342 Abstracts/Lung Gmcer 13 (1995) 323-356

Combined pulmonary and thoracic wall resection for stage III

lung cancer Shah SS, Goldsttaw P Deparmentof Thoracic Suqery, RoyaiBmnpton Hospital, Sydney Stmet, London SW3 6NP Thorax 1995;50:782-4.

Backgmund - Carcinoma of the lung with thoracic wall involvement constitutes stage III disease. The management of patients with this condition is complicated. However, improvement in perioperative care coupled with advances in surgical technique have enabled a more aggressive approach to tbe problem to be adopted. Methods - A retrospective review was carried out of 58 patients (40 men) of mean age 63 years who underwent thorawtomy for lung cancer with chest wall invasion between 1980 and 1993. Results - Chest wall resection was performed in 55 patients (94.8%); in three patients the discovery of N2 disease at operation precluded resection. The TNM status was T3NOMO in 38 patients, T3NIMO in 13, and T3N2MO in seven. Squamous cell carcinoma was the commonest cell type (26 patients). ReconsU’uction of the chest wall was performed in 29 patients (Marlex mesh in six, Marlex-methacrylate in 22, myocutaneous flap in one patient). The morbidity and mortality were 22.4% and 3.4% respectively. Follow up was complete in 5 I patients. Nineteen (37 2%) survived 5 years. The absolute five year survival for NO and Nl disease was 44.7% and 38.4%. respectively. No patients with N2 disease survived five years. Conclusions - In patients with carcinoma of the lung and chest wall invasion, combined pulmonary and thoracic wall resection offers he prospect of cure with minimal morbidity and mortality. The prognosis of patients with coexistent N2 disease remains poor.

Prognosis in primary, resected non-small cell carcinoma cases with intrapulmonary metastasis Fujisawa T. Yamaguchi Y. Saito Y. Iizasa T. Baba M. Shiba M et al. Department of Sutge~, Inst. of Pulmonary Cancer Reseamh, Chiba

UniversitySchoolofMedicine, Chiba. Jpn JLung Cancer 1995;35:247- 52.

The objective was to evaluate the prognosis of primary non small cell carcinoma cases in a total of 794 casea resected during the past 10 years, including 64 cases with intrapulmonary metastasis (pm) and 730 cases without intrapulmonic metastasis (control). The overall 5 year survival rates in the pm group was 25% and there were no significant differences in survival between adenocarcinoma and squamous cell carcinoma, or between cases of Tl, T2, T3 and T4 disease. However, the survival rates of cases with metastasis to primary lobe tended to be better than cases of ipsilateral metastasis to non-primary lobe(s). Furthermore, significant differences of survival curves were demonstrated between cases with NO and NZ diseases and between cases with solitary and multiple metastasis (both P < 0.05, Cox Mantel test). The survival rates of cases with intrapulmonary metastasis were rcemhtated according to the classification proposed by the AJCC and no significant differences were demonstrated in TZNO, T3N0, T4N0, Nl, N2 diseases between the pm group and control group without intrapulmomuy metastasis, supporting the suitability ofthe AJCC stage criteria for intrapulmonary metastasis.

Predicting postoperative pulmonary function in patients undergoing lung resection Z&her BG, Gross TJ, Kern JA, Lanza LA, Peterson MW. Univ. ofIowu Hospitals and Clinics, Iowa City, LA 52242. Chest 1995;108:68-72.

Objective: Our aim was to determine the effect of lung resection on spirometric lung function and to evaluate the accuracy of simple calculation in predicting postoperative pulmonary tiction in patients undergoing lung resection. Design: We reviewed preoperative and postoperative pulmonary function test results on patients who were followed in the multidisciplinary lung cancer clinic between July 1991

and March 1994 and who underwent lung resection. The predicted postoperative FEV, and FVC were calculated based on the number of segments resected and mere wmpared with the actual postoperative FEV, and FVC. Setting: Tbis study was conducted at a university, tertiary referral hospital. Patients: All patients were evaluated at a multi- disciplinary lung cancer clinic and underwent lung resection by one surgeon (L.A.L.). A4emutwnents and main results: Sixty patients undergoing 62 pulmonary resections were reviewed The predicted postoperative FEV, and FVC were calculated using the following formula: predicted postoperative FEV, (or FVC)lpreoperative FEV, (or FVC)x(l-fSxO.O526)); where S=number of segments resected. The actual postoperative PEV, and FVC correlated well with the predicted postoperative FEV, and FVC for patients undergoing lohectomy (r=O.867 and H.832, respectively); however, the predicted postoperative FEV, consistently underestimated the actual postoperative FEV, by approximately 250 mL. For patients undergoing pneumonectomy, the actual postoperative FEV, and FVC did not correlate as well with the predicted postoperative FEV, and FVC (r=0.677 and r=0.741, respectively). Although there was considerable variability, the predicted postoperative FEV, consistently underestimated the actual postoperative FEV, hy nearly 500 mL. Of the patients undergoing lobectomy, eight also received postoperative radiation therapy. When analyzed separately, patients receiving combined therapy lost an average of 5.47% of FEV per segment resected. This contrasts with a 2.84% per segment teductior in FEV, for patients who did not rtive radiation therapy. Conclusions This simple calculation of predicted postoperative FEV, and FVC correlates well wilh the actual postoperative FEV, and FVC in-patients undergoing lobectomy. The predict4 postoperative FEV, consistently underestimated the actual postoperative FEV, by approximately 250 tuL. The. postoperative FEV, and FVC for patients undergoing pneumon- ectomy is not accurately predicted using this equation. The predicted postoperative FEV, for patients undergoing pneumonectomy was nr~derestimatcd by an average of 500 mL and by greater than 250 mL in 12 of our 13 patients. Thus, by adding 250 mL lo the above calculation of predicted postoperative FEV,, we improve our ability to estimate FEV, for patients undergoing lobectomy and we identify a minimal postoperative FEV, for patients undergoing pneumonectomy. Finally, combined modality treatment with surgery followedby radiation therapy may result in additive lung function loss.

