95) and younger (n ? 240) patients. (B):
HCC-specific survival for elderly (n ? 90) and younger
(n ?193) patients after exclusion of patients who underwent
orthotic liver transplantation. p-values were calculated with
the use of the log-rank test.
Kozyreva, Chi, Clark et al.
and a lower rate of HCV/HBV co-infection in the elderly
group. As opposed to our finding where no difference in
stage distribution between the two age groups was ob-
served, they found that the younger group had higher clin-
ical tumor-node-metastasis stage . The differences
found in stage between the elderly and younger patients in
the two studies may in part be due to the fact that elderly
patients selected for transarterial embolization might have
lower stage on average than younger patients.
It is interesting that a higher proportion of women in el-
derly HCC patients were observed in a recent epidemio-
logic study that analyzed age-adjusted trends in HCC
incidence using U.S. Surveillance, Epidemiology, and End
Results (SEER) registry data . Although the reason for
this difference has not been defined, it is possible that be-
havioral risk factors in younger males leading to earlier in-
fection with HCV or HBV, and alcohol abuse might lead to
a disproportionate increase in HCC incidence in younger
males . However, further studies are needed to confirm
this finding, which could have implications for public
rate of HCC in younger males. Moreover, SEER registry
data demonstrated increased HCC incidence rates among
Hispanic and black middle-aged men over the last 3 de-
cades . In our study, a higher proportion of Hispanic and
black patients in the younger group were seen, although the
numbers were small and not statistically different.
HCC screening and surveillance in a well-defined risk
population is considered the standard of care in the United
States. Nevertheless, in our study only 32.6% of patients in
the elderly group were diagnosed via active screening and
surveillance, as compared to 62% of the younger patient
group. Despite this, there was no difference in stage distri-
elderly patient undergoing state-of-the-art medical care for
comorbidities. It also reflects the relative inefficiency of
current surveillance and screening approaches in detecting
In contrast to other solid tumors, the presence of under-
dimension that cannot be overemphasized when the prog-
nosis and treatment of HCC are assessed. Interestingly, el-
derly patients in our study had less advanced liver disease,
with CTP class B/C in 25.3% of patients compared to
35.8% in younger counterparts, although it did not reach
statistical significance (p ? .063). A higher proportion of
younger patients (92.5%) had underlying chronic liver dis-
ease, based on histological and/or clinical and radiological
Table 3. Estimated hazard ratios from Cox proportional hazards analysis for patients without liver transplant
(A) Overall survival
hazard ratio (95% CI)Factors
(B) HCC-specific survival
hazard ratio (95% CI)
(C) Competing risk hazard
ratio (95% CI)
Elderly versus younger
ECOG ?2 versus 0–1
Symptoms present versus absent 1.66 (1.22, 2.26), p ? .001
Child Pugh class
PVT present versus absent
BMIahigh versus low
HCV positive versus negative
1.23 (0.89, 1.71), p ? .21
1.88 (1.19, 2.97), p ? .007
0.90 (0.62, 1.30), p ? .57
2.34 (1.45, 3.78), p ? .001
0.90 (0.59, 1.36), p ? .61
2.34 (1.27, 4.31), p ? .006
1.48 (0.96, 2.28), p ? .076
1.80 (1.15, 2.81), p ? .011
4.93 (2.77, 8.77), p ? .0001 6.39 (3.38, 12.1), p ? .0001 6.39 (3.30, 12.4), p ? .0001
1.63 (1.16, 2.29), p ? .005
1.67 (1.02, 2.80), p ? .044
2.23 (1.34, 3.72), p ? .002
1.69 (1.01, 2.80), p ? .044
2.23 (1.39, 3.58), p ? .001
1.63 (1.11, 2.39), p ? .013
1.51 (0.93, 2.45), p ? .099
2.25 (1.28, 3.93), p ? .004
4.15 (2.02, 8.53), p ? .004
1.71 (1.19, 2.47), p ? .004
0.65 (0.48, 0.87), p ? .004
1.43 (1.04, 1.96), p ? .028
1.45 (0.85, 2.46), p ? .17
2.06 (1.12, 3.79), p ? .020
3.96 (1.82, 8.62), p ? .001
1.88 (1.27, 2.79), p ? .002
0.63 (0.45, 0.87), p ? .004
1.27 (0.90, 1.80), p ? .18
1.45 (0.87, 2.41), p ? .15
2.06 (1.12, 3.78), p ? .020
3.96 (1.80, 8.74), p ? .001
1.88 (1.24, 2.85), p ? .003
0.63 (0.44, 0.90), p ? .011
1.27 (0.85, 1.91), p ? .24
Abbreviations: ECOG, Eastern Cooperative Oncology Group; HCC, hepatocellular carcinoma; HCV, hepatitis C virus;
PVT, portal vein thrombosis.
