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NCI CANCERLIT^® Search: Radiation, Surgery for Non-small Cell Lung Cancer - August 2002

National Cancer Institute^®
Last Modified: August 1, 2002

Stage III non-small cell lung cancer and metachronous brain metastases.
The early rad catches the tumor?
Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell
Influence of tumor volume on survival in patients irradiated for non-small-cell lung cancer.
Quality of life after curative radiotherapy in Stage I non-small-cell lung cancer.
Management of small cell lung cancer.
New strategies in the treatment of resectable non-small cell lung cancer.
Neoadjuvant chemotherapy in early-stage non-small cell lung cancer.
New DNA polymorphisms of human MMH/OGG1 gene: prevalence of one polymorphism among lung-adenocarcinoma patients in Japanese.
[Neo-adjuvant chemotherapy of non-small cell bronchial cancers (NSCLC)]
[The Will-Rogers phenomenon. Stage migration in bronchogenic carcinoma after applying certainty criteria]
Systematic postoperative radiologic follow-up in patients with non-small cell lung cancer for detecting second primary lung cancer in stage IA.
Personal experience in lung cancer sleeve lobectomy and sleeve pneumonectomy.
Blood hemoglobin as an independent prognostic factor in surgically resected stages I and II non-small cell lung cancer patients.
A palliative accelerated irradiation regimen for advanced non-small-cell lung cancer vs. conventionally fractionated 60 Gy: results of a
Sleeve lobectomy for non-small cell lung cancer and carcinoids: results in 160 cases.
A new method of segmental resection for primary lung cancer: intermediate results.
Is the reduction of forced expiratory lung volumes proportional to the lung parenchyma resection, 6 months after pneumonectomy?
Risk factors for early mortality and major complications following pneumonectomy for non-small cell carcinoma of the lung.
Has 3-D conformal radiotherapy (3D CRT) improved the local tumour control for stage I non-small cell lung cancer?
Optimizing radiation treatment plans for lung cancer using lung perfusion information.
HER-2/neu overexpression in patients with radically resected nonsmall cell lung carcinoma. Impact on long-term survival.
Current and future therapeutic approaches in locally advanced (stage III) non-small cell lung cancer.

1
UI - 12091816
AU - Moazami N; Rice TW; Rybicki LA; Adelstein DJ; Murthy SC; DeCamp MM;
TI - Barnett GH; Chidel MA; Suh JH; Blackstone EH Stage III non-small cell lung cancer and metachronous brain metastases.
SO - J Thorac Cardiovasc Surg 2002 Jul;124(1):113-22
AD - Department of Thoracic and Cardiovascular Surgery, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
OBJECTIVES: This study was undertaken to identify management strategies that maximize survival of patients with stage III non-small cell lung cancer and metachronous brain metastases and to determine whether any apparent improved survival was due to treatment or simply to patient selection. METHODS: Treatment evaluations of both primary non-small cell lung cancer and brain metastases were performed in 91 patients. Optimal treatment was identified by multivariable analysis. Propensity scoring and multivariable analysis were used to separate treatment benefit from patient selection. RESULTS: Risk-unadjusted median, 12-, and 24-month survivals were 5.2 months, 22%, and 10%, respectively. Younger age (P =.006), good performance status (P =.003), stage IIIA (P =.001), lung resection (P =.02), no other systemic metastases at time of diagnosis of brain metastases (P =.02), and either metastasectomy (P <.001) or stereotactic radiosurgery (P <.001) predicted best survival. However, metastasectomy or stereotactic radiosurgery was more common after lung resection (P =.02) and in patients with good performance status (P =.006), no other systemic metastases at time of diagnosis of brain metastases (P =.01), and fewer brain metastases (P <.001), suggesting that the patients with the best risk profile were selected for aggressive therapy of both lung primary and brain metastases. Despite this selection, analysis of propensity-matched patients demonstrated the benefit of lung resection and metastasectomy or stereotactic radiosurgery (P <.001). CONCLUSIONS: Younger patients with resected stage IIIA non-small cell lung cancer who have isolated metachronous brain metastases and good performance status do best when treated with metastasectomy or stereotactic radiosurgery. This survival benefit is a brain treatment effect, not the result of selecting the best patients for aggressive therapy.

2
UI - 12118015
AU - Machtay M
TI - The early rad catches the tumor?
SO - J Clin Oncol 2002 Jul 15;20(14):3045-7

3
UI - 12118018
AU - Takada M; Fukuoka M; Kawahara M; Sugiura T; Yokoyama A; Yokota S;
TI - Nishiwaki Y; Watanabe K; Noda K; Tamura T; Fukuda H; Saijo N Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104.
SO - J Clin Oncol 2002 Jul 15;20(14):3054-60
AD - Osaka Prefectural Habikino Hospital, Osaka City General Medical Center, Kinki National Hospital for Chest Disease, Osaka, Japan.
PURPOSE: To evaluate the optimal timing for thoracic radiotherapy (TRT) in limited-stage small-cell lung cancer (LS-SCLC), the Lung Cancer Study Group of the Japan Clinical Oncology Group conducted a phase III study in which patients were randomized to sequential TRT or concurrent TRT. PATIENTS AND METHODS: We treated 231 patients with LS-SCLC. TRT consisted of 45 Gy over 3 weeks (1.5 Gy twice daily), and the patients were randomly assigned to receive either sequential or concurrent TRT. All patients received four cycles of cisplatin plus etoposide every 3 weeks (sequential arm) or 4 weeks (concurrent arm). TRT was begun on day 2 of the first cycle of chemotherapy in the concurrent arm and after the fourth cycle in the sequential arm. RESULTS: Concurrent radiotherapy yielded better survival than sequential radiotherapy (P =.097 by log-rank test). The median survival time was 19.7 months in the sequential arm versus 27.2 months in the concurrent arm. The 2-, 3-, and 5-year survival rates for patients who received sequential radiotherapy were 35.1%, 20.2%, and 18.3%, respectively, as opposed to 54.4%, 29.8% and 23.7%, respectively, for the patients who received concurrent radiotherapy. Hematologic toxicity was more severe in the concurrent arm. However, severe esophagitis was infrequent in both arms, occurring in 9% of the patients in the concurrent arm and 4% in the sequential arm. CONCLUSION: This study strongly suggests that cisplatin plus etoposide and concurrent radiotherapy is more effective for the treatment of LS-SCLC than cisplatin plus etoposide and sequential radiotherapy.

4
UI - 12095548
AU - Etiz D; Marks LB; Zhou SM; Bentel GC; Clough R; Hernando ML; Lind PA
TI - Influence of tumor volume on survival in patients irradiated for non-small-cell lung cancer.
SO - Int J Radiat Oncol Biol Phys 2002 Jul 15;53(4):835-46
AD - Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.
PURPOSE: To investigate the importance of CT-defined total tumor volume (TTV) on overall survival (OS) in patients with unresectable or medically inoperable non-small-cell lung carcinoma (NSCLC). METHODS AND MATERIALS: Between 1991 and 1998, 150 evaluable patients with Stage I-IIIB NSCLC were treated with three-dimensionally planned conformal radiotherapy and curative intent at Duke University Medical Center. On the treatment-planning CT, the primary tumor and nodal volumes were identified and subsequently combined to form the TTV. The TTV was compared with the stage and outcome with respect to OS, local progression-free survival, and distant failure-free survival using the Kruskall-Wallis analysis of variance and Kaplan-Meier actuarial method. To account for the potentially confounding effects of therapeutic and patient-specific covariates on survival, the Cox proportional hazard regression model was used. RESULTS: The TTVs in patients with Stage I disease (median 19 cm3) were smaller than in patients with Stage II (median 80 cm3) or Stage III (median 97 cm3; p <0.001) disease. The Stage II TTVs were not significantly different from those of Stage III (post-hoc test according to Bonferroni). Prolonged OS was independently associated with a small TTV (<80 vs. >80 cm3 [median]; p = 0.01), young age (<60 vs. > or =60 years; p = 0.03), high Karnofsky performance status (< o r =70 vs. >70; p = 0.04), and female gender (p = 0.04). Both stage (p = 0.7) and T stage (p = 0.06) were of less importance for OS than was the TTV, according to multivariate modeling. Increased local progression-free survival (p = 0.001) and distant failure-free survival (p = 0.03) were independently associated with a small TTV (i.e., <80 cm3). The results were unchanged if the TTV was analyzed as a continuous variable. CONCLUSION: A strong independent association between a small CT-defined TTV and prolonged survival in patients with NSCLC selected for curative/definitive RT was found. Future therapeutic studies in NSCLC should consider stratifying/adjusting for differences in TTV to avoid confounding effects on survival from variations in the TTV at baseline.

5
UI - 12095549
AU - Langendijk JA; Aaronson NK; de Jong JM; ten Velde GP; Muller MJ; Slotman
TI - BJ; Wouters EF Quality of life after curative radiotherapy in Stage I non-small-cell lung cancer.
SO - Int J Radiat Oncol Biol Phys 2002 Jul 15;53(4):847-53
AD - Radiotherapeutisch Instituut Limburg, Heerlen, The Netherlands. ja.langendijk@vumc.nl
PURPOSE: The aim of this study was to investigate changes in quality of life (QOL) among medically inoperable Stage I non-small-cell lung cancer (NSCLC) patients treated with curative radiotherapy. PATIENTS AND METHODS: The study sample was composed of 46 patients irradiated for Stage I NSCLC. Quality of life was assessed before, during, and after radiotherapy using the European Organization for the Research and Treatment of Cancer QLQ-C30 and QLQ-LC13. Changes in symptom and QOL scores over time were evaluated with a repeated measurement analysis of variance using the mixed effect modeling procedure, SAS Proc Mixed. Twenty-seven patients were treated only at the primary site, whereas for 19 patients, the regional lymph nodes were included in the target volume as well. RESULTS: The median follow-up time of patients alive was 34 months. The median survival was 19.0 months. None of the locally treated patients developed regional recurrence. A significant, gradual increase over time was observed for dyspnea, fatigue, and appetite loss. A significant, gradual deterioration was observed also for role functioning. No significant changes were noted for the other symptoms or the functioning scales. Significantly higher levels of dysphagia, which persisted up to 12 months, were observed in those in which the regional lymph nodes were treated, as compared to the locally treated patients. Radiation-induced pulmonary changes assessed with chest radiograph were more pronounced in the group treated with locoregional radiotherapy. CONCLUSIONS: After curative radiotherapy for Stage I medically inoperable NSCLC, a gradual increase in dyspnea, fatigue, and appetite loss, together with a significant deterioration of role functioning, was observed, possibly because of pre-existing, slowly progressive chronic obstructive pulmonary disease and radiation-induced pulmonary changes. Taking into account the low incidence of regional recurrences after local irradiation, the higher incidence and severity of radiation-induced changes, and the higher levels of dysphagia persisting up to 12 months, local irradiation of the primary tumor without elective irradiation of the regional lymph nodes may be the most appropriate treatment for patients with small, peripherally located tumors.

6
UI - 12113025
AU - Yip D; Karapetis C; Steer C
TI - Management of small cell lung cancer.
SO - Expert Rev Anticancer Ther 2001 Aug;1(2):197-210
AD - Medical Oncology Unit, Canberra Hospital, Garran ACT 2605, Australia. dyip@med.usyd.edu.au
Small cell lung cancer is a tumor that has a very poor prognosis without treatment. It is however, highly responsive to chemotherapy and radiotherapy. Pretreatment clinical and laboratory parameters--in addition to staging--can prognosticate outcome and help define the aim of treatment. Different schedules of chemotherapy have been developed and varied strategies, such as chemotherapy dose intensification have been tried to improve outcomes. New agents, such as irinotecan, gemcitabine and topotecan have also been tested. Clinical trials have helped to define strategies of integrating thoracic radiotherapy and prophylactic cranial radiotherapy into management of those patients with limited disease to improve survival further. Despite good initial responses to treatment, most patients eventually relapse. Maintenance strategies with ongoing chemotherapy or novel agents, such as interferon, matrix metalloproteinase inhibitors, thalidomide and vaccines are discussed.

7
UI - 12113027
AU - Felip E; Rosell R
TI - New strategies in the treatment of resectable non-small cell lung cancer.
SO - Expert Rev Anticancer Ther 2001 Aug;1(2):224-8
AD - Medical Oncology Service, Hospital Germans Trias i Pujol, Ctra Canyet s/n, 08916 Badalona, Barcelona, Spain.
Non-small cell lung cancer is a systemic illness. Given the systemic nature of lung cancer, it seems that chemotherapy should play an essential role. In stage IIIA disease neoadjuvant chemotherapy plus surgical resection improves survival when compared with surgical resection alone. However, randomized trials using postoperative adjuvant chemotherapy with 'older' drugs has shown no substantial improvement in survival. Since new chemotherapeutic agents may provide additional benefits, there are various studies incorporating new agents in the resectable disease treatment setting. One focus for ongoing research is to find better treatment approaches in earlier stages of disease. Some data suggest that induction chemotherapy in stage I-II is feasible and appears not to compromise surgery. Another promising more individual approach is to tailor chemotherapy according to the pattern of genetic variants or abnormalities found in DNA and/or RNA extracted from the bloodstream. Furthermore, at present many types of new agents are available for testing as 'consolidation treatment' following induction treatment, including, angiogenesis inhibitors, antibodies to growth factor receptors, gene therapy and vaccines.

8
UI - 12113028
AU - Edelman MJ
TI - Neoadjuvant chemotherapy in early-stage non-small cell lung cancer.
SO - Expert Rev Anticancer Ther 2001 Aug;1(2):229-35
AD - University of Maryland, Greenebaum Cancer Center, Baltimore, Maryland, USA. medelman@umm.edu
Of the patients that undergo complete resection of early-stage non-small cell lung cancer (NSCLC), 30-60% will die. Postoperative adjuvant chemotherapy has yet to demonstrate an unequivocal benefit and there are significant difficulties in administering postoperative chemotherapy to patients with the significant comorbidities found in NSCLC. Currently, several trials are evaluating the role of preoperative chemotherapy in stage I and II NSCLC. This paper reviews the rationale for this approach and potential future developments.

