P-715 Hypofractionated radiation therapy (HRT) alone as the curative treatment for patients with early stage, medically inoperable non-small cell lung cancer (NSCLC)

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Posters t Radiotherapy

(15-20Gy) over a one to two week penod (BED > 100Gy). Each treatment lasted approximately two hours Ra.=uR.=: The tTeatments were well tolerated FalJgue has been the only appreciable acute side effect Early imaging and pulmonary funct]on testing results are premising and the patients will be followed closely Conduslons: CyberKrlfe ® image guided sterectactic radiosurgery with the Synchreny T M module is a premising, well tolerated, user fi'lendly definitive treatment oplJon ~ r inoperable, small peripheral lung tumors

[P-712~ Breath p/n/arm as a marker of lipid peroxldatlon during radiotherapy of lung career patients M Crohns I S Saarelalnen ~. J Lalfinen ~. K Peltonen 4. H A/he ~. P Kellokurnpe-Lehfinen 6 ~Tampers University Hospital, Tampers, Finland,

2 Tampers University Hospital, Tampers, Fin/and, a Tampers University Hosptal, Tampers, Fin/arid, ~Nattonal V~tennary and Food Research Institute, Helsinlo, Finland, ~Nabonal Public Health Institute, Hal/in,d, Fin/and, Tampers University Hospital, Tampers, Finland Background: Raciotherapy causes o~dat~ve stress and inflammation. Volat]le hydrocarbons such as ethane and pontane, are known to be produced by perexidat]on of membrane lipids. Previous studies have shown that analysis of exhaled breath pentane can be used as non4nvaslve method to analyze lipid perexidat]on. The aim of our study was to assess the amount of lipid perexidat]on in lung cancer patients compared to healthy controls as well as explore changes in exhaled breath pentane dunng radiotherapy of lung cancer. Methods: Eleven lung cancer pal~ents (7 male. 4 female) and thirthy healthy controls (21 male. 9 female) participated in our study Most of the patients (n 9) had squamous cell carcinoma, two had adenocercinoma All the patients were scheduled ~ r radiotberapy for t]'eatment Radiotherapy (RT) was given via a linear accelerator 2 Gy/d. the mean dose being 4b 4 Gy A four-minute wash out period was used when colle~ng the breath samples Expired air samples were collected to impermeable Quint~on gas colle~on bags and analyzed by gas chromatography. Breath samples were collected at baseline before the onset of RT. after 30 min fi'om the onset of RT tTcatment and after 120 min from the onset of RT treatment. This procedure was repeated on Day 1. Day 4 and Day ,5. Breath pentane collection was done once to healthy conb-ols. We also measured diane coqugat]on (DC) and thiobarbltunc acid reactive me/anal (TE~ARIVI) IYom the serum of the pat]ants at baseline before the radiotherapy treatment on day 1. Ra.=uR.=: We found statistically significant differences in the baseline values ~r e0¢haled breath pentane between the patients and the centToIs The geomel~ic mean for e~haled breath pentane ~r the patients was 1 8.7 ngil (0 87 3 76 ngfl) and 0 94 ngfl (0 04 5 59 ng/I) for the contTOIS ] h e ratio patJents/centTelS was 1 73 (9,5%C1:1 03 to 2 88). p 0 038 There was no statistically significant changes in the e0¢haled breath pentane values during radiotherapy on Day 1 or dudng the first week of radiotherapy The mean serum values ~r conjugated dienes was 46.79 umoVI (32.00-66.40 umoUl) and 3.10 umoLtl (1.16-6.62 umolll) for TBARM for pat]ants at baseline. There was no cerrelat]on between the serum lipid perexidat]on markers and exhaled breath pentane values. Conclusions: This is the first clinical study to analyze exhaled breath pentane dunng radiotherapy of lung cancer. In our study lung cancer pat]ants had higher baseline exhaled breath pentane values than healthy contTels this being in aceordance w~th some previous studies suggesting that cancer itself produces oxidative s/Teas and lipid perexidatJon Also radiotherapy is known to cause inflammation and lipid pemxidatJon, however there were no statistically significant changes in the values for e0¢haled breath pentane during radiotherapy According to our finding, radiotherapy doesn't induce pentane into exhaled breath and this might be due to body's own antiexidafive defense mechanisms that compensate lipid perexidafion caused by irraclation [ P ~ 3 ~ l m p a c t of amlfostlna on radlatlon-lnducad u o p h a g l t l s and pnaumonltls In patlants wlt~ lung cancer C Daly. N Holloway Saint Joseph Hospital, Chicago, ///inois, USA