aHigh if BMI ?27 (median); low otherwise.
Clinical Features of Elderly HCC Patients
partially explained by the fact that a proportion of patients
with poor liver function might succumb to liver failure and
not survive into elderly age. It is also possible that fewer
HCV infections in the elderly group may partially contrib-
ute to these findings, although genetic, environmental, and
other less clearly defined factors of hepatocarcinogenesis
may play a role.
The prognosis of HCC patients is largely determined by
tumor burden, hepatic function, and performance status
den, hepatic function, and symptomatic presentation in the
two groups, although performance status was worse in the
elderly group. Given that HCC disease characteristics
(number of lesions, AFP levels, and stage) were similar be-
tween the elderly and younger patients, this poor perfor-
mance status is likely a reflection of the higher number of
comorbidities in the elderly, rather than directly related to
Several trends in selection of treatment modalities were
jority of patients with HCC have underlying cirrhosis, it is
the degree of hepatic dysfunction that dictates the choice of
treatment [29, 30]. Not surprisingly, liver transplantation
was uncommon in the elderly group, as only 10% of liver
transplantation across the United States is performed in pa-
tients over 65 years old . Supportive care alone was a
more common course of action in the elderly, despite equal
stage distribution and more preserved liver function on av-
erage in the elderly group. This discrepancy likely reflects
decisions based on a poor performance status and compet-
ing medical conditions. Age-based patterns of care, as de-
this complex decision process. Our study complements the
findings from the largest retrospective Western HCC data-
base presented at ASCO 2009. Although this work illumi-
nates differences in the pattern of care in different age
function, comorbidities, and performance status, which are
important for HCC treatment decisions .
In recent years, the chemotherapeutic armamentarium
for HCC has expanded with introduction of the targeted
tients have been underrepresented in clinical trials . In
contrast to lung cancer, lymphoma, breast cancer, and my-
eloma, there are few prospective studies designed for el-
derly patients with liver cancer. Elderly subgroup analyses
have not been reported from the largest clinical trials in-
volving patients with HCC. As a consequence, limited data
are available about toxicity and tolerability of systemic
therapy in this population. In our study, 27% of elderly pa-
tients received chemotherapy at some point of their treat-
patient group. Moreover, 15% of elderly patients in our
study were enrolled in clinical trials, a number similar to
that of their younger counterparts. Advanced liver disease
commonly presents a major limitation, when considering
enrolling a HCC patient into a clinical trial. Given our re-
sults suggesting that elderly patients, on average, have less
participate in appropriate clinical trials. On the basis of our
observations, elderly patients as a group are as willing to
participate in clinical research as younger patients, when
presented with an opportunity to enroll into a clinical trial.
