This document summarizes a study on the 5-year survival of non-small cell lung cancer patients after adjuvant chemoimmunoradiotherapy compared to surgery alone or postoperative radiotherapy. The study found that adjuvant chemoimmunoradiotherapy significantly improved 5-year survival and lifespan for patients with lymph node metastases (N1-2) compared to the other treatments. However, for patients without lymph node metastases (N0), the 5-year survival was not significantly different between adjuvant chemoimmunoradiotherapy and surgery alone or postoperative radiotherapy.

1. 5-Year Survival of Non-Small Cell Lung Cancer Patients after Adjuvant Chemoimmunoradiotherapy Oleg Kshivets, M.D., Ph.D. Department of Surgery, Siauliai Public Hospital, Lithuania The 53 rd Annual Cancer Symposium of Society of Surgical Oncology New Orleans, The USA, 2000

2. Abstract: FIVE-YEAR SURVIVAL AND LIFE SPAN OF NON-SMALL CELL LUNG CANCER PATIENTS AFTER ADJUVANT CHEMOIMMUNORADIOTHERAPY O.Kshivets* Siauliai Cancer Center, Siauliai, Lithuania Purpose : This study aimed to determine expediency of adjuvant chemoimmunoradiotherapy (AT) for radical operated non-small cell lung cancer (C) patients (LCP) with pathologic stage II-III (T1-4N0-2M0G1-3). Methods : In randomised trial (1985-1998) 5-year survival (5YS) of 54 radical operated LCP after AT (age=54.4  1.0 years; males=49, females=5; C size=4.7  0.2 cm) was compared with 5YS of 264 LCP after radical procedures (S) (age=55.8  0.5 years; males=240, females=24; C size=4.5  0.1 cm) and with 5YS of 86 radical operated LCP after postoperative radiation (R) (45-50 Gy) (age=58.0  0.8 years; males=74, females=12; C size=4.7  0.2 cm). Variables selected for 5YS study were sex, age, TNMG, cell type, C size. 1 cycle of chemoimmunotherapy (CAVT: cyclophosphamid 500 mg/m 2 IV+doxorubicin 50 mg/m 2 IV+vincristin 1.4 mg/m 2 IV on day 1; thymalin/taktivin 20 mg IM daily for 5 days) was given on 10-14 day after S. R (45-50 Gy) was administered since 7 day after 1 cycle. After R 3-4 courses of CAVT were repeated every 21-28 day. Representativeness of samplings was reached by means of randomisation based on unrepeated random selection. Multiple correspondence analysis (A), cluster A, confirmatory factor A, structural equation modeling, Monte Carlo simulation were used to determine any significant overall differences between survival of LCP after AT, S, R. Results : 5YS was superior in AT group (64.8%: 35 from 54 LCP with N0-2; life span: LS=1998.2  156.9 days) compared with R group (45.3%: 39 from 86 LCP with N0-2; LS=1296.4  109.5 days) (P<0.001). 5YS of S group was 63.6% (168 from 264 LCP with N0-2; LS=1738.3  63.4 days) (P>0.05 for AT and P<0.001 for R). For LCP with N1-2 5YS was significantly superior for AT group (63.6%: 21 from 33; LS=1934.0  189.9 days) compared with S group (28.1%: 25 from 89; LS=1056.9  91.1 days) (P<0.001) and with R group (35.6%: 21 from 59; LS=1051.7  119.6 days) (P<0.001). Rates of age, sex, T1-4, G1-3, cell type, C size for LCP after AT, S and R were not significantly different. Structural equation modeling and Monte Carlo simulation confirmed significant overall differences between 5YS (P<0.05) and LS (P<0.001) of LCP with N1-2 after AT with respect to S or R; however, 5YS of LCP for N0 with or without AT and R were not significantly different.

3. Samplings: Lung Cancer Patients Lived More than 5 Years after Complete Resections..…... 242 Lung Cancer Patients Died Because Generalization During First 5 Years after Complete Resections.…….…………... 162 In All…………………………………...404

4. Samplings: Adjuvant Chemoimmunoradiotherapy………….. 54 Postoperative Radiotherapy..……...….. 86 Surgery Alone………………………… 264 In All…………………………………...404

5. Radical Procedures: Pneumonectomy…………………..175 Upper/Lower Bilobectomy…………21 Upper Lobectomy…………………136 Lower Lobectomy………………….66 Middle Lobectomy………………….6 Combined Procedures……………..49 In All…………………………...….404

6. Staging: T1…..118 N0..…223 G1…..100 T2…..187 N1……97 G2…..104 T3……84 N2……84 G3…..200 T4……15 Stage II...111 Stage III...293 Squamous Cell Carcinoma…..……….263 Adenocarcinoma………………………116 Large Cell Carcinoma………………….25

7. 5-Year Survivors and Losts

8. Results of Factor Analysis

9. Results of Factor Analysis

10. Nucloids of Lung Cancer Patients with N0-2, n=404

11. Results of Cluster-Analysis of Clinicopathologic Characteristics of Lung Cancer Patients with N0-2, n=404

12. Nucloids of Lung Cancer Patients with N1-2, n=181

13. Results of Cluster-Analysis of Clinicopathologic Characteristics of Lung Cancer Patients with N1-2, n=181

14. Network-Model of Lung Cancer Patients with N0-2 (n=404)

15. Network-Model of Lung Cancer Patients with N0 (n=223)

16. Network-Model of Lung Cancer Patients with N1-2 (n=181)

17. Survival of Lung Cancer Patients with N0-2 (n=404)

18. Proportional Hazard (Cox) Regression Model of Lung Cancer Patients with N0-2, n=404

19. Logistic Regression Model of Lung Cancer Patients with N0-2, n=404

20. Logistic Regression Model of Lung Cancer Patients with N0-2, n=404

21. SEPATH-Model: Clinicopathologic Characteristics-Survival of Lung Cancer Patients with N0-2 metastases (n=404)

22. Survival of Lung Cancer Patients with N0-2 (n=404)

23. Survival of Lung Cancer Patients with N1-2 (n=181)

24. Proportional Hazard (Cox) Regression Model of Lung Cancer Patients with N1-2, n=181

25. Logistic Regression Model of Lung Cancer Patients with N1-2, n=181

26. Logistic Regression Model of Lung Cancer Patients with N1-2, n=181

27. SEPATH-Model: Clinicopathologic Characteristics-Survival of Lung Cancer Patients with N1-2 metastases (n=181)

28. Results of Monte Carlo Simulation

29. Life Span of Died Lung Cancer Patients with N0-2 (n=162)

30. Conclusions: Adjuvant chemoimmunoradiotherapy significantly improved 5-year survival and life span of non-small cell lung cancer patients with N1-2 metastases after complete resections compared with surgery alone and postoperative radiotherapy. One must be careful in using adjuvant chemoimmunoradiotherapy for lung cancer patients without lymph node metastases.

31. Address: Oleg Kshivets, M.D., Ph.D. Consultant Thoracic/Abdominal Surgeon Department of Surgery Siauliai Public Hospital Tilzes:42-16, LT78206, Siauliai, Lithuania tel (37041)416614 e-mail: [email_address]