Background: The incidence of grade 3/4 asophagitis or pneurnonitis is as high as 80% and 50%. respectively, in patients Izeated with radiochemotherapy (RCT) or radiotherapy (RT) alone for lung cancer (LC). Amifoshne is an aminothiol prodrug that protects mucosal tissue I~om chemotherapy and RT induced damage The Evaluating Cytoprotect]on Health Outcomes RegistTy prospectively followed 71 patients with LC receiving pretTeatment amifostine with RT or RCT in elirtcel practice ]his report descnbes the incidence of esophagil~s and pneumortfis in patients with LC who received amifosfine before RT or RCT Mathods: Data were collected using elirtcel report forms and patient questionnaires Primary end points included the incidence of grade 3/4 esophagi/Is or pneumonitis. Weight change dunng treatment was also recorded. Results: Of 66 evaluable patients (35 men. 31 women). 4 (6%) received R].. and 62 (94%) received RCT. Mean age of patients was 63.3 years ( + 1 2 7 y). The maJonty (80%) of patients had non small cell lung cancer.

Forty four patients (67%) had stage Ill/IV LC; cisaase stage data were unavailable for 14 palJents Mean raclalJon dose was ,59 5 (±9 50) Gy The majority of patients (94%) received subcutaneous (SC) amifostJne (mean dose 492 3 mg±44 31 mg) Nine patients (14%) e0¢periencad grade 3/4 esephagilJs and 2 patients (3%) e~perienced grade 3/4 pneumonitJs Median weight loss was 227 kg: 17 (29%) palJents gained weight during tTeatment The most frequently reported grade 3/4 adverse events were nausea (17%). rash (5%). hypotension (3%). and vomiting (2%) Conclusions: In this study, the incidence of grade 3/4 esophagi/Is or peeumorlt]s in patients wtth LC who received amifoshne before RT or RCT was far lower (14% and 3%. respectively) than the 80% or 50% incidences reported without amifostine. The addt]on of amifost]ne to RT or RCT appears to be well tolerated in patients with LC. Since 94% of patients recarved SC amifost]ne, these hndings also support further investigation of this route of administrat]on in this incicat]on.

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Selective medlastlnal node Irraclatlon on basis of the FDG-PET scan In patients wlth non-small cell lung cancer: A prospective ctlnlcal study

D De Ruysscher ~,2. S Wanders I . E van Haren ~. M Hochstenbag I . W. Geraedts 4. I. Utama ~. J. Simons 6. G. Snoep ~ . U. Buell 7. P. Lambin 1'2.

1University Hospital Maastncht, Maastncht, The Nethedanda, 2MAAS TRO c/m/c, Maastncht, The Netherlands. aAtnum Medtcal Centre, Hear/an, The Netherlands, 4 Maasland Hospital, Sittard, The Netherlands, Sin/Laurentius Hospital, Roermond, The Netherlands, Sin/Jans Gasthuis, Weert, The Netherlands, z University Hospital Aachen, Department of Nuclear Medicine, Aachen, Germany Background: As FDG PET scans are more accurate than CT scans for staging the mediast]num of patients v~th NSCLC. we evaluated the patterns of reourmnce when select/re mediaSshnal node irradiation on basis of the FDG PET scan is used in pat]ants with non small cell lung cancer (NSCLC). Methods: A prospec0ve phase UII study was undertaken on 44 patients with NSCLC without detectable distant metastases on CT and FDG~ET scan. delivenng either 61 2 Gy/34 fraction~23 days or 64 8. Gy/36 fract]ons/24 days (1 8 Gy BID with 8. h interval) OHy the primary tumour and the positive mediasfinal areas on the pre-tTeatment FDG~ET scan were irraclated Isolated nodal failure was defined as recurrence in the regional nodes outside of the clinical target volume, in the absence of in-feld failure ResuRs: The CT and FDGJJET stage dis~bution was as follows: Stage I: 8 pt (18%) and 13 pt (29%). stage I1:6 pt (14%) and 10 pt (23%). stage IliA: 15 pt (34%) and 7 pt (16%). stage IIIB: 15 pt (34%) and 14 pt (32%). respectively. After a median follc~Jp/]me of 16 months (95%C1:11-21) post radiotherapy. 11 patients (25%) developed a local recurrence. Only 1 patient (crude rate 2.3%. upper bound 95%C1:10.3%). both on CT and PETwlth a stage II tumour. developed an isolated nodal failure. The median actuanal overall survival was 21 months (9b%Cl: 14 28). and the median actuarial progression free survival was 18. months (gb%CI: 12 24) Conclusions: Select3ve mediasfinal node irraclation on the basis of FDG~ET scan in palJents with NSCLC results in low isolated nodal failure rates In the phase I component of this 1Tial. radialJon dose escalation up to 64 8Gy/36 fra~ons/24 days is feasible

