PD-091 Pretreatment prognostic factors in patients with early stage(VII) nonsmall cell lung cancer treated wth hyperfactionated radiation therapy alone

Poster D i s c u s s i o n s / N o n - s m a l l cell lung cancer - Early disease (I-/I/A) ~ D ~ 8 ~ NATCH Trlal update M Canela ~ J Maestro ~, M Rodriguez~aniagua ~, J Astucillo 3. J Borro ~. R. A~Jilb ~, A TonTesG, A Cantb 7, J. Padilla ~, L. Molins g. ~Ho~p/taJ

Universitario Vail D'hebron, Bamelona, Spain, ~Hosp~tal Genera/Unviersita#o de A/icanfa, AJicanfa, Spain, 3Hosptta/ Universitario Germans Tries i Pujet, BaCalona, Baroa/ona, Spain; ~Hospta/ Juan Cana/ejo, La Cotu~a, Spain; ~Hosp~ta/ C#r~co Un/versttano Lozano Blesa, Zarsgoza, Spain; ~Hosp/ta/ Cllmco Umvers~tano San Carlos, Madrid, Spare: 7Hospta/ Genera/ Umvers~tano de Va/encia, Valencta, Spain; eHospttal Umvers~tano de la Fe, Valencia, Spare: gHosp/tal Sagrst Cor, Barcelona, Spare Background: Although radical surgery is the most eff~ct]ve treatment for earlystage non-small-cell lung cancer (NSCLC). the long-term survival of patients who undergo surgery alone is largely disappoint]ng The NATCH thai was designed to evaluate the effect of oarbopiatin/paclitaxel chemotherapy in earlystage NSCLC pat]ents. Methods: Since 2000.492 stage I. I1. T3N1 NSCLC pat]ents of a planned 628 have been included in a three arm randomized thai comparing surgery alone versus three cycles of neoadjuvant paclitaxel 200 m~m2/carboplat]n AUC 6 q3wk versus surgery followed by three cycles of the same regimen The primary objective isthe comparison of cisease-free survival times Pat]ents are selected from the Lung Canoer Committee in each center Mediast]noscepy is performed in these pat]ents with radiologicel mediast]nal lymph node involvement in the CT scan. Signed genet]e consent was obtained from all pat]ents. Blood samples are to be extracted at baseline, and then at six months and 12 months of follow up. Sub analyses of several genetic abnormalities in paraffir~embedded tumor samples are being carried out. Results: Irlt]al domograptle data is available for 293 pat]ents: 248 male. 45 female; 52% squamous cell. 35% adenocarOnoma. 7% large cell. 6% unspecified: 15% stage IA, 67% lB. 3% IIA. 12% liB. 4% Ilia (T3N1) No significant toxicitiea were observed in chemotherapy arms Radiographic response with neoadjuvant chemotherapy: 5 (,5%) complete response. 49 (54%) partial response. 31 (34%) stable disease Lobectomy was performed in 60% of all pat]onts, pneumonectomy in 24%. bilobectomy in 7%. other procedures in remaining pat]ents Complete surgical r o s e , o n was feasible in 92% of pat]ents Conclusions: This study increases the esperlence of mult]disc~plinary treatment teams. Genet]e results could help us to ident]fy patients who v~ll most benefit from chemotherapy. Accrual is ongoing to 628 patients.

~lmage-guIdad proton radiotherapy for madlcally Inoperable stage I non-small call lung cancer

advantage in sparing normal organs (such as contralateral lung. heart, and spinal cord), especially at low dose levels Conclusions: Tumor motion has a significant effect on radiat]on dose cistdbut]on This mot]on should be considered for both photon and proton raciotherapy Compared with photon 3 D ~ R T and IMRT with gated or nongated radiotherapy, proton raciotherapy (gated or free~roathing with ITV approach) significantly improves normal tissue sparing Our data showed that it is possible to have esoalated/accelerated proton radiotherapy without s~geificantly increasing normal tissue toxlcit]es. This approach may translate to better local con/]'el and survival for patients with stage I NSCLC. PaUants' outcome and pattern of relapses following radical

~

surgery and adjuvant chemotherapy (CT) In non-small call lung cancer (NSCLC) M Dediu I , T Horvat 2, R Anghel I . A Tadea I . A Ale0(andru ~. C Nistor ~, P. Iorga I . C. Savu2, C. Grozevu 2. llns~ute of Oncotogy Bucharest,

