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

Imprima English

National Cancer Institute^®
Ultima Vez Modificado: 1 de octubre del 2002

Characteristics and prognosis of resected T3 non-small cell lung cancer.
Management of superior sulcus tumors: experience with 139 cases treated by surgical resection.
Sleeve lobectomy for bronchogenic cancers: factors affecting survival.
Expression of dihydrodiol dehydrogenase in the resected stage I non-small cell lung cancer.
The impact of fluorodeoxyglucose F 18 positron-emission tomography on the surgical staging of non-small cell lung cancer.
A response to "Clinical trials in lung cancer: truth, justice, and the American way".
[Randomized controlled trials in Japan--lung cancer]
Prognostic factors in patients with surgically resected stages I and II non-small cell lung cancer.
Blood hemoglobin as an independent prognostic factor in surgically resected stages I and II non-small cell lung cancer patients.
CEA and survival in patients with stage IA-B NSCLC.
Newer techniques of radiation therapy in lung cancer.
Small-volume image-guided radiotherapy using hypofractionated, coplanar, and noncoplanar multiple fields for patients with inoperable Stage I
Lung cancer.
T2 tumors larger than five centimeters in diameter can be upgraded to T3 in non-small cell lung cancer.
Surgical resection of unilateral lung metastases: is bilateral thoracotomy necessary?
Where is the boundary between N1 and N2 stations in lung cancer?
Survival after resection of metachronous non-small cell lung cancer in 127 patients.
Survival after resection of metachronous non-small cell lung cancer.
Prognostic significance of surgical-pathologic N1 disease in non-small cell carcinoma of the lung.
Postoperative complications of lung resection after induction chemotherapy using Paclitaxel (and radiotherapy) for advanced non-small
Biological markers in non-small cell lung cancer. Retrospective study of 10 year follow-up after surgery.
Real-time tumor-tracking radiation therapy for lung carcinoma by the aid of insertion of a gold marker using bronchofiberscopy.
Postoperative radiotherapy in completely resected, early-stage, non-small-cell lung cancer: reflections and future directions.
Postoperative radiotherapy in non-small-cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised
Dose-volume factors contributing to the incidence of radiation pneumonitis in non-small-cell lung cancer patients treated with
High-dose conformal radiotherapy for treatment of stage IIIA/IIIB non-small-cell lung cancer: technical issues and results of a phase I/II
Comorbidity and Karnofksy performance score are independent prognostic factors in stage III non-small-cell lung cancer: an institutional
Phase III trial comparing chemotherapy plus once-daily or twice-daily radiotherapy in Stage III non-small-cell lung cancer.

1
UI - 11834019
AU - Riquet M; Lang-Lazdunski L; Le PB; Dujon A; Souilamas R; Danel C;
TI - Manac'h D Characteristics and prognosis of resected T3 non-small cell lung cancer.
SO - Ann Thorac Surg 2002 Jan;73(1):253-8
AD - Department of Thoracic Surgery and Pathology, Hopital Europeen Georges Pompidou, Paris, France. marc.riquet@hop.egp.ap-hop-paria.fr
BACKGROUND: T3 tumors can be divided into several subgroups depending on the type of anatomical structure invaded: chest wall, mediastinal pleura, or main bronchus. The aim of this study was to analyze the characteristics and prognosis of each subgroup of T3 tumors. METHODS: The results of surgical treatment were retrospectively analyzed for 261 patients with T3 non-small cell lung cancer invading either the mediastinal pleura or parietal pericardium by direct extension (mediastinal pT3, n = 68), or main bronchus (bronchial pT3, n = 68), or chest wall (chest wall pT3, n = 125) that were operated on between 1984 and 1996. Complete resection including radical mediastinal lymph node dissection was intended in all patients. One patient had segmentectomy, 91 had lobectomy (34.9%), and 169 had pneumonectomy (64.8%). One hundred and fifty-eight patients received adjuvant radiation therapy and 7 patients received both adjuvant chemotherapy and radiation therapy. Actuarial survival curves were drawn using the Kaplan-Meier method and risk factors for late death were identified. RESULTS: In-hospital mortality was 6.1%. Follow-up was 98% complete. Global 5-year survival was 28%, with survival being not significantly different among the three subgroups: 34.9%, 30.6%, and 22.5% (p = 0.19) in the bronchial pT3, mediastinal pT3, and chest wall pT3 subgroups, respectively. Resection margins were microscopically invaded in 33 patients (12.6%). Seventy-four patients had N1 involvement (28.4%) and 78 patients had N2 involvement (29.8%). N0 involvement was more prevalent in the chest wall pT3 subgroup, whereas N1 involvement was more prevalent in the bronchial pT3 subgroup and N2 involvement was more prevalent among patients with mediastinal invasion. Pathologic factors influencing the 5-year survival were tumor size (p = 0.03) and N involvement (p = 0.003). Histology, type of surgical resection (lobectomy versus pneumonectomy), and use of adjuvant therapy did not influence survival significantly. CONCLUSIONS: Five-year survival was not significantly different among the three subgroups of pT3 non-small cell lung cancer, although bronchial pT3 tumors tended to have a better prognosis and chest wall pT3 tumors tended to have a worse prognosis. The pathologic characteristics of each pT3 subgroup seems different. Further research is warranted to explore the pathologic and biological factors influencing prognosis for each pT3 subgroup.