9
UI - 9935223
AU - Ishida T; Takashima R; Fukayama M; Hamada C; Hippo Y; Fujii T; Moriyama
TI - S; Matsuba C; Nakahori Y; Morita H; Yazaki Y; Kodama T; Nishimura S; Aburatani H New DNA polymorphisms of human MMH/OGG1 gene: prevalence of one polymorphism among lung-adenocarcinoma patients in Japanese.
SO - Int J Cancer 1999 Jan 5;80(1):18-21
AD - Third Department of Internal Medicine, University of Tokyo, Japan.
MMH/OGG1 is an 8-hydroxyguanine-specific DNA glycosylase/AP-lyase, one of the mutator enzymes for the excision repair of 8-hydroxyguanine. DNA polymorphisms in human MMH/OGG1 gene were newly identified and analyzed to examine a possible association with lung-cancer risk by a population-based study. Polymorphic allele 3 in hMMH/OGG1 exon 1 was significantly prevalent among Japanese patients with adenocarcinoma of the lung [odds ratio (OR): 3.152, 95% confidence interval (CI): 1.266-7.845], indicating that the excision repair of 8-hydroxyguanine may play a role in predisposition to lung cancer.

10
UI - 12148364
AU - Milleron B; Westeel V; Depierre A
TI - [Neo-adjuvant chemotherapy of non-small cell bronchial cancers (NSCLC)]
SO - Presse Med 2002 May 11;31(17):797-801
AD - Service de pneumologie, Hopital Tenon, 4, rue de la Chine, 75020 Paris.
TO PROLONG SURVIVAL: Systemic neo-adjuvant chemotherapy attempts to reduce the development of metastases. Data available on neoadjuvant chemotherapy of NSCLC come from three types of clinical trials. NEO-ADJUVANT CHEMOTHERAPY PHASE II TRIALS: Many trials have demonstrated that the neo-adjuvant approach is feasible, that it leads to a high rate of response, to the order of 50 to 70%, that it does not compromise surgery, and exhibits acceptable toxicity. High survival rates have been obtained, notably in total responders. NEO-ADJUVANT CHEMO-RADIOTHERAPY PHASE II TRIALS: Have essentially demonstrated that this approach is feasible, exhibits acceptable toxicity, worse in pneumonectomy. High response rates have been obtained and relative improved survival, since most of the cases concerned extensive forms that could not be treated surgically. RANDOMIZED PHASE III TRIALS: Gave varying results: two of them only concerned small series of patients (60 in all) with stage IIIA NSCB, with positive results. The third study concerned 373 patients with stage I, II and IIIA cancers: survival at 3 years was increased by 11%, but this difference is not yet significant. Benefits were essentially apparent for stage I and II patients. IN THE FUTURE: Continued active clinical research, oriented differently, on stage I and II, and stage IIIA is necessary.

11
UI - 11953268
AU - Lopez Encuentra A; Gomez De La Camara A; Varela De Ugarte A; Manes N;
TI - Llobregat N [The Will-Rogers phenomenon. Stage migration in bronchogenic carcinoma after applying certainty criteria]
SO - Arch Bronconeumol 2002 Apr;38(4):166-71
AD - Servicio Neumologia, Hospital Universitario, Madrid, Spain. lencuent@eresmas.net
OBJECTIVE: To quantify changes in tumor-node-metastasis (TNM) staging (numerical migration) and survival (prognostic migration) that arise when certainty criteria are applied to a patient population with non-small cell lung cancer (NSCLC) treated surgically. METHODS: The population consisted of 1,844 patients with NSCLC who underwent surgery between 1993 and 1996 at hospitals participating in the Bronchogenic Carcinoma Co-operative Group of the Spanish Society of Pneumology and Thoracic Surgery (GCCB-S). For every patient, surgical-pathological TNM staging (p) was based on two classifications: initial staging by each participating GCCB-S center (pTNM-i) and a second classification bearing greater classificatory certainty (pTNM-cc) resulting from the application of stricter criteria. Numerical migration was said to have occurred in cases where the two classifications did not coincide, and the possible prognostic migration under the new staging was then assessed. RESULTS: The results revealed great numerical migration in the pN0 classification (from 1,091 cases to 665). The changes did not result in prognostic migration either for the group as a whole or for pT1-2N0M0 cases. However, for pT3N0M0 cases, median survival increased by 13 months. The difference in three-year survival (S3) for pT3N0M0-i without certainty confirmation [S3 = 0.30 (95%CI 0.18-0.42), n=59] and pT3N0M0-cc [S3=0.54 (95%CI = 0.44-0.64), n = 92] was significant (log-rank, p = 0.035). Such behavior was not observed for pT1-2N0M0. CONCLUSIONS: The numerical migration observed as a result of applying surgical-pathological classificatory certainty criteria is relevant but the prognostic repercussion is scarce, except in cases classified as pT3N0M0, in which a significant positive prognostic migration is observed (the "Will Rogers phenomenon").

