Int. J. Med. Sci. 2012, 9
I In nt te er rn na at ti io on na al l J Jo ou ur rn na al l o of f M Me ed di ic ca al l S Sc ci ie en nc ce es s
2012; 9(2):163-173. doi: 10.7150/ijms.3827
Cancer Survivors in the United States: A Review of the Literature and a Call
Manuel Valdivieso1,2, Ann M. Kujawa2, Tisha Jones3, Laurence H. Baker1
1. Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
2. Office of the Medical and Administrative Director, ProMedica Cancer Institute, Toledo, OH, USA.
3. Department of Research Grants and Contracts, ProMedica Cancer Institute, Toledo, OH, USA.
Corresponding author: Manuel Valdivieso, M.D., M.S., C.P.E., Division of Hematology/ Oncology, Department of Internal Medicine,
University of Michigan, 24 Frank Lloyd Wright, Ste. A3400, P.O. Box 483, Ann Arbor, Michigan 48106. Telephone: 734-998-7130; Fax:
734-998-7118; e-mail: email@example.com
© Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/
licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.
Received: 2011.11.17; Accepted: 2012.01.11; Published: 2012.01.17
Background: The number of cancer survivors in the U.S. has increased from 3 million in
1971, when the National Cancer Act was enacted, to over 12 million today. Over 70% of
children affected by cancer survive more than 10 years, and most are cured. Most cancer
survivors are adults, with two-thirds of them 65 years of age or older and two-thirds alive at
five years. The most common cancer diagnoses among survivors include breast, prostate and
colorectal cancers. This review was conducted to better appreciate the challenges associated
with cancer survivors and the opportunities healthcare providers have in making a difference
for these patients.
Methods: Comprehensive review of literature based on PubMed searches on topics related
to cancer survivorship, and associated physical, cognitive, socio-economic, sexual/behavioral
and legal issues.
Results: At least 50% of cancer survivors suffer from late treatment-related side effects,
often including physical, psychosocial, cognitive and sexual abnormalities, as well as concerns
regarding recurrence and/or the development of new malignancies. Many are chronic in na-
ture and some are severe and even life-threatening. Survivors also face issues involving lack of
appropriate health maintenance counseling, increased unemployment rate and workplace
Conclusions: Advances in the diagnosis and treatment of cancer will lead to more survivors
and better quality of life. However, tools to recognize potentially serious long-lasting side
effects of cancer therapy earlier in order to treat and/or prevent them must be developed. It
is incumbent upon our health care delivery systems to make meeting these patients’ needs a
Key words: Cancer survivorship, detection of treatment complications, side effects of therapy,
secondary malignancies, socioeconomic/legal/healthcare policy issues.
Cancer remains a major public health problem.
The American Cancer Society projected over 1.5 mil-
lion new cancer cases would be diagnosed in 2010,
with an estimated over half a million deaths from this
disease . It is estimated that the aging of America
will contribute to a 45% increase in cancer incidence
by 2030 . Cancer continues as the second most
common cause of death (22.8%) following heart dis-
Int. J. Med. Sci. 2012, 9
eases (26.6%) . The comparison of new diagnoses
and mortality from cancer in 1971, when the National
Cancer Act was enacted as a U.S. federal law, and
2010 indicates that although the number of cancer
diagnoses increased, the mortality proportion over
those years declined (Table 1). This accounts for the
increase in cancer survivors from 3 million in 1971 to
nearly 12 million in 2007 . Of those, it is estimated
that 328,652 are survivors of childhood cancer .
Table 1. Cancer in the U.S.a
New Diagnosis 563,000 1,529,560
Deaths 335,000 569,490
Percent Mortality 53 37
Survivors (millions) 3 12
aAmerican Cancer Society comparison.
The expected survivorship from cancer in the
U.S. is summarized in Table 2. Almost 80% of children
and 60% of adult cancer patients are expected to sur-
vive at least five years from diagnosis and many of
them are, in fact, cured from cancer. As expected,
most cancer survivors are adults 65 years of age or
Table 2. Survival Information from the National Cancer
Institute and Centers for Disease Control and Prevention.
* 79% of childhood cancer survivors will be living five years after
diagnosis and nearly 75% will be living 10 years following diagno-
* 64% of adults whose cancer is diagnosed today can expect to be
alive in five years.
* 61% of cancer survivors are age 65 and older.
* An estimated one of every six persons over the age of 65 is a can-
* Breast cancer survivors make up the largest group of cancer sur-
vivors (22%) followed by prostate cancer survivors (17%) and col-
orectal cancer survivors (11%).
The most common diagnoses include breast,
prostate and colorectal cancers . Similar trends
have been reported from other countries but with
appreciable regional differences. In a study of three
common and one less common cancers (breast, colo-
rectal, lung and ovary) in Australia, Canada, Den-
mark, Norway, Sweden and the United Kingdom, the
survival of patients improved between 1995 and 2007,
though survival was consistently higher in Australia,
Canada, Sweden, intermediate in Norway, and lower
in Denmark, England, Northern Ireland and Wales
. The majority of cancer survivors have been treated
with aggressive medical, radiation and surgical ther-
apies administered either at a time when a patient’s
organs were still developing, leading to complications
later in life, or when the patient was already suffering
from underlying degenerative processes where the
side effects of therapy represent insult over injury. As
a result, long-term follow-up of cancer survivors re-
veals significant concern for cancer recurrence or de-
velopment of a new primary cancers, as well as
physical, cognitive, socioeconomic, sexual and legal
issues. This review highlights some of these problems
and brings to the attention of healthcare institutions,
medical providers, health policy makers and society
in general the urgent need to address these issues.
Chronic and Late-Effect Health Conditions
in Adult Survivors of Childhood Cancer
The treatment of childhood cancer has been as-
sociated with risk for developing several chronic
conditions that appear later in life, including physical,
psychological, cognitive abnormalities - some of
which are severe and debilitating. In addition, survi-
vors from childhood cancer are at risk for developing
secondary malignancies .
post-cancer-treatment chronic conditions have been
reviewed by Oeffinger et al. . Among participants
of the Childhood Cancer Survivor Study cohort,
comparative data were reported on the experiences of
10,397 survivors and of 3,034 siblings. A chronic con-
dition was more common among survivors than their
siblings (62.3% vs. 36.8%, respectively). Chronic se-
quela of treatments was frequently multiple. Among
patients with three or more chronic conditions, they
were more common among survivors than in their
siblings (23.8% vs. 5.4%, respectively). The cumulative
incidence of chronic conditions increased with time;
66.8% at 25 years and 73.4% at 30 years.
