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Radiotherapypluschemotherapywithorwithout surgical
resectionfor stageIII non-small-cell lungcancer:aphaseIII
randomisedcontrolledtrial
KathySAlbain,RSuzanneSwann, ValerieWRusch,AndrewTTurrisi III,FrancesAShepherd, ColumSmith,YuhchyauChen,Robert BLivingston,
RichardHFeins,DavidRGandara,WillardAFry,Gail Darling,DavidHJohnson,MarkRGreen,Robert CMiller,JoanneLey,WillliamTSause,JamesDCox
Summary
Background Results from phase II studies in patients with stage IIIA non-small-cell lung cancer with ipsilateral
mediastinal nodal metastases (N2) have shown the feasibility of resection after concurrent chemotherapy and
radiotherapywithpromisingratesof survival. WethereforedidthisphaseIII trial tocompareconcurrent chemotherapy
and radiotherapy followed by resection with standard concurrent chemotherapy and definitive radiotherapy without
resection.
MethodsPatientswithstageT1-3pN2M0 non-small-cell lungcancer wererandomlyassigned ina1:1ratiotoconcurrent
induction chemotherapy (two cycles of cisplatin [50 mg/m² on days 1, 8, 29, and 36] and etoposide [50 mg/m² on
days 1–5 and 29–33]) plus radiotherapy (45 Gy) in multiple academic and community hospitals. If no progression,
patients in group 1underwent resection and those in group 2 continued radiotherapy uninterrupted up to61Gy. Two
additional cycles of cisplatin and etoposide were given in both groups. The primary endpoint was overall survival
(OS). Analysiswasby intention to treat. Thisstudy isregisteredwith ClinicalT rials.gov, number NCT00002550.
Findings 202 patients (median age 59 years, range 31–77) were assigned to group 1 and 194 (61 years, 32–78) to
group 2. Median OSwas 23· 6 months (IQR 9· 0–not reached) in group 1versus 22· 2 months (9· 4–52· 7) in group 2
(hazard ratio [HR] 0· 87 [0· 70–1· 10]; p=0· 24). Number of patients alive at 5 years was 37 (point estimate 27%) in
group 1and 24 (point estimate 20%) in group 2 (odds ratio0· 63 [0· 36–1· 10]; p=0· 10). With N0 statusat thoracotomy,
the median OS was 34· 4 months (IQR 15· 7–not reached; 19 [point estimate 41%] patients alive at 5 years).
Progression-free survival (PFS) wasbetter in group1than in group2, median 12· 8months(5· 3–42· 2) vs10· 5months
(4· 8–20· 6), HR 0· 77 [0· 62–0· 96]; p=0· 017); the number of patients without disease progression at 5 years was
32 (point estimate 22%) versus 13 (point estimate 11%), respectively. Neutropenia and oesophagitis were the main
grade 3 or 4 toxicitiesassociated with chemotherapy plusradiotherapy in group 1(77 [38%] and 20 [10%], respectively)
and group 2 (80 [41%] and 44 [23%], respectively). In group 1, 16 (8%) deathswere treatment related versus four (2%)
in group 2. In an exploratory analysis, OS was improved for patients who underwent lobectomy, but not
pneumonectomy, versuschemotherapyplusradiotherapy.
Interpretation Chemotherapy plus radiotherapy with or without resection (preferably lobectomy) are options for
patientswith stage IIIA(N2) non-small-cell lungcancer .
Funding National Cancer Institute, Canadian Cancer Society, andNational Cancer Instituteof Canada.
Introduction survival rates that werehigher than expected.11–13 However,
Lancet 2009;374:379–86
Published Online
July27,2009
DOI:10.1016/S0140-
6736(09)60737-6
See Comment page359
LoyolaUniversityChicago
StritchSchool of Medicine,
Maywood, IL, USA
(Prof KSAlbainMD);Radiation
TherapyOncologyGroup,
Philadelphia, PA, USA
(RSSwann PhD, JLeyRN);
Memorial Sloan-Kettering
CancerCenter, NewYork, NY,
USA(Prof VWRuschMD);
WayneStateUniversity,
Detroit, MI, USA
(Prof ATTurrisi III MD);
UniversityHealthNetwork,
PrincessMargaret Hospital
Site, Toronto, ON, Canada
(Prof FAShepherdMD);
TomBakerCancerCenter,
Calgary, AB, Canada
(Prof CSmithMD);University
of RochesterMedical Center,
Rochester, NY, USA
(Prof YChenMD);University of
ArizonaCancerCenter,Tucson,
AZ, USA
(Prof RBLivingstonMD);
Universityof NorthCarolina,
Chapel Hill, NC, USA
(Prof RHFeinsMD);University
of Californiaat DavisCancer
Center, Sacramento, CA, USA
(Prof DRGandaraMD);
EvanstonHospital of Albain KS. et al. Lancet 2009;374
Role of Induction CT-RT: Lung Intergroup Trial 0139
 429 Stage IIIA (pN2) patients
 Group 1:
• Cisplatin + Etoposide x 2
• RT 45 Gy
• Surgery
• 2 additional CT cycles
 Group 2:
• Cisplatin + Et poside x 2
• RT 61 Gy
• 2 additional CT cycles