12
UI - 12146993
AU - Lamont JP; Kakuda JT; Smith D; Wagman LD; Grannis FW Jr
TI - Systematic postoperative radiologic follow-up in patients with non-small cell lung cancer for detecting second primary lung cancer in stage IA.
SO - Arch Surg 2002 Aug;137(8):935-8; discussion 938-40
AD - Department of General and Oncologic Surgery, City of Hope National Medical Center, 1500 E Duarte Rd, Duarte, CA 91010, USA.
HYPOTHESIS: Systematic postoperative evaluation of patients with non-small cell lung cancer will identify treatable second primary lung cancer and local recurrences. DESIGN: Retrospective review from January 1, 1996, to December 31, 2000. The follow-up protocol included an annual computed tomographic examination of the chest with interval chest radiography every 4 months for 2 years and every 6 months for 3 additional years. SETTING: A National Cancer Institute-designated comprehensive cancer center. PATIENTS: One hundred twenty-four patients with resected non-small cell lung cancer. MAIN OUTCOME MEASURES: Number and size of second primary and locally recurrent tumors, secondary surgical procedures, and survival of patients who underwent resection. RESULTS: The median diameter of resected second primary tumors detected by computed tomography was 14 mm (range, 8-28 mm) and by chest radiography was 26.5 mm (range, 23.0-35.0 mm) (P<.001). Of 14 patients with second primary lung cancer treated surgically, 9 were without evidence of disease at a median of 20 months (range, 4-56 months), 2 were alive with disease at 13 and 37 months, 2 died of unrelated causes but without evidence of disease at 7 and 35 months, and 1 died intraoperatively of a cardiac arrhythmia. CONCLUSIONS: Systematic follow-up of non-small cell lung cancer, including annual computed tomography, detects second primary lung cancer in stage IA. Limited pulmonary resections are often feasible in these patients. Locally recurrent lung cancer is infrequently resectable.

13
UI - 12078762
AU - Mezzetti M; Panigalli T; Giuliani L; Raveglia F; Lo Giudice F; Meda S
TI - Personal experience in lung cancer sleeve lobectomy and sleeve pneumonectomy.
SO - Ann Thorac Surg 2002 Jun;73(6):1736-9
AD - San Paolo Hospital, and School of Specialization of Thoracic Surgery, Milan, Italy. maurizio.mezzetti@unimi.it
BACKGROUND: Sleeve lobectomy (SL) and tracheal sleeve pneumonectomy (TSP) represent valuable alternative techniques to standard resections in the treatment of benign and malignant conditions of the airway and allow preservation of lung parenchyma. METHODS: Eighty-three sleeve lobectomies and 27 tracheal sleeve pneumonectomies have been performed for nonsmall cell lung cancer in the thoracic department of the University of Milan from 1979 to 1999. There were 46 upper right lobectomies, 11 upper and middle lobectomies, 18 upper left lobectomies, 8 lower left lobectomies, and 27 right pneumonectomies. RESULTS: Mortality rate was 3.6% in SL and 7.4% in TSP. Complications were 10.8% of all SLs and 15% of all TSPs. The overall 5-year survival rate was 43% for SL and 20% for TSP; the 10-year survival rate was 34% and 14%, respectively. There was a highly significant difference in survival between patients with N0 and N1-N2 disease. CONCLUSIONS: Sleeve lobectomy is an appropriate surgical procedure and an alternative to pneumonectomy in patients with limited respiratory reserve whenever the situation permits. Trachael sleeve pneumonectomy is associated with more complications and poor survival.

14
UI - 12078827
AU - Watine J
TI - Blood hemoglobin as an independent prognostic factor in surgically resected stages I and II non-small cell lung cancer patients.
SO - Ann Thorac Surg 2002 Jun;73(6):2034-5; discussion 2035

15
UI - 11417531
AU - Byhardt R; Scott C
TI - A palliative accelerated irradiation regimen for advanced non-small-cell lung cancer vs. conventionally fractionated 60 Gy: results of a randomized equivalence study: regarding Nestle et al. IJROBP 2000; 48:95-103.
SO - Int J Radiat Oncol Biol Phys 2001 Jul 1;50(3):837