The severity of post-treatment chronic condi-
tions varies substantially, but could be severe and
even life threatening. Serious conditions were also
more common among survivors than in their siblings
(27.5% vs. 5.2%) and were usually associated with
chemo-radiation regimens and/or with those con-
taining Doxorubicin and alkylating agents. The rela-
tive risk of the five most common serious conditions
were major joint replacement at 54.0; congestive heart
failure at 15.1; secondary malignant neoplasm at 14.8;
severe cognitive dysfunction at 10.5; and coronary
artery disease at 10.4.
Cognitive impairment is associated with brain
irradiation and can impact academic achievement.
The most common cognitive late-effect of moder-
and severity of
Int. J. Med. Sci. 2012, 9
ate-to-high dose whole brain radiation is diminished
intellectual capacity . Central nervous system
(CNS) and acute lymphoblastic leukemia (ALL) sur-
vivors are at risk for educational deficits . The
Children’s Cancer Group investigated the impact of
treatment on scholastic performance of 593 adult sur-
vivors of ALL in comparison with 409 sibling controls
. Survivors treated with 24 Gy of cranial irradia-
tion were more likely to enter special education or
learning disability programs. Survivors were as likely
to finish high school and enter college as controls, but
those treated with 24 Gy or treated before the age of
six years were less likely to enter college.
Significant psychosocial distress has been re-
ported in survivors of childhood sarcoma treated with
combined modality therapy . The majority, 77%,
had abnormalities in the Brief Symptom Inventory
test that demonstrates severity scores for nine psy-
chiatric symptoms. Twelve percent of patients met
diagnostic criteria for Post-traumatic Stress Disorder.
Psychological distress usually consisted of intrusive
thoughts, avoidant behaviors and health well-being
Adult Cancer Survivors: Cardiac and Pul-
The late cardiac and pulmonary effects of ther-
apy on cancer survivors have recently been reviewed
. The estimated aggregate incidence of radia-
tion-induced cardiac disease is 10% - 30%, occurring 5
to 10 years from treatment. Radiation pneumonitis is
reported in 5% - 15% of lung cancer patients, with a
smaller percent developing progressive pulmonary
fibrosis. However, in patients with severe underlying
chronic obstructive pulmonary disease before radia-
tion therapy or chemoradiation therapy the outcomes
are substantially worse.
Valdivieso et al. reported an increase in pulmo-
nary and infection morbidity during induction
chemoradiation therapy, including mitomycin C,
etoposide and cisplatin, in 43 patients with stage IIIB
non-small cell lung cancer compared to a group of 41
stage IV non-small cell lung cancer patients receiving
the same chemotherapy but without chest irradiation.
The frequency of these complications was greater ac-
cording to the pre-treatment severity of underlying
small airway disease measured by forced expiratory
flow (FEF25-75). In the group who received chemora-
diation therapy, there were 14/24, 4/8 and 0/11 epi-
sodes of pneumonia in patients with severe, moderate
or normal FEF25-75, respectively (p 0.005) . Brooks
et al. also reported on the increase in pulmonary tox-
icity of 80 small cell lung cancer patients receiving
combined chemoradiation versus chemotherapy
alone for limited disease (p 0.017). Bilateral pulmo-
nary infiltrates beyond the radiation therapy port
were found in 28% of patients compared to 5% in
those receiving chemotherapy alone. Eight of 13 pa-
tients died from pulmonary complications with no
clinical evidence of tumor in five. Pretreatment pul-
monary function tests (PFT) revealed a significantly
lower forced vital capacity (FVC) (p 0.03) and forced
expiratory volume in 1 second (FEV-1) (p 0.04) in pa-
tients with subsequent pulmonary complications .
Theuws reported results of pulmonary function
evaluations of 69 breast cancer patients and 41 lym-
phoma patients before and after radiation therapy
alone or combined with chemotherapy, including
combinations of mechlorethamine, vincristine, pro-
carbazine, prednisone, doxorubicin, bleomycin, vin-
blastine, cyclophosphamide, epidoxorubicin, fluor-
ouracil, thiotepa, carboplatin and methotrexate. After
an initial reduction in PFTs at 3 months, significant
recovery took place at 18 months for all patients.
Thereafter, no further improvement could be docu-
mented . Thus, pretreatment pulmonary abnor-
malities have a significant impact on the pulmonary
complications from radiation therapy as they could be
mild and transient or more severe and long lasting.
Because of the increased risk associated with
cancer treatment administered at a young age, adult
survivors of pediatric cancer who received mediasti-
nal radiation (most commonly patients with Hodg-
kin’s disease) have a reported increase in the inci-
dence of coronary artery disease, fatal myocardial
infarction and other cardiac complications. Hodgkin’s
disease patients receiving mediastinal radiation have
up to a 7.2 higher risk for fatal cardiovascular events
than age and sex matched general population controls
Doxorubicin-induced cardiomyopathy is the
most frequent and most studied chemothera-
py-induced cardiotoxicity. The risk of developing
cardiotoxicity is mainly related to the cumulative dose
of doxorubicin (1% to 5% up to 550 mg/M2, 30% at
600 mg/M2, and 50% at 1 g/M2 with individual vari-
ation) . Other anthracyclines are also cardiotoxic.
Cardiac abnormalities are likely to be observed in
survivors from childhood cancer and in adults un-
dergoing long-term follow-up. A higher risk popula-
tion is described as those in the extremes of age,
higher cumulative dose, mediastinal radiation and
female sex. An overall 9% incidence of doxorubi-
cin-related cardiac abnormalities in asymptomatic
survivors that required treatment and close follow-up
has been reported . An abnormality of systolic
function (abnormal wall stress, hypertrophy, contrac-
tility) was reported in 65 (43%) of 151 patients.
Int. J. Med. Sci. 2012, 9
The cardiotoxicity of breast cancer therapy
among survivors has recently been reviewed .
