Concurrent Chemoradiation in Inoperable, Locally Advanced Non-small Cell Lung Cancer
Table 1: Retrospective Subgroup Analyses of Chemoradiation Trials for Non-small Cell Lung Cancer Comparing Treatment Outcomes between Elderly and Younger Patients
Study Langer et al.18
Trials No. of Patients Efficacy
Phase III trial CCRT <70 y: 491 (qd or bid) versus SCRT
≥70 y:104
Schild et al.19
Phase III trial: CCRTbid versus CCRTqd
trials: SCRT versus CCRT
Movsas et al.17
RT, SCRT or CCRT Six Phase II and III trials: RT, SCRT or CCRT
<70 y: 181 ≥70 y: 63
Rocha-Lima Two CALGB Phase III <70 y: 222 et al.14
≥70 y: 31
Werner-Wasik Nine Phase I–III trials: <70 y: 1,565 et al.16
≥70 y: 429 <70 y: 835 ≥70 y: 144
Toxicity
In favour of CCRT Short-term toxicities (G>3 for >70 y
Survival not age-related
Survival not age-related
Survival age-related
<70 y: improved NR survival with CMT
>70 y: best quality- adjusted survival with RT alone
CCRT = concurrent chemoradiation; CCRTbid = concurrent chemoradiation twice a day; CCRTqd = concurrent chemoradiation daily; CMT = combined modality treatment; G = grade; LA-NSCLC = locally advanced non-small cell lung cancer; MST = median survival time in months; NR = not reported; RT=radiotherapy; SCRT = sequential chemoradiation; y = years. Source: Table modified from Gridelli C. et al.27
MST ≥70 y: 10.8 months (SCRT) versus 16.4
more neutropenia and oesophagitis) months (CCRTbid) versus 22.4 pronounced in elderly,
months (CCRTqd)
long-term toxicities similar More myelosuppression and pneumonitis in elderly
More haematologic toxicity in elderly
NR
<70 y: 5-y survival rate = 18 % ≥70 y: 5-y survival rate = 13 %
<70 y: 11–15 months ≥70 y: 13 months
<70 y: 10–16 months ≥70 y: 3–6 months <70 y: 12–14 months ≥70 y: 11 months
to guide physicians in treatment decisions for elderly patients. Controlled clinical trials especially designed toward the elderly, including geriatric evaluations, are indicated.14
Only one prospective elderly-specific Phase III trial has evaluated CCRT versus radiotherapy (RT) alone.15
Patients were randomly assigned to
RT alone (60 Gy) or to CCRT (same RT with concurrent administration of carboplatin 30 mg/m2). The trial was prematurely closed for accrual after the occurrence of four treatment-related deaths, of which three occurred in the CCRT arm. For the 46 patients treated at that time, the median survival time was not significantly different between both arms (14.3 months with RT alone compared with 18.5 months in the CCRT arm). Because of the small number of patients included and protocol violations concerning the radiation field that might have influenced half of the treatment-related deaths attributed to pneumonitis, the investigators concluded that the efficacy of concurrent carboplatin plus radiotherapy in elderly patients remains unclear and no definitive conclusions can be drawn from this trial.
Movsas et al. reported that the best quality-adjusted survival in older patients was achieved with RT alone.17 analyses of several other trials14,18–20 Group meta-analysis21
chemoradiation was not related to age.
Valuable information can be obtained from population-based studies that examined the effects of combined modality treatment in the elderly population. These are treatment results obtained in the heterogeneous population of older patients with co-morbid conditions and poorer performance status (PS) that are not treated in
EUROPEAN ONCOLOGY & HAEMATOLOGY
When looking at retrospective subgroup analyses of randomised chemoradiation trials comparing treatment outcomes between elderly and younger patients, results are inconsistent (see Table 1). For example, secondary analysis of a Radiation Therapy Oncology Group (RTOG) study demonstrated inferior outcomes of chemoradiation in the elderly and those with poorer performance status.16
In contrast, subset and the NSCLC Collaborative concluded that the survival advantage of
a clinical trial setting. Davidoff and colleagues22
investigated the
effects of combined modality treatment in elderly LA-NSCLC patients using Surveillance, Epidemiology and End Results – Medicare data and concluded that survival benefits associated with combined modality treatment in clinical trials can be extended to the elderly population in routine daily practice. The absolute survival duration observed is shorter than that reported in clinical trials, reflecting the higher co-morbid conditions or poorer PS of the elderly patients treated outside the clinical trial setting.
Concurrent Chemoradiation in the Frail Elderly We could only identify one institutional report, by Semrau et al., on CCRT in elderly LA-NSCLC patients presenting with multiple morbidities. They reported their six-year experience of CCRT with vinorelbine plus a platinum compound. The frail elderly population was defined as patients with an increased risk profile of treatment side effects due to World Health Organization (WHO) performance status 2–3, cardiac, renal or pulmonary failure, extensive weight loss before treatment or age 71–78 years. A total of 66 patients received CCRT, with manageable toxicity. The dose intensity of chemotherapy and radiotherapy was 62 % and 94 %, respectively. In this population with poor prognostic factors, dose-adjusted chemotherapy and radiotherapy was feasible, and the survival rates of 25 % at two years and 8 % at five years were comparable to those achieved in other studies.23
Technological Advances in the Field of Radiotherapy
Technological advances in radiotherapy treatment planning and delivery have occurred in the past five years, including incorporation of functional imaging by [18F]deoxyglucose-positron emission tomography (PET) scan in the planning process,5
three-dimensional
conformal radiotherapy, respiratory gating, four-dimensional computed tomography,7
intensity-modulated radiotherapy, helical
tomotherapy and image-guided radiotherapy. These newer radiation techniques significantly reduce toxicity by limiting the volume of irradiated lung tissue.7
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