Radiotherapy Tuesday, 5 July 2005

10:00-17:00

JP-715J Hyparractlonated radiation ~erapy (HRT) alone as me curative b'eatmant for patients wlttz early stage, medically inoperable non-small cell lung cancer (NSCLC) S. Fana~. L. Souhami I . M. Dulcos I . L. Portelanca ~. J. Guerra ~. J. Gruber 2.

V Hitch. ~Department Ra~ation Oncetogy, McGtll University Montreal, Canada, 2Respiro/ogy, McGill University Montreal, Canada, 3Medical Onco/ogy, McGi// University Montreal, Canada PurposetObJectlve: ]here are several reasons to use aocelerated HRT in patients with eady stage NSCLC medically unfit for surgery: 1) a shortened raciotherapy regimen may be beneficial for rabicly repopelating tumors as lung cancer: 2) the convenience of leas visits for sick/eldedy patients who have cifficulty to come to the hospital: and 3) the reduced cost Toxicity has been the limitation ofHRT Ne.~er technologies providing better target definition and spadng of normal tissues have allowed us to use this approach We report the preliminary results of a prospective phase I./11tnal of HRT in a homogeneous group of patients, carefully evaluated for texic~ty. Meterlal/Methods: 32 patients with stage I NSCLC (only 8 patients had PET scan), unfit for surgery, were treated between Augustl2002 and May/2004 with 18MV photons HRT alone, v~th. 3D conformal planning. Lung breathing mot]on was morltored by fluoroscopy or electronic c~ne vision. P ] V was defined by the

Posters I Radiotherapy radiologically visible turner vath ~>10mm margin in all clrect]ons. The presolbed dose was ,52 5Gy/15fractions in 3 weeks, biologically (BED biological effec~ve dose) similar to 74Gy/37fractJons Acute/late toxicity was evaluated using the RTOG/CTC morbidity criteria Result,=: There were 23 males and g females: 1,5 stages T1 and 17 T2 Medianagewas76years(range:56 90) MeclanPTVvolume 1,50co(range: 40-361) Median V20 of both lungs 13% (range: 3-29) Acute toxicity was minimal Two patients had lung toxicity (one grade 1 and another grade 2) and 3 patients had grade 1 acute esephagltis. There was no skin t~iclty. To date. no late t o , city has been observed. As of December 2004. at a median follow up of 9 months (range: 3 26). five patients died (2 from metastatic and 3 from co-morbid disease), with no evidence of disease progression in the irradiated lung. The remaining 27 patients are alive. 2 of them with progressive disease In the irradiated lung and 22 are NED. Conclusions: The aocelerated HRT regimen of 52Gy In 3 weeks shortens by half the tTeatment duration, appears to be safe and was well tolerated by this group of patients with early stage NSCLC and severe co-morbid diseases Further follow-up is needed to evaluate long-term outcome We are now routinely staging these pafients with BE scans to better define disease extension and properly select the patients for this promising approach

rP-716TRadlcal radiotherapy (RRT) for non-small call lung career (NSCLC), results from racurelvs partition amalgamaUon analysis (RECPAM) R Fuentes lns~ut Cafala D'oncologia - H Jossp Trueta, Gitona, Spain

Background: Surgery is the treatment of choice for localized non small cell lung cancer (NSCLC). However. some patients having severe co-morbidity, age over 7,5 years or refusing surgery are treated with radiation therapy as unique treatment We present a study of a cohort of patients from a mulficantTe prospecfive study carried out in Catalonia and Mallorca We have carried out a multicenter prospecfive study with a cohort of patients in Catalonia in order to assess clinical and therabeu'dcal prognosfie factors Methods: From March 1992 to October 1997. prospeetJve data were collected on 610 consecutive patients attenclng the Oncology Units of three Regional Hospitals (Girona. Reus and Palma de Mallorca). Inclusion cntena were newly diagnosed NSCLC and Kamofsky Performance Status (KPS) >60%. Variables recorded were: age. s ~ . smoking habit, symptoms. KPS. weight loss. pulmonary function tests (PFTs). histology, cTNM and b-eatment. /.e. surgery, non4"adical radiotherapy, radical radetherapy (l:~J~ and clsplat]n based chemotherapy. Survival time was calculated from the data of Pistological clagnosis to death Cummulafive survival was estimated by Kaplan4Meier (K-M)and survival was calculated by log rank and Willcoxon tests A multivariate estJmafion was produced using the Cox model and finally a RECPAM analysis (using the method of Ciampi et al (1)) was performed Results: According to the K-M analyses the most important variables associated to survival were KPS and TNM staging The Cox model identified as independent prognostic factors: KPS. cTNM and presence of meclastinal invasi on. Using the RECPAIVI model, eight prognostic subgroups were identified having 24. 14. 8.5.8. 4.5 and 2.5 months of median survival respectively. Patients b-sated with raclcal radiotherapy were the second most favorable subgroup in terms of survival when analyzed in a model incluclng most important prognostic factors and treatment modalWes. Conclusion,=: Radical radiotherapy is able to ~ provide a very good survival time for operable lung cancer not operable Bearing in mind that our subgroup of patients represent a population having severe co-morbidity and being treated with old-fashioned techniques, better results can be anticipated applying 3D planning, stereotactJe techniques and/or combining RT with chemotherapy or MoAbs Influence of radiauon dose to the head on survival In radical r•TT The treated stage III NSCLC O. Hansen I . C. Bnnk 2. M. Nielsen 2. T. StolbergJ~ohr I . 1Department ct Onco/ogy, Odenss University Hospital Denmark, 2Ra~ophysic Lab Odanse University Hosptfal, Denmark Cytogenefic analyses have established that numerous somatic genetic changes are involved in the mulfi-step process of lung cancer tumorogenesis New techniques to unequivocally disfinguish neoplastic from benign disease of a small number of cells obtained by bronchoscopy are required to reach an accurate diagnosis in lung cancer Despite technical advances in cell culture, the rate of successful karyotypic analysis of lung cancer has remained low because of tissue culture failure, karyotype complexity and chromosome morphology. Fluorescence in s~u Plybnd[zation (FISH) is a powerful technique for detecting chromosomal changes in tumor cells. Both numencal and structural chromosomal aberrations can be visualized using suitable probes or a probe cocktail. Combined simultaneous analysis of the automated bnght

