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Surgical treatment for small cell lung cancer (SCLC): Long-term survival
105
Modini, C., Cicconetti, F0, Botti, C., Buttini, G.L., Moreschi, M., Micozzi, I., Fazio, M., Stipa, S. ist Department of Surgery, U n i v e r s i t y of Rome, Italy. i00 out of 527 pts. with a m i n i m u m follow-up; of 15 yrs. were r e t r o s p e c t i v e l y s e l e c t e d according to the following criteria: h i s t o l o g i c a l l y p r o v e n b r o n c h o p u l m o n a r y carcinoma, p r e s u m e d curative resection, no a d j u v a n t t h e r a p y before or a f t e r the surgical treatment. Data were c o l l e c t e d and p r o c e s s e d by on I.B.M. 370/158 computer. The m e d i a n survival of the study g r o u p was 15 mths (7 o p e r a t i v e m o r t a l i t i e s were excluded) and 5, i0 and 15 yrs crude survival rates were 23.65% (22/93), 16.1% (15/93) and 10.7% (10/93) respectively. A s s u m i n g the m e d i a n survival as d e p e n d e n t v a r i a b l e (0=less than 15 mths, l=more than 15 mths) 41 d i f f e r e n t p a r a m e t e r s were considered as independent variables in a multivariate analysis (stepwise m u l t i p l e regression). Three p a r a m e t e r s were accepted: TNM stages (stage I-II vs stage III), kind of r e s e c t i o n (lobectomy vs p n e u m o n e c t o m y ) , extent of r e s e c t i o n (simple vs extended) (F05.355, F=4.249, F=0.168). C o m b i n i n g these c h a r a c t e r i s t i c s it was p o s s i b l e to o b t a i n 8 groups able to u n e q u i v o c a l l y define every single patient. We used the same d e p e n d e n t v a r i a b l e and these 8 groups as i n d e p e n d e n t ones to set up a new stepwise r e g r e s s i o n analysis. A c c o r d i n g to the o b t a i n e d "t values" for each step we assigned a score to each individual. Only for p u r p o s e of t a b u l a t i o n we d i v i d e d our p a t i e n t s in four score groups (from 0.644 to 2.136). The mean scores of each group were c o r r e l a t e d to the survival rates at 3-5-10 and 15 yrs, showing that the higher was the score the higher was the survival rates in the study group. The scoring system was then tested in a control group of 65 p a t i e n t s with h o m o g e n e o u s c h a r a c t e r i stics, looking for the r e g r e s s i o n equations of m e a n scores vs survival at 3-5 yrs (Y=21.93 + 12.76 x at 3 yrs; Y=15.57 + 9.21 x at 5 yrs). The goodness o f the fit b e t w e e n study and control groups was furtherly tested under the null h y p o t h e s i s of identity w h i c h was a c c e p t e d at an alfa value of 0.001 with 6 d f. In c o n c l u s i o n this score system b a s e d on a c o m p a r i s o n against m e d i a n value of survival enables us to p r e d i c t long term survival after a b r i e f e r p e r i o d of observation, waiting the death's o c c u r r e n c e of 50% of the p a t i e n t s plus one.
Surgical Treatment For Llmg Cancer: A ~,itivaried Analysis of Long-Term Survival. Di Giorgio, A., Sammartino, P., Mosticoni, S., Di Lauro, G., Baffoni, S. I C l i n i c a Chirurgica, U n i v e r s i t ~ di Roma, Italia. In a series of 456 lung cancer patients
treated with surgical resection from a m i n i m u m of 5 years and b e i n g followed-up, the survival rate was a n a l y z e d with relation to several p r o g n o s t i c parameters. Particularly, the survival rate was related with the h i s t o l o gical type, p-stage, host immune response, exp r e s s e d as degree of lymphocyte infiltration of the p r i m a r y tumor (LI). The significance of such correlations was evaluated by the analysis of variance p e r f o r m e d w i t h a data bank from a computer UNIVAC ii00 at the EDP Center of Rome University. This test has shown that the survival data are statistically related with the p stage and LI but not with the h i s t o l o g i c a l type (Tab.). As for the p r o g n o s t i c value of such parameters, it was p o s s i b l e to assess that patients with neoplasms at an early stage and with evident immune response (LI > 2) had better survival rates as compared to the other cases, apart from the histological type of neoplasm. ANOVA 3 WAYS SOURCE HISTOLOGICAL TYPE (A)
SSq
d I
M Sq
F
p
166...
1
168_.
0.46...
N,S.
p STAGE (B)
28.52.-
1
28.52..,
7.87.
< 0.01
3168.
LI (C)
31,68..
I
8.75_
<0.01
A X B
O 02 .
1
0.02 ..
5 7... E.03
N.S.
A X C
4.68...
I
4.68 ..
1.29-
N,S.
B X C
2.52..
I
2.52 ..
0.69...
N.S.
17.52.,
1
~7 52,..
4,83..,
=0,05
A X BX C
Surgical T r e a t m e n t For Small Cell Lung C a n c e r (SCLC): L o n g - T e r m Survival. Di Giorgio, A., Sammartino, P., Di Lauro, G., Caramanico, L., Baffoni, S. I Clinica Chirurgica, Universit~ di Roma, Italia. The best t h e r a p e u t i c approach to small cell lung cancer (SCLC) has long been a rather controversial issue. The present research was undertaken in o r d e r to assess results of surgical treatment for SCLC o b t a i n e d at a single institution and to analyze some possible prognostic factors w h i c h m i g h t influence longterm results. The clinical records of all lung cancer p a t i e n t s o b s e r v e d at our institution during the period 1950-1982 were examined. Complete data were available in 1802 cases; h i s t o l o g i c a l m a t e r i a l was reviewed and classified according to W.H.O. criteria. SCLC was d i a g n o s e d in 288 p a t i e n t s (intermediate cell c a r c i n o m a 189 cases, oat cell carcinoma 99 cases). Resection was p e r f o r m e d in 150 cases (147 curative, 3 palliative), 73 patients were explored, and 65 were deemed unsuitable for surgical treatment. Overall 5-year survival rate after resection was 20,7%. Longterm p r o g n o s i s was significantly correlated to p - T N M (p< 0,002) and host's immune response as evidenced by c i r c u l a t i n g p e r i p h e r a l lymphocytic infiltration (p < 0,03), regional lymph node reactivity (P.C.A., S.H. and C.A. development) (p < 0,0001). Patients treated
106
for stage I disease and showing enhanced immune reactivity had a significantly better long term prognosis than stage II, III and non reactive patients. Oat cell subtype had worse 5-year survival rate (10,7%) than intermediate cell subtype (25,4%); this difference however is devoid of statistical significance (P: not significant).
Small Cell Lung Cancer (SCLC) and Non Small Cell Lung Cancer (NSCLC): Comparative Evaluation of Survival After Surgical Treatment by Computer. Di Giorgio, A., Sammartino, P., Di Lauro, G., Basile, M., Almansour, M. I Clinica Chirurgica, Universit~ di Roma, Italia. The authour have worked out an automatic procedure of analysis permitting the selection of samples homogeneous as for features and size from a given data bank. This procedure has been exemplified in a comparative evaluation of survival in patients surgically treated for SCLC and NSCLC. The data bank, processed by Univac ll00 series computer from the E.D.P. Center of the University of Rome, consists of 1802 cases of lung cancer, observed at our Institute during the period 1950-1982. The cases were stored by means of a computer oriented medical record fitted for 1600 ITEMS. The study was carried out on 461 cases submitted to radical surgery before 1980 and with known follow-up. In 87 cases the histological type was classified as SCLC and in 374 as NSCLC according to W.H.O. criteria. From the series, two samples homogeneous as for qualitative features (sex, age, immune response, p-TNM) and size (63 cases for each sample) were selected. The size was matching through randomized sampling by computer. The subsequent statistical analysis by the chi-square Yates test showed no significant differences in longterm survival values between the samples under study (5-years survival: SCLC 19,1% and NSCLC 20,6%). In order to evalu-. ate the reliability of the procedure the sampling was repeated (50 times) and no significant modifications of resluts of the comparative analysis were detected.
