Thoracic sequelae in long-term survivors treated by alternating radiotherapy and chemotherapy for limited small cell lung cancer (SCLC)

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NEUROPSYCHOLOGICAL EVALUATION OF 20 LONG TERM SURVIVORS WITH SMALL CELL LUNG CANCER. A.G. Pedersen, A.L. Christensen, I. Albrecht, H.H. Hansen. Oncology Dept. ONB, Finsen Institute, Strandboulevarden 49, 2100 Copenhagen, Denmark. Late neurotoxicity with severe psychological dysfunction has been reported in patients treated for Small Cell Lung Carcinoma (SCLC). Patients have all received combined treatment with chemotherapy and elective cranial irradiation (PCI). The contribution of PC1 to this observation is unknown as no evaluation of patients only treated with chemotherapy has been reported. We examined 20 patients with SCLC disease free 4-10 years from the start of 18 months treatment with combination chemotherapy. No one received cranial irradiation. All patients were submitted to a 4 hour neuropsychological evaluation consisting of: 1) a preliminary conversation, 2) Raven-matrices included patients. The defined score system took into account two factors: the grading of radiological changes and the involved area in each chest x-ray. The total score was the addition of all areas. Each chest x-ray was graded twice by 4 medical observers. Intraobserver and inter-observer variations and were considered acceptable reproducible. However, the radiological lung fibrosis score did not sigcorrelate with clinical nificantly symptoms. A deeper thoracic assessment was conducted in 18 patients alive diseasefree after 30 months of follow-up. The assessment for long-term survivors inclinical examination, cluded quantification of dyspnea using Borg scale, chest CBC and chemistries, x-ray, fiberoptic bronchoscopy, ECG, cardiac spirometry, ultrasonography, flow/volume curve, TLC0 in steady state, compliance and exercise testing. Exertional dyspnea was observed in 8 patients (44%) and was disabling in 2 patients with previous symptomatic chronic obstructive lung disease. Fiberoptic bronchoscopy found sequelae in 65% of cases: cicatricial stenosis, mucosal vessel dilation and localized abnormal secretions. Arterial blood gases at rest and after exercise were nearly normal. A mild obstructive ventilatory defect was usually observed. stitute Gustave-Roussy, Rue Camille Desmoulins, 94905 Villejuif, France. We report here results concerning thoracic toxicity in 73 consecutive patients included in the first two schedules of alternating radiotherapy CRT) and chemotherapy (CT) conducted in our group. These 73 patients presented with limited SCLC and were treated from May 1980 to July 1983. The common schedule was as follows: CT---CT-RT-CTRT-CT-RT-CT---CT, where (-) represents a gap of 1 week. In the first protocol (002; 28 patients; 05/80-10/81) CT comprised doxorubicin 40 mg/m” d 1; VP16213 75 mg/m2 d 1, 2, 3; cyclophos-

phamide 300 mg/mz d 3, 4, 5, 6 and methotrexate 400 mg/m2 d 2 - plus folinic acid rescue. Each of the 3 delivered 15 Gy/6 courses of RT fractions/l0 days by anterior-posterior (AP) fields (Total dose: 45 Gy). In the second protocol (004; 45 patients; 11/81-07/83) methotrexate was replaced by cis-platinum 100 mglm’ d 2. The first 2 courses of RT delivered 20 Gy/8 fractions/l2 days by AP fields and the third course 15 Gy/6 fractions/l0 days by lateral fields avoiding the spinal cord (Total dose: 55 Gy). Prophylactic cranial irradiation -PCI- was given systematically in both protocols (30 Gy/lO fractions/l2 days). A grading system of lung fibrosis was used in 218 chest x-rays of the 73 a result of RT or RT+CT by the regional PF data depended on the degree of PF reserve and the location of the tumor. For patients in group A with FEV, > 70% of predicted, there was a 69% (61-80%) correlation rate between the predicted and measured VF indices. The change in blood gases were minor and didn't correlate with the predicted values. For patients in group A with FEV, 5069% of predicted, the correlation rate between the predicted and measured VF indices was 50%. For group B patients a small increase (l-10%) in VF indices was noted in 50% of patients, and another 40% of the patients showed rather a small decrease (< 10%) in these VF indices. Only 10% of the patients this group showed a decrease ini;F indices as predicted. None of these patients with upper lobe lesions showed a decrease in VF indices as predicted. Changes in VF indices of group C patients consisted of a small increase (l-10%) in 60%, a small decrease (< 10% in 20%, and a decrease as predicted in 20% of patients. THORACIC SEQUELAE IN LONG-TERM SURVIVORS TREATED BY ALTERNATING RADIOTHERAPY AND CHEMOTHERAPY FOR LIMITED SMALL CELL LUNG CANCER (SCLC). R. Arriagada, P. Balbyrou, H. De Cremoux, T. Le Chevalier, P. Ruffie, D. Couanet, M. Martin and the GROP, InChanges in PF indices of group A patients after RT or RT+CT were as follows: Ventilatory function (VF) indices, i.e., FEV,, FVC, MBC, Peak Expiratory Flow Rate were (PEFR), decreased by 15-25% (p = 0.006); TLC was decreased by 11% (p = 0.007); airway resistance was increased by 18% (p = 0.12); and DLCO was decreased by 6% (P = 0.67). There was no significant change in PaO, and PaCO,. With regard to the changes in PF by RT vs. RT+CT, the VF indices of patients treated with RT+CT (45-52 Gy for SCLC) were decreased by 13-21%, and this was less than a 15-25% decrease of these indices in patients treated with RT alone (5564 Gy for NSCLC using a higher radiation dose). The changes in TLC and blood gases of RT group were not different from those of RT+CT group. Changes in PF indices of group B patients are of special interest. Con-

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to the prediction, there was a Wary small increase (l-8%) in VF indices at 12 M after RT. TLC was unchanged. Air way resistance was increased by 25% (p = 0.25). PaO, and PaCO, were unchanged. Group C patients also showed a

small range of changes (-4% to +3%) in VF indices at 12 M after RT. TLC was decreased by 21% (p = 0.04). PaO,, PaC02 and DLCO also showed a minor range of changes (-1% to +4%). The predictability of loss of PF as