PD-101 Review of practice patterns for adjuvant chemotherapy inpatients with completely resected non-small cell lung cancer (NSCLC)

Poster Discussions/Non-small cell lung cancer- Early disease (I-IliA)

$96

68 5% of patients respectively Using mul~variate Cos propert]onal hazards analysis, increes4ng tumour Islet macrophage density (p < 0 001) and tumour isiet/st]-omal macrephage rafio (p < 0 001 )om erged as favourable Independent prognostic indicators. In contrast, increasing StTomal macrophage density was an independent predictor of reduced survlval (p 0 001) The presence of tumour islet mast cells (p-0.018) end increasing isietist]omal mast cell ratio (,o-0.032) wore also favourable independent progncetc indicators Macrophage islet density showed the stiongest effect: 5-year sun/lval was 52 99{. with an islet macrophage dens4ty >median versus 7 7% when
successive gating bins at endexplrafion (ITVgatlng) These data were compared with target volumes denved us4ng ) s4mplified approaches (i) For 34 tumors. (3TVs In 'bins' at the 2 most exlreme tumor pesit]ons wore contoured and planning target volumes (PTV's) generated by adding a margin of 3 mm. The intersecting and encompassing volumes of these PTVs wore determined. (li) For 12 tumors, a new software tool in Advantage 4D was used to generate both maximum intensity projection (MIP) images and minimum intensity projection (min-IP) images, on which target volumes wore contoured. Briefly, a MIP generates a composite image with the highest dens4ty object encountered by rays Iravorsing the selected stack of images Similarly. the mlnlP involves detecting the minimum pixel value encountered along the ray paths in each view obtained fi'om a 4DCT scans Both the ratio of intersecting and encompassing volumes, end ratio of mln-IP and MIP volumes, were correlated with reductions in gated target volumes as determined by the ratio of r]~./gatlng and ITV1Dblns 70% 6O%

Initial r e s u l t s o f pro-operative pulmonary f u n c t i o n t e s t i n g in p a t i e n t s w i t h s t a g e I-II Non-Small C e l l L u n g C a n c e r (NSCLC) b'eated with naoadjuvant chemotherapy with gern citabine-containin g r e g i m e n s

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M. RiveraI , F. Detterbeck I , M. Socinsld I , D. Moore 1, M. Edelman2, T. Jahan 3, R - ~ , J Luketich ~, C Obassju 6, R Gralla ~ ~UmversityefNorth

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Carohna at Chapel Hill, Chapel Hilt, USA: 2 University of Maryland BaffJmem, USA: 3 Un/verarty of Catdomta-San Francisco, San Francisco, USA: 4Memorial Hospital of South Bend, South Bend, USA, 5 Univers~y of Pfftsburgh Medical Center, Pittsburgh, USA, eLifly Research Labs, tnchanapo#s, USA: ;'New York Lung Cancer Afltance, New "fork, USA

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Several chemotherapy agents including gemcitabine ((3am) and paclitaxal (Tax) have been reported to cause interstitial pneumonltis The incidence of pulmonary toxicity from the combination of Gem-Tax is reported to be 5 10% Methods: In two similar randomized phase II multi-insfitutional t~als testing platinum and nor. platinum regimens preoperatively in pafients with Stage I or II NSCLC, PFFs and dyspnea scores wore obtained pre and pest chemotherapy (chemo) to assess one of several secondary endpeints drug induced pulmonary Injury and effect on ability to undergo surgical resection The regimens in Trial 1 included (3em/carboplafin (CCb) and (3ern/paditaxal (GT): in t]lal 2. GCb and Gem/sisp~at]n (GC) Results: Pro end post chorea PFT data was available in 42/54 pts in thai 1 and in 20/28 pts in hlal 2 In this combined group of 6~ pts. the diffusing capaclty (DLCO) % predicted was reduced by 99£ pest chemo vath a p value of 0 0030 and 0 0012 respectivaly The change in FVC. FEV1 and TLC wore not stafistically significant after chemo. In this same group of pts, g (15%) had a >20% reduction in the DLCO (a change considered significant) pest chorea 12 pts (g in thai 1 and 3 in thai 2) reported a mild change in thor dyspnea scale post chemotherapy. 2 of which were included in the group with a >20% reduction in the pest cheme DLCO No severe respiratory events wore reported in any of the patients. 2/62 did not undergo surgery due to a reduction in the FVC and FEV~ after cheme Conclusion: In the preoperative setting. Gem-based chemotherapy is safe The most commonly affected PFT parameter pest chemo was the DLCO While 15% of had a s~gnificant reduc~on in the DLCO post chemo, it did not correlate with clinical symptoms nor did it impact on abihty to undergo surgical resection Background:

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Approaches for identifying patients suitable for reapirationgated radiotherapy in s t a g e I l u n g c a n c e r S Senan. R Under'borg. B Sloh~an, E Lagerwaard Department of

Radiation Oncology, VU Unrvers/ty Mechcal Center, Amsterdam, Netherlands Background: Respiration gated radiotherapy permits the use of smaller ~eatment fields in tumors that show signrficent mobility. As gated-radiotherapy is labor intensive, the development of reliable criteria for pafient select]on Is important Respira~on-cerrelated or 4DCT scans enable a full assessment of int]'a fractional mobility of lung tumors [Underborg '04]. thereby allovang for indlvidualb, ed determination of the potential benefits of ga'ang As toxicity for high dose radiotherapy of stage I nor~small cell lung cancer is low. we assumed that a reduction in internal target volume (ITV) of at least 50% would make gating worth pursuing. We evaluated two simplified techniques for evaluating the benefits of gafing using 4DCT scans M e t h o d s : 4DCT scans wore performed for 34 tumors on a CT scan equipped with a Real lime Position Management system (RPM. Vadan Medical Systems) for radiotherapy planning. Scans were acquired dunng quiet un-coached respirafion for at least the duration of a full respiratory cycle Advantage 4D software ((3E Medical Systems) was used to sort each CT image into one of 10 'bins' corresponding to the respiratory phase at which the image was captured Gross tumor vclumes ((3TVs) were contoured in each 'bin'. and IWs that encompassed GTVs were contoured for all 10 bins (ITV~0blns). or 3

R e s u l t s : Of the 34 stage I tumors (11 lower lobe. 1 middle lobe), a ~50% reduction in ITV's with gating was observed for only 5 pa'aents (14.7%). Method (i): The rafio of the intersecting and encompass4ng volumes of PTVs at exkem e pesi~ons dunng quiet respiration showed a high corrolafion (regression coefficient 0 g8) with the reduction in ITV achieved with gating Method (ii): The ratio of the mir. IP and MIP also showed a high correlation (regression coefficient 090) vath the PTV reduc'aon achieved vath a gabng approach Conclusions: Significant benefits from respiratory gating, i e a ~>50% reduction in ITVs end PTVs. wore limited to 15% of stage I pafients. Indrvidual pafients who benefit can rapidly be identified by either contouring GTVs at exl]eme pesitions or by using MIP images.

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Neoadjuvant chemotherapy with gemcltabina a n d vinorsibina in reeectable non-small-ceil l u n g c a n c e r ( N S C L C )

E. Sommers 1, N. Ramnath 2, L. Robinsen 1, C. Nwogu ~, D Tar~, A. Sharma 1 , A. Cantor ~, A. Chiappon ~, C. Williams ~, (3. Bapler ~. ~Mofhtt Cancer Center,

Tampa, Florida, USA; 2Roswefl Park Cancer lnst~ute, Buffalo, ~

Buffalo, USA

B a c k g r o u n d : We assessed the efficacy of a nor. platinum doublet chemotheF apy ef gem citabine and vineralbine as induc~en therapy In surgically resoctable pathological stage IB-IIIA end selected IIIB NSCLC. The pnmary endpc~nt was

Poster Discussions t Non-smafl

carl l u n g c a n c e r - E a r l y d i s e a s e ( I - I l i A )

radiographic response rate (RR). The secondary endpoints ware pathological RIO,. treatment-related toxicity, surgical resectability, overall and disease-free survival (OS. DFS) Methods: All palJents ware staged with computed tomography of chest and abdomen. FDG positron emission tomography and meclastJnoscopy Gemcitabine (1000mg/m 2) and vlnorclblne (25mg/m 2) were administered on days 1. 8. 22. and 29. Imaging studies ware repeated between days 43-50. Disease response was assessed by IRECIST criteria; patients without prregressive disease ware offered surgery between days 50 70 Patients were followed avery 3 months for 2 years after rese~en Results: There were 62 palJents, meclan age of 67 (range 32 8.2 years) Fortyfive were men. 17 women Twenty-seven palJents had pathologic stage lB. 15 stage II and 20 stage III After indu~on chemotherapy 21/61 (34%) had objective clinical response. 1/61 (3%) had complete pathological response. b6/62 (90%) underwent thoracotomy, and 48/62 (?'7%) had a complete resection. There wore 4 postoperattve deaths. Chemotherapy texlat]es wore moderate with no mortality. The 1 and 2year OS rates ware 78% (95%C1: 67-89%) and 68% (95%C1: 54-82%). and the median OS was 38.2 months. Conclusions: Induction chemotherapy with gemcitabine and vinorelbine had lower raclagraphic and pathologic RIR compared with platinum doublets. However. 1.2 year and median survival times are comparable to those obtained with platinum doublets.