Bucharest. Romania. 2 MJ/Jtaty Hospital Bucharest, Bucharest. Romania Background: The impact of adjuvant CT in the management of resectable NSCLC is highly debated We evaluated the outcome of this category of patients (pts) tTeated at The Military Hospital Bucharest (surgery) and Inst]tute of Oncelogy Bucharest (CT) PaUents and methods: We rsl]'espectlvely analyzed the survival data according to vanous patients' charactenstios (stage. type of surgery, pathologic NSCLC type), the correspondng pattern of relapse, along with the data concerning the CT program. Results: A number of 356 censecutrvely patients, treated between January 1994 and November 2003. was evaluated. All patients were radically rosected and received adjuvant CT. Chemotherapy was planned to be osplatin based and to be delivered for six cycles In adcit]on 147 pts (41%) received postoperative RT Demographics: se0¢: M 289 (81%)/F 67 (19%). median age: 58. years, stage: I 94 (18%). II 85 (24%). Ilia 154 (42%). Ills 53 (1,5%) Type of surgery: Iohectomy 192 (54%). pneumectomy 129 (36%). other interventions 35 (10%) After a median follow up of 40 months, the median overall survival (MS) was 42 months with an estimated 5 year survival rate (SySR) of 40% A number of 105 (29%) relapses occurred, of which distant 56 (16%). local 33 (9%) and both 14 (4%) (table). Platinum based CT was delivered in 340 pts. (96%). The medium number of cycles was 5. Conclusion. Our analysis showed survival data comparable to those communicated for other recently presented adjuvant thals. Overall. the patients' compliance was good. The positive impact of C T in this setting is indirectly sustained by the pattern of relapses, which place the brain sanctuary on the frst rank.

J Chang ~. L Dong2. R Mchan 2. Z Liao ~. J Cox~. R Komaki I ~Radiaben Oncotogy, Un/verstty ot Texas, 2Ra~atlon Physics, Un/versrty o~ Texas,

MD Anderson Canoar Center, Houston, Texas, USA Background: Photon-based radiotherapy is the standard tTeatment for medically inoperable stage I non small cell lung cancer (NSCLC). Dose escalation can improve local cont]'cl but toxlclt]es limit its potential. Because of its physical characteristics (the Bragg peak), proton radiotherapy may allow further radiation dose escalat]orv'acceleratton without increasing toxicit]es. In adclt]on, tumor mot]on management is an important factor to achieve opt]mal treatment effect. In this study, we designed and evaluated several image guided escalated/accelerated proton radiotherapy approaches in medically inoperable stage I NSCLC Methods: twenty-two pat]ents with medically inoperable stage I NSCLC will be studied with image~]uided proton radiotherapy We pian to deliver a total dose of 8.7 5 cobalt Gray equivalents at 2.5 GY per fraction A 4
S93

Stage Stage Stage Stage

I II IliA IIIB

Survival Data MS (months)

5ySR (%)

Relapse (%) Distant* Local

Both

not reached 48 26 20

88 56 34 28

O 14 21 23

3 4 4 3

3 ,5 12 15

*Pattern of distant relapses: BRA. 48%: OSS. 21%: PUL. 16%: OTH. 12%

PP•-•]

Prognostic significance of neuroendocrlne dlfferenUatlon In petlents with stage I non-small cell lung carolnoma

E Gor~alez-Aragpneses 1. E Alvarezq:ernandez ~. N Moreno 1. M Cebollero ~. J Torres 2. M Garcia-Yuste 3. M CaSizares 4. L Molins ~. S Quevede G 1Hospital Gragorio Maraf~on, Madrid, Spain, 2Hospita]

~4rgen de Arnxaca, Murc/a, Spare: ~Hosp/tal Universe/erie, Valladd//¢, Spain; 4Hospital Genera/, Vigo, Spain, 5Hospital Sagrado Corazon, Bamelona, Spain; ~Hosp/tal Insular, Las Palmas, G/an Canana, Spa/n Background: In the literature. 10-20% of nor~small cell lung ca~nomas 0NSCLC) show neurcendoorlne ONE) diff~rentiat]on. It is suggested that the identification of NE differentiation in large cell carcinoma and adenocarOnoma of the lung may be of prognostic signlfK:ance, but other studies have failed to demonstrate any correlat]on with prognosis Therefore. we have evaluated the prognost]c value of NE cifferent]at]on in NSCLC Methods: A total of 224 resected specimens of Stage I NSCLC (pT1 -T2NOM0) were reviewed histologically in a single inst]tut]on (116 adenooarcinomas. 92 squamous cell carcinomas. 8. large cell carcinomas. 6 mixed, and 2 others) We performed immunohistochemicel analysis for a panel of NE markers [Synaptophysin (SY). Chromogranin A (CgA) and LeLPT] to determine the degree of NE clffersnt]at]on. 91 (40.6%) NSCLC specimens with NE clfferont]at]on (NSCLC NE) were identified, with the presence of SY in 62 cases. CgA in 26 cases and Leu 7 in 23 cases. The 91 NSCLCNE included 56 adenocarOnomas. 29 squamous cell ca~nomas. 4 large cell carcinomas. 1 mixed, and 1 other.