2
UI - 12022545
AU - Martinod E; D'Audiffret A; Thomas P; Wurtz AJ; Dahan M; Riquet M; Dujon
TI - A; Jancovici R; Giudicelli R; Fuentes P; Azorin JF Management of superior sulcus tumors: experience with 139 cases treated by surgical resection.
SO - Ann Thorac Surg 2002 May;73(5):1534-9; discussion 1539-40
AD - Department of Thoracic and Vascular Surgery, Hopital Avicenne, Bobigny, France. emartinod@wanadoo.fr
BACKGROUND: The management of non-small cell carcinomas of the lung involving the superior sulcus remains controversial. The goal of this retrospective study was to evaluate the role of surgery, radiotherapy, and chemotherapy for the treatment of superior sulcus tumors, to define the best surgical approach for radical resection, and to identify factors influencing long-term survival. METHODS: Between 1983 and 1999, 139 patients underwent surgical resection of superior sulcus tumors in seven thoracic surgery centers. According to the classification of the American Joint Committee, 51.1% of cancers were stage IIB, 13.7% stage IIIA, 32.4% stage IIIB, and 2.9% stage IV. RESULTS: The resections were performed with 74.1% using the posterior approach and 25.9% using an anterior approach. A lobectomy was accomplished in 69.8% of the cases and a wedge resection in 22.3%. Resection of a segment of vertebrae or subclavian artery was performed, respectively, in 19.4% and 18% of the cases. Resection was complete in 81.3% of cancers. The overall 5-year survival rate was 35%. Preoperative radiotherapy improved 5-year survival for stages IIB-IIIA. Surgical approach, postoperative radiotherapy, or chemotherapy did not change survival. CONCLUSIONS: The optimal treatment for superior sulcus tumors is complete surgical resection. The surgical approach (anterior/posterior) did not influence the 5-year survival rate. Preoperative radiotherapy should be recommended to improve outcome of patients with a superior sulcus tumor.

3
UI - 12238850
AU - Fadel E; Yildizeli B; Chapelier AR; Dicenta I; Mussot S; Dartevelle PG
TI - Sleeve lobectomy for bronchogenic cancers: factors affecting survival.
SO - Ann Thorac Surg 2002 Sep;74(3):851-8; discussion 858-9
AD - Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Hopital Marie-Lannelongue, Paris-Sud University, Le Plessis Robinson, France. fadel@ccml.com
BACKGROUND: Sleeve lobectomy is a parenchyma-sparing procedure that is particularly valuable in patients with cardiac or pulmonary contraindications to pneumonectomy. The purpose of this study is to report our experience with sleeve lobectomy for bronchogenic cancer and to investigate factors associated with long-term survival. METHODS: lobectomy for non-small-cell lung cancer (n = 139) or carcinoid tumor (n = 30), including 61 with a preoperative contraindication to pneumonectomy. Mean age was 59 +/- 14 years (range, 19 to 82 years). Vascular sleeve resection was performed in 11 patients. The remaining bronchial stump contained microscopic disease in 7 patients. RESULTS: Major bronchial anastomotic complications occurred in 6 (3.6%) patients: one was fatal postoperatively, three required reoperation, and two were managed conservatively. In the non-small-cell lung cancer group, operative mortality was 2.9% (4 of 139), and overall 5-year and 10-year survival rates were 52% and 28%, respectively. Six patients experienced local recurrence after complete resection. By multivariate analysis, two factors significantly and independently influenced survival: nodal status (N0 or N1 versus N2; p = 0.01) and microscopic invasion of the bronchial stump (p = 0.02). In the carcinoid tumor group, there were no operative deaths, and overall 5-year and 10-year survival rates were 100% and 92%, respectively. CONCLUSIONS: Sleeve lobectomy achieves local tumor control and is associated with low mortality and bronchial anastomotic complication rates. Long-term survival is excellent for carcinoid tumors. For patients with non-small-cell lung cancer, N2 disease or incomplete resection is associated with a worse prognosis; outcome is not affected by presence of a preoperative contraindication to pneumonectomy.

4
UI - 11956619
AU - Chen CY; Hsu CP; Hsu NY; Shih CS; Lin TY; Chow KC
TI - Expression of dihydrodiol dehydrogenase in the resected stage I non-small cell lung cancer.
SO - Oncol Rep 2002 May-Jun;9(3):515-9
AD - Chung-Shun Medical College and Taichung Veteran General Hospital, Taichung, Taiwan.
Recently, by using differential display on specimens of non-small cell lung cancer (NSCLC), we detected overexpression of dihydrodiol dehydrogenase (DDH) that was rarely expressed in the corresponding normal lung tissue. DDH overexpression was correlated with poor prognosis of patients with advanced NSCLC. Because DDH could metabolize polycyclic aromatic hydrocarbons (PAH) in the liver, DDH overexpression in NSCLC would suggest an association with carcinogenesis and disease progression. In this study, we investigated DDH expression in 103 patients with resected stage I NSCLC. Expression of DDH was detected by using immunohistochemistry. Relation between DDH expression and clinicopathological parameter (age, gender, smoking habit, tumor status, histological type, cell differentiation, local recurrence, distant metastasis or survival) was analyzed by statistical analysis. DDH overexpression was detected in 39 (37.9%) of 103 pathological sections. Frequency of DDH overexpression was significantly higher in male patients (p=0.043) and patients with squamous cell carcinoma (p<0.005). Among 103 patients, 14 patients had local recurrence and 28 patients had distant metastasis during follow-up examination. The 5-year survival rate of these patients was poorer than those who did not have local recurrence or distant metastasis (both were p<0.005, respectively). Although patients with low DDH expression had more favorable outcome than those with DDH overexpression, in terms of survival rate no statistical significance was detected (p=0.889). The results suggest that DDH expression may serve as an early but not prognostic biomarker for patients with resectable stage I NSCLC.