Results of Surgical Treatment for N 2 Lung Cancer. Picchiotti, R., Di Giorgi, A., Di Lauro, G., Basile, M., Bellezza, F. I Clinica Chirurgica, Universit~ di Roma, Italia. The study was carried out on a series of 106 lung cancer (p N~) patients treated wath surglcal resectlon from a minimum of 5 years and followed-up. Pneumonectomy was performed in 66 patients and lobectomy or bilobectomy in 41. As for the histological type 31 cases were diagnosed as epidermoid carcinoma, 29 as adenocarcinoma, i0 mixed (epidermoid + adenocarci-
noma)~ 8 as large cell and 24 as small cell carcinoma. As for staging, 14.2% was scored as T , 61.9% as T 2 and 24 as T,; for the evaluation 1 of the parameter N, 136~ ~ymph nodes were analyzed (mean 13.2 per pt). Long-term survival (5 years) was analyzed with respect to the histological type, _T and degree of lymphocyte infiltration of primary tumor (LI), expressing the host immune response. The overall survival at 5 years were sho~n to be 6.6% and not statistically related ( ~ t e s t ) with the parameter under study; however, better prognosis was observed in patients with neoplasms scored as T_ as compared to pT 2 and T ~ , and in cases ~i~h a marked immune respons~ ~LI ~ 2) as compared to those where the response was poor or absent (LI<2). 5.YEAR SORVtVAL p STAGE
HISTOLOGICAL TYPE
LI
~t
SCLC
42%
LI>2
mC~
? 3%
LI < 2
~
~% 4a%
12E% 4%
l~nediate and Long-Term Results of Surgical Treatment of Lung Cancer With Pleural and Extrapleurical Invasion. Virno, F., Di Giorgio, A., Di Lauro, G., Bellezza, F., Carrozzini, A. I Clinica Chirurgica, Universit~ di Roma, Italia. Immediate and long-term results were evaluated in a series of 226 lung cancer patients with pleural diffusion treated with surgical resection. In 121 there was only a pleural involvement (in 104 the parietal pleura, in 17 the mediastinal pleura), in 105 the neoplastic process involved also extrapleural structures (diaphragma, pericardium, atrium, chest wall etc.). Pneumonectomy was performed in 123 patients, lobectomy or bilobectomy in 97 and segmental or atypical resection in 6. In all cases the resection has involved the "en bloc" removal of the parietal pleura and other structures possibly affected by the neoplastic process. Operative mortality was 23% and 5-year survival 11%. The high rate of operative mortality was shown to be related to the extent of resection, the age and cardiorespiratory function of the patient. Prognosis was shown to be poorly related to the degree of neoplastic spread to the adjacent structures and to the histological type, while it appears to be markedly affected by the presence of mediastinal lymph node metastases.
Results of Surgery for Second Lung Primary. Todd, T.R., Ginsberg, R.J., Pearson, F.G., Cooper, J.D. Division of Thoracic Surgery, Toronto General Hospital, Toronto, Canada. Eighty five patients fulfilled our criteria for second lung primaries; metachronus (52), synchronous (33); in that there were two distinct cell types (28) or a second lesion quite separate from resection margins and not bronchoalveolar in type. There were 28 inoperable patients either at the first (4) or subsequent evaluation (24). Fifty seven patients completed the surgical
Modini, C., Cicconetti, F0, Botti, C., Buttini, G.L., Moreschi, M., Micozzi, I., Fazio, M., Stipa, S. ist Department of Surgery, U n i v e r s i t y of Rome, Italy. i00 out of 527 pts. with a m i n i m u m follow-up; of 15 yrs. were r e t r o s p e c t i v e l y s e l e c t e d according to the following criteria: h i s t o l o g i c a l l y p r o v e n b r o n c h o p u l m o n a r y carcinoma, p r e s u m e d curative resection, no a d j u v a n t t h e r a p y before or a f t e r the surgical treatment. Data were c o l l e c t e d and p r o c e s s e d by on I.B.M. 370/158 computer. The m e d i a n survival of the study g r o u p was 15 mths (7 o p e r a t i v e m o r t a l i t i e s were excluded) and 5, i0 and 15 yrs crude survival rates were 23.65% (22/93), 16.1% (15/93) and 10.7% (10/93) respectively. A s s u m i n g the m e d i a n survival as d e p e n d e n t v a r i a b l e (0=less than 15 mths, l=more than 15 mths) 41 d i f f e r e n t p a r a m e t e r s were considered as independent variables in a multivariate analysis (stepwise m u l t i p l e regression). Three p a r a m e t e r s were accepted: TNM stages (stage I-II vs stage III), kind of r e s e c t i o n (lobectomy vs p n e u m o n e c t o m y ) , extent of r e s e c t i o n (simple vs extended) (F05.355, F=4.249, F=0.168). C o m b i n i n g these c h a r a c t e r i s t i c s it was p o s s i b l e to o b t a i n 8 groups able to u n e q u i v o c a l l y define every single patient. We used the same d e p e n d e n t v a r i a b l e and these 8 groups as i n d e p e n d e n t ones to set up a new stepwise r e g r e s s i o n analysis. A c c o r d i n g to the o b t a i n e d "t values" for each step we assigned a score to each individual. Only for p u r p o s e of t a b u l a t i o n we d i v i d e d our p a t i e n t s in four score groups (from 0.644 to 2.136). The mean scores of each group were c o r r e l a t e d to the survival rates at 3-5-10 and 15 yrs, showing that the higher was the score the higher was the survival rates in the study group. The scoring system was then tested in a control group of 65 p a t i e n t s with h o m o g e n e o u s c h a r a c t e r i stics, looking for the r e g r e s s i o n equations of m e a n scores vs survival at 3-5 yrs (Y=21.93 + 12.76 x at 3 yrs; Y=15.57 + 9.21 x at 5 yrs). The goodness o f the fit b e t w e e n study and control groups was furtherly tested under the null h y p o t h e s i s of identity w h i c h was a c c e p t e d at an alfa value of 0.001 with 6 d f. In c o n c l u s i o n this score system b a s e d on a c o m p a r i s o n against m e d i a n value of survival enables us to p r e d i c t long term survival after a b r i e f e r p e r i o d of observation, waiting the death's o c c u r r e n c e of 50% of the p a t i e n t s plus one.