Patients with doxorubicin-induced congestive heart
failure (CHF) had an 87% improvement with cardiac
medications; combined treatment with β-blockers and
ACE inhibitors seemed superior to ACE inhibitors
alone . These results contrast with retrospective
reviews that reported mortality rates of 43% to 59% in
similar patients .
Epirubicin appears less cardiotoxic than doxo-
rubicin at equimolar doses, due to a lower level of
secondary alcohol metabolites produced from epiru-
bicin . Cumulative epirubicin doses of >950
mg/m2 are associated with an exponential increase in
CHF risk . Little cardiotoxicity was observed with
a cumulative epirubicin dose of 300 mg/m2 .
Dexrazone is the sole cardioprotective agent
proved to decrease anthracycline-induced cardio-
myopathy. However, some suggest that it may inter-
fere with anthracycline chemotherapy because an-
thracyclines enhance DNA cleavage by topoisomerase
II, but the closed ring form of dexrazone stabilizes
DNA-topoisomerase II complexes .
Taxanes, particularly paclitaxel, have shown
evidence of cardiotoxicity. In contrast to previous
reports, a large database has shown that only 0.1% of
patients have serious bradycardia and could not con-
firm that taxanes increased the frequency of ventric-
ular tachycardia or myocardial infarction . Tax-
anes interfere with the metabolism and excretion of
anthracyclines and potentiate anthracycline-induced
cardiotoxicity, especially at high cumulative an-
thracycline doses. When combined with paclitaxel,
the cumulative doxorubicin dose should not exceed
360 mg/m2, and doxorubicin should be given before
paclitaxel . Combination treatments with epirubi-
cin and taxanes may be less cardiotoxic. A cumulative
epirubicin dose limit of 990 mg/m2 in combination
treatments with paclitaxel has been proposed .
Recently, interest regarding the potential cardiac
toxicity of trastuzumab has developed. Trastuzumab
is a humanized monoclonal antibody that binds to the
extracellular portion of the receptor HER2, a product
of the HER2/neu gene. Although the exact mecha-
nism of cardiotoxicity of trastuzumab is unknown,
HER2 is required for cardiac development. Single
agent trastuzumab is toxic to rat myocytes in-vitro
because it induces activation of the mitochondrial
apoptosis pathway and the caspase cascade. Neuro-
regulin, a cardiac stress peptide, may have a role in
this problem . The cardiotoxicity of trastuzumab
has been recognized when given in combination with
doxorubicin (A) and cyclophosphamide (C). The
combination produces a 16% incidence of NYHA
(New York Heart Association) classes III and IV rela-
tive to 3% with AC alone. Trastuzumab-related car-
diac dysfunction differs from anthracycline-induced
myocardial damage in that it rarely causes death, is
not dose related, and, in most instances, is reversible
with improvement in cardiac function when the drug
is discontinued and/or the patient is treated with
Detection and Monitoring for Cardiac Tox-
The present detection of cardiac abnormalities in
asymptomatic patients is suboptimal. Left ventricular
ejection fraction (LVEF) is the most widely used
measure in the monitoring of cardiac toxicity. Patients
with a healthy LVEF might experience subclinical
changes, such as diastolic dysfunction, therefore, un-
derestimating possible cardiac damage. Echocardi-
ography and multiple gated acquisition (MUGA)
scintigraphy are the gold standard to measure LVEF.
Echocardiography, however, provides more infor-
mation about the structure and function of the heart,
including assessment of diastolic dysfunction and,
thus, offers greater potential for the monitoring of
cardiac function during and after cancer treatment.
Several biomarkers, such as troponins and natriuretic
peptides, have shown promising results and they
should be studied prospectively and in conjunction
with echocardiography to detect subclinical signs of
cardiac dysfunction .
There is growing evidence of the importance for
measuring global cardiac strain by Doppler imaging
technology to identify heart damage in asymptomatic
patients and in patients where standard echocardio-
gram is normal. Promising results using this tech-
nique have been reported in patients with silent cor-
onary ischemia, ventricular failure, wall motion ab-
normalities, amyloidosis [35-38] and cancer chemo-
therapy . Sawaya and coworkers reported a de-
crease in longitudinal strain measured by echocardi-
ography in 43 patients at 3 months predicted cardio-
toxicity of anthracycline and trastuzumab treatment
(p = 0.01) before any other test measuring LVEF. In
addition, troponin 1 also significantly predicted car-
diotoxicity at 6 months (p = 0.006) .
Subsequent Neoplasms in Cancer Survi-
One of the most serious complications of cancer
and its therapy is the development of additional ma-
lignancies (Table 3). The reported incidence of second
malignancies in cancer survivors varies considerably,
but according to the NCI Surveillance, Epidemiology,
Int. J. Med. Sci. 2012, 9
and End Results (SEER) Program, they account for
16% of all cancers . The development of these ma-
lignancies can be attributed to a number of factors,
including prior chemotherapy and/or radiation
therapy, lifestyle choices, the genetics of the individ-
ual, environmental exposures and their interactions.
Second cancers and beyond have been well described
in survivors of childhood and adult-onset cancers,
particularly in patients with Hodgkin’s disease, as
well as in patients with a history of prior cancer of the
breast, prostate, testis, lung and cervix . In general,
the most commonly occurring second malignancies in
adults are represented by the most common cancers
overall (i.e., breast, prostate, lung and colorectal),
although leukemia has also been described [43-52].
Among children, Meadows et al reported on a
long-term follow up of 14,358 childhood cancer sur-
vivors that were part of the Childhood Cancer Survi-
vor Study Cohort . At 30 years, the cumulative
incidence of secondary malignant neoplasms was
9.3%, and that of non-melanoma skin cancer was
6.9%. By multivariate analysis, greater risk was de-
scribed for those receiving radiation therapy, older
age at diagnosis, female sex, family history of cancer
and primary childhood cancer. Female survivors from
Hodgkin’s disease or sarcoma and those who received
radiation therapy were at increased risk. Compared to
the general population, the largest risk excesses were
found for breast cancer, bone cancers and thyroid
Over the years, greater emphasis has been placed
on long-term surveillance of patients with Hodgkin’s
disease. It has been recognized since the 1970’s that
these patients are at greater risk for second malignan-
cies because of the type of chemotherapy, radiation
therapy or combination therapy administered to
them. Among 18,862 5-year survivors from Hodgkin’s
disease, Hodgson reported a 30-year cumulative risk
for second malignancies of 18% and 26% for men and
women respectively . Metayer et al. described 195
second cancers among 5,925 patients with Hodgkin’s
disease who were diagnosed before the age of 21
years in the US, Europe and Canada. Eighty-one per-
cent of second cancers were solid tumors from dif-
ferent sites that occurred at an average of 16 years
after diagnosis of Hodgkin’s disease. Twenty-year
survivors experienced significantly increased risks of
cancers of the female breast, thyroid, digestive tract,
lung, uterine cervix, bone and connective tissue .
A British study of 5,519 patients identified 322 second
malignancies among Hodgkin’s disease patients
treated between 1963 and 1993. They found a signifi-
cant increase in relative risk for gastrointestinal, lung,
breast, bone and soft tissue cancers and leukemia
among younger patients at first treatment. Absolute
excess risks and cumulative risks of solid tumors and
leukemia were greater at older ages .
Table 3. Subsequent Malignancies among Cancer Survivors.
Author No. Patients Diagnosis New Cancers
Ng & Travis  1,319 Hodgkin’s Disease 189 (14.3%)
Hodgson, et al.  18,862 Hodgkin ’s disease Men (18%)
195 (3.2%) Metayer, et al.  5,925 Hodgkin’s Disease
Swerdlow, et al.  5,519 Hodgkin’s Disease 322 (5.8%)
Okines  3,764 Malignant Lymphoma 68 (1.9%)
Heyne, et al.  47 Small Cell Lung Cancer 14 (30%)
van der Gaast, et al.  81 Small Cell lung cancer 5 (6.1%)
Takigawa, et al.  90 Stage III Non-Small Cell Lung Cancer 7 (7.8%)
4/19 (21%) long-term Survivors
40,068 (12%) Raymond & Hogue  332,014 Breast Cancer
Kirova, et al.  16,705 Breast Cancer 709 (4.2%)
Gianni, et al.  1,035 Breast Cancer 55 (5.3%)
Travis, et al.  40,576 Testicular cancer 2,285 (5.6%)
Stava, et al.  968 Malignant Melanoma 111 (11.4%)
Fernebro, et al.  818 Soft Tissue Sarcoma 113 (13.8%)
Chaturvedi, et al.  85,109 Squamous Cell Ca. Cervix 10,559 (12.4%)
10,280 Adenocarcinoma of Cervix 920 (8.9%)
Int. J. Med. Sci. 2012, 9
Among patients with Hodgkin’s disease, Ng
reported on the risk of developing multiple malig-
nancies in 1,319 survivors; 181 patients developed a
second malignancy and 18 developed a third malig-
nancy . The median time between the second and
the third malignancy was 34 months. Similar experi-
ences have been described in survivors from child-
hood cancer and in adult cancer survivors who de-
veloped up to five subsequent malignancies [46, 58].
In a data base of consecutive small cell lung
cancer patients entering clinical trials at MD Ander-
son Cancer Center, Heyne et al. reported the devel-
opment of second cancers in fourteen of forty- seven
(30%) survivors of two-years or more. Second cancers
continued to develop during follow-up with an actu-
arial risk of 9.1%, 26.8% and 50% at 3, 5 and 8 years
survival, respectively. The most common second
cancers were non-small cell lung, with others being
bladder, esophagus, breast, bone, rectum and multi-
ple primaries. The study demonstrates that careful
and long-term follow-up of small cell lung cancer
survivors reveals a very high incidence of second ma-
lignancies . The development of second malig-
nancies in small and non-small cell lung cancers has
been reported to be lower by others, in the range of 6.1
% to 21% [45,47].
Matesich reported that adjuvant chemotherapy
for breast cancer is not associated with an increased
risk for development of other solid tumors beyond
what is expected with normal aging. However, alkyl-
ating agents, such as cyclophosphamide and topoi-
somerase II inhibitors, are associated with two types
of cytogenetically distinct leukemias. The risk of de-
veloping leukemia, however, is significantly lower
than the survival benefit from adjuvant chemothera-
py. Tamoxifen, on the other hand, is associated with a
two- to threefold increase in the risk of developing
endometrial cancer that is equivalent to approxi-
mately 80 excess cases per 10,000 treated women at 10
Quality of Life in Survivors
Several studies have addressed quality of life
issues in cancer survivors. Among young adults sur-
vivors of childhood cancer, Langeveld et al. reported
that many survivors, except those with bone tumors,
reported being in good health and that most were
functioning well psychologically. It was also reported
that survivors had lower rates of marriage and
parenthood . The same authors reported that, in a
sample of 400 long-term survivors of childhood can-
cer, predictors of a diminished quality life included
female gender, unemployment, severe late ef-
fects/health problems and low self-esteem. Addi-
tionally, it was found that female survivors had more
cancer-specific concerns than males survivors .
Factors associated with serious psychological distress
in long-term survivors of adult-onset cancer include
age younger than 65 years, being unmarried or not
living with a partner, having less than high school
education, being uninsured, having co-morbidities, or
having difficulty performing activities of daily living
. Among adult long-term survivors of breast,
prostate, colorectal cancer and lymphoma (5-10 years
post-diagnosis), older respondents expressed better
quality of life (p = 0.004), mental health (p < 0.001),
but worse physical health (p = 0.04) . Physical
functioning was worse among those reporting low
income (p = 0.02) and co-morbidities (p = 0.003). The
evaluation of the impact of cancer score demonstrated
that higher positive scores were associated with better
mental health (p = 0.0004) and better overall quality of
life (p = 0.005).
Sexual disturbances are common among adult
survivors and they are often not addressed. Physical
abnormalities and low hormone levels resulting from
gonadal injury from cancer therapy contribute to
lower self-esteem, depression, less desire for sexual
activity and lower libido. This is particularly signifi-
cant for younger women undergoing breast cancer
therapy and for those recovering from gynecologic
In breast cancer patients, ovarian abnormalities
from chemotherapy are related to a number of factors
including the direct damage of ovarian follicules, the
ovarian function at the time chemotherapy begins and
the specific chemotherapeutic agent employed par-
ticularly alkylating agents such as cyclophosphamide
. Transient or permanent amenorrhea develops
with associated symptoms of treatment induced
ovarian suppression such as hot flashes and osteopo-
rosis . These abnormalities will also have a nega-
tive effect on fertility.
Even though most cancer patients suffer from
some degree of sexual dysfunction, patients with gy-
necologic malignancies, much like men with treated
prostate cancer, develop early reduction in sexual
activity that for some could be permanent [66, 69-71].
In addition, gynecologic patients have been found to
have higher levels of depressive symptoms than pa-
tients with breast, gastrointestinal and urologic cancer
Great progress has taken place in our knowledge
of reproductive physiology to assure the existence of
fertility preservation options for patients interested in
having children after cancer therapy. These methods
Int. J. Med. Sci. 2012, 9
include reducing the impact of chemotherapy on
gonadal function, removing and preserving ovarian
tissue before starting chemotherapy, sperm banking
and methods designed to produce mature oocytes or
fertilized embryos for use in the future . Cancer
treatment choices and age have been considered in the
development of an algorithm to influence fertility
Sexual dysfunction abnormalities are frequent
among cancer survivors regardless of gender and de-
serve close attention by care providers.
Counseling Health Behaviors among Can-
It has been reported that cancer survivors receive
less counseling by their primary care physicians on
three important health behaviors: diet, exercise and
smoking . Utilizing the 2000 National Health In-
terview Survey, 1,600 cancer survivors and 24,636
adults without cancer or non-melanomatous skin
cancer history (controls) were studied. Among cancer
survivors, 96% were diagnosed after the age of 18,
there was a slight predominance of women (56% vs.
44%) and the majority was Caucasian (82%). Few
survivors reported having discussions with their
health care providers related to diet (30% survivors
vs. 23% controls; p < .0001), exercise (26% of survivors
vs. 23% of controls; p < .005), or smoking cessation
(42% of survivors vs. 41% of controls; p = .41). Survi-
vors reporting discussion with their physicians on all
three health behaviors were even less (10% of survi-
vors and 9% of controls). Colorectal cancer survivors
were less likely than controls of similar age range to
report exercise recommendations (16% vs. 27%; p <
.003) or smoking cessation (31% vs. 41%; p < .05), and
cervical cancer survivors were more likely than con-
trols of similar age range to have discussions regard-
ing smoking (58% vs. 43%; p <.001). Thus, many pro-
viders are missing the opportunity to counsel their
cancer survivors on modification of important health
Survivors and Unemployment, Health In-
surance and Legal Issues
Since the approval of the National Cancer Act of
1971, many changes have occurred, including a
greater understanding of cancer and its biology, better
methods for early detection, improved treatment
outcomes and a larger number of cancer survivors in
the U.S. The attitudes of patients and the public have
also changed. Patients are less likely to be considered
victims, their expectation of surviving is greater and
so are their prospects with regard to employment,
health insurance and preservation of their human
Many survivors are ready to maintain or seek
employment, though there are concerns because of
employer and co-worker misconceptions regarding
their ability to successfully return to work after ther-
apy. To address this issue, there are several federal
and state laws in place to protect survivors from dis-
crimination. These include the Americans with Disa-
bility Act (ADA), Federal Rehabilitation Act, Family
and Medical Leave Act (FMLA) and Employment
Retirement and Income Security Act (ERISA) .
There is also increasing concern among patients and
their families regarding employer’s discrimination
based on genetic history. Several federal laws provide
limited protection to cancer survivors: the Genetic
Privacy Act, Genetic Privacy and Nondiscrimination
Act, the ADA, and the Health Insurance Portability
and Accountability Act. More than 30 states have ge-
netic non-discrimination laws. The levels of protection
provided by these laws vary considerably .
Survivors report problems with job discrimina-
tion and obtaining health and life insurance . A
meta-analysis and meta-regression study of 20,366
long-term cancer survivors, all with cancer diagnosis
beyond the age of 18, has identified a higher percent
of unemployment among cancer survivors than a
healthy control population of 157,603, 33.8% vs.
15.2%, respectively . Specifically, unemployment
was higher among survivors from breast cancer, gas-
trointestinal cancers and cancers of the female re-
productive tract. Overall, survivors in the U.S. were
1.5 times more likely to be unemployed than their
counterparts in Europe. Given the present poor status
of our economy, it is likely that this figure will in-
Park et al. studied the prevalence and predictors
of health insurance coverage in 12,358 5-year survi-
vors of childhood cancer and 3,553 sibling controls
participating in the Childhood Cancer Survivor Study
. Health insurance coverage was reported by
83.9% of adult survivors and 88.3% of siblings.
Twenty-nine percent of survivors reported difficulty
obtaining health insurance coverage, compared to 3%
of siblings (p < .01). Additionally, survivors were
more likely to report exclusions or restrictions on their
policies. Among survivors 18 years of age or older,
factors associated with being uninsured included be-
ing diagnosed with cancer before the age of 15, male
gender, lower level of attained education, income less
than $20,000, marital status, smoking status and
treatment that included cranial radiation. Other fac-
tors include prior diagnosis of leukemia, second ma-
lignancy and recurrence of original cancer.