Results of a limited resection for compromised or poor-risk patients with clinical stage I non-small cell carcinoma of the lung Yano T, Yokoyama H. Yoshino I, Tayama K, Asoh H, Hata K et al. Department of Chest Sugery. National Kyushu Cancer Cente,: 3-1-l. Notame, Afinomi-ku, Fukuoka 815. J Am Coll Surg 1995;181:33-7.

Bockgtvund: Patients with stage I non-small cell carcinoma of the lung may be unable to undergo a standard curative resection, such as lobectomy, due to various medical reasons. Whether or not a limited resection is superior to radiotherapy in these patients, both in terms of long-term prognosis and treatment morbidity, is unknown. Stu&designt We retrospectively reviewed our results in treating compromised or poor- risk patients with clinical stage I non-small cell carcinoma ofthe lung who had received either a limited resection or radiotherapy. Seventeen patients underwent a limited resection (nine wedge resections and eight segmentectomies), while 18 patients received radiation therapy. Rest&s: The five-year survival rates for patients in the limited resection group and the radiation treatment group were 55.0 and 14.4 percent, respectively. A log-rank analysis showed a significant difference between the two groups @=0.004). Furthermore, the survival rate of the patients having a limited operation was significantly better than that of patients achieving either complete response or partial response from radiotherapy (18.8 percent at five years, p=O.OOS). Recurrence at the surgical margin

Abstracts/Lung Gutter 13 (1995) 3.23-356 343

occurred in four patients in whom the tumor was greater than 2 cm in longest diameter. The incidence of severe treatment-related complica- lions was not different between the limited operation group and the radiotherapy group ( 1 I .8 compared to Il. 1 percent). Conclusions: The results Indicate that a limited resection for patients with poor-risk clinical stage I carcinoma of the lung has an advantage over radiotherapy, especially for tumors measuring less than 2 cm in longest diameter.

Surgical treatment of pulmonary carcinoma in individuals over

80 years of age Aitakov ZN, Kurek SV, Borodkina TG, Klimov AB. Mask. Gorodskoj Onkol. Dispansec A4oskvuXhimrgiya 1995;7 135-7.

Growth of the specitic fraction of individuals over 80 years of age among patients witi lung carcinoma is illustrated by its incidence in Moscow. These patients account today for up lo 8% of the total number of cases. Some of them may be successfXly treated by operation. This was demonstrated in 11 cases. Recommendations on pre- and post- operative management of such patients are given. The authors emphasize that the patient’s fate and the method of treatment should be prescribed only in an oncological medical institution.

Chemotherapy

Glutathione S transferase Pi is a powerful indicator in chemotherapy of human lung squamous-cell carcinoma Inoue T, lshida T, Sugio K, Maehara Y, Sugimachi K. Faculty oJ Aledlcine, Kyushu Clniversiry, Department ofSu)gety II, Maidashi 3-l- I, Hlgashi-ku. Fukuoka 812. Respiration 1995$2:223-l.

We immunohistochemically investigated the expression of glutathione S transferase 6 @ST-t)) and ciarified the correlation between GST-i) and the results of chemosensitivity testing on the tissue of primary human squamous-cell carcinoma of the lung. The expression of GST& was evaluated in 105 cases and their level of chemosensitivity was estimated by the in vitro succinate dehydrogenase inhibition test for cisplatin. Adriamycin, cyclophosphamide, mitomycin C, vindesine and flurouracil. Tumors in which 25% and more of the cells stained for GST& were classified as having a high GST& expression, while those tumors demonstrating less than 25% of the cells staining for GST& were considered lo have a low expression GST-& The percentage of high GST& was 52% (53 of 105) while that of low GST-C) was 48% (S2 of 105). No significant correlation between the expression of GST- b and clinicopathologic factors was observed, while no significant difference in the survival of the two groups was found either. An increase in succinate dehydrogenase activity was recognized in the high-GST& group compared with the low-GST& group for each anticancer dm&; however, no statistical signiticance was seen except for cisplatin. In the cases with adjuvant combination chemotherapy using cisplatin after a complete resection, all cases demonstrating a relapse were associated with a high GST&. These findings thus indicate that an over-expression of GST-6 is related lo the resistance to cisplatin in human lung squamouscell carcinoma. It is therefore important to select carefully the optimal anticancer drug for high-GSTa cases.