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Review of pracUca pattems for adjuvant chemo~erapy In patients w l ~ completely resected non-small call lung cancer (NSCLC)

A. Vlsbal ~. F. Kessam ~. M. Johnston 2, IR. Feld ~. F. Shepherd ~. G. Dading ~, S Keshavjee~. A Pierre a. T Waddell a. N Leighl I 1Princess Margaret

Hospital, UHN, University or Toronto, Toronto, Canada, 2Mount Sinai Hospital, Umvers~ty of Toronto, Canada: 3 Toronto General Hospital, UHN, Untverslty ot Toronto, Canada Background: Lung Cancer is the leading cause of cancer death waddwide In North America. it is the most common cause of cancer-related mortality in men and women Even the eadiest stage of lung cancer, after curative reseetJon. is associated with a b-year survival of only ?'0% Many palJents post4ung cancer rese~on relapse with distant metastases, highlighting the importance of adjuvant therapy. Evidence support]og adjuvant therapy has been mounting. The IALT study (ASCO 2003) and two separate meta analyses demonstrated an absolute five year survival benefit of 4-5%. More recently at ASCO 2004. two large randomized thals (CALGB 9633 and NCIC JBR 10) revealed an even larger survival benefit (12-15%) for platinurn4~ased chemotherapy in Stage IB/II disease. This study evaluates whether this evidence has been translated into clinical pract]co in a large met]'opolitan area in North America. Methods Retrospact~ve chart revie,~ was undertaken of patients with completely resected stage I-IliA NSCLC palJents from May 2003 to Nov 2004. in hospitals with a pract~siog thoracic surgeon in the greater Toronto area (Canada) Patients tTeated with nee-adjuvant therapy ware excluded Complete data were obtained from medical records Results: 160 palJents were identified (27% IA. 38% lB. 4% Iia. 22% liB. g% Ilia) From May 2003 to Apr 2004.30% of stage 1-11ia patients were referred E)r adjuvant chemotherapy versus 56% from May to Nov 2004. Reasons for non referral include: stage IA disease, surgeon felt no role for chemcthorapy, patient dedined, comorbidlt]es, complicated post~)perattve course, and advanced age. Of the patients referred. 46% received adjuvant chemotherapy; of these. 48% received vlnorelblne/asplatin. 15% etoposide/cisplat]n chemotherapy. The most frequent reasons Ibr not presorlbing chemotherapy despite referral to a medical onoologist included: patient declined (31%). stage 1A disease 27%. co-morbidilJes 22%. and advanced age 20% Conduslons: The presental~on of pos~ve studies CALGB 9633 and NCIC BIR 10 at ASCO 2004 has doubled the rate of referral for adjuvant chemotherapy of patients with completely resected stage I-IliA NSCLC ~norelbineiCisplatin is the most commohiy prescribed regimen in the area stucled In adcil~on to educelJng clinicians about the benefits of adjuvant chemotherapy in NSCLC. pal~ents also need further educal~onal and other support, and barners to both referral for and treatment with adjuvant chemotherapy should be further explored.

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Randomized clinical trial of adjuvant chemotherapy wRh docotaxel and carboplaUn for completely resected stags IB to IliA non-small call lung cancer (NSCLC): Prsilmlnary result of Chinese society of lung cancer (CSLC) protocol 0201

X Yano "1. Y. Wu '1, G. Cben I , L. Xu;', L. Gu ~, P. Tang 4, Y. Zhu 5, P. XJaoI ,

J Tang~. L YdeI 1Cancer Canter & Lung Cancer Research lnst]tute, Guangdong Pro~nc/al People's Hospital, Gouangzhou, C_,h/na: 2Jtanshu Provincial People's Hospital, China, ~ The Third Hospttal or Zhongshan Uruverst~, China: 4Haman Prownctal People's Hospital, C~na: ~Yuel,~el People's Hospital, Chma Background: The value of adjuvant chemotherapy in resectable lung cancer remains controversial. The International Adjuvant Lung Thai (IALT) reported a modest but statist]celly significant survival advantage with cisplatin~)ased adjuvant chemotherapy in stages IB to III NSCLC. On the other hand. Adjuvant Lung Project Italy (ALPI) failed to demonstrate benefit for adjuvant chemotherapy in patients of similar stage. Recently. CALGB 9633 and JBR.10 shows third-generatJen drug have higher survival and better toleration Docetaxel's effectiveness and safety are wall studied in non-resectable NSCLC. and is one of the standard ~ r advanced NSCLC CSLC 0201 was designed to evaluate the effectiveness of adjuvant docetaxel plus carboplalJn in Chinese palJents with stage IB to Ilia NSCLC Methods: Within 4 8.weeks of resection, patients were randomized to adjuvant chemotherapy with docetaxel (75mgtm 2 over 1 hours, dl) and carboplat]n (ALIC 5. dl). avery three weeks for 3 to 4 o/cles, orto observation The use of 5-HT antagonist and colony slJmulators were determined by the investigators Eligibility: age >18. years, no prior chemotherapy and/or radiotherapy. histologically documented NSCLC. pathological staged IB to Ilia. completely resected 0obectomy or pneumonectomy). PS (~1 After 10/31/2004. as to the request of ethic committee, palJents with stage Ilia disease were e~cluded The primary endpolnt was overall survival and secondary endpoints were progression free survival and texicity associated with adjuvant b'eatment. Results: Between September 2002 and December 2004. 105 patients were randomized. 51 Ibr adjuvant chemotherapy and 54 for observation. Median age was 59.2 years (range 33-74 years), and 69 patients (65.7%) were male. The patients were performed Iobectomy except 2 patients performed left pfleumonectomy. 29.6% squamous carcinoma and 55.3% adenocarclnoma. 49.5% had pathological stage IB disease. 24.8% stage I1. and 25.7% stage II1. 23 8% N2 and 20% N1 For 48 patients in adjuvant chemotherapy arm that can evaluated. 30/48. palJents finished 3 to 4 o/des of docetaxel plus carboplabn. 14 palJents with 1 to 2 o/des In 4 palJents randomized to adjuvant chemotherapy arm. one experienced allergy and 3 choose no chemotherapy One palJent randomized to observation arm insists to receive chemotherapy after randomized Adjuvant chemotherapy was well tolerated, and there were no chemotherapyrelated toxic deaths. 18% experienced leucopenia grade 3 or 4; one patient experienced grade 4 thremboo/topenia; 32% nausea/romPing grade 1 or 2; 16% peripheral neuretoxlaty grade 2 or 3; 6% experienced phlebitis grade 2 or 3; and 6% diarrhea grade 2 or 3. Conclusions: Adjuvant docetaxel plus carboplatin chemotherapy is well tolerated and feasible in the adjuvant setting for Chinese patients with completely resected stage IB to IliA NSCLC. ~ B A X , BCL-2 AND C-KIT expression In non-small cell lung cancer amd ~ e l r effects on prognosis A Yaren~. I Oztop2 . A Kargi ~. C Ulukus 3. U Yilmaz 2. A Onen 4. A Sanli 4. A. Al~oclu 5, M. Alakavukla~. l pemukkale Un/vers~ Faculty of Medtcme,

Department of Internal MeOlcme, D~wston of Hematology Ontology, Deruzlt, Turkey, 2Dokuz Eylul University Institute of Ontology, tzmir, Turkey, 3Dokuz Eylul Untverslty, Faculty ot Meal/c/he, Department ot Petttology, tzmir, Turkey, 4Dokuz Eylul University, Faculty or MeOfcine, Department of Thorac/c Surgery, tzrmr, Turkey, ~Dokuz Ey/ul Untverstty, Faculty ot Medtcme, Department of Chest t~sease, lznur, Turkey Background: In norrsrnall cell lung cancer 0NSCLC) stage of the disease is still the most important prognostic factor. Other than stage, many biological markers and many other prognostic factors are studied to define their effects on prognosis of lung cencar. In this study, we aimed to evaluate the expressions of Bax and bd-2 genes which are important in apoptosis and c~kit, which is a tymsine Idnese transmembrane receptor, as wall as searched their response to treatment medalities and effects on survival Methods: Sixty-nine NSCLC cases' pathological samples wore stained with specific B ~ . bcl-2 and c~kit dyes by immunohistochemical (IHC) methods Immunohistochomical evaluation was done by the somichanfitafive method according to the disthbution and intensity of the staining Results: Twelve of 69 cases (17.4%) were stage I. 28 (40.5%) were stage I1. 17 wore (24.6%) stage Ilia. 9 cases ware (13.1%) stage IIIB and 3 cases (4.4%) were stage IV patients (lots). Their histological subtypes ware as follows: Of 69 cases 36 (52.2%) were squamous cell caranoma. 28 (40.6%) were adenocarcinoma. 5 (7.2%) ware adenosquamous cell carcinoma (2 pts) and