Despite a higher prevalence of comorbidities and a sig-
nificantly higher mean age, overall and HCC-specific sur-
vival of elderly patients was comparable to that of their
younger counterparts. Low survival rate in both groups in-
dicating morbid nature of HCC could potentially explain
this result as HCC mortality surpasses the impact of both
comorbidity and age-adjusted life expectancy. These find-
ings are in line with results previously reported focusing on
liver-directed therapy and surgical intervention, which in-
clude a healthier subset of the HCC population [12, 25, 32,
33]. Given the high mortality for HCC in both the younger
and the elderly populations, clinical trials that have propor-
tionate representation of the elderly would permit extrapo-
lation of the results to the elderly and allow for direct
comparisons of outcomes for younger and older patients.
The complexity of HCC diagnosis and management argues
for development of a prospective multi-institutional HCC
registration database. Prospective data collection is re-
priate for elderly patients with HCC and ensure meaningful
gains in survival and quality of life in the elderly popula-
An advantage of this analysis is that there was access to de-
ulation-based databases, providing the ability to analyze
associations that have not been well characterized in the
past. However, the retrospective nature of this study is its
biggest limitation. All patients in this study were managed
at tertiary care hospitals with liver transplant programs, in-
terventional radiology experts, and clinical trials available.
Thus, our findings may not be applicable to the patients
managed in settings without similar resources available.
We thank the registrars of the Massachusetts Cancer Reg-
istry for collecting additional data on mortality.
Kozyreva, Chi, Clark et al.
AUTHOR CONTRIBUTIONS Download full-text
Conception/Design: Olga N. Kozyreva, Dorcas Chi, Jeffrey W. Clark, Hejing
Wang, Andrew X. Zhu
Provision of study material or patients: Olga N. Kozyreva, Kathy P. Theall,
David P. Ryan, Andrew X. Zhu
Collection and/or assembly of data: Olga N. Kozyreva, Dorcas Chi
Data analysis and interpretation: Olga N. Kozyreva, Dorcas Chi, Jeffrey W.
Clark, Hejing Wang, Andrew X. Zhu
Manuscript writing: Olga N. Kozyreva, Jeffrey W. Clark, David P. Ryan,
Andrew X. Zhu
Final approval of manuscript: Olga N. Kozyreva, Dorcas Chi, Jeffrey W.
Clark, Hejing Wang, Kathy P. Theall, David P. Ryan, Andrew X. Zhu
1 Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma in-
cidence, mortality, and survival trends in the United States from 1975 to
2005. J Clin Oncol 2009;27:1485–1491.
2 Lok AS, Seeff LB, Morgan TR et al; HALT-C Trial Group. Incidence of
hepatocellular carcinoma and associated risk factors in hepatitis C-related
advanced liver disease. Gastroenterology. 2009;136:138–148.
3 Sarbah SA, Gramlich T, Younoszai A et al. Risk factors for hepatocellular
carcinoma in patients with cirrhosis. Dig Dis Sci 2004;49:850–853.
4N?Kontchou G, Paries J, Htar MT et al. Risk factors for hepatocellular car-
cinoma in patients with alcoholic or viral C cirrhosis. Clin Gastroenterol
5 Horner MJ, Ries LAG, Krapcho M et al. SEER Cancer Statistics Review,
1975–2006. Bethesda, MD: National Cancer Institute. Available at http://
seer.cancer.gov/csr/1975_2006/. Accessed December 1, 2009.
6 El-Serag HB. Hepatocellular carcinoma: recent trends in the United States.
7 Armstrong GL, Wasley A, Simard EP et al. The prevalence of hepatitis C
virus infection in the United States, 1999 through 2002. Ann Intern Med
8 Bouchardy C, Rapiti E, Blagojevic S et al. Older female cancer patients:
importance, causes, and consequences of undertreatment. J Clin Oncol
9 Gross CP, Smith BD, Wolf E et al. Racial disparities in cancer therapy: did
the gap narrow between 1992 and 2002? Cancer 2008;112:900–908.
10 Hazama H, Omagari K, Matsuo I et al. Clinical features and treatment of
hepatocellular carcinoma in eight patients older than eighty years of age.