S 94

P o s t e r D i s c u s s i o n s t N o n - s m a l l cell l u n g can cer - E a r l y d i s e a s e ( I - I l i A )

Results: After a median follow4Jp of 37.6 months, the fweyear survival accorcing to the Kaplan-Meier method was 80% ( S Y ) vs 60% (SY+) (log rank: ,5 95 P 0 014) Adjusted by histology (adenocsroinoma and squamous call carcinoma), significant differences were observed in the survival (log rank: 4 40 P 0 03,5) In the rnulfivariate Cox's regression analyses (inducing the variables SY. CgA. Leu-7. histology and Stage la and Ib) the presence of SY predicted a poorer prognosis (P 0 016: hazard ratio. 2 18: 95%C1:1 15 4 14)

1.0 ~ , ~ , 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0

Curative-Intent surgery for non-small cell lung cancer In patients with prior spinal cord Injury

i~_~.:::..

==~il B l m l i

20

40

60

Umverst~, St. Louis, USA, 2Department of Veterans AttaJrs Medical Canter, USA, 3St Barthotomevv's and The Royal London School ~ Medicine, London, UK

sY(-) i

SY(+:

i

80

100

120

140

Survival (months) Conclusions: Stage I non-small (:ell lung carcinomas with the presence of SY are clinically aggressive tumors and emerge as a poor prognostic factor ~D~

[•

F. Johnson 1, L Brunworth 1. D Dharmasena 2. K Virgo 3 1Saint Louis

"~ ~f~l

0

undergoing surgery being of borderline slgnificanoe. Finally. only KPS and weight loss indenepdently influenced cistant metastasis-free survival Conclusions: Identification of progncstlc factors remains an important goal in raclation therapy of techhicelly operable. Ix,it medically inoperable early stage (I/11) NSCLC

Prel]-eatment prognostic factors In patients wl~ early stage (vii) nonsmall cell lung cancer ITeated wth hyperfactlonated r e l a t i o n ~ e r a p y alone

B JeremiE B Milicic 1. A Dagevic 1. G Radosavljevic-Asic 2 ~Department of Oncolog~, University Hospital, Kragujevac, Serbia, 2Institute of Lung Disease and TB, University ~ Belgrade, Serbia

Background: Characteristics of patients can influence the clinical course of the patients This particularly relates to the design and execu'don of clinical tdals and evaluation of the tTeatment outcome The maghitude of difference in outcome for categones of the stTongest prognostic factors can be larger than those for the type of therapy used Separation of patients into cistinct prognostic subgroups should, therefore, represent an important contnbut]on to the design and stratlfieatlon in raciabon therapy (RT) of eady NSCLC trials and should enable the accrual of the individual patients in the more appreprlate treatment groups/studies. This may also help correctly interpret the results of studies companng different treatment regimens and help assess the potential of new treatment approaches. This study was undertaken to investigate influence of various pre~reatment prognostic factors in 116 patients with eady stage (lfll) non-small-cell lung cancer (NSCLC) treated with hyperfraotionated (Hfx) RT alone Methods: There were 49 patients with stage I and 67 patients with stage II Eight-six patients were males and 30 patients were females Eighty patients had KPS 90 1000 and 95 patients had <5% weight loss Tumor location was equally cistdbuted between peripheral (n ,57) and central (n ,59) The majority of patients had squamous histology (n 70) as well as the majodty had concomitant disease prohibiting surgery (n = 72). Tumor doses of 69.6 Gy. 1.2 Gy b i d . fract]onatlon were administered uslog an interlYaction interval of 4.5 6 hours. The target volume for stage I patients included the primary tumour and ipsllateral hilum with a 2 orn margin No to 50.4 Gy followed by the treatment of primary tumour only up to 69.6 Gy. For Stage II patients the target volume included the primary tumour and ipsilateral hilum with a 2 cm margin and the ipsilateral mediastinum from the suprastemal notch to a level 6 cro below the canna (upper or midcle lobe lesions) or to the diaphragm (lower lobe lesions), followed by the treatment of pnmary tumour and ipsilateral hilum up to 69 6 Gy Results: The meclan survival time for all patients was 29 months and ,5-year survival was 29% The meclan time to local progression was not achieved and b-year local progression-free survival was 50 01%% The median time to distant metastasis was not achieved yet, while the ,5-year distant metastasis free survival was 72% Multivariate analysis identified KPS. weight loss. location, histology and reason for not undergoing surgery as independent prognosticators of survival. When local progression flee survival was used as endpolnt. KPS. location and histology independently influenced local preogresslon free survival, with weight loss. T stage and reason for not