6
UI - 11603492
AU - Grannis FW Jr
TI - A response to "Clinical trials in lung cancer: truth, justice, and the American way".
SO - Ann Thorac Surg 2001 Oct;72(4):1438-9

7
UI - 12355937
AU - Ichinose Y
TI - [Randomized controlled trials in Japan--lung cancer]
SO - Gan To Kagaku Ryoho 2002 Sep;29(9):1516-21
AD - Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka 811-1395, Japan.
Randomized controlled trials conducted in Japan were reviewed. Using PubMed, 12 papers published after 1990 were selected. Six papers presented at the annual meeting of the American Society of Clinical Oncology from 1999 to 2002 were also added for use in this review. According to the results of those trials, cisplatin plus either irinotecan or docetaxel for advanced non-small cell lung cancer, cisplatin plus irinotecan for small cell lung cancer and concurrent chemoradiotherapy for a localized disease of both small and non-small cell lung cancers have been established as standard treatments. No adjuvant treatment method for resected patients has been proved to be sufficiently effective.

8
UI - 11081863
AU - Jazieh AR; Hussain M; Howington JA; Spencer HJ; Husain M; Grismer JT;
TI - Read RC Prognostic factors in patients with surgically resected stages I and II non-small cell lung cancer.
SO - Ann Thorac Surg 2000 Oct;70(4):1168-71
AD - Division of Hematology/Oncology, University of Arkansas for Medical Sciences, Little Rock 72205, USA. jaziehabdulr@exchange.uams.edu
BACKGROUND: About one-third to one-half of patients with early stages of non-small cell lung cancer (NSCLC) succumb to their disease. In this study, we attempted to identify prognostic factors that predict outcome in patients with stages I and II NSCLC. METHODS: A retrospective evaluation of 454 patients with surgically resected stages I and II NSCLC was performed to determine the impact of various clinical, laboratory, and pathological factors on patient outcome such as overall survival (OS) and event-free survival (EFS). RESULTS: Patients older than 65 years had shorter EFS and OS than younger patients (p = 0.002). Patients with preoperative hemoglobin less than or equal to 10 g% had shorter EFS and OS compared to patients with a hemoglobin greater than 10 g% (p = 0.001). Expectedly, OS and EFS were shorter in patients with stage II as compared to stage I patients (p < 0.001). In a multivariate analysis, age, hemoglobin level, and stage remain significant predictors for EFS and OS. CONCLUSIONS: Older age, anemia, and higher stage are important prognostic factors in patients with surgically resected stage I and II NSCLC.

9
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

10
UI - 12165878
AU - Ishikawa H; Satoh H; Yamashita YT; Ohtsuka M; Sekizawa K
TI - CEA and survival in patients with stage IA-B NSCLC.
SO - Thorac Cardiovasc Surg 2002 Aug;50(4):253
AD - Division of Respiratory Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsuskuba-City, Ibaraki, Japan.

11
UI - 12206473
AU - Rath GK; Sharma DN
TI - Newer techniques of radiation therapy in lung cancer.
SO - Indian J Chest Dis Allied Sci 2002 Jul-Sep;44(3):155-7

12
UI - 12237924
AU - Fukumoto S; Shirato H; Shimzu S; Ogura S; Onimaru R; Kitamura K;
TI - Yamazaki K; Miyasaka K; Nishimura M; Dosaka-Akita H Small-volume image-guided radiotherapy using hypofractionated, coplanar, and noncoplanar multiple fields for patients with inoperable Stage I nonsmall cell lung carcinomas.
SO - Cancer 2002 Oct 1;95(7):1546-53
AD - First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
BACKGROUND: Occasionally, medically compromised and/or elderly patients with nonsmall cell lung carcinomas (NSCLCs) cannot be treated surgically. We investigated small-volume hypofractionated image-guided radiotherapy (IGRT) without the need for breath control in patients with 1999, 22 patients with Stage I NSCLCs, including 19 males and 3 females, were treated with IGRT. Among these patients, there were 13 Stage IA and 9 Stage IB tumors. The tumors ranged in size from 14.2 to 58.5 mm, with a median size of 26.7 mm. Of the 22 patients, 19 were unfit for surgical treatment due to poor pulmonary function, complications, and/or advanced age and 3 refused surgery. Computed tomographic scans (CT) of the primary tumor were taken during three respiratory phases and they were analyzed to determine the planning target volume, which included only the primary tumor with allowances for respiratory movement. The radiation doses administered at the edge of the moving tumor during normal breathing were 80% of the prescribed dose, either 48 or 60 Gy given in eight fractions over 2 weeks. Clinical evaluation, chest CT scan, and pulmonary function tests were performed before irradiation and at regular intervals for the post-IGRT follow-up. The median follow-up period was 24 months (range, 2-44 months; mean, 21.8 months) (at least 24 months for survivors). RESULTS: Of 17 tumors assessed at the initial follow-up 2-6 months after treatment (5 complete responses, 11 partial responses, and 1 progressive disease), 16 (94%) were controlled locally. One local recurrence was observed during the follow-up. The lung carcinoma-specific survival rate at 1 year was 94% and the 1-year actuarial recurrence-free survival rate was 71%. The lung carcinoma-specific survival rate at 2 years was 73% and the 2-year actuarial recurrence-free survival rate was 67%. The treatment was well tolerated and no major side effects were observed. Localized radiation pneumonitis was observed in all patients who were examined by CT scan, but the patients were asymptomatic. Parameters of pulmonary function, including vital capacity, total lung capacity, and diffusion capacity for carbon monoxide, decreased very little or not at all, indicating that IGRT rarely deteriorated pulmonary functions. CONCLUSIONS: Small-volume hypofractionated IGRT without breath control is a feasible and beneficial method for the curative treatment of patients with Stage I NSCLCs. It has the potential of a high local tumor control rate and low morbidity. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10853

13
UI - 12230752
AU - Neville A
TI - Lung cancer.
SO - Clin Evid 2002 Jun;(7):1369-83
AD - McMaster University, Hamilton, Canada.

14
UI - 11689795
AU - Carbone E; Asamura H; Takei H; Kondo H; Suzuki K; Miyaoka E; Tsuchiya R;
TI - Motta G T2 tumors larger than five centimeters in diameter can be upgraded to T3 in non-small cell lung cancer.
SO - J Thorac Cardiovasc Surg 2001 Nov;122(5):907-12
AD - Division of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan.
OBJECTIVE: Among the TNM criteria, tumor size is a well-assessed factor in the prognosis of small tumors. A 3-cm cutoff point separates T1 from T2 tumors, whereas a size larger than 3 cm is not ascribed any prognostic value. Instead, N2 is considered to be the worst prognostic factor for intrathoracic extended disease. METHOD: The prognosis of 545 patients with non-small cell lung cancer larger than 3 cm in diameter (T2, T3, and T4) was studied. These tumors were completely resected by pneumonectomy (n = 126) or lobectomy (n = 411) or were partially resected (n = 8). Survivals were compared according to the following factors: tumor size (3.1-5 cm, 5.1-7 cm, >7 cm), nodal status, age, sex, histologic type, degree of pleural involvement, operative procedure, stage, and T factor. For the multivariate analysis, the Cox proportional hazard model was used with the same variables. RESULTS: The univariate analysis showed that age, sex, degree of pleural involvement, operative procedure, tumor size, nodal status, and stage were all significant prognostic factors. Further comparison of survival between different tumor sizes (< or =5 cm vs >5 cm) in the same nodal category demonstrated a significantly poor prognosis for larger tumors in N0 (P =.00374) and N2+N3 (P =.0157), but not in N1 (P =.3452). T2 tumors (n = 349) were divided, according to size, into T2a (n = 238) and T2b (n = 111), and survival was compared with those in T3 and T4. The 5-year survivals were 51.3%, 35.1%, 47.8%, and 25.3%, respectively. The difference between T2a and T2b was statistically significant (log-rank P =.0170, Breslow P =.0055). CONCLUSIONS: A tumor size of more than 5 cm in diameter was indicative of a poor prognosis in non-small cell lung cancer, because patients with T2b tumors had a significantly different survival from that of patients with T2a tumors, and the survival curve was located between those for patients with T3 and T4 tumors. Consequently, T2b might be upgraded to at least T3.

15
UI - 12045865
AU - Younes RN; Gross JL; Deheinzelin D
TI - Surgical resection of unilateral lung metastases: is bilateral thoracotomy necessary?
SO - World J Surg 2002 Sep;26(9):1112-6
AD - Department of Thoracic Surgery, Hospital do Cancer AC Camargo, Fundacao Antonio Prudente, LIM-62, UNIP, 211, Sao Paulo, Brazil 01509-010.
Surgical resection of lung metastases is routine procedure for selected patients with pulmonary nodules and solid tumors. In some cases, patients present with unilateral pulmonary metastases amenable to surgical resection. Surgeons are still divided between unilateral approach directed to the radiologically detected nodules, or bilateral exploratory thoracotomy. This study evaluates the need for bilateral thoracotomy in patients diagnosed with unilateral lung metastases. A retrospective evaluation was made of a prospective database from a single institution (1990-1997) of all consecutive patients (n = 267) diagnosed on admission with unilateral (n = 179) or bilateral (n= 88) lung nodules. Ipsilateral thoracotomy was performed on all patients with unilateral disease. Bilateral thoracotomy was performed on all patients with bilateral lung metastases. Histology: adenocarcinoma (25%), osteosarcoma (23%), squamous cell carcinoma (18%), soft-tissue sarcoma (18%), and other (16%). Median follow-up was 17 months. Contralateral disease-free survival and overall survival were determined. Univariate and multivariate analyses were performed to determine prognostic factors for overall and contralateral disease-free survival. The two groups of patients with confirmed bilateral metastases (synchronous or metachronous) were compared. Actuarial overall 5-year survival was 34.9%. Contralateral recurrence-free 6-month, 12-month, and 5-year survival were 95%, 89%, and 78%, respectively. Patients who experienced recurrence in the contralateral lung within 3, 6, or 12 months had an overall 5-year survival rate of 24%, 30%, and 37%, respectively. When patients with recurrence in the contralateral lung were compared to patients with bilateral metastases on admission, there was no significant difference in overall survival. Only histology and the number of pathologically proven metastases significantly (p < 0.05) predicted recurrence in the contralateral lung. Bilateral exploration of unilateral lung metastases is not warranted in all cases. Most patients will have only unilateral disease, and delaying contralateral thoracotomy until disease is detected radiologically does not appear to affect outcome.

