Trial Of Postoperative Adjuvant Chemotherapy Research Articles

Abstract CT211: Biomarker search using gene expression databases in a phase III controlled clinical trial of postoperative adjuvant chemotherapy for stage III colon cancer (ACTS-CC): correlation between clinicopathological factors and gene expression level

Abstract Background: The ACTS-CC trial is a randomized, controlled phase III study designed to validate the noninferiority of S-1 to UFT/leucovorin as adjuvant chemotherapy for stage III colon cancer and rectosigmoid cancer. A prospective biomarker search was performed as an auxiliary study of the ACTS-CC trial, using formalin-fixed, paraffin-embedded (FFPE) specimens obtained from 892 patients. The gene expression levels of 5-FU metabolizing enzymes and folate metabolizing enzymes and alterations of genome-wide copy numbers in tumor have been reported (2012, 2013 and 2014 Annual Meetings of AACR). In the present study, we performed correlation analyses of clinicopathological feature and gene expression level. Methods: Blocks of resected tumor specimens for this biomarker study were obtained after receiving informed consent from 892 of 1535 patients enrolled between April 2009 and January 2010. Macro-dissections were manually performed to extract total RNA and genomic DNA from 10-μm-thick FFPE specimens of colon cancer. Gene expression levels of 11 enzymes (TS, DPD, TP, OPRT, FPGS, GGH, DHFR, MTHFR, MTHFD, FOLRA, GART) related to 5-FU and folic acid metabolism were studied according to the Danenberg Tumor ProfileTM method (Shirota, Y. JCO 2001). Results: Gene expression levels were successfully estimated in 521-808 samples (84.0-90.0%, median 89.4%). Among 11 genes, GGH most strongly correlated with tumor locations: expression level of GGH in the distal colon was 1.8 times higher than those in the proximal colon. Gene expressions of DPD and GGH were significantly influenced by differentiation of tumor. DPD and GGH mRNA levels in poorly differentiated tumors were 2.0 or 2.5 times higher than those in well differentiated tumors, respectively. Likewise, TS most strongly correlated with tumor depth: expression level in T1 or T2 tumor was 1.3 times higher than those in T4 tumor. Conclusions: Location, differentiation and depth of the tumor correlated with each gene expressions. Our findings will facilitate understanding the characteristics of colon cancer. Further investigation on gene expressions including genome-wide copy number analysis may contribute to the exploration of valid biomarkers. Citation Format: Hiroyuki Uetake, Toshiaki Ishikawa, Megimi Ishiguro, Shigeyuki Matsui. Biomarker search using gene expression databases in a phase III controlled clinical trial of postoperative adjuvant chemotherapy for stage III colon cancer (ACTS-CC): correlation between clinicopathological factors and gene expression level. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT211. doi:10.1158/1538-7445.AM2015-CT211

Abstract 283: Biomarker search using gene expression databases in a phase III, controlled clinical trial of postoperative adjuvant chemotherapy for stage III colon cancer (acts-cc): Correlation between gene expression and DNA copy number

Abstract Background: The ACTS-CC trial is a randomized, controlled phase III study designed to validate the noninferiority of S-1 to UFT/LV as adjuvant chemotherapy for stage III colon cancer and rectosigmoid cancer. A prospective biomarker search was performed as an auxiliary study of the ACTS-CC trial, using formalin-fixed, paraffin-embedded (FFPE) specimens obtained from 892 patients. The gene expression levels of 5-FU metabolizing enzymes and folate metabolizing enzymes and alterations of genome-wide copy numbers in tumor have been reported (2012 and 2013 Annual Meetings of AACR). In the present study, we performed correlation analyses of gene expression and DNA copy number data to characterize colorectal cancer and to prepare for a pre-planned analysis of predictive or prognostic biomarkers. Methods: FFPE specimens for this biomarker study were obtained after receiving informed consent from 892 (gene expression analysis) or 795 (DNA copy number analysis) of 1535 patients enrolled between April 2009 and January 2010. Macro-dissections were performed to extract total RNA and genomic DNA from 10-μm-thick FFPE specimens of colon cancer. Gene expression levels of 11 enzymes (TS, DPD, TP, OPRT, FPGS, GGH, DHFR, MTHFR, MTHFD, FOLRA, GART) related to 5-FU and folic acid metabolism were studied according to the Danenberg Tumor ProfileTM method (Shirota, Y. JCO 2001). Somatic copy-number alterations in cancer were analyzed by high-density SNP array analysis (Human 250K StyI array, Affymetrix, Santa Clara, CA). To detect copy-number alterations, the scanned image CEL files were imported into Partek Genomics Suite v6.6 (Partek Inc., St. Louis, MO, USA). We compared mRNA level, gene copy number and genome-wide segment copy number across a total of 161 colorectal cancers. Results: Gene expression levels were successfully estimated in 521-808 samples (84.0-90.0%, median 89.4%). Genome-wide DNA copy numbers profiles of 161 samples were obtained by GeneChip. Extracted genomic DNA from 616 of 777 samples that were not subjected to microarray analysis served as validation samples. Frequencies of copy number gain (>2.3) ranged from 0% to 57% for 11 genes, whereas frequencies of copy number loss (<1.7) ranged from 24.8% to 87%. Among 11 genes, the DNA copy numbers of GART, GGH, MTHFD1, and FPGS most strongly correlated with mRNA expression: correlation coefficients of these genes were 0.48, 0.45, 0.42, and 0.41, respectively. Gene expressions of OPRT or TP were influenced not only by their own DNA copy numbers but also by other genomic segments of 20q or 18q on genome-wide analysis. Conclusions: Gene expression of folate metabolizing enzymes positively correlated with DNA copy numbers in patients with stage III colorectal cancer. Such correlations may merit further evaluation to identify potential biomarkers. Citation Format: Hiroyuki Uetake, Toshiaki Ishikawa, Megimi Ishiguro, Shigeyuki Matsui, Kenichi Sugihara, ACTS-CC Study Group. Biomarker search using gene expression databases in a phase III, controlled clinical trial of postoperative adjuvant chemotherapy for stage III colon cancer (acts-cc): Correlation between gene expression and DNA copy number. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 283. doi:10.1158/1538-7445.AM2014-283

Is Marital/Partner Status Associated With Survival in Patients With Resectable Pancreatic Cancer Treated With Adjuvant Postoperative Multi-Modality Therapy?: Results of Secondary Analysis of RTOG 9704

Two recently published studies based on analyses of Surveillance, Epidemiology, and End Results (SEER) data disclosed a statistically significant survival advantage for married/partnered patients with pancreatic cancer. However, the SEER data base does not contain detailed treatment information and therefore neither study specifically looked at survival in patients with resected pancreatic cancer who underwent combined modality adjuvant therapy. Since the impact of marital/partner status on survival in this cohort of aggressively treated patients has not been reported, this study was undertaken. A secondary analysis of RTOG 97-04, a phase III clinical trial of post-operative adjuvant chemotherapy and chemo-radiation therapy for patients with resected pancreatic carcinoma, was performed. Socio-demographic co-variables analyzed with respect to survival included gender (male vs female), age (<60 years vs ≥ 60 years), and marital status (married/partnered vs single). Survival analysis was performed using the product limit method and compared using the log rank test. Multivariable analysis was performed using the Cox proportional hazards regression model. Of the 531 patients enrolled in RTOG 97-04, complete socio-demographic data was available for 451. At the time of the secondary analysis 368 (82%) of the patients had died. Median patient age was 61 years (range 33 to 85 years), 271 (74%) were married/partnered, and 256 (56%) were male. Multivariable analysis disclosed that marital/partner status was not statistically significantly (p = 0.52) associated with overall survival. This secondary analysis of data from RTOG 97-04 demonstrated no association between marital/partner status and survival in patients with resected pancreatic cancer who received adjuvant post-operative chemo-radiation therapy. This finding suggests that while married patients with pancreatic cancer in general have a survival advantage, being married/partnered does not provide a survival advantage for patients with resected pancreatic cancer who undergo aggressive post-operative adjuvant multi-modality therapy.

402. Randomized Phase II Trial of Post-Operative Adjuvant Chemotherapy ±FANG™ Autologous Tumor Cell Vaccine in Colorectal Carcinoma with Liver Metastases

402. Randomized Phase II Trial of Post-Operative Adjuvant Chemotherapy ±FANG™ Autologous Tumor Cell Vaccine in Colorectal Carcinoma with Liver Metastases

A feasibility trial of postoperative adjuvant chemotherapy with S-1, an oral fluoropyrimidine, for elderly patients with non-small cell lung cancer: a report of the Lung Oncology Group in Kyushu (LOGIK) protocol 0901

The present study was designed to determine whether adjuvant chemotherapy with S-1 after surgical resection is feasible in elderly patients with non-small cell lung cancer (NSCLC), using a multi-institutional trial. From July 2009 to July 2011, 25 patients received the following regimen: 2 weeks of administration and 1 week of withdrawal of S-1 at 50-100 mg/body per day in an outpatient setting. The primary endpoint of this trial was the completion rate of eight cycles. The completion rate of eight cycles was 70.8 % [95 % confidence interval (CI) 52.7-89.0 %]. The perfect completion rate of eight cycles on schedule with full doses without delays was 50 % (95 % CI 30.0-70.0 %). The reasons for incomplete cycles were: patient refusal in four cases, anorexia in two cases and thrombocytopenia in one case. As a consequence of delays and/or dose reductions, the relative dose intensity of S-1 was 76.3 %. Adjuvant chemotherapy with S-1 at a reduced dose and schedule was therefore found to be a feasible treatment for elderly Japanese patients who had undergone surgical resection for NSCLC (UMIN Clinical Trials Registry number UMIN000002383).

O2-015 - Feasibility Trial of Postoperative Adjuvant Chemotherapy with S-1, an Oral Fluoropyrimidine, for Elderly Patients with Non-Small Cell Lung Cancer: Report of the Lung Oncology Group in KYUSHU (LOGIK) Protocol 0901

ABSTRACT Objective The present study was designed to determine whether adjuvant chemotherapy with S-1 after surgical resection is feasible in elderly patients with non-small-cell lung cancer (NSCLC) in a multi-institutional trial. Methods Adjuvant chemotherapy consisted of eight cycles (2-week administration and 1-week withdrawal) of S-1, at 50-100 mg/body per day in an outpatient setting. The primary end point of this trial was the completion rate of eight cycles. Results From July 2009 to July 2011, 25 patients were enrolled in the study. However, one patient withdrew the consent before administration of S-1. Patient characteristics: male/female = 16/9, median age = 76 (range 71–85), ECOG PS 0/1 = 17/8, pathological stage IB/IIA/IIB/IIIA/IIIB = 10/6/3/5/1, and adenocarcinoma (Ad)/non-Ad = 17/8. Toxicity was generally mild. Only one patient experienced grade 3 anorexia. No hematological toxic effects ≥grade 3 occurred. The completion rate of eight cycles was 70.8% (90% confidence interval (CI), 52.1% to 85.4%). The reasons for incomplete cycles were patient refusal in four patients, anorexia in two and thrombocytopenia in one. Conclusions Adjuvant chemotherapy with S-1 in the reduced doses and schedule was found to be a feasible treatment of Japanese elderly patients following surgical resection for NSCLC.

187. Randomized Phase II Trial of Post-Operative Adjuvant Chemotherapy ±FANG™ Autologous Tumor Cell Vaccine in Colorectal Carcinoma with Liver Metastases

187. Randomized Phase II Trial of Post-Operative Adjuvant Chemotherapy ±FANG™ Autologous Tumor Cell Vaccine in Colorectal Carcinoma with Liver Metastases

A randomized trial of postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus neoadjuvant chemotherapy for clinical stage II/III squamous cell carcinoma of the thoracic esophagus (JCOG 9907)

4510 Background: The phase III trial (JCOG9204) comparing postoperative adjuvant chemotherapy using cisplatin plus 5- fluorouracil (5-FU) with surgery alone showed superior disease-free survival in...

Ratio of metastatic to examined lymph nodes is a powerful predictor of overall survival in rectal cancer: An analysis of Intergroup 0114

4006 Background: Lymph node (LN) metastasis is associated with decreased survival in rectal cancer. It has been suggested that at least 14 LN be evaluated for adequate staging. However, a large percentage of patients have fewer than the recommended number of LN examined. We hypothesized that LN ratio would be predictive of overall survival in rectal cancer. Methods: Data was analyzed from Intergroup 0114, a mature trial of postoperative adjuvant chemotherapy and radiation in T3/4 and/or LN positive rectal cancer. Survival was the same for all arms allowing the entire group to be considered as one. The primary endpoint evaluated was overall survival. A proportional hazards model was used to determine the relative prognostic impact of LN ratio compared to number of LN examined, number of positive LN, number of negative LN and AJCC nodal stage. LN ratio was defined as the number of positive LN divided by the total number of LN examined. Four groups were analyzed based on proportion of positive LN: =0.25, &gt;0.25–0.50, &gt;0.50–0.75 and &gt;0.75. Results: 1,648 patients were evaluable. There were 251 T1/2, 1,251 T3 and 146 T4 tumors. 513 patients were N0, 743 N1 and 392 N2. Median number of LN was 9. LN ratio was predictive of 5-year overall survival with rates of 0.71, 0.56, 0.50 and 0.43 respectively when analyzed by quartile (p&lt;0.0001). LN ratio remained significant when overall survival was analyzed by number of LN examined and grouped into &lt;10, &lt;15 and &gt;15 nodes evaluated (p&lt;0.0001 for all). LN ratio also predicted overall survival in N1 (p=0.04) and N2 (p=0.0002) disease. When comparing LN ratio (χ2=79.5, p&lt;0.0001) to number of LN examined (χ2=4.7, p=0.03), number of positive LN (χ2=38, p&lt;0.0001), number of negative LN (χ2=32, p&lt;0.0001) and AJCC nodal stage (χ2=55.5, p&lt;0.0001), LN ratio appears to be the strongest predictor of overall survival. Conclusion: LN ratio predicts overall survival in patients with resected rectal cancer. Importantly, this is true in patients who have had a small number of LN evaluated, in addition to those with a large number of LN examined. LN ratio also appears to be a stronger predictor of overall survival than other described LN prognostic factors. LN ratio may be a useful variable to stratify outcome in patients with node-positive rectal cancer. No significant financial relationships to disclose.

Influence of regular aspirin use on survival for patients with stage III colon cancer: Findings from Intergroup trial CALGB 89803

3530 Background: Regular aspirin use reduces the risk of colorectal neoplasia. In animals, aspirin and COX-2 inhibitors appear to inhibit tumor growth. The effect of aspirin use on outcome in patients with established colon cancer is unknown. Methods: We prospectively studied aspirin use in 830 pts with stage III colon cancer enrolled in a randomized trial of post-operative adjuvant chemotherapy (5-fluorouracil/leucovorin +/− irinotecan). Patients completed a detailed survey of medication use and lifestyle midway through adjuvant therapy and then again 6 months after completion of therapy. We computed Cox proportional hazards for recurrence-free (RFS), disease-free (DFS) and overall survival (OS) according to aspirin use. Time intervals were measured from completion of the 2nd questionnaire to recurrence or death, excluding events within the 1st 60 days to avoid bias from analgesic use due to underlying disease. Median follow-up after the last questionnaire was 2.4 years. Results: Among 830 patients who completed both questionnaires, 72 (8.7%) pts reported aspirin use both midway and 6 months after adjuvant therapy (consistent users). Compared to those who did not report consistent use, consistent aspirin users experienced a hazard ratio (HR) for disease recurrence (RFS) of 0.45 (95% CI, 0.21–0.97), after adjustment for age, gender, baseline performance status, N stage, T stage, preoperative CEA, bowel obstruction, perforation, tumor differentiation, and treatment arm. After identical adjustment, consistent aspirin use was associated with a HR for disease recurrence and/or death (DFS) of 0.48 (95% CI, 0.24–0.99) and a HR for death (OS) of 0.52 (95% CI, 0.19–1.46). Regular users of either celecoxib or rofecoxib (n=35; 4.3%) experienced a HR for recurrence of 0.56 (95% CI, 0.21–1.54). To assess whether these associations reflected a non-specific analgesic effect, we assessed regular acetaminophen use and found no recurrence or survival benefit. Conclusions: Consistent aspirin use may be associated with improved outcome in patients with stage III colon cancer. Ongoing randomized trials are assessing the addition of COX-2 inhibitors to chemotherapy in patients with advanced disease. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Pfizer, Sanofi

O-180 A randomized trial of postoperative adjuvant chemotherapy for p-stage I non-small cell lung cancer (4th cooperative study)

O-180 A randomized trial of postoperative adjuvant chemotherapy for p-stage I non-small cell lung cancer (4th cooperative study)

Determining prognostic factors for gastric cancer using the regression tree method.

The regression tree method is a useful statistical technique that has been little used in the analysis of prognosis. The prognostic factors of gastric cancer were investigated, using the regression tree method, in 555 patients who had undergone curative resection for serosa-negative gastric cancer and who were enrolled in a randomized controlled trial of postoperative adjuvant chemotherapy (JCOG [Japan Clinical Oncology Group] 8801 study). By the regression tree method, the first divided prognostic factor (the most important factor) was lymph node metastasis; in particular, extent of lymphatic spread had the greatest impact on prognosis. In addition, age, tumor size, depth of invasion, and individual dose intensity were found to be significant prognostic factors, whereas sex, tumor location, macroscopic tumor type, and extent of lymph node dissection were not. The resulting tree structure consisted of nine terminal nodes with different prognostic factors, and four clusters were obtained by the merging of terminal nodes that showed a similar prognosis. The cluster which showed the best survival rate (5-year survival rate, 0.986) consisted of two terminal nodes: node 12, which contained N0T1 patients who were younger than 62 years and had a tumor size of less than 7.5 cm, and node 14, which contained N1 patients who were younger than 46 years. In serosa-negative gastric cancer, lymph node metastasis was the most important prognostic factor. Utilization of the regression tree method enabled visual interpretation of the results of statistical analyses through the graphic representation of prognostic factors. It allowed the identification of the optimal combination of these prognostic factors that defined several groups of patients with distinct prognoses and may serve as a useful reference for the individualization of treatment strategy.

Rapunzel syndrome

33 Jones B, Dale RG. Mathematical models of tumour and normal tissue response. Acta Oncol 1999; 38: 883–93. 34 Withers HR, Peters LJ, Taylor JMG. Dose-response relationship for radiation therapy of subclinical disease. Int J Radiat Oncol Biol Phys 1995; 31: 353–59. 35 Feinstein AR, Sosin DM, Wells CK. The Will Rogers’ phenomenon: stage migration and new diagnostic techniques as a source of misleading statistics for survival in cancer. N Engl J Med 1985; 312: 1604–08. 36 Gelman R, Gelber R, Henderson IC, et al. Improved methodology for analyzing local and distant recurrence. J Clin Oncol 1990; 8: 548–55. 37 Swedish Rectal Cancer Trial. Initial report from a Swedish multicentre study examining the role of preoperative irradiation in the treatment of patients with resectable rectal carcinoma. Br J Surg 1993; 80: 1333–36 38 Frykholm GJ, Glimelius B, Pahlman L. Pre-operative or postoperative irradiation in adenocarcinoma of the rectum: final treatment results of a randomized trial and an evaluation of late secondary effects.Dis Colon Rectum 1993; 36: 564–72. 39 Holm T, Singnomklao T, Rutqvist LE, Cedermark B. Adjuvant preoperative radiotherapy in patients with rectal carcinoma. Adverse effects during long-term follow-up of two randomised trials. Cancer 1996; 78: 968–76. 40 Lindmark G, Elvin A, Pahlman L, et al. The value of endosonography in preoperative staging of rectal cancer. Int J Colorectal Dis 1992; 7: 162–66. 41 Quirke P, Durdey P, Dixon MF, Williams NS. Local recurrence of rectal adenocarcinoma due to inadequate surgical resection. Histopathological study of lateral tumour spread and surgical excision. Lancet 1986; 2: 996–99. 42 Heald RJ, Ryall RD. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet 1986; 1: 1479–82. 43 Kapiteijn E, Marijnen CAM, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 2001; 345: 638–46. 44 NIH Consensus Conference: adjuvant cancer therapy. JAMA 1990; 264: 1444–50. 45 Cancer Guidance Subgroup of the Clinical Outcomes Group. Improving outcomes in colon cancer: The Research Evidence. London: NHS Executive, Department of Health 1997. 46 Wolmark N, Wieand HS, Hyamns DM, et al. Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum. National Surgical Adjuvant Breast and Bowel Project Protocol R-02. J Natl Cancer Inst 2000; 92: 388–96. ARTICLES

Postoperative prediction of and strategy for metastatic recurrent hepatocellular carcinoma according to histologic activity of hepatitis