Int. J. Med. Sci. 2012, 9
Clinical Research in Cancer Survivors
There is significant interest in the understanding
of the many problems cancer survivors face as a result
of their disease process and or their treatment. The
Children’s Oncology Group has pioneered the careful
follow up of these patients resulting in carefully de-
veloped guidelines of care for survivors from child-
hood cancers and the study of some of their problems
such as psychosocial, cognitive and academic
achievement, and developmental issues. The guide-
lines of care for adults are more limited. Ongoing re-
search in adults focuses on symptom control, sexual
dysfunction, obesity-nutrition-exercise, prevention of
recurrence and of second malignancies. Examples of
these studies by the SWOG cancer research coopera-
tive group, for instance, include: a. A feasibility study
of physical activity and dietary change weight loss
intervention in breast and colorectal cancer survivors;
b. A Phase IIb randomized controlled biomarker
modulation study of Vitamin D in premenopausal
women at high risk for breast cancer; c. A randomized
placebo controlled trial of Omega-3-fatty acid for the
control of Aromatase inhibitor induced musculoskel-
etal pain in women with early breast cancer; d. A
L-Carnitine for the prevention of Taxane induced
neuropathy and; e. Phase III trial of LHRH Analog
administration during chemotherapy to reduce ovar-
ian failure following chemotherapy in early stage
hormone-receptor negative breast cancer. What is
needed, however, are studies aimed at the early de-
tection and treatment of organ toxicity by the use of
new and promising technologies, such as those fo-
cusing in the cardiopulmonary system.
trial of Acetyl
It is clear that surviving cancer today is associ-
ated with significant risk for cancer recurrence and/or
the development of a new cancer plus physical, cog-
nitive, social, legal and economic problems. Although
it is anticipated that modern cancer therapies will
alleviate some of these problems, they will not pre-
vent worsening of already existing degenerative pro-
cesses in adults, since it has been demonstrated that
treatments hasten the development of future cardiac
and pulmonary problems. Nor will they lessen the
socioeconomic issues experienced by cancer survivors
either. The interactions between the individual’s ge-
netics, prior cancer therapy, environment and lifestyle
choices will continue. While the genetic underpin-
nings of these interactions are unknown today, they
represent a fruitful source of research in the future.
Healthcare organizations, members of the med-
ical profession and advocacy groups need to heighten
public awareness of these patients’ problems to assure
that comprehensive programs are developed to attend
to the many issues described here.
Prospective sets of guidelines of care and sup-
portive services need to be established taking into
account the needs of children, adolescents and adults.
A comprehensive multidisciplinary program or clinic
that includes pediatric and adult hematologists and
medical oncologists, primary care and internal medi-
cine physicians, as well as other medical and surgical
specialists, social services, geneticists, legal and fi-
nancial counselors, would be necessary to better un-
derstand and optimally assist these patients. The
amount of physical and staff resources necessary for
these types of efforts are beyond what most commu-
nity settings or even academic cancer centers would
be able to afford.
A good alternative to comprehensive multidis-
ciplinary survivor clinics is the expanded oncology
clinics, provided there is the appropriate physician
and patient support systems to deliver cost-effective
care under circumstances where most survivor pro-
grams generate limited revenue. Thus, oncology
trained physician extenders and nurse clinicians
could staff these clinics under the guidance of a phy-
sician interested in survivor issues. Together, they
will implement survivorship guidelines into an over-
all survivor healthcare plan; they will refer patients to
specialty clinics for specific problems requiring that
type of expertise; and will work collaboratively with
primary care physicians, or other home physicians, to
assure patients get the appropriate health mainte-
nance programs at home. Social services support will
be required in these clinics. An excellent level of ver-
bal and written communication among healthcare
providers will be essential for these programs to suc-
Cancer survivors need all members of the
healthcare team to assist them in coping with many
evolving challenges, and to live with dignity and re-
spect. We learn from them after they conquer cancer
and, as providers, we join them at a new level of team
approach that is ever-inspiring.
The authors wish to thank Patricia Arlauskas for
editorial assistance in the preparation of this manu-
Int. J. Med. Sci. 2012, 9
This review was supported in part by PHS Co-
operative Agreement grant
awarded by the National Cancer Institute, DHHS.
Conflict of Interest
Dr. Baker serves on the Board of Directors for
Merck & Co., Inc. (uncompensated).
1. American Cancer Society. Cancer Facts & Figures 2010. Atlanta:
American Cancer Society. 2010.
2. Smith BD, Smith GL, Hurria A, et al. Future of cancer incidence
in the United States: burdens upon an aging, changing nation. J
Clin Oncol 2009;27(17):2758-2765.
3. Heron M. Deaths: Leading causes for 2006; National vital sta-
tistics reports Vol 58. Hyattsville, MD: National Center for
Health Statistics; 2010.
4. [Internet] Altekruse SF, Kosary CL, Krapcho M, et al. SEER
Cancer Statistics Review, 1975-2007; based on November 2009
SEER data submission, posted to the SEER web site, 2010.
5. Mariotto AB, Rowland JH, Yabroff KR, et al. Long-term
survivors of childhood cancers in the United States. Cancer
Epidemiol Biomarkers Prev 2009;18(4):1033-1040.
6. Centers for Disease Control and Prevention (CDC). Cancer
survivorship--United States, 1971-2001. MMWR Morb Mortal
Wkly Rep 2004;53(24):526-529.
7. Coleman MP, Forman D, Bryant H, et al. and the ICBP Module 1
Working Group. Lancet 2011; 377 (9760): 127-138.
8. Oeffinger KC, Hudson MM. Long-term complications
following childhood and adolescent cancer: foundations for
providing risk-based health care for survivors. CA Cancer J
9. Oeffinger KC, Mertens AC, Sklar CA, et al. Chronic health
conditions in adult survivors of childhood cancer. N Engl J Med
10. Mulhern RK, Palmer SL. Neurocognitive late effects in pediatric
cancer. Curr Probl Cancer 2003;27(4):177-197.
11. Langeveld NE, Stam H, Grootenhuis MA, et al. Quality of life in
young adult survivors of childhood cancer. Support Care
12. Haupt R, Fears TR, Robison LL, et al. Educational attainment in
long-term survivors of childhood acute lymphoblastic
leukemia. JAMA 1994;272(18):1427-1432.
13. Wiener L, Battles H, Bernstein D, et al. Persistent Psychological
Distress in Long-Term Surviviors of Pediatric Sarcoma: The
Experience at a Single Institution. Psychooncology, 2006; 15
14. Carver JR, Shapiro CL, Ng A, et al. American Society of Clinical
Oncology clinical evidence review on the ongoing care of adult
cancer survivors: cardiac and pulmonary late effects. J Clin
15. Valdivieso M, Kraut M, Lattin P, et al. Pulmonary functions
tests predict for pulmonary toxicity in non-small cell lung
cancer patients receiving chemotherapy and radiotherapy. Proc
AACR. 1992; 33:226.
16. Brooks BJ, Jr., Seifter EJ, Walsh TE, et al. Pulmonary toxicity
with combined modality therapy for limited stage small-cell
lung cancer. J Clin Oncol 1986;4(2):200-209.