16
UI - 12062281
AU - Terzi A; Lonardoni A; Falezza G; Furlan G; Scanagatta P; Pasini F;
TI - Calabro F Sleeve lobectomy for non-small cell lung cancer and carcinoids: results in 160 cases.
SO - Eur J Cardiothorac Surg 2002 May;21(5):888-93
AD - Division of Thoracic Surgery, Ospedale Maggiore, Azienda Ospedaliera, P. le Stefani 1, 37128 Verona, Italy. aterzi@tiscalinet.it
OBJECTIVE: To assess operative mortality (OM), morbidity and long-term results of sleeve lobectomies performed for non-small cell lung cancer (NSCLC) and carcinoids during a 35-year period. METHODS: A retrospective review of patients who underwent a sleeve lobectomy for NSCLC and carcinoids was undertaken, univariate and multivariate analyses of factors influencing early mortality in NSCLC were performed and for this purpose the series was split into an early and a contemporary phase, the Kaplan-Meier method was used to calculate the cumulative survival rate, and statistical significance was calculated with the log-rank test. Causes of death were evaluated in relation to the stage of the disease. RESULTS: OM for NSCLC was 14.6% in the early phase and 6% in the contemporary one; late stenosis occurred in 7.7% of NSCLC patients in the early phase and in 2% in the contemporary one. No OM or late stenosis occurred in carcinoid patients. Three, 5 and 10-year survival rates excluding carcinoids were 77, 62 and 31% for stage I(A-B), 45, 34 and 27% for stage II(A-B), 33, 22 and 0% for stage III(A-B). The 10-year survival rate for carcinoids was 100%. There was no significant difference in long-term survival between stages II and III, while the difference between stage I and stages II and III was significant (P<0.001). When survival was analyzed in relation to nodal status, 3, 5 and 10-year survival rates were 71, 57 and 33% for N0 disease, 42, 33 and 22% for N1 disease, and 34 and 19% with the last observation at 82 months of 19% for N2 disease; there was no significant difference in survival between N1 and N2 disease. A second primary lung cancer occurred in six patients (3.7%) who underwent resection. Late mortality was not related to cancer in most stage I patients while in stages II and III patients it was related to local and distant recurrences. CONCLUSIONS: Sleeve lobectomy is a valid alternative to pneumonectomy: careful patient selection and surgical technique make it possible to achieve a mortality rate comparable to or lower than that for pneumonectomy along with a better quality of life. In addition, it allows further lung resection, if necessary.

17
UI - 12062282
AU - Bando T; Yamagihara K; Ohtake Y; Miyahara R; Tanaka F; Hasegawa S; Inui
TI - K; Wada H A new method of segmental resection for primary lung cancer: intermediate results.
SO - Eur J Cardiothorac Surg 2002 May;21(5):894-9; discussion 900
AD - Department of Thoracic Surgery, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto, Japan.
OBJECTIVE: To improve the postoperative results of limited resection for small lung cancer, we have developed a new operative method, pulmonary artery-guided segmentectomy. This resection begins with identification of the pulmonary arterial branches involved in the tumor, then the pulmonary tissue is divided along the pulmonary arteries (i.e. guided by pulmonary arteries) from the hilum toward the periphery by electrocautery. The advantages of this method include the facilitation of securing adequate margin from the tumor, and the feasibility of intralobar lymph node dissection during operation. To examine the efficacy of the new method of segmental resection, we retrospectively reviewed 74 cases of T1N0M0 disease who underwent the pulmonary artery-guided segmentectomy. METHODS: From 1993 to 2000, 74 patients with pathological T1N0M0 lung cancer were treated by the pulmonary artery-guided segmentectomy. Forty-one patients (55.4%) who underwent the segmentectomy had been considered suitable candidates for lobectomy (intentional resection group). The other 33 patients (44.6%) were considered poor candidates for lobectomy because of poor cardiopulmonary reserve (compromised resection group). RESULTS: The overall survival rate at 5 years was 82.0%. The 5-year survivals in the intentional and the compromised resection groups were 81.6 and 77.6%, respectively, and no significant differences were detected between the groups. According to tumor size, the 5-year survival rate for patients with tumors of 20 mm or smaller (92.9%, n=53) was higher than that for the patients with tumors of 21-30 mm (63.0%, n=21), but the difference did not reach statistical significance. Median follow-up time of 27.0 months revealed eight locoregional recurrences and four deaths due to lung cancer. Sixty-three patients (85.1%) are alive with no evidence of disease, and six patients (8.1%) are alive with recurrent disease. Locoregional recurrences occurred in one of 53 patients (1.9%) with tumors 20 mm or smaller and in seven of 21 patients (33.3%) with tumors 21-30 mm, the difference being statistically significant (P<0.01). CONCLUSIONS: Our intermediate results demonstrated that the new pulmonary artery-guided segmentectomy could be an alternative method for selected patients with small lung cancer, particularly with tumors 20 mm or smaller in diameter.

19
UI - 12065354
AU - Licker M; Spiliopoulos A; Frey JG; Robert J; Hohn L; de Perrot M;
TI - Tschopp JM Risk factors for early mortality and major complications following pneumonectomy for non-small cell carcinoma of the lung.
SO - Chest 2002 Jun;121(6):1890-7
AD - Department of Anesthesiology, Pharmacology, and Surgical Intensive Care, the University Hospital of Geneva, Geneva, Switzerland. marc-joseph.licker@hcuge.ch
STUDY OBJECTIVES: To assess the mortality rate and the incidence of cardiopulmonary complications after pneumonectomy for non-small cell lung carcinoma (NSCLC) and to identify possible associated risk factors. DESIGN: Observational study of patients who underwent pneumonectomy. Potential risk factors were analyzed from a local database including all thoracic surgical cases. SETTING: A university hospital and a chest medical center. PATIENTS AND METHODS: From January 1, 1990, to April 30, 2000, 193 consecutive pneumonectomies were performed for NSCLC in two affiliated institutions. The following information was recorded: demographic, clinical, functional, and surgical variables; as well as intraoperative and postoperative events. The risk of mortality and cardiopulmonary complications was evaluated using multiple logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: After undergoing pneumonectomy, all patients were successfully extubated in the operating room and then transferred to a postanesthesia care unit (126 patients) or ICU (67 patients). The 30-day mortality rate was 9.3%, and cardiovascular and/or pulmonary complications occurred in 47% of cases. Coronary artery disease (CAD) was a predictor of 30-day mortality (OR, 2.9; 95% CI, 1.1 to 8.9). Cardiac morbidity (mainly arrhythmias) was significantly related to advanced age (OR, 3.7; 95% CI, 1.6 to 8.6) and pathologic stages III/IV (OR, 1.4; 95% CI, 1.1 to 4.7), whereas continuous epidural analgesia was associated with a reduced incidence of respiratory complications (OR, 0.2; 95% CI, 0.1 to 0.6). CONCLUSIONS: Pneumonectomy for lung cancer is a high-risk procedure, the risk for which is significantly related to the presence of CAD and advanced pathologic stages. Importantly, the provision of epidural analgesia contributes to lower the risk of respiratory complications.

20
UI - 12063004
AU - Lagerwaard FJ; Senan S; van Meerbeeck JP; Graveland WJ; Rotterdam
TI - Oncological Thoracic Study Group Has 3-D conformal radiotherapy (3D CRT) improved the local tumour control for stage I non-small cell lung cancer?
SO - Radiother Oncol 2002 May;63(2):151-7
AD - Department of Radiation Oncology, University Hospital Rotterdam, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands.
AIMS AND BACKGROUND: The high local failure rates observed after radiotherapy in stage I non-small cell lung cancer (NSCLC) may be improved by the use of 3-dimensional conformal radiotherapy (3D CRT). MATERIALS AND METHODS: The case-records of 113 patients who were treated with curative 3D CRT between 1991 and 1999 were analysed. No elective nodal irradiation was performed, and doses of 60Gy or more, in once-daily fractions of between 2 and 3Gy, were prescribed. RESULTS: The median actuarial survival of patients was 20 months, with 1-, 3- and 5-year survival of 71, 25 and 12%, respectively. Local disease progression was the cause of death in 30% of patients, and 22% patients died from distant metastases. Grade 2-3 acute radiation pneumonitis (SWOG) was observed in 6.2% of patients. The median actuarial local progression-free survival (LPFS) was 27 months, with 85 and 43% of patients free from local progression at 1 and 3 years, respectively. Endobronchial tumour extension significantly influenced LPFS, both on univariate (P=0.023) and multivariate analysis (P=0.023). The median actuarial cause-specific survival (CSS) was 19 months, and the respective 1- and 3-year rates were 72 and 30%. Multivariate analysis showed T2 classification (P=0.017) and the presence of endobronchial tumour extension (P=0.029) to be adverse prognostic factors for CSS. On multivariate analysis, T-stage significantly correlated with distant failure (P=0.005). CONCLUSIONS: Local failure rates remain substantial despite the use of 3D CRT for stage I NSCLC. Additional improvements in local control can come about with the use of radiation dose escalation and approaches to address the problem of tumour mobility.