11 Dohmen K, Shirahama M, Shigematsu H et al. Optimal treatment strategy
for elderly patients with hepatocellular carcinoma. J Gastroenterol Hepatol
12 Kaibori M, Matsui K, Ishizaki M et al. Hepatic resection for hepatocellular
carcinoma in the elderly. J Surg Oncol 2009;99:154–160.
13 Nomura F, Ohnishi K, Honda M et al. Clinical features of hepatocellular
carcinoma in the elderly: a study of 91 patients older than 70 years. Br J
14 Poon RT, Fan ST, Lo CM et al. Hepatocellular carcinoma in the elderly:
results of surgical and nonsurgical management. Am J Gastroenterol 1999;
15 Hoshida Y, Ikeda K, Kobayashi M et al. Chronic liver disease in the ex-
tremely elderly of 80 years or more: clinical characteristics, prognosis and
patient survival analysis. J Hepatol 1999;31:860–866.
16 Zhou L, Rui JA, Wang SB et al. Clinicopathological features, post-surgical
survival and prognostic indicators of elderly patients with hepatocellular
carcinoma. Eur J Surg Oncol 2006;32:767–772.
17 Fujishima T, Ishikawa T, Shiratori Y et al. Age-related comparison of the
18 Ferna ´ndez-RuizM,Guerra-ValesJM,Llenas-GarcíaJetal.Hepatocellular
carcinoma in the elderly: clinical characteristics, survival analysis, and
prognostic indicators in a cohort of Spanish patients older than 75 years.
Rev Esp Enferm Dig 2008;100:625–631.
19 Pignata S, Gallo C, Daniele B et al. Characteristics at presentation and out-
cer of the Liver Italian Program (CLIP). Crit Rev Oncol Hematol 2006;59:
20 Bruix J, Sherman M, Llovet JM et al. Clinical management of hepatocel-
lular carcinoma. Conclusions of the Barcelona-2000 EASL conference.
J Hepatol 2001;35:421–430.
21 Balducci L. Geriatric oncology: challenges for the new century. Eur J Can-
22 Jing-Lin X, Sharma D, Bing-Hui Y et al. Analysis of the clinicopathologi-
cal features of hepatocellular carcinoma in elderly patients. J Nepal Med
J Gastrointest Surg 2009;13:1627–1635.
24 Tsukioka G, Kakizaki S, Sohara N et al. Hepatocellular carcinoma in ex-
tremely elderly patients: an analysis of clinical characteristics, prognosis
and patient survival. World J Gastroenterol 2006;12:48–53.
25 Thornton RH, Covey A, Petre EN et al. A comparison of outcomes from
younger or older than 70 years. Cancer 2009;115:5000–5006.
26 Paulozzi L, Annest J. Unintentional poisoning deaths—United States,
1999–2004. CDC. MMWR 2007;56:93–96.
27 Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the
BCLC staging classification. Semin Liver Dis 1999;19:329–338.
28 Marrero JA, Fontana RJ, Barrat A et al. Prognosis of hepatocellular carci-
29 The Organ Procurement and Transplantation Network. Available at http://
optn.transplant.hrsa.gov/latestData/rpt. Accessed December 1, 2009.
of elderly compared with nonelderly patients (pts) with newly diagnosed
hepatocellular carcinoma (HCC). J Clin Oncol 2009;27:abstract 9552.
31 Townsley CA, Chan KK, Pond GR et al. Understanding the attitudes of the
elderly towards enrolment into cancer clinical trials. BMC Cancer 2006;6:
32 Hanazaki K, Kajikawa S, Shimozawa N et al. Hepatic resection for hepa-
tocellular carcinoma in the elderly. J Am Coll Surg 2001;192:38–46.
33 Mirici-Cappa F, Gramenzi A, Santi V et al. Treatments for hepatocellular
carcinoma in elderly patients are as effective as in younger patients: a 20-
year multicentre experience. Gut 2010;59:387–396.
Clinical Features of Elderly HCC Patients