Role of sodium pump systems to determine sensitivity to mitomycin C in non-small cell lung cancer cell lines Bando T, Kasaham K, Sbibata K, Numata Y, Nakatsumi Y, Fujimura M et al. Third Department Internal Medicine, Kanazawa University School Medicine, 13-l Takara-machi, Kana.zmva 920. Anticancer Res 1995;15:769-72.

There are some active tmnspmt systems in the cell membrane, such as potassium pump, and proton pump. Although it has been reported

that sodium@otassium and sodiumlcalcium pumps of cell membrane play roles in the intracelhdar accumulation of anticancer agents, the significance of the active transport channels in accumulation of mitomycin C (MMC), one of the most active agents for non-small cell lung cancer (NSCLC) has been unclear. In this study, we evaluated the role of the potassium pump, calcium pump, and proton pump as determinants of the sensitivity to Mh4C in vitro by using the selective inhibitors, ouabain, verapamil or AG-2000 (an active metabolite of Lansoplazole), respectively. PC-9 and PC-9/MC4 cell lines which are sensitive and resistant to MMC were used for these experiments. PC-9/ MC4 was 9.4-fold more resistant lo MMC than PC-9 cells. Relative resistance was not significantly changed by co-incubation with a non- cytotoxic dosage of these inhibitors. From these results, it was revealed that the active transport systems in cell membrane do not play a role in determining the sensitivity to MMC and the acquisition of resistance lo Mh4C in PC-9 cell lines. Intracellular bioactivation may be an important factor to determine sensitivity to MMC in NSCLC ceils under aerobic conditions.

Schedule dependency of 21-day oral versus 3&y intravenous

etoposide in combination with intravenous cisplatin in extensive- stage small-cell lung cancer: A randomized phase III study of the cancer and leukemia group B Miller AA, Hemdon JE II. HoUis DR, Ellerton I, Langkben A, Richards F II et al. University of Tennessee, 3 N Dunlap, Memphis, TN 38163. J Clin Oncol 1995;13:1871-9.

Purpose: This was a randomized phase III study to test t schedule dependency of etoposide given as a conventional 3day intravenous (IV) regimen versus a prolonged 2 1 day oral regimen for extensive-stage small-cell lung cancer (SCLC). Both regimens contained IV cisplatin. The objectives were to compare survival (Primary end point) and to establish response rates, failure-free survival, and toxicity (secondary end points). Patients ondMefhods: Patients with untreated measurable or assessable disease and normal organ function were eligible. Randomization was strati&d according to performance status 0 versus 1 or 2. Treatment consisted of etoposide 130 mg/ma/d IV for 3 days and cisplatin 25 mg/m*/d IV for 3 days every 21 days for eight courses (schedule 1) versus etoposide 50 mg/m?d orally for 2 1 days and cisplatin 33 mg/m2/d IV for 3 days every 28 days for six courses (schedule 2). In 1990, bioavailability of oral etoposide was assumed to be 50%, and the study was designed to deliver the same total doses of etoposide and cisplatin on both regimens over 24 weeks without the use of growth factors. Results: Between December 1990 and OUober 1993,306 eligible patients were entered. Of these, 69% were male and 66% were 60 years of age; 2 1% bad a performance status of 0,47% a performance status of 1, and 32% a performance status of 2; 156 were randomized to receive s&e4iule 1 and 150 to receive schedule 2. Overall median survival estimates were 9.5 and 9.9 months (ditference not significant) for schedule I and schedule 2, respectively. The 95% confidence interval (CI) for overall survival, 8 to 11 months, was the same for both schedules, with 126 and 117 deaths on schedule 1 and 2, respectively. Both acheduks ala0 reankd in the same median failure-free survival estimate of 7 months (95% CI, 6 to 8 months on either schedule). Complete and partial responses were observed in 15% and 42%of patients on schedule 1 and 14% and 47% on schedule 2, respectively. The overall maximal hmatologic toxicities pde 3 and 4 for leukocytes, neutmphils, platelets, and hemoglobin were, mspectively, as follows: schedule 1.62%. SS%, 32%. and 32y’ s&&de 2.83% 83% 520/* and 55%. Lethal toxicity due to neutmpenia and infection occumd in 4% of patients on schedule 1 and 10% on schedule 2 (difference not statistically significant).

Concfttston: The two schedules of etoposide in combination with ciaplatin did not result in differences in treatment outcome with respect