PD-116 Early versus late chest radiotherapy for limited stage small cell lung cancer: A systematic review and meta-analysis

Poster Discussions t Radiotherapy ~PD-1i4~ Mature results of combined high dose 3D conforrnal radletlon (74Gy) and chemotherapy In trealmant of Inoperable and/or unresectabfa localized NSCLC. Efficacy, tolerance, relationship wl~ dose and volumes 0/20) F. Mornee I . A. Belliere I , O. Chapet I , B. Floury I , M. Khodrl I , I. Flandin ~, R Souquet 2 lCentea Hospitalier Lyon Sud, Radiabon oncotogy Department,

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before the onset of clinical symptoms. The other one had normal levels at the (ompletion of raclation therapy All of their serum KL-6 levels increased with the development of pulmonary texicl'dee Conclusions: Serum KL-6 might be a useful clagnostie marker of radiation pneumonltis related to radiation therapy ~r primary lung cancer

Lyon, France: 2Centre Hosp/talter Lyon Sud, Pneumology Department, Lyon, Franoa

~

Background: The purpose of this work is to analyze the tolerance of lung and

M Pills~. D De Ruysscher 1'2. I Rutten ~. R Lambin 1,2. J Vansteenldste 4

heart of patients Cots) presenting with a NSCLC. treated with 3D (onformal radiation therapy (74 Gy) The first objective was to evaluate the feasibility of ti'ts chemo-raclation, the second one was to look for a relationship between V20 and the incidence of radiation pneumonitis, as well as the assessment of heart events The ultimate goal is to elaborate recommendations ~ r a future dose escalation tnal. based on the observed texicl'des, and to optimize the heart DVH curves. Methods: Fifty pts. 41 men. 9 females, meclan age 63 years (27-80). stage 1/11 7%. Ilia 51% and IIIB 42%. squamous car~noma 56%. adenocaranema 24%. large (oil indiffererx~ated 12% and neur(ondcorlne 6%. have been treated between june 1996 and april 2002. Raclotherapy delivered a moan dose of 72 Gy (range 66-74 Gy). using 3D conformal therapy (2 Gy/day. ICRU point. 5 days'week). The mean P ] V volume was 648 co (range 220-1876). the mean lung V20 38.% (range 19 68%). Vz5 31%. V~0 27,5% Thirty nine pts (78%) received platinum~ased chemotherapy, as an indu~on (25 pts) and/or as a concurrent (14 pts) scheme Acute texicitiea were scored according to the NCI critena, late effects using the SOMA/LENT scoring system Rssults: The last roll,v-up was 12/04 Eight pts expedeneed a grade 3 4 acute lung toxicity, all of them had a V20 ~>2,5%. 3 presented a late grade 3 fibrosis, they all had a high V20 (36%. 54% and 68.%) Pts with low FEV1 (<1 51) presented more frequently a lung toxicity, without statistical correlation. Three pts died of cardiac failure dunng the first 3 months of the Izeatment (1 after 25 Gy. 2 after 66 Gy). Grade 4 acute heart texlcity occurred in 1 pt. Grade 3 esophagltis o(oured in 3 pts. wtthout any late stenesis. Eighteen months complete response rate was 45%. Median survival time was 17.3 months, the 12 and 24 month overall su~val rates ware 72.2% and 37.1%. respectively. A local failure o(oured in 55% of pts. either as sole site (21%) or as a component of distant failure The metastatic rate was 49 2%. with 16% brain metastases Four pts are alive, without disease Conclusions: This retrospective analysis assesses the feasibility of delivenng 74 Gy to the tumor in association with concomitant or sequential chemotherapy The results show a relationship between the V20 value and the dsk for occurrence of radiation-induced lung toxicity Parameters like FEVI. V20. V~0 for heart and lung will be integrated in the dose level choice of the future thai. The heart toxicity is highly difficult to preasely assess, late deaths are rarely documented, the treatment responsibility might be underestimated in tnls population of mostly smoking patients. Heart DVH optim=ation wll be an important goal in the next study (nonceplanar and m~xe~energy beams. beam ponderation. IMRT). These encouraging results form a basis for an dose escalating phase I thai. currently under elaboration, integrating the predictive to~c~ty parameters and the DVH optim=ation. ~

Corrslatlon between serum KL-6 level and radiation pneumonltls

related to radiation therapy for primary lung cancer M. Noz;~ki~. M. Furuta ~. M. Kaweehima ~. M. limure ~. A. Okayama ~. Y Hamastima ~. K Nagao~ ~Dep~ ofRa~dogy, Koshigaya Hosptfal, Dokkn/o