InWoductlon: There are about 250.000 people with spinal cord injury (SCI) in the USA. and they have a high prevalence of smoking A literature search yielded no published information concerning the clinical course of SCI patients who subsequently develop bronchogenic carcinoma and undergo pulmonary resection for this concitlon We hypothesized that poorer outcomes of surgery would be observed in this population, as compared to neurally4ntact patients. Methods: We conducted a nationwide study of all veterans at Department of Veterans Affairs (DVA) Medical Centers Ibr fiscal years 1993-2002 who were diagnosed with SCI. subsequently developed non small (:ell lung cancer and were then surgically treated vath curative intent. Inclusion cnterla included American Spinal Injury Assooation type A injury (complete loss of neural function cistal to the injury s~te) and traumatic etiology. Data were compiled from national DVA datasets and supplemented by operative reports, pathology reports, progress notes, and discharge summaries Results: Of 12.634 patients who underwent surgery for lung cancer. 5,5 also had codes for prior SCI: 7 were evaluable The mean age was 64 Five (7"1%) had one or more co-morbid condi'dons in addi'don to their spinal cord injuries All .seven underwent pulmonary Iobectomy Post-operative complications occurred in four patients (57%) Two patients died pest-operatively on days 29 and 499. ylelclng a 30
[•-•

Prophylactic cranial IrradlaUon In redlcally treated non-small cell lung cancer. A Cochrane review

J Lester F Macbeth. B Coles Ve/indre HospitaJ NHS Trust, UK

Background: Non-small (:ell lung cancer (NSCLC) is one of the commonest malignant turnouts Between and 10 to 20% of patients are potentially curable. and following potentially curative treatment, the brain is a site of first relapse in 6.8 to 19% of cases. Brain metastases impair quality of life (QOL). and survival is poor. The benefit of prophylactic cranial irraciabon (PCI) in small (:ell lung can(or is well established. At three years, survival is increased by ,5.4%. and the cumulative rate of brain metastases reduced by 25.3% in those patients achieving complete remission with chemotherapy. This review was can-led out to establish whether PCI prevents the development of brain metastases and increases survival in NSCLC patients tTeated with curative intent Methods: A search strategy was designed to identify randomized controlled trials (RCTs) companng PCI with no PCI in NSCLC patients tTeated with curative intent The electronic databases MEDLINE. EMBASE. LILACS and Cancedit were searched, along with relevant journals, books, and review articles to identify potentially eligible tnals Two independent reviewers assessed the randomized thals identified by the search to establish if predetermined inclusion criteria were met (random[zabon. blinclng, statistical methods, quality of life assessment, data completeness, follow up). Data were extracted from included studies using guidelines set out in the Cochrane Reviewers' Handbook. Results: Four RCTs were identified and reviewed (table). Due to the small patient numbers, and vanat]ons in RT dose. no meta analys~s was attempted. PCI did s~gnifieantly reduce the inc~denoe of brain metastases in 3 thals [2-4]. No thai reported a survival advantage with PCI over observation In one trial median survival was lower in the PCI arm Stuay

PCI Dose

Inclaence of # Dram mets (PCl vs no PCI)

Mediansu~val (PCI vs no PCI]

RTOG[1] SWOG[2]

30Gy/10F/2wea~s

9%vs19%

84vs81 months 036 0004

VALG [4]

20G'//10F/2weeks

010

p

375Gy/15F[3wea~sor 1%vs 11% 0003 8vs 11 months 30G'I/15F[3 wee~s Umsawasal [3] 30GylIOF[2 wea~s 4% versus 27% 0 02 N/A

8%versus 13% 0038 354vs 414weeks 05