16
UI - 11156081
AU - Asamura H; Suzuki K; Kondo H; Tsuchiya R
TI - Where is the boundary between N1 and N2 stations in lung cancer?
SO - Ann Thorac Surg 2000 Dec;70(6):1839-45; discussion 1845-6
AD - Division of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan. hasamura@gan2.ncc.go.jp
BACKGROUND: The anatomical definition of N1 stations, its boundary to N2 stations, and its prognostic implication are yet to be defined in lung cancer. Metastasis in lymph nodes close to the pleural reflection has been classified differently as N1 or N2 according to the lymph node maps promulgated so far. METHODS: The pattern of lymphatic involvement and prognosis were retrospectively analyzed in 180 N1 patients who underwent at least lobectomy and complete hilar/mediastinal lymphadenectomy from 1987 through 1997. For comparison, the prognoses of 166 N2 patients were also analyzed. RESULTS: The overall 5-year survival of N1 and N2 patients was 67% and 37%, respectively, and the difference was statistically significant (p = 0.0000, log-rank test). The prognosis was compared between N1 without No. 10 involvement (N1-, n = 145), N1 with No. 10 involvement (N1+, n = 35), and N2 (n = 166). Their 5-year survival was 70%, 54%, and 37%, respectively. A significant difference was observed only between N1+ and N2 (p = 0.04), and not observed between N1- and N1+. However, survival curves of single-node N2 (n = 66) and N1+ were superimposed. CONCLUSIONS: In terms of prognosis, a pleural reflection does not seem an appropriate anatomical boundary between N1 and N2 stations in lung cancer.

17
UI - 11216767
AU - van Rens MT; Zanen P; de la Riviere AB; Elbers HR; van Swieten HA; van
TI - den Bosch JM Survival after resection of metachronous non-small cell lung cancer in 127 patients.
SO - Ann Thorac Surg 2001 Jan;71(1):309-13
AD - Department of Pulmonary Diseases, Sint Antonius Hospital, Nieuwegein, The Netherlands. antolong@knmg.nl
BACKGROUND: In a number of patients with treated primary non-small cell lung cancer (NSCLC) a second primary tumor will be diagnosed. Our experience with surgery in these patients was analyzed and possible prognostic parameters were defined. METHODS: Patients with metachronous NSCLC (n = 127) who underwent resection from 1970 through 1997 were analyzed. All tumors were classified postsurgically. Median interval between the tumors was 3.7 years. Actuarial survival time was estimated and risk factors influencing survival were evaluated. RESULTS: Overall 5-year survival after the first resection was 70% and after the second resection was 26%. Patients with stage IA of the second primary tumor did have a significantly better survival (p < 0.005) as compared with patients with higher staged second primaries. Stage of second primary tumor and age were significant predictors of survival, whereas stage of first tumor, interval between resections, histology, and type of resection were not. CONCLUSIONS: Survival of patients with metachronous NSCLC and resection of both tumors is high, but poorer than after resection of the first tumor. Irrespective of the interval, patients with stage IA second primary tumor may benefit more from pulmonary resection.

18
UI - 12022594
AU - Jeremic B
TI - Survival after resection of metachronous non-small cell lung cancer.
SO - Ann Thorac Surg 2002 May;73(5):1694

19
UI - 10391257
AU - Riquet M; Manac'h D; Le Pimpec-Barthes F; Dujon A; Chehab A
TI - Prognostic significance of surgical-pathologic N1 disease in non-small cell carcinoma of the lung.
SO - Ann Thorac Surg 1999 Jun;67(6):1572-6
AD - Service de Chirurgie Thoracique, Hopital Laennec, Paris, France. marc.riquet@inc.ap-hop-paris-fr
BACKGROUND: N1 disease represents a heterogeneous group of non-small cell lung carcinoma with varying 5-year survival rates. Specific types of N1 lymph node involvement need to be further investigated and their prognostic significance clarified. METHODS: From 1984 to 1993, 1,174 patients with non-small cell lung cancer had complete mediastinal lymph node dissection: N0, 50.25% (n = 590); N1, 21.8% (n = 256); and N2, 27.95% (n = 328). The N1 subgroup cases were reviewed. Four levels of N1 nodes were identified using the New Regional Lymph Node Classification for Lung Cancer Staging. Their prognostic significances were tested and 5-year survival rates were compared with those of N0 and N2 patients of the whole group. RESULTS: The overall 5-year survival rate of N1 patients was 47.5%. Survival was not related to site of the primary lung cancer, pathologic T factor, histologic type, type of resection, number of N1 station involved, nor type of N1 involvement (direct extension or metastases). Five-year survival was significantly better when N1 involvement was intralobar (levels 12 and 13, n = 102), as compared with extralobar (hilar) involvement (levels 10 and 11, n = 154): 53.6% versus 38.5% (p = 0.02). Intralobar N1 5-year survival was similar to that of N0 (53.6% vs 56.5%, p = 0.01), and extralobar 5-year survival with that of N2 (38.5 vs 28.3%, p = 0.01) when N2 was present in only one station in the ipsilateral mediastinum. CONCLUSIONS: N1 disease is a compound of two subgroups: one located inside the lobes is related to N0, and the other (extralobar or hilar) behaves like an early stage of N2 disease. This offers further information for clinical, therapeutic, and research purposes.