Eerly versus late chest ra~otherapy for IImRed stage small ceil

lung cancer: A systematic review and msta-analys|s

1MAAS TRO Clinic, Maasthcht The Netherlands, 2Universifal Hospital Maas~cht, The Netherlands, ~University Hospital U~Je, Belgium, 4University Hospital Leuven, Belgium Background: Chest radiotherapy and chemotherapy are (ombinad in standard clinical practice Ibr patients suffering fi'om limited stage small (oil lung can(or. However, the beet way to integrate both modalitlea is unclear. The objective of this rovlow was to dis(over the optimal way to combine (:;host radiotherapy chemotherapy for patients wlth limited stage small (ell lung cancer in order to improve long-term survival Methods: Search s~'ate~/: The electronic databases MEDLINE. EMBASE. Cancedit and the Cochrana Central Register of Controlled Thals. refemn(o lists, hand searching of journals and confemn(o proceedings, and ciscussion with experts were used to identify potentially eligible thals, published and unpublished Selection chteda: Randomised controlled dinical b-ials comparing ciffemnt timing of chest radiotherapy in patients with limited stage small cell lung can(or. Data (olloction & analy~s: Seven randomised thals wore reviewed There were differences in the timing of chest radiotherapy, the overall treatment time of theraclc radiation, and the type of chemotherapy used. Results: No significant differences in the 2year and the ,~year survival wore Ibund whether chest radiotherapy was delivered within 30 days after the start of chemotherapy or later. When the only study was excluded that delivered chest radiotherapy dunng the cydos of non platinum chemotherapy, only for 5-year survival a tTend was observed (RR:0 93. p 0 07) in favour of early raclation, but not the 2-year survival Survival at ,5 years, but not at 2 years. was significantly in favour of early chest radiotherapy delivered in an overall treatment time of less than 30 days compared with a longer treatment time (RR: 0 gO. p 0 006) These results, however, should be interpreted with caution ~r the largest tnal has follow-up data at 3 years, but net later It remains to be seen what the effect of longer follow-up will be for the b-year survival Local tumour (onb'cl was not significantly different between early and late chest radotherapy The incidence of severe pneumonltis or severe oesophagltis was net significantly different for eady versus late thoracic rac|otherapy: However. a Izend for a higher chan(o to develop pneumonlt]s when early chest radiotherapy was delivered during nonlJlatinum based chemotherapy was observed. Conclusions: At present. It is uncertain whether the timing of chest raclotherapy as such is important for survival. The optimal integration of chemotherapy and chest radiotherapy in patients with limited stage small cell lung cancer are unlmown Therefore. further research is needed to define parameters to optimise the combination of radiotherapy and chemotherapy in this disease Palliative thoracic ra~otherapy (TRT) In locally advarmed non-small call lung cancer: Which paUonts should not be b'eated with short course TRT? S. Sundsb--,rnI . R. Bremnes 2, P. Brunsvtg ~. S. Kaasa ~. lDept Ontology,

Umvers~ty S~oot ot Medicine, Koshtgaya, Japan: 2Dept. of Respratory Internal Medcine, Koshigaya Hosp~fal, DoloYyo University School of Medicine, Koshigaya, Japan

University Hospfal of Ttundheim, Norway, 2Dept Oncotogy, University Hospttal ot Northern Norway, Norway; 3Dept Oncotogy, The Noweg/an Radium Hospital, Norway

Background: The purpose of this study is to assess whether serum KL-6

Background: Different palliative TRT fra~onation schedules appear to give

might be a useful clagnostic marker of raclation pneumonitis related to raclation therapy of primary lung cancer. Methods: We treated 129 pnmary lung can(or patients by using external pul monary irradiation in doses of 40 Gy or more without (oncurrent chemotherapy. between Ap¢l11999 and June 2002. Mec~an age of patients is 69 years (range; 42-65 years). Patients w~th stage 1. 2. 3 and 4 were 37. 26. 55 and 11. respectively. All patients underwent irradiation of a dally 2Gy fraction dose with 6 M Y photon beams by using opposed portals. Serum KL~ levels were measured by enzyme4inked immunoserbeit assay at the start and completion of radiation therapy, and adcitional eeaminations ware made when pulmonary toxicitiea developed Serum KL-6 level was evaluated with a cut-off level of ,500U/ml and increasing rates from base lines Minimal follow-up times were six months Pulmonary texicitiee ware evaluated with the grading system of NCI-Common Tmdcity Criteria ver2 Rssults: Ninety-nine had normal levels of serum K]L-6 and thirty had high levels at the start of radiation therapy. Ten of the 99 patients with normal levels showed serum KL 6 levels of higher than 500U/ml at the completion of radiation therapy. Within 6 months after radiation therapy, seven patients developed pulmonary texiclties with a grade of 2 or mere. Among them. six had increased levels of serum KL6 at the completion of radiation therapy

similar symptom palliation in advanced non-small cell lung cancer (NSCLC) However. in locally advanced NSCLC some evidence indicate that good porlbrman(o status patients may benefit from a modest increase in survival (Cochrane Collaboration database) if normofract]onated TRT at larger total RT doses are given. In this study, clfferent prognostic factors ware explored to evaluate whether they may help determining ]]:;tT strategy. Methods: A phase III tnal eeamining the effect of three different ] R T fractionation schedules included 301 stage III patients. Different pre~reatment variables such as demographic, clinical and health-related quality-of-li~ (HRQOL) scores ware evaluated by univariate analysis (log-rank test) The HRQOL baseline scores were dichotomised according to ~meclan score Variables with p-values <0 10 inthe univariate analysis were entered into a Cox multivanate regression model Results: 10,5 patients received short course TRT (17Gy/2 frac~ons), while 196 re(owed higher dose TRT (42 Gy/15 fractions or 50 Gy/25 fractions) Median survival was (omparable with 9.2 and 7.5 months Co= 0.47). while Ion~Tterm survival was resthcted to the higher ]]:;tT doses as 3year survival was 1% and 6%. and 5 year survival 0% and 5% in the patient group receiving the short versus the high dose schedule, respectively. Univarlate analysis revealed porlbrman(o status (PS). weight loss and six different baseline HRQOL s(oree