Journal of Cancer Therapy, 2012, 3, 359-363 Published Online September 2012 (
Elderly Lung Cancer Patients and Radiochemotherapy: A
Francesco Fiorica*, Antonio Stefanelli, Silvia Princivalle, Giuliana Pascale, Francesco Cartei
Department of Radiation Oncology, University Hospital Ferrara, Ferrara, Italy.
Email: *
Received July 18th, 2012; revised August 20th, 2012; accepted September 4th, 2012
More than 60% of lung cancer patients in Europe and the USA are older than 65 years at the time of diagnosis. Despite
this, elderly patients are generally under-represented in clinical trials. That being so, a general consensus on how to treat
elderly patients is still far from being achieved. In this review, we address some of the issues and challenges surround-
ing the treatment of older cancer patients and radiochemotherapy. We discuss the existing evidence related to radio-
chemotherapy in the elderly, focusing primarily on the lung cancer (NSCLC and SCLC) most commonly seen in older
patients, and making general treatment recommendations.
Keywords: Radiochemotherapy; Lung Cancer; Elderly Patients; Geriatric Oncology; Clinical Trials
1. Introduction
Lung cancer is the leading cause of cancer deaths in the
United States and worldwide [1] and it is a typical cancer
of elderly patients. Incidence data from the National
Cancer Institute’s (NCI) surveillance epidemiology and
results (SEER) have shown that older persons have a 10
times greater risk of developing lung cancer than those
with an age of less than 65 years.
As the survival of elderly population increases in de-
veloped countries worldwide, it is expected that oncolo-
gists will be increasingly confronted with the therapeutic
challenge of an elderly patient presenting with NSCLC
or SCLC. It is by now widespread that radiochemother-
apy is standard treatment for unresectable non small cell
lung cancerand for small cell lung cancer; however in
elderly cancer patients there is no clear evidence of
safety and efficacy of radiochemotherapy approach.
Manly, elderly patients are underrepresented in rando-
mized clinical trials and those treated are normally with-
out significant comorbidity and with a good functional
organ reserve. Since elderly patients are an extremely
heterogeneous population, subjects can vary from very fit
to not being able to live independently due to co-mor-
bidities, it is not so clear whether the toxicity of treat-
ment is justified by the level gained as measured by life
prolongation and whether co-morbidities can influence
the acute and late toxicities due to radiochemotherapy.
Nevertheless, patients who have reached their 80th year
still have a mean life expectancy of seven years for men
and nine years for women [2].
Age alone is not a sufficient reason to withhold radio-
chemotherapy treatment. Although there is a lack of
clinical trials to drive evidence-based decision making in
the elderly lung cancer patients, we review some of the
important studies germane to the lung cancer radio-
chemotherapy treatment in elderly patients.
2. Elderly Cancer Patients
Traditionally the cut-off point at which an adult is con-
sidered “elderly” is 65 years. However, it is increasingly
recognised that aging is a highly individualised process
and all the changes involved in this process cannot be
predicted solely on the basis of chronologic age. Indeed,
at the age of 75 years, some will be as fit if not even
more fit than many at the age of 60 years [3]. Efficacy/
toxicity ratio of an oncological treatment is clearly re-
lated to biological age and frail patients can be young [4].
Clinical evaluation of age should account for the diver-
sity in terms of life-expectancy, incidence and prevalence
of disease, degree of functional dependency, cognition,
emotions and socio-economic resources [5]. The most
studied instrument to provide information for risk strati-
fication of elderly cancer patients is the comprehensive
geriatric assessment (CGA). This assessment is based on
evaluation of functional status, co-morbidities, polyphar-
macy, nutritional status, cognitive function, physiological
status, socio-economic issues and geriatric syndromes.
*Corresponding author.
Copyright © 2012 SciRes. JCT
Elderly Lung Cancer Patients and Radiochemotherapy: A Review
Each CGA may aid in personalising care for the patient
with cancer [6]. Thereafter, patient’s tolerance to radio-
chemotherapy can be assessed and monitoring can be
3. Rationale of Cominbing Radiotherapy and
Chemotherapy in Clinical Practice
Combined modality therapy has become a standard
treatment for lung cancer. There are two main reasons to
combine chemotherapy and external beam irradiation to
improve therapeutic ratio [7,8]:
Spatial cooperation two anti-tumor agents act inde-
pendently, controlling primary tumor (radiotherapy)
and distant (micro-)metastases (chemotherapy);
Enhancement of radiation effects produces a greater
anti-tumor response than would be expected from the
response achieved with radiotherapy used separately.
Spatial cooperation is effective if both anti-cancer mo-
dalities can be used at effective dosages, so that no inter-
action between radiotherapy and chemotherapy is re-
quired and differing toxicities are needed. This hypothe-
sis underlies sequential radio-chemotherapy studies.
Besides independent cell killing of both modalities,
chemotherapy may synchronize cells in a vulnerable
phase for radiotherapy, decrease repopulation after ra-
diotherapy, and enhance re-oxygenation by shrinking a
tumor, which is advantageous for radiotherapy. However,
this concept has failed in most clinical trials, meta-
analyses, clearly, demonstrated inferiority of sequential
approach in non small [9] and small cell lung cancer [10]
compared to concomitant approach.
Probably, chemotherapy induces a fast repopulation of
tumor cells [11] obtaining a rapid tumor progression be-
tween the end of chemotherapy and the start of radio-
therapy. Otherwise, chemotherapy increases the number
of quiescent cells that are as well radioresistant.
Enhancement of radiation with concomitant chemo-
therapy increases the effects in the irradiated volume
leading to an increased local tumor control probably re-
lated to reduction of overall treatment time and therefore
minimising the risk of repopulation. This increased tu-
mor control can lead to an improved overall survival.
However, cytostatic drugs, used as radiosensitiziers (cis-
platin, 5-fluorouracil, taxanes) can increase damage to
normal tissues. A therapeutic benefit is only achieved if
enhancement of the tumor response is greater than that
for normal tissues.
4. Tolerance of Radiotherapy and
Chemotherapy in Elderly Patients
Combining radiotherapy and chemotherapy can result in
increased therapeutic activity but also in increased toxi-
city, in fact:
Effects of radiotherapy can be increased by chemo-
therapy on tumor and organ at risk;
Effects of chemotherapy on target organ can be in-
creased by radiotherapy;
Independent injuries can be caused by the individual
treatment modality in the same organ which can com-
bine to increase the resulting dysfunction;
An injury can be produced that is not commonly seen
with either modality alone.
One of the reasons for difference in cancer treatment
of elderly patients is the fear that advanced age may be
associated with a reduced tolerance of treatment.
Data related to treatment tolerance in elderly patients
are scarce, mainly because elderly patients are under re-
presented in oncological clinical trials (account for only
Along with increasing age a decrease in physiologic
reserve is observed. This is a complex process that varies
in how it affects different people and even different or-
gans. Moreover, this process is accelerated by the deve-
lopment of intercurrent illness. Elderly patients have a
high prevalence of diseases, about 80% having three or
more chronic conditions. It is likely that this population
is compensated under normal condition, but when a pa-
tient is subjected to a stress, there may be inadequate
functional reserve. Certainly, a combined radio-chemo-
therapy program represents a systemic and loco-regional
distress. Its impact on daily functioning or its long-term
impact on organ functions may be very important in
many of these elderly patients. Therefore, it is essential
to acquire a multidisciplinary assessment of patients in
order to understand the clinical state of the individual and
functional organ reserve independently from the diagno-
sis of cancer [12]. Obviously, evaluation of co-morbidity
is very important in geriatric functional assessment, in
order to recognise potentially treatable conditions, to
assess functional reserve and to estimate life expectancy.
Co-morbidity scores can be divided into two groups:
those that have been validated in elderly people but not
in malignant disease (geriatric index of co-morbidity
[GIC] [13] and those that have been developed in elderly
people and validated in patients with cancer (adult co-
morbidity evaluation-27 [ACE-27] [14], cumulative ill-
ness rating scale for geriatrics [CIRS-G] [15], and the
Charlson index [16]. After geriatric assessment, patients
should be divided in fit, vulnerable, or frail. These cate-
gories of patients have different physiological reserves to
tolerate a course of combined radiochemotherapy [17].
Frail patients have a poor prognosis, present high toxicity
with standard treatments, and are candidates to palliative
treatments. Physiologically fit patients are able to tolerate
radical treatments, and may be treated similarly to
younger patients. Vulnerable patients are those with re-
ducted functional reserve and partial limitations, and may
Copyright © 2012 SciRes. JCT
Elderly Lung Cancer Patients and Radiochemotherapy: A Review 361
be candidates for customized radiotherapy and chemo-
therapy treatment according to organ functional reserve.
That being so, elderly patients require therapeutic stra-
tegies adapted to their individual risk profile, scoring and
monitoring physiological organ reserve and co-morbidi-
5. Non Small Cell Lung Cancer
NSCLC is a predominant disease in elderly patients, with
a median age at diagnosis of 71 years. 20% of lung can-
cer-related deaths occur in patients aged 80 years [18].