17. Theuws JC, Muller SH, Seppenwoolde Y, et al. Effect of
radiotherapy and chemotherapy on pulmonary function after
treatment for breast cancer and lymphoma: A follow-up study.
J Clin Oncol 1999;17(10):3091-3100.
18. Hancock SL, Tucker MA, Hoppe RT. Factors affecting late
mortality from heart disease after treatment of Hodgkin's
disease. JAMA 1993;270(16):1949-1955.
19. Lee CK, Aeppli D, Nierengarten ME. The need for long-term
surveillance for patients treated with curative radiotherapy for
Hodgkin's disease: University of Minnesota experience. Int J
Radiat Oncol Biol Phys 2000;48(1):169-179.
20. Mauch PM, Kalish LA, Marcus KC, et al. Long-term survival in
Hodgkin's disease relative impact of mortality, second tumors,
infection, and cardiovascular disease. Cancer J Sci Am
21. Lipshultz SE, Lipsitz SR, Mone SM, et al. Female sex and drug
dose as risk factors for late cardiotoxic effects of doxorubicin
therapy for childhood
22. Pein F, Sakiroglu O, Dahan M, et al. Cardiac abnormalities 15
years and more after adriamycin therapy in 229 childhood
survivors of a solid tumour at the Institut Gustave Roussy. Br J
23. Bird BR, Swain SM. Cardiac toxicity in breast cancer survivors:
review of potential cardiac problems. Clin Cancer Res
24. Tallaj JA, Franco V, Rayburn BK, et al. Response of
management strategy of heart failure. J Heart Lung Transplant
25. Von Hoff DD, Layard MW, Basa P, et al. Risk factors for
doxorubicin-induced congestive heart failure. Ann Intern Med
26. Minotti G, Licata S, Saponiero A, et al. Anthracycline
metabolism and toxicity in human myocardium: comparisons
between doxorubicin, epirubicin, and a novel disaccharide
analogue with a reduced level of formation and [4Fe-4S]
reactivity of its secondary alcohol metabolite. Chem Res Toxicol
27. Ryberg M, Nielsen D, Skovsgaard T, et al.Epirubicin
cardiotoxicity: an analysis of 469 patients with metastatic breast
cancer. J Clin Oncol 1998;16(11):3502-3508.
28. Roche H, Fumoleau P, Spielmann M, et al. Five years analysis of
PACS 01 trial: 6 cycles of FEC 100 vs 3 cycles of FEC 100
followed by 3 cycles of docetaxel (D) for the adjuvant treatment
of node-positive breast cancer. Breast Cancer Res Treat
29. Sehested M, Jensen PB. Mapping of DNA topoisomerase II
poisons (etoposide, clerocidin) and catalytic inhibitors
(aclarubicin, ICRF-187) to four distinct steps in the
topoisomerase II catalytic
30. Arbuck SG, Strauss H, Rowinsky E, , et al. A reassessment of
cardiac toxicity associated with Taxol. J Natl Cancer Inst
Monogr 1993; (15):117-130.
31. Giordano SH, Booser DJ, Murray JL, et al. A detailed evaluation
of cardiac toxicity: a phase II study of doxorubicin and one- or
three-hour-infusion paclitaxel in patients with metastatic breast
cancer. Clin Cancer Res 2002;8(11):3360-3368.
32. Gennari A, Salvadori B, Donati S, et al. Cardiotoxicity of
epirubicin/paclitaxel-containing regimens: role of cardiac risk
factors. J Clin Oncol 1999;17(11):3596-3602.
33. Sawyer DB, Zuppinger C, Miller TA, et al. Modulation of
anthracycline-induced myofibrillar disarray in rat ventricular
myocytes by neuregulin-1beta and anti-erbB2: potential
mechanism for trastuzumab-induced
34. Altena R, Perik PJ, van Veldhuisen DJ, et al. Cardiovascular
toxicity caused by cancer treatment: strategies for early
detection. Lancet Oncol 2009;10(4):391-399.
cancer. N Engl J Med
to the current
cycle. Biochem Pharmacol
Int. J. Med. Sci. 2012, 9
35. Lafitte S. Do we need new echocardiographic prognosticators
for the management of heart failure patients? J Am Coll Cardiol
36. Cho GY, Marwick TH, Kim HS, et al. Global 2-dimensional
strain as a new prognosticator in patients with heart failure. J
Am Coll Cardiol 2009;54(7):618-624.
37. Koyama J, Falk RH. Prognostic significance of strain Doppler
imaging in light-chain amyloidosis. JACC Cardiovasc Imaging
38. Marwick TH, Raman SV, Carrio I, et al. Recent developments in
heart failure imaging.
39. Jassal DS, Han SY, Hans C, et al. Utility of tissue Doppler and
strain rate imaging in the early detection of trastuzumab and
anthracycline mediated cardiomyopathy.
40. Sawaya H, Sebag I, Plana JC, et al. Early Detection and
Prediction of Cardiotoxicity in Chemotherapy-Treated Patients:
An Echocardiographic and Biomarker Study. American Society
of Echocardiography - 21st Annual Scientific Sessions; San
Diego, California. 2010:AbstractP1-42.
41. [Internet] Reis L, Melbert D, Krapcho M, et al. SEER Cancer
Statistics Review, 1975-2004, National Cancer Institute.
42. Ng AK, Travis LB. Subsequent malignant neoplasms in cancer
survivors. Cancer J 2008;14(6):429-434.
43. Travis LB, Fossa SD, Schonfeld SJ, et al. Second cancers among
40,576 testicular cancer patients: focus on long-term survivors. J
Natl Cancer Inst 2005;97(18):1354-1365.
44. Stava C, Beck M, Weiss LT, et al. Health profiles of 996
melanoma survivors: the M. D. Anderson experience. BMC
45. van der Gaast A, Postmus PE, Burghouts J, et al. Long term
survival of small cell lung cancer patients after chemotherapy.
Br J Cancer 1993;67(4):822-824.