21
UI - 12063006
AU - Seppenwoolde Y; Engelsman M; De Jaeger K; Muller SH; Baas P; McShan DL;
TI - Fraass BA; Kessler ML; Belderbos JS; Boersma LJ; Lebesque JV Optimizing radiation treatment plans for lung cancer using lung perfusion information.
SO - Radiother Oncol 2002 May;63(2):165-77
AD - Department of Radiotherapy, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
PURPOSE: To study the impact of incorporation of lung perfusion information in the optimization of radical radiotherapy (RT) treatment plans for patients with medically inoperable non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The treatment plans for a virtual phantom and for five NSCLC patients with typical defects of pre-RT lung perfusion were optimized to minimize geometrically determined parameters as the mean lung dose (MLD), the lung volume receiving more than 20 Gy (V20), and the functional equivalent of the MLD, using perfusion-weighted dose-volume histograms. For the patients the (perfusion-weighted) optimized plans were compared to the clinically applied treatment plans. RESULTS: The feasibility of perfusion-weighted optimization was demonstrated in the phantom. Using perfusion information resulted in an increase of the weights of those beams that were directed through the hypo-perfused lung regions both for the phantom and for the studied patients. The automatically optimized dose distributions were improved with respect to lung toxicity compared with the clinical treatment plans. For patients with one hypo-perfused hemi-thorax, the estimated gain in post-RT lung perfusion was 6% of the prescribed dose compared to the geometrically optimized plan. For patients with smaller perfusion defects, perfusion-weighted optimization resulted in the same plan as the geometrically optimized plan. CONCLUSION: Perfusion-weighted optimization resulted in clinically well applicable treatment plans, which cause less radiation damage to functioning lung for patients with large perfusion defects.

22
UI - 12173335
AU - Selvaggi G; Scagliotti GV; Torri V; Novello S; Leonardo E; Cappia S;
TI - Mossetti C; Ardissone F; Lausi P; Borasio P HER-2/neu overexpression in patients with radically resected nonsmall cell lung carcinoma. Impact on long-term survival.
SO - Cancer 2002 May 15;94(10):2669-74
AD - Department of Clinical and Biological Sciences, University of Torino, Azienda Ospedaliera S. Luigi, Regione Gonzole, 10, 10043 Orbassano, Torino, Italy.
BACKGROUND: Using immunohistochemistry, the authors prospectively investigated the expression of HER-2/neu protein in radically resected specimens of nonsmall cell lung carcinoma (NSCLC) and evaluated its underwent radical resection for NSCLC (60 squamous cell carcinoma, 48 adenocarcinoma cases, and 22 large cell carcinomas) and that were staged (according to the TNM staging system) pathologically as Stage I (41 cases [32%]), Stage II (37 cases [28%]), and Stage IIIA (52 cases [40%]) were investigated for the expression of HER-2/neu using an avidin-biotin complex immunohistochemical technique. A semiquantitative four-stage grading system was used (0%, 1-5%, 6-20%, and > 20% positive cells) and an average number of 1500 cells/section was considered. Data were correlated with clinical and pathologic variables. RESULTS: Normal bronchial tissue was found to be completely negative for HER-2/neu expression whereas 21 of the 130 tumor specimens (16%) were positive (range 1-> 20%). HER-2/neu positivity did not appear to differ significantly among pathologic stages and histotypes. Using a predetermined cutoff value of 5% positive cells, 15 tumor specimens (12%) were found to be above this value. The median survival time (85 weeks vs. 179 weeks) and overall survival rate were significantly lower in patients with > 5% HER-2/neu-positive tumors (hazard ratio for the group with > 5% positive cells: 2.94, 95% confidence interval, 1.62-5.34; P < 0.0004). On multivariate analysis, HER-2/neu and extent of tumor emerged as independent factors for disease-related mortality. CONCLUSIONS: In NSCLC, the negative impact of HER-2/neu overexpression on survival was maintained in the long-term follow-up of radically resected patients. HER-2/neu overexpression may be a valuable prognostic factor as well as a potential target for biologic therapies.

23
UI - 12170446
AU - Davies A; Gandara DR; Lara P; Goldberg Z; Roberts P; Lau D
TI - Current and future therapeutic approaches in locally advanced (stage III) non-small cell lung cancer.
SO - Semin Oncol 2002 Jun;29(3 Suppl 12):10-6
AD - Division of Hematology/Oncology, University of California Davis Cancer Center, Sacramento, CA 95817-2229, USA.
In the treatment of locally advanced (stage III) non-small cell lung cancer, randomized clinical trials have shown that sequential administration of platinum-based chemotherapy followed by radiotherapy improves outcome compared with radiotherapy alone. More recently, concurrent chemoradiotherapy has been shown to be superior to sequential therapy. Incorporating full-dose chemotherapy into induction or consolidation phases is aimed at the eradication of distant micrometastases. These approaches are currently being examined in clinical trials. The role of neoadjuvant and adjuvant therapy in resectable stage IIIA patients remains controversial. Integration of newer cytotoxic agents (paclitaxel, docetaxel, gemcitabine, vinorelbine, and irinotecan) and molecularly targeted agents into the treatment of stage-III patients may result in improved long-term outcomes and is currently under study. Copyright 2002, Elsevier Science (USA). All rights reserved.

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