The hepatitis activity index (HAI) score describes the histologic status of accompanying chronic hepatitis and was established by pathologists. The aim of this study was twofold: 1) to investigate the correlation between intrahepatic metastatic recurrence (IM) and the HAI score of the noncancerous region of the liver and 2) to estimate the usefulness of postoperative preventive chemotherapy in patients with hepatocellular carcinoma (HCC). The study included 158 consecutive patients who underwent curative resection for HCC and had been observed for > 1 year. Based on the HAI scores of the noncancerous region the patients were classified into 3 groups: those with mild hepatitis (n = 33) (i.e., with HAI scores of 0-5), those with moderate hepatitis (n = 77) (with HAI scores of 6-9), and those with severe hepatitis (n = 48) (those with HAI scores of > or = 10). In addition, a prospective randomized trial of postoperative adjuvant chemotherapy was performed for 21 patients with moderate hepatitis. The patients in the moderate hepatitis group were found to be at higher risk for IM recurrence within 2 years after HCC resection compared with those patients in the mild (P = 0.05) and severe (P < 0.01) hepatitis groups. The incidences of more than two tumors and portal vein involvement in patients with moderate hepatitis were much higher than in those patients with mild or severe hepatitis. Multivariate analysis showed that intraoperative bleeding volume, the number of nodules, portal vein involvement, and moderate hepatitis were independent predictive factors for IM recurrence free survival. Ten patients with moderate hepatitis had received postoperative intrahepatic arterial chemotherapy (2-3 courses with a maximum dose of 80 mg of cisplatin and 10 mg of mitomycin C at 1-month intervals) for the last 3 years. Although the number of patients was small, the therapy improved the disease free survival rate significantly compared with 11 patients who received no therapy. The patients with moderate hepatitis (HAI score of 6-9) had the highest rate of IM recurrence among the three HAI groups. Postoperative hepatic arterial chemotherapy may be useful in improving the rate of disease free survival after surgery among these patients.

A randomized trial of postoperative adjuvant chemotherapy in non-small cell lung cancer (the second cooperative study): Imaizumi M, Abe T, Kunishima K, Suyama M, Namikawa S, Kusakawa M et al. Department of Thoracic Surgery, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466. Eur J Surg Oncol 1995;21:69–77

A randomized trial of postoperative adjuvant chemotherapy in non-small cell lung cancer (the second cooperative study): Imaizumi M, Abe T, Kunishima K, Suyama M, Namikawa S, Kusakawa M et al. Department of Thoracic Surgery, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466. Eur J Surg Oncol 1995;21:69–77

A randomized trial of postoperative adjuvant chemotherapy in non-small cell lung cancer (the second cooperative study)

A prospective randomized trial (the second cooperative study) was conducted from July 1985 to December 1987 to investigate the benefits of postoperative adjuvant chemotherapy in patients for whom non-small cell lung cancer had been resected completely. Patients were randomly assigned either to a chemotherapy group (group A) treated postoperatively with CDDP (66 mg/m² × 1), ADM (26 mg/m² × 1) and UFT (8 mg/kg/day) during 6 months, or to a control group (group B) which had undergone surgery only. Three hundred and thirty-three resected cases were registered. Among them, 24 cases (7.2%) were excluded, because of incomplete resection (15), pathologically benign tumour (3), small cell lung cancer (2) and other factors (4). Three hundred and nine cases were eligible: 155 cases in group A (p-Stage 193, 1119, III 43) and 154 in group B (1109, 1110, III 35). The 5-year survival rate in group A was 61.8%, and that in group B 58.1%. The 5-year disease-free survival rate for each group was 61.8% and 57.4%, respectively. There were no significant differences in the 5-year survival between the two groups. However, since a significant difference was observed between the two groups regarding pathological lymph node metastasis (pN), the prognostic factors were adjusted using Cox's proportional hazard model. Thereafter the adjusted survival rate and disease-free survival rate for group A became significantly higher than for group B (<i>P</i> = 0.044 and <i>P</i> = 0.036, respectively). Thus, from these results, it is concluded that the role of surgery for non-small cell lung cancer still remains of primary importance, and postoperative adjuvant chemotherapy is effective to improve the results of surgery and prolong life of patients with non-small cell lung cancer.

無作為化比較試験による非小細胞肺癌切除例に対する術後補助化学療法の有用性の検討

無作為化比較試験による非小細胞肺癌切除例に対する術後補助化学療法の有用性の検討