Surgical Treatment For Llmg Cancer: A ~,itivaried Analysis of Long-Term Survival. Di Giorgio, A., Sammartino, P., Mosticoni, S., Di Lauro, G., Baffoni, S. I C l i n i c a Chirurgica, U n i v e r s i t ~ di Roma, Italia. In a series of 456 lung cancer patients
treated with surgical resection from a m i n i m u m of 5 years and b e i n g followed-up, the survival rate was a n a l y z e d with relation to several p r o g n o s t i c parameters. Particularly, the survival rate was related with the h i s t o l o gical type, p-stage, host immune response, exp r e s s e d as degree of lymphocyte infiltration of the p r i m a r y tumor (LI). The significance of such correlations was evaluated by the analysis of variance p e r f o r m e d w i t h a data bank from a computer UNIVAC ii00 at the EDP Center of Rome University. This test has shown that the survival data are statistically related with the p stage and LI but not with the h i s t o l o g i c a l type (Tab.). As for the p r o g n o s t i c value of such parameters, it was p o s s i b l e to assess that patients with neoplasms at an early stage and with evident immune response (LI > 2) had better survival rates as compared to the other cases, apart from the histological type of neoplasm. ANOVA 3 WAYS SOURCE HISTOLOGICAL TYPE (A)
SSq
d I
M Sq
F
p
166...
1
168_.
0.46...
N,S.
p STAGE (B)
28.52.-
1
28.52..,
7.87.
< 0.01
3168.
LI (C)
31,68..
I
8.75_
<0.01
A X B
O 02 .
1
0.02 ..
5 7... E.03
N.S.
A X C
4.68...
I
4.68 ..
1.29-
N,S.
B X C
2.52..
I
2.52 ..
0.69...
N.S.
17.52.,
1
~7 52,..
4,83..,
=0,05
A X BX C
Surgical T r e a t m e n t For Small Cell Lung C a n c e r (SCLC): L o n g - T e r m Survival. Di Giorgio, A., Sammartino, P., Di Lauro, G., Caramanico, L., Baffoni, S. I Clinica Chirurgica, Universit~ di Roma, Italia. The best t h e r a p e u t i c approach to small cell lung cancer (SCLC) has long been a rather controversial issue. The present research was undertaken in o r d e r to assess results of surgical treatment for SCLC o b t a i n e d at a single institution and to analyze some possible prognostic factors w h i c h m i g h t influence longterm results. The clinical records of all lung cancer p a t i e n t s o b s e r v e d at our institution during the period 1950-1982 were examined. Complete data were available in 1802 cases; h i s t o l o g i c a l m a t e r i a l was reviewed and classified according to W.H.O. criteria. SCLC was d i a g n o s e d in 288 p a t i e n t s (intermediate cell c a r c i n o m a 189 cases, oat cell carcinoma 99 cases). Resection was p e r f o r m e d in 150 cases (147 curative, 3 palliative), 73 patients were explored, and 65 were deemed unsuitable for surgical treatment. Overall 5-year survival rate after resection was 20,7%. Longterm p r o g n o s i s was significantly correlated to p - T N M (p< 0,002) and host's immune response as evidenced by c i r c u l a t i n g p e r i p h e r a l lymphocytic infiltration (p < 0,03), regional lymph node reactivity (P.C.A., S.H. and C.A. development) (p < 0,0001). Patients treated
106
for stage I disease and showing enhanced immune reactivity had a significantly better long term prognosis than stage II, III and non reactive patients. Oat cell subtype had worse 5-year survival rate (10,7%) than intermediate cell subtype (25,4%); this difference however is devoid of statistical significance (P: not significant).
