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

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

Differentiated thyroid cancer in children and adolescents.
Three-dimensional conformal radiotherapy for lung cancer: promises and pitfalls.
Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non-small-cell lung cancer: a Southwest Oncology Group phase
Non-small cell lung cancer. The role of chemoimmunoradiotherapy after surgery.
[Radio-chemotherapy combinations in non operable localized non small cell lung carcinoma: updates and perspectives]
More power to trials for non-small-cell lung cancer.
A randomized study of high-dose split course radiotherapy preceded by high-dose chemotherapy versus high-dose radiotherapy only in locally
Predictors of subclinical nodal involvement in clinical stages I and II non-small cell lung cancer: implications in the inoperable and
A palliative accelerated irradiation regimen for advanced non-small-cell lung cancer vs. conventionally fractionated 60 GY: results of a
Median sternotomy versus thoracotomy to resect primary lung cancer: analysis of 815 cases.
Elective nodal irradiation in the treatment of non-small-cell lung cancer with three-dimensional conformal radiation therapy.
Vindesine-ifosfamide-platinum (VIP) induction chemotherapy in surgically staged IIIA-N2 non-small-cell lung cancer: a prospective study. Leuven
[Principles of radiotherapy of non-small cell lung cancer]
A randomized trial of systematic nodal dissection in resectable non-small cell lung cancer.
A phase II study of continuous concurrent thoracic radiotherapy in combination with mitomycin, vindesine and cisplatin in unresectable
Survival and risk model for stage IB non-small cell lung cancer.
Low morbidity of bronchoplastic procedures after chemotherapy for lung cancer.
Quality of life following lung cancer resection: video-assisted thoracic surgery vs thoracotomy.
Major surgery in lung cancer in elderly patients? Risk factors analysis and long-term results.
Treatment of advanced non-small cell lung cancer.
Immediate versus delayed palliative thoracic radiotherapy in patients with unresectable locally advanced non-small cell lung cancer and
Intraoperative lymphatic mapping for non-small cell lung cancer: the sentinel node technique.
Regular follow-up after curative resection of nonsmall cell lung cancer: a real benefit for patients?
The role of neoadjuvant chemotherapy in marginally resectable or unresectable stage III non-small cell lung cancer.
Completion pneumonectomy for non-small cell lung cancer: experience with 59 cases.
[Place of radiotherapy in treatment of non small cell lung cancer]
[Late results of the combined treatment with the use of preoperative chemotherapy and surgery of locally advanced non-small cell lung cancer]
Radiotherapy alone in technically operable, medically inoperable, early-stage (I/II) non-small-cell lung cancer.
Small cell lung carcinoma (SCLC): a clinicopathologic study of 100 cases with surgical specimens.
Advanced non-small cell lung cancer: induction chemotherapy and chemoradiation before operation.
Comorbidity and KPS are independent prognostic factors in stage I non-small-cell lung cancer.
In regard to Jeremic et al., IJROBP 2001;50:19-25.
Sleeve lobectomy for bronchogenic cancers: factors affecting survival.
Sentinel nodal assessment in patients with carcinoma of the lung.
High-resolution computed tomography in clinical T1 N0 M0 adenocarcinoma of the lung.
Preoperative evidence of circulating tumor cells by means of reverse transcriptase-polymerase chain reaction for carcinoembryonic antigen

1
UI - 11883862
AU - Giuffrida D; Scollo C; Pellegriti G; Lavenia G; Iurato MP; Pezzin V;
TI - Belfiore A Differentiated thyroid cancer in children and adolescents.
SO - J Endocrinol Invest 2002 Jan;25(1):18-24
AD - Medical Oncology Unit, S. Luigi Hospital, University of Catania, Italy. dariogiuffrida@netscape.net
In this retrospective study we analyzed cancer characteristics and outcome in a consecutive series of 48 young patients (< or =20 yr of age) with a differentiated thyroid cancer (DTC), observed during the period 1977-1998. In none of them was thyroid cancer related to ionizing radiation. The median age was 18.1 yr, range 7-20, and the female/male ratio was 2.5/1. Papillary thyroid cancer (PTC) occurred in 83% and follicular thyroid cancer (FTC) in 17% of cases. All patients underwent total or near total thyroidectomy plus pre- and/or paratracheal lymphnode dissection. Surgery complication rate was low (4% permanent hypoparathyroidism; no permanent lesion of recurrent laryngeal nerve). Extrathyroid disease was present in 52% of patients with PTC and in 50% of patients with FTC, while nodal metastases were present in 62.5% of patients with PTC and in 12.5% of patients with FTC. Lung metastases occurred in 10 patients with PTC (25%) and in none with FTC. Twenty-one patients required radioiodine treatment for metastatic disease: 11 patients for relapsing lymph-node metastases, 4 patients for lung metastases, 6 patients for both lymph-node and lung metastases. After a mean follow-up of 85+/-12 months all patients followed regularly (no.=47) were alive; 37 patients (79%) were free of disease and 10 (21%) had residual disease. Our results indicate that non-radiation-related DTC occurring in young patients often presents at an advanced stage. For this reason, although the prognosis is usually good in these patients, we believe that total or near total thyroidectomy with lymphadenectomy is always the required initial surgical treatment.