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field morphology and inter'phase fluorescence in situ hybridization (I FISH) on a cell4~y-cell basis, without cell culturing, has recently been intToduced by our team in the detection of a small number of malignant cells This method is based on automated bright field in conjun~on with fluorescence scanning and Classification of large numbers of cells, allowing rapid and efficient idenfification of small populafions of pathological cells The detecfion of chromosome and gene alterations in interphase nuclei of oftological specimens is the only technique available for the simultaneous visualization of genetic changes and cell morphology on a single cell level. The growtng body of knowledge on tumor specific genetic and chromosomal aberrations can. therefore, be translated to clagnostic pathology. Fndobronchial brushings and wasilngs of bronchoscepically obtained cells from lung cancer patients were subjected to I4~ISH analysis with DNA probes specific for the amplification of the gene ~myc and the deletions oftbe genes p53 (17p) and p16 (9p21). In all pnmary tumors, highly aneupic~d cells were detectable by I£1SH analysis. Using chromosomal aneuploidy as a marker of malignancy, material obtained by bronchoscopy was then examined for the presence of malignant cells In specimens, evidence for malignancy was obtained by I-FISH. including specimens which appeared to be normal or rea~vely changed by oftolngic criteria The sensitivity of the combined technique was determined by lung cancer cells dilution ~periments We suggest that this technique of combined simultaneous analysis of the automated bnght field scanning cytomorphology and interphase fluorescence in sltu hybridization (I£1SH) on the same cell is a novel, sensitive and specific method to detect small populations of lung cancer cells obtained by bronchoscopy.

] ~ 1 8 ] Continuous hypsrfractlonated accelerated radiotherapy (CHART) In non small cell lung cancer. A single cantTs expsdsrme as standard trestment M. Hatton. D. Omar. P. Fisher. R Peter. K. Mohanamurali. Weston Park Hosprtal, ShekelS, Untte¢ l~ng¢om

Background: CHART (54 Gy in 38 fractions over 12 days) has been a recommended standard of care in the UK for the radical radiotherapy treatment of NSCLC since 1998 [1] In 199?" Saunders et al [2] pubiished the results of the randomized, multicentre comparison of CHART with conventional radiotherapy (6OGy in 30 fractions ever 6 weeks) and showed improved local control and survival for the CHART fractJonalJon Weston Park Hospital parlJclpated in this study and adopted CHART as cur standard regimen in 1999 This study has audited the outcome of CHART tTeatment at cur centTe and compares it with the results in the onginal pubiicat]on. Methods: Members of the clinical team used radiotherapy department records to identify consecutrve patients b-sated vath CHART from June 1999 to December 2003. All patients were planned and treated with volumes and field arrangements descnbod by Saunders st. el. [2] The radetherapy records wore supplemented by a reb-espectrve review of the case notes. Basic patient demographics, tumcur characteristics and survlval were recorded in a database and stafistical analysis was performed using SPSS version 11 5 statisfical software Survival analyses were completed using Kaplan4~eier methodology and log rank test for significance Results: 121 palJents with histologically proven NSCLC were identified and case notes were ravie.~red in 114 patients 65% of the palJents were male: the median age was 66 (range 41 - 81) The majority of palJents (83%) were performance status O or 1. and 11% of palJents had stage 1 or 2 disease 36 patients had chemotherapypnor to CHART. Meclan sunaval from the start of radotherapy treatment was 16 months and the 2 year survrval figure of 28% is almost identical to that reported in the original study. Further analysis found survival was significantly influenced by stage (13= 0.03) but not by age. se~. performance status, previous chemotherapy or histological subgroup. 4 patients suffered grade 4/5 pulmonary t~iclty. 3 had some pre4~xist]ng lung fibrosis and two had received pnor chemotherapy treatment. Other t~iclt]es were mild and manageable in keeping with the published report [2] Conclusions: This audit demonstTates that the reported survival rates for patients with locally NSCLC for the CHART radiotherapy frac~onafion can be reproduced in roufine clinical practice 3D conformal stngls hlgtt-doss boost radlosurgery(SRS) for perlphsral stags I non-small cell lung cancer(NSCLC) using C-Arm .near accelerator and a splro-analyzsr K~ Hayakawa ~. Y Niibe I . M Kltano I . H Ishlyama I . M Uemae 2. N Masuda ~. H. Yeshimura ~. l KJtasato Un/verstty S~oot of MeStcme, Sagam/hara, Japan. 2Kffasato University HospitaJ, Japan

Background: To reduce the normal tissue damage, we have developed a respiratory gating system using spire-analyzer to contToI respiratory organ motion This study was performed to evaluate the clinical outcomes ofthreedmensional (3D) conformal single high dose boost radiosurgery (SRS) for peripheral T1 NSCLC using tlls system. Methods: From November 2000 to December 2003.24 patients with peripheral stage I NSCLC were Izeated in our hospital and were followed for >one year.