Small Cell Lung Cancer (SCLC) and Non Small Cell Lung Cancer (NSCLC): Comparative Evaluation of Survival After Surgical Treatment by Computer. Di Giorgio, A., Sammartino, P., Di Lauro, G., Basile, M., Almansour, M. I Clinica Chirurgica, Universit~ di Roma, Italia. The authour have worked out an automatic procedure of analysis permitting the selection of samples homogeneous as for features and size from a given data bank. This procedure has been exemplified in a comparative evaluation of survival in patients surgically treated for SCLC and NSCLC. The data bank, processed by Univac ll00 series computer from the E.D.P. Center of the University of Rome, consists of 1802 cases of lung cancer, observed at our Institute during the period 1950-1982. The cases were stored by means of a computer oriented medical record fitted for 1600 ITEMS. The study was carried out on 461 cases submitted to radical surgery before 1980 and with known follow-up. In 87 cases the histological type was classified as SCLC and in 374 as NSCLC according to W.H.O. criteria. From the series, two samples homogeneous as for qualitative features (sex, age, immune response, p-TNM) and size (63 cases for each sample) were selected. The size was matching through randomized sampling by computer. The subsequent statistical analysis by the chi-square Yates test showed no significant differences in longterm survival values between the samples under study (5-years survival: SCLC 19,1% and NSCLC 20,6%). In order to evalu-. ate the reliability of the procedure the sampling was repeated (50 times) and no significant modifications of resluts of the comparative analysis were detected.
Results of Surgical Treatment for N 2 Lung Cancer. Picchiotti, R., Di Giorgi, A., Di Lauro, G., Basile, M., Bellezza, F. I Clinica Chirurgica, Universit~ di Roma, Italia. The study was carried out on a series of 106 lung cancer (p N~) patients treated wath surglcal resectlon from a minimum of 5 years and followed-up. Pneumonectomy was performed in 66 patients and lobectomy or bilobectomy in 41. As for the histological type 31 cases were diagnosed as epidermoid carcinoma, 29 as adenocarcinoma, i0 mixed (epidermoid + adenocarci-
noma)~ 8 as large cell and 24 as small cell carcinoma. As for staging, 14.2% was scored as T , 61.9% as T 2 and 24 as T,; for the evaluation 1 of the parameter N, 136~ ~ymph nodes were analyzed (mean 13.2 per pt). Long-term survival (5 years) was analyzed with respect to the histological type, _T and degree of lymphocyte infiltration of primary tumor (LI), expressing the host immune response. The overall survival at 5 years were sho~n to be 6.6% and not statistically related ( ~ t e s t ) with the parameter under study; however, better prognosis was observed in patients with neoplasms scored as T_ as compared to pT 2 and T ~ , and in cases ~i~h a marked immune respons~ ~LI ~ 2) as compared to those where the response was poor or absent (LI<2). 5.YEAR SORVtVAL p STAGE
HISTOLOGICAL TYPE
LI
~t
SCLC
42%
LI>2
mC~
? 3%
LI < 2
~
~% 4a%
12E% 4%
l~nediate and Long-Term Results of Surgical Treatment of Lung Cancer With Pleural and Extrapleurical Invasion. Virno, F., Di Giorgio, A., Di Lauro, G., Bellezza, F., Carrozzini, A. I Clinica Chirurgica, Universit~ di Roma, Italia. Immediate and long-term results were evaluated in a series of 226 lung cancer patients with pleural diffusion treated with surgical resection. In 121 there was only a pleural involvement (in 104 the parietal pleura, in 17 the mediastinal pleura), in 105 the neoplastic process involved also extrapleural structures (diaphragma, pericardium, atrium, chest wall etc.). Pneumonectomy was performed in 123 patients, lobectomy or bilobectomy in 97 and segmental or atypical resection in 6. In all cases the resection has involved the "en bloc" removal of the parietal pleura and other structures possibly affected by the neoplastic process. Operative mortality was 23% and 5-year survival 11%. The high rate of operative mortality was shown to be related to the extent of resection, the age and cardiorespiratory function of the patient. Prognosis was shown to be poorly related to the degree of neoplastic spread to the adjacent structures and to the histological type, while it appears to be markedly affected by the presence of mediastinal lymph node metastases.
Results of Surgery for Second Lung Primary. Todd, T.R., Ginsberg, R.J., Pearson, F.G., Cooper, J.D. Division of Thoracic Surgery, Toronto General Hospital, Toronto, Canada. Eighty five patients fulfilled our criteria for second lung primaries; metachronus (52), synchronous (33); in that there were two distinct cell types (28) or a second lesion quite separate from resection margins and not bronchoalveolar in type. There were 28 inoperable patients either at the first (4) or subsequent evaluation (24). Fifty seven patients completed the surgical