Nevertheless, no clinical trials are designed specifically
for elderly NSCLC patients. Population-based analyses
also report an undertreatment of these patients, only 46%
of individuals aged > 65 with NSCLC IIIb and IV stage
received RT, 24% of them combined with chemotherapy
[19]. In 2000, the Radiation Therapy Oncology Group
performed a recursive partitioning analysis of 1999 pa-
tients enrolled in various protocols and identified age as a
factor in therapeutic outcome in locally advanced
NSCLC [20]. The susceptibility of combined radio-che-
motherapy approach for elderly patients has only been
studied in subset analyses of clinical trials in a post hoc
The North Central Cancer Treatment Group NCCTG
[21] conducted a randomized clinical trial to compare the
results of adding chemotherapy to once-daily or twice-
daily radiotherapy. Despite increased toxicity, elderly pa-
tients have 2- and 5-year survival rates which are equi-
valent to younger individuals. Similarly, evaluating el-
derly patients of two randomized clinical trials of Cancer
and Leukemia Group B (CALGB), Rocha Lima et al.
showed that the efficacy outcomes were comparable be-
tween patients aged 70 years and older and those aged
less than 70 years. None of the patients included in these
studies were older than 80 years of age. Same results
were reported in the subset analyses of the RTOG 94-10
study [22].
In addition to these subset analyses, several reports
have been published with recommendations on the treat-
ment of elderly. Two retrospective analyses in patients
receiving combined modality therapy showed no nega-
tive impact of age on treatment tolerance, response to
treatment, or survival [23,24]. Semrau et al. [25], retro-
spectively examined 66 patients with inoperable NSCLC
suffering from substantial co-morbidities or at advanced
age (>70 years) treated with chemo-radiotherapy, ana-
lysed according to co-morbidity, and concluded that
chemo-radiotherapy was safely feasible in elderly pa-
tients with NSCLC, although elderly patients had a
higher prevalence of higher degree hematological toxi-
city than younger patients.
A recent study [26] shows that patients without or with
mild co-morbidities have a significantly better survival.
The increasing severity of co-morbidities may suffi-
ciently shorten the remaining life expectancy, cancel the
gains obtained by radiotherapy and increase the acute
lung toxicity.
Thus, based on current evidence, we recommend that
elderly patients with advanced NSCLC and a good per-
formance status be offered combined treatment. However,
in the oldest/old and in frail patients, single modality
treatment may be most appropriate.
6. Small Cell Lung Cancer
A multimodality approach consisting of radiotherapy and
platinum-etoposide chemotherapy is recommended treat-
ment for patients with limited stage SCLC. Adding che-
motherapy to thoracic radiotherapy leads to an approxi-
mately 30% increase in disease control and up to 14%
reduction in mortality. Combined treatment produces a
significant improvement in survival of 5.4% at 3 years
compared with chemotherapy alone [27,28]. From subset
analyses of these two meta-analyses, it appears that the
benefit is confined to younger patients (aged less than 55)
with a trend toward on adverse outcome in patients aged
more than 70 years. All these facts are justified by au-
thors with an increased toxicity, however no data are
available. In 1999, a retrospective review of two ran-
domized trials of the National Cancer Institute of Canada
[29] clearly demonstrated that here was no statistical
difference noted with regard to the rates of RT-related
toxicities, response, local control, or survival between the
young and older age groups. Similarly, Yuen et al., ana-
lyzing retrospectively elderly patients in Intergroup Trial
0096 [30], showed that elderly patients had similar re-
sponse and survival rates compared with those younger
than 70 years. However, toxicity, particularly hemato-
logic, was greater among the elderly. The retrospective
analysis of North Central Cancer Treatment Group [31]
revealed that elderly patients may experience greater
toxicity due to preexisting illnesses, decreased clearance
of chemotherapy, and limited bone marrow reserve. In
spite of increased toxicities, elderly patients had disease
control and survival rates similar to those of younger
patients. In addition to these subset analyses, several re-
ports have been published with conflicting results as
some studies reported similar survival between young
and elderly patients [32,33] and other studies reported
lower survival for the elderly [34,35].
A less aggressive treatment approach has been inves-
tigated in two prospective phase II studies of radioche-
motherapy treatment specifically designed for elderly
patients with small cell lung cancer. Jeremic et al. evalu-
ated a regimen of carboplatin and etoposide combined
with accelerated hyperfractionated radiation, obtaining a
Copyright © 2012 SciRes. JCT
Elderly Lung Cancer Patients and Radiochemotherapy: A Review
tolerable and active regimen [36]. Murray et al. evaluated
an abbreviated regimen plan consisting of two cycles of
chemotherapy plus thoracic irradiation obtaining useful
palliation and potential for long-term survival [37].
Concurrent radiochemotherapy can be administered to
fit elderly patients with limited stage SCLC. For patients
with multiple comorbidities, the sequential approach or
an abbreviated approach is better alternative.
7. Conclusions
In geriatric oncology, the key question is to achieve the
best outcomes and avoid unnecessary or ineffective treat-
ments. Radiochemotherapy maintains its activity and
feasibility in lung cancer elderly patients. It is difficult to
determine a standard therapy for elderly patients based
only on chronological landmarks, as the effects of aging
depend on the individual. It is very important to assess
comorbidity with its severity in order to aid in the deve-
lopment of plans for treatment.
Lung cancer elderly patients, correctly stratified, should
be allowed and encouraged to participate in clinical
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