46. Raymond JS, Hogue CJ. Multiple primary tumours in women
following breast cancer,
47. Takigawa N, Kiura K, Segawa Y, et al. Second primary cancer in
survivors following concurrent chemoradiation for locally
advanced non-small-cell lung
48. Okines A, Thomson CS, Radstone CR, et al. Second primary
malignancies after treatment for malignant lymphoma. Br J
49. Fernebro J, Bladstrom A, Rydholm A, et al. Increased risk of
malignancies in a population-based study of 818 soft-tissue
sarcoma patients. Br J Cancer 2006;95(8):986-990.
50. Kirova YM, De Rycke Y, Gambotti L, et al. Second malignancies
after breast cancer: the impact of different treatment modalities.
Br J Cancer 2008;98(5):870-874.
51. Gianni L, Gelber S, Ravaioli A, et al. Second non-breast primary
cancer following adjuvant therapy for early breast cancer: a
report from the International Breast Cancer Study Group. Eur J
52. Chaturvedi AK, Kleinerman RA, Hildesheim A, et al. Second
cancers after squamous cell carcinoma and adenocarcinoma of
the cervix. J Clin Oncol 2009;27(6):967-973.
53. Meadows AT, Friedman DL, Neglia JP, et al. Second Neoplasms
in Survivors of Childhood Cancer: Findings From the
Childhood Cancer Survivor Study Cohort. J Clin Oncol 2009;
27: 2356 - 2362.
54. Hodgson DC, Gilbert ES, Dores GM, et al. Long-term solid
cancer risk among 5-year survivors of Hodgkin's lymphoma. J
Clin Oncol 2007;25(12):1489-1497.
JACC Cardiovasc Imaging
J Am Soc
1973-2000. Br J Cancer
cancer. Br J Cancer
55. Metayer C, Lynch CF, Clarke EA, et al. Second cancers among
long-term survivors of Hodgkin's disease diagnosed in
childhood and adolescence. J Clin Oncol 2000;18(12):2435-2443.
56. Swerdlow AJ, Barber JA, Hudson GV, , et al. Risk of second
malignancy after Hodgkin's disease in a collaborative British
cohort: the relation to age at treatment. J Clin Oncol
57. Ng AK, Bernardo MV, Weller E, et al. Second malignancy after
Hodgkin disease treated with radiation therapy with or without
chemotherapy: long-term risks and risk factors. Blood
58. Bhatia S, Yasui Y, Robison LL, et al. High risk of subsequent
neoplasms continues with extended follow-up of childhood
Hodgkin's disease: report from the Late Effects Study Group. J
Clin Oncol 2003;21(23):4386-4394.
59. Heyne KH, Lippman SM, Lee JJ, et al. The incidence of second
primary tumors in long-term survivors of small-cell lung
cancer. J Clin Oncol 1992;10(10):1519-1524.
60. Matesich SM, Shapiro CL. Second cancers after breast cancer
treatment. Semin Oncol 2003;30(6):740-748.
61. Langeveld NE, Grootenhuis MA, Voute PA, et al. Quality of
life, self-esteem and worries in young adult survivors of
childhood cancer. Psychooncology 2004;13(12):867-881.
62. Hoffman KE, McCarthy EP, Recklitis CJ, et al. Psychological
distress in long-term survivors of adult-onset cancer: results
from a national survey.
63. Zebrack BJ, Yi J, Petersen L, et al. The impact of cancer and
quality of life for long-term survivors. Psychooncology
64. Partridge AH, Gelber S, Peppercorn J, et al. Web-based survey
of fertility issues in young women with breast cancer. J Clin
Oncol 2004; 22: 4174-4183.
65. Thewes B, Meiser B, Taylor A, et al. Fertility- and meno-
pause-related information needs of younger women with a di-
agnosis of early breast cancer. J Clin Oncol 2005; 23: 5155-5165.
66. Carpenter KM, Andersen BL, Fowler JM, et al. Sexual self
schema as a moderator of sexual and psychological outcomes
for gynecologic cancer survivors. Arch Sex Rehab 2009; 38(5):
67. Hickey M, Peate M, Saunders CM, et al. Breast cancer in young
women and its impact on reproductive function. Human Re-
production Update; 2009; 15 (No 3): 323-339.
68. Sverrisdottir A, Fornander T, Jacobsson H, et al. Bone mineral
density among premenopausal women with early breast cancer
in a randomized trial of adjuvant endocrine therapy. J Clin
Oncol 2004; 22: 3694-3699.
69. Bertero C. Altered sexual patterns after treatment for prostate
cancer. Cancer Practice 2001; 9: 245-251.
70. Jenkins R, Schover LR, Fouladi RT, et al. Sexuality and
health-related quality of life after prostate cancer in Afri-
can-American and while men treated for localized disease.
Journal of Sex & Marital Therapy 2004; 30: 79-93.
71. Gershenson DM, Miller AM, Champion VL, et al. Reproductive
and sexual function after platinum-based chemotherapy in
long-term ovarian germ cell tumor survivors: A Gynecologic
Oncology Group study. J Clin Oncol 2007; 25: 2792-2797.
72. Parker PA, Baile WF, De Moor C, et al. Psychosocial and de-
mographic predictors of quality of life in a large sample of
cancer patients. Psycho-Oncology 2003; 12: 183-193.
73. Sonmezer M, Oktay K. Fertility preservation in young women
undergoing breast cancer therapy. Oncologist 2006; 11: 422-434.
74. Sabatino SA, Coates RJ, Uhler RJ, et al. Provider counseling
about health behaviors among cancer survivors in the United
States. J Clin Oncol 2007;25(15):2100-2106.
75. Hoffman B. Cancer survivors at work: a generation of progress.
CA Cancer J Clin 2005;55(5):271-280.
Arch Intern Med
Int. J. Med. Sci. 2012, 9 Download full-text
76. Jemal A, Clegg LX, Ward E, et al. Annual report to the nation on
the status of cancer, 1975-2001, with a special feature regarding
survival. Cancer 2004;101(1):3-27.
77. de Boer AG, Taskila T, Ojajarvi A, et al. Cancer survivors and
unemployment: a meta-analysis and meta-regression. JAMA
78. Park ER, Li FP, Liu Y, et al. Health insurance coverage in
survivors of childhood cancer: the Childhood Cancer Survivor
Study. J Clin Oncol 2005;23(36):9187-9197.