20
UI - 12124570
AU - Torre W; Sierra A
TI - Postoperative complications of lung resection after induction chemotherapy using Paclitaxel (and radiotherapy) for advanced non-small lung cancer.
SO - J Cardiovasc Surg (Torino) 2002 Aug;43(4):539-44
AD - Service of General Thoracic Surgery, Clinica Universitaria, Universidad de Navarra, Pamplona, Spain.
BACKGROUND: Locally advanced non-small-cell lung carcinoma is currently treated by multidisciplinary protocols using a combination of chemotherapy, radiotherapy and surgery. However the best strategy for applying these therapeutic measures has not yet been established. One of the difficulties of using these forms of treatment is their toxicity. Our aim was to determine whether the postoperative course of the disease can be influenced by preoperative chemotherapy in any way. METHODS: Nineteen patients were surgically treated after receiving induction giving induction treatment were: stage III disease in 12 patients (1 Pancoast tumor), lung cancer and solitary brain metastasis in 4 patients, double primary lung cancer in 3 patients (1 synchronous and 2 metachronous). Variables were the chemotherapy treatment time interval from the beginning to surgery, the type of surgery, postoperative mortality and morbidity. Mean age was 55.9 years old (range between 25 and 70 years). Predominant gender was male (18 men and 1 woman). Neoadjuvant treatment consisted of chemotherapy in all patients (Paclitaxel, Cysplatin and Vinorelbine in cycles for a mean period of 3 months), and radiotherapy (14 patients). Pulmonary resections were: pneumonectomy (2 patients), lobectomy (16 patients) and wedge resection (1 patient). There were no exploratory thoracotomies. Bronchoplasty procedures were necessary in 5 cases and angioplasty in 5. Cardiopulmonary bypass was necessary in 1 case in order to resect an infiltrated pulmonary vein. Intraoperative radiotherapy (IORT) was used in 9 cases. RESULTS: Complications occurred in the immediate postoperative period in 9 patients: 1 postpneumonectomy respiratory distress syndrome, 2 bronchopleural fistulae, 4 prolonged air leaks, 1 complete dehiscence of the thoracotomy scar and 1 colitis caused by anaerobes. The postoperative mortality (within 30 days) was 2 patients (10.5%): 1 died from bronchopleural fistula and the other from postpneumonectomy respiratory distress syndrome. However, if we take into account the fact that the case of anaerobic colitis also ended with the patient's death on the 48th postoperative day, and we include it in the mortality rate, the final mortality is higher (15.8%). CONCLUSIONS: Surgery for non-small-cell lung carcinoma has to be considered a high-risk procedure. But, if patients are selected appropriately and the perioperative management is satisfactory, reasonable rates of morbidity and mortality can be achieved. More studies are needed in order to define the exact role of these therapeutic measures.

21
UI - 12124571
AU - Carbognani P; Tincani G; Crafa P; Sansebastiano G; Pazzini L; Zoni R;
TI - Bobbio A; Rusca M Biological markers in non-small cell lung cancer. Retrospective study of 10 year follow-up after surgery.
SO - J Cardiovasc Surg (Torino) 2002 Aug;43(4):545-8
AD - Department of Thoracic and Vascular Surgery, University of Parma, Italy. Paolo.Carbognani@Unipr.It
BACKGROUND: The biological markers in non-small cell lung cancer (NSCLC) have been widely studied and encouraging results have shown that products of some oncogenes and other molecular markers can predict the aggressiveness of the disease and the outcome of the patients. METHODS: To verify the reliability of these prognostic markers we have studied retrospectively the expression of c-erbB-2 and 67Ki (growth regulation), p53 (cell cycle regulation and apoptosis), bcl-2 (apoptosis) and CD31 and CD34 (angiogenesis) in 78 patients operated on for NSCLC with for 10 years. For the determination of the biological markers we have used the ABC (Avidin-Biotin-Peroxidase complex) immunohistochemical method. The Cox regression model was used for the univariate and multivariate analysis. RESULTS: Nineteen patients (24%) were alive after 10 years and 59 (76%) died. The univariate analysis of the relationship between the 10-year survival and the expression of the markers was significant only for p53 (p=0.0097). Stratifying the patients according to the 3 histological subtypes (squamous cell carcinoma, adenocarcinoma and large cell undifferentiated carcinoma) the correlation between markers and survival pointed out that the only significant one was p53 (p=0.0459) in adenocarcinoma. In the same way considering the stages p53 was significant in stage IIIa (p=0.0357). The multivariate analysis emphasized that p53 was the only significant marker with respect to the 10-year survival (p=0.0091). Examining the histological groups significant was only p53 in adenocarcinoma (p=0.0192) and in large cell undifferentiated carcinomas (p=0.0290). This marker is also significant in pathological stage II (p=0.0271) and IIIa (p=0.0402). Apart from histology and staging the 10-year survival was 33% for p53 negative versus 10% for p53 positive. In patients with adenocarcinoma the 10-year survival was 40% for p53 negative and 6% for p53 positive. CONCLUSIONS: In conclusion our results emphasize the importance of p53 as a prognostic factor in 10-year survival in patients with adenocarcinoma and in stage II and IIIa.

22
UI - 12365020
AU - Harada T; Shirato H; Ogura S; Oizumi S; Yamazaki K; Shimizu S; Onimaru
TI - R; Miyasaka K; Nishimura M; Dosaka-Akita H Real-time tumor-tracking radiation therapy for lung carcinoma by the aid of insertion of a gold marker using bronchofiberscopy.
SO - Cancer 2002 Oct 15;95(8):1720-7
AD - First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
BACKGROUND: The authors developed fluoroscopic real-time tumor-tracking radiation therapy (RTRT) by insertion of a gold marker using bronchofiberscopy to reduce uncertainties in organ motion and set-up error in external radiotherapy for moving tumors. The purpose of the current study was to evaluate RTRT's feasibility in lung carcinoma treatment. METHODS: The three-dimensional position of a 1.0-2.0 mm gold marker in or near the tumor was detected by two sets of fluoroscopies every 0.03 seconds. The treatment beam was gated to irradiate the tumor only when the position of the marker coincided with its planned position using the RTRT system. Bronchofiberscopic equipment for insertion of the marker into the lung tumor was developed and used for 20 lung tumors in 18 patients. Patients were given high dose hypofractionated focal irradiation (35-48 Gy in 4-8 fractions in 4-10 days) with a planning target volume margin of 5 mm for the tumor. RESULTS: The markers were successfully inserted and maintained at the inserted position during and after the radiotherapy in 14 (88%) of 16 peripheral-type lung tumors and in none of four central-type lung tumors, indicating that this method of RTRT was not feasible for central-type lung tumors. Tracking of the marker was successfully performed in 1 of 2 tumors with a 1.0 mm marker and in all of 12 tumors with a 1.5-2.0 mm marker. On the whole, 13 (65%) of the 20 tumors were successfully treated with RTRT. Local tumor control was achieved and maintained for all 12 patients (13 tumors), who were treated with RTRT, with a median followup of 9 months (range, 5-15). Localized radiation pneumonitis was found radiographically at the lung volume that was irradiated with about 20 Gy, without symptoms in all but one patient. CONCLUSIONS: The insertion of a gold marker into or near peripheral-type lung tumors using bronchofiberscopy is a feasible and safe technique. Excellent initial response and low incidence of clinical complications suggest that the high dose hypofractionated focal irradiation using the RTRT system can be a good local treatment for peripheral-type lung tumors. Copyright 2002 American Cancer Society.

23
UI - 12372718
AU - Granone P; Keller S; Trodella L; Cesario A; Margaritor S; Porziella V;
TI - Valente S; Corbo GM; d'Angelillo R Postoperative radiotherapy in completely resected, early-stage, non-small-cell lung cancer: reflections and future directions.
SO - Lancet Oncol 2002 Oct;3(10):589-90; discussion 590-1
AD - Division of Thoracic Surgery, Catholic University of the Sacred Heart, Rome, Italy.

24
UI - 9690404
AU - Anonymous
TI - Postoperative radiotherapy in non-small-cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised controlled trials. PORT Meta-analysis Trialists Group.
SO - Lancet 1998 Jul 25;352(9124):257-63
BACKGROUND: The role of postoperative radiotherapy in treatment of patients with completely resected non-small-cell lung cancer (NSCLC) remains unclear. We undertook a systematic review and meta-analysis of the available evidence from randomised trials. METHODS: Updated data were obtained on individual patients from all available randomised trials of postoperative radiotherapy versus surgery alone. Data on 2128 patients from nine randomised trials (published and unpublished) were analysed by intention to treat. There were 707 deaths among 1056 patients assigned postoperative radiotherapy and 661 among 1072 assigned surgery alone. Median follow-up was 3.9 years (2.3-9.8 for individual trials) for surviving patients. FINDINGS: The results show a significant adverse effect of postoperative radiotherapy on survival (hazard ratio 1.21 [95% CI 1.08-1.34]). This 21% relative increase in the risk of death is equivalent to an absolute detriment of 7% (3-11) at 2 years, reducing overall survival from 55% to 48%. Subgroup analyses suggest that this adverse effect was greatest for patients with stage I/II, N0-N1 disease, whereas for those with stage III, N2 disease there was no clear evidence of an adverse effect. INTERPRETATION: Postoperative radiotherapy is detrimental to patients with early-stage completely resected NSCLC and should not be used routinely for such patients. The role of postoperative radiotherapy in the treatment of N2 tumours is not clear and may warrant further research.

25
UI - 12243805
AU - Yorke ED; Jackson A; Rosenzweig KE; Merrick SA; Gabrys D; Venkatraman
TI - ES; Burman CM; Leibel SA; Ling CC Dose-volume factors contributing to the incidence of radiation pneumonitis in non-small-cell lung cancer patients treated with three-dimensional conformal radiation therapy.
SO - Int J Radiat Oncol Biol Phys 2002 Oct 1;54(2):329-39
AD - Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. yorkee@mskcc.org
PURPOSE: To analyze acute lung toxicity data of non-small-cell lung cancer patients treated with three-dimensional conformal radiation therapy in terms of dosimetric variables, location of dose within subvolumes of the lungs, and models of normal-tissue complication probability (NTCP). METHODS AND MATERIALS: Dose distributions of 49 non-small-cell lung cancer patients treated in a dose escalation protocol between 1992 and 1999 were analyzed (dose range: 57.6-81 Gy). Nine patients had RTOG Grade 3 or higher acute lung toxicity. Correlation with dosimetric and physical variables, as well as Lyman and parallel NTCP models, was assessed. Lungs were evaluated as a single structure, as superior and inferior halves (to assess significance of dose to upper and lower lungs), and as ipsilateral and contralateral lungs. RESULTS: For the whole lung, Grade 3 or higher pneumonitis was significantly correlated (p 0.5 for superior lung indices, and >0.1 for contralateral lung indices studied). CONCLUSIONS: For these patients, commonly used dosimetric and NTCP models are significantly correlated with >or= Grade 3 pneumonitis. Equivalently strong correlations are found in the lower portion of the lungs and the ipsilateral lung, but not in the upper portion or contralateral lung.

26
UI - 12243807
AU - Rosenman JG; Halle JS; Socinski MA; Deschesne K; Moore DT; Johnson H;
TI - Fraser R; Morris DE High-dose conformal radiotherapy for treatment of stage IIIA/IIIB non-small-cell lung cancer: technical issues and results of a phase I/II trial.
SO - Int J Radiat Oncol Biol Phys 2002 Oct 1;54(2):348-56
AD - Department of Radiation Oncology, Lineberger Comprehensive Cancer Center of the University of North Carolina--University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA. rosenman@radonc.unc.edu
PURPOSE: We completed a Phase I/II clinical trial (Lineberger Comprehensive Cancer Center 9603), in which we treated 62 Stage IIIA/IIIB inoperable non-small-cell lung cancer (NSCLC) patients with two cycles of induction carboplatin/paclitaxel chemotherapy, followed by concurrent weekly carboplatin/paclitaxel with radiation doses escalated from 60 to 74 Gy. The median survival of 24 months, 3-year survival rate of 38%, and the high dose of radiation used justified a critical analysis of the technical and clinical components of this trial. METHODS AND MATERIALS: Between 1996 and 1999, 62 sequential patients with inoperable Stage IIIA/IIIB NSCLC were enrolled and treated with two cycles of induction carboplatin (area under the concentration curve = 6 using the Calvert equation) and paclitaxel (225 mg/m(2)), followed by an escalating radiation dose of 60-74 Gy with concurrent carboplatin weekly (area under the concentration curve = 2) and paclitaxel weekly (45 mg/m(2)). The goals of the trial were to determine whether 74 Gy of radiation could be safely delivered under these circumstances and whether patients could potentially benefit in terms of survival. The radiation treatment plans for all 62 patients were reviewed to determine the prechemotherapy and postchemotherapy tumor volume, as well as the dose-volume histograms of the normal lung and esophagus. RESULTS: Of the 62 patients who entered the trial, 48 completed the entire course of treatment. At last follow-up, 20 patients were alive (crude survival rate 32%). With a median follow-up of 43 months, the median survival was 24 months. The survival rate was 50% at 2 years and 38% at 3 years. Cox regression analysis showed that survival was best predicted by whether the patient had received radiotherapy (finished the trial), performance status, disease stage, and log postchemotherapy tumor volume. The 3-year survival rate for the 48 patients finishing the trial was 45%. Eight patients (13%) suffered locoregional relapse as the only site of failure. Only 1 patient had Grade 2 radiation pneumonitis. Five patients (8%) had Radiation Therapy Oncology Group Grade 3 or 4 esophagitis; 40 (65%) had a Grade 1 or 2 esophagitis. Esophageal toxicity could be predicted by the length of esophagus receiving 40 or 60 Gy. CONCLUSION: Radiation doses of 74 Gy, when given under the guidelines of the Lineberger Comprehensive Cancer Center 9603, appear to be safe and may possibly contribute to increased survival in patients with inoperable Stage IIIA/IIIB NSCLC.

27
UI - 12243808
AU - Firat S; Byhardt RW; Gore E
TI - Comorbidity and Karnofksy performance score are independent prognostic factors in stage III non-small-cell lung cancer: an institutional analysis of patients treated on four RTOG studies. Radiation Therapy Oncology Group.
SO - Int J Radiat Oncol Biol Phys 2002 Oct 1;54(2):357-64
AD - Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. sfirat@mcw.edu
PURPOSE: To determine the prognostic role of comorbidity in Stage III non-small cell lung cancer (NSCLC) treated definitively with radiotherapy alone. METHODS AND MATERIALS: A total of 112 patients with clinical Stage III NSCLC (American Joint Commission on Cancer 1997) enrolled in four Radiation Therapy Oncology Group studies (83-11, 84-03, 84-07, and 88-08 nonchemotherapy arms) at a single institution were analyzed retrospectively for overall survival (OS) and comorbidity. Of the 112 patients, 105 (94%) completed their assigned radiotherapy. The median assigned dose was 50.4 Gy to the lymphatics (range 45-50.4 Gy) and 70.2 Gy to the primary tumor (range 60-79.2 Gy). Comorbidity was rated retrospectively using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) and Charlson scales. Karnofsky performance scores (KPSs) and weight loss were prospectively recorded. Because only 8 patients had a KPS of <70, these patients were combined with patients who had a KPS of 70. The OS of this group was compared with that of the patients with better KPSs (>70). RESULTS: The median survival was 10.39 months (range 7.87-12.91). The 2-, 3-, and 5-year OS rate was 20.5%, 12.5%, and 7.1%, respectively. On univariate analysis, clinical stage (IIIA vs. IIIB) was found to be a statistically significant factor influencing OS (p = 0.026), and the histologic features, grade, tumor size as measured on CT scans, age, tobacco use, weight loss >or=5%, and total dose delivered to the primary tumor were not. A KPS of 2 (p <0.0001) were associated with statistically significant inferior OS. Multivariate analysis with clinical stage, KPS, and comorbidity (severity index) of all patients showed that a KPS 2 were independently associated with inferior OS; clinical tumor stage was not found to be an independent prognostic factor. CONCLUSION: KPS and comorbidity are important independent prognostic factors in Stage III NSCLC. Comorbidity should be included in protocols studying advanced stage NSCLC and used for stratification.

28
UI - 12243810
AU - Schild SE; Stella PJ; Geyer SM; Bonner JA; Marks RS; McGinnis WL; Goetz
TI - SP; Kuross SA; Mailliard JA; Kugler JW; Schaefer PL; Jett JR Phase III trial comparing chemotherapy plus once-daily or twice-daily radiotherapy in Stage III non-small-cell lung cancer.
SO - Int J Radiat Oncol Biol Phys 2002 Oct 1;54(2):370-8
AD - Mayo Clinic and Mayo Foundation, Rochester, MN, USA. sschild@mayo.edu
PURPOSE: This Phase III study was performed to determine whether chemotherapy plus b.i.d. or q.d. radiotherapy (RT) resulted in superior survival for patients with Stage III non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Patients with Stage III NSCLC and an Eastern Cooperative Oncology Group performance status of

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