2
UI - 12044245
AU - Patel RR; Mehta M
TI - Three-dimensional conformal radiotherapy for lung cancer: promises and pitfalls.
SO - Curr Oncol Rep 2002 Jul;4(4):347-53
AD - Department of Human Oncology, University of Wisconsin Medical School, 600 Highland Avenue K4/3, Madison 53792, USA.
Lung cancer represents a major source of morbidity and mortality. Despite recent advances, long-term survival remains elusive in most patients with locally advanced cancer. A substantial proportion of these patients experience a relapse at the original site of disease within the thorax, making radiotherapy an important component of treatment. Of several approaches investigated to improve the therapeutic ratio in radiotherapy, three-dimensional conformal radiotherapy holds the most promise, primarily because it allows higher doses to be delivered to the target by improved shaping of radiation portals and conformal avoidance of normal structures. The rationale and evolution of this technology and its potential pitfalls are presented in this review.

3
UI - 12177106
AU - Albain KS; Crowley JJ; Turrisi AT 3rd; Gandara DR; Farrar WB; Clark JI;
TI - Beasley KR; Livingston RB Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non-small-cell lung cancer: a Southwest Oncology Group phase II study, SWOG 9019.
SO - J Clin Oncol 2002 Aug 15;20(16):3454-60
AD - Loyola University Stritch School of Medicine, Maywood, IL, USA.
PURPOSE: There are no published survival data after chemoradiotherapy (chemoRT) in pathologically documented stage IIIB non-small-cell lung cancer. Studies of radiotherapy (RT) alone or chemotherapy followed by RT yield 5-year survivals less than 10%. The Southwest Oncology Group (SWOG) employed the same concurrent chemoRT induction regimen used in its predecessor trimodality trial to determine the efficacy, safety, and long-term outcome of replacing postinduction surgery with additional chemoRT. PATIENTS AND METHODS: Eligible patients for SWOG-9019 had pathologic documentation of T4N0/1, T4N2, or N3 stage IIIB non-small-cell lung cancer. They had pulmonary function adequate to withstand combined-modality therapy, identical to the requirements of the previous trial with postchemoRT surgery. Induction therapy was two cycles of cisplatin plus etoposide (PE) concurrent with once-daily thoracic RT (45 Gy). In the absence of progressive disease, RT was completed to 61 Gy, with two additional cycles of cisplatin plus etoposide. RESULTS: Fifty eligible patients were accrued with tumor-node (TN) substage confirmed on central review: 18, T4N0/1; 12, T4N2; and 20, N3. Grade 4 neutropenia was the most common toxicity (32%). Grade 3/4 esophagitis occurred in 12% and 8%. Median follow-up was 52 months, and overall median survival was 15 months (10 to 22, 95% confidence interval). Three- and 5-year survivals were 17% and 15% (5-year T4N0/1, 17%; T4N2, 13%; and N3, 15%). CONCLUSION: Feasibility and long-term survival support the application of these results as a standard against which mature outcomes of chemoRT trials with new chemotherapy agents can be compared. These results also justify use of the SWOG-9019 approach as a control arm in ongoing phase III trials.

4
UI - 11876542
AU - Kshivets O
TI - Non-small cell lung cancer. The role of chemoimmunoradiotherapy after surgery.
SO - J Exp Clin Cancer Res 2001 Dec;20(4):491-503
AD - Dept. of Surgery, Siauliai Cancer Center, Lithuania. kshivets@hotmail.com
The aim of this study was to determine expediency of adjuvant chemoimmunoradiotherapy for radically operated non-small cell lung cancer patients (LCP) with pathologic stage II-III (T1-4N0-2M0G1-3). In retrospective trial (1985-1998) a 5-year survival of 54 consecutive radically operated LCP after adjuvant chemoimmunoradiotherapy (group A) was compared with 5-year survival of 264 LCP, after radical procedures (group C) and with 5-year survival of 86 radically operated LCP after postoperative radiotherapy (group B) (45-50 Gy). I cycle of chemoimmunotherapy was given on day 10-14 after complete resections. Radiotherapy (45-50 Gy) was administered since day 7 after 1 cycle. After irradiation 3-4 courses of CAVT were repeated every 21-28 day. Variables selected for 5-year survival and life span study were sex, age, TNMG, cell type, tumor size. Survival curves were estimated by the Kaplan-Meier method. Differences in curves between groups of LCP were evaluated using a log-rank test. Multivariate proportional hazard Cox regression, multi-factor clustering, structural equation modeling and Monte Carlo simulation were used to determine any significant overall regularity. 5-year survival was superior in group A (64.8%: 35 out of 54 LCP with N0-2; life span=1998.2+/-156.9 days) compared with group B (45.3%: 39 out of 86 LCP with N0-2; life span=1296.4+/-109.5 days) (P<0.001). 5-year survival of group C was 63.6% (168 out of 264 LCP with N0-2; life span=1738.3+/-63.4 days) (P>0.05 for group A and P<0.001 for group B). For LCP with N1-2 5-year survival was significantly superior for group A (63.6%: 21 from 33; life span=1934.0+/-180.9 days) compared with group C (28.1%: 25 out of 89; life span=1056.9+/-91.1 days) (P<0.001) and with group B (35.6%: 21 out of 59; life span=1051.7+/-119.6 days) (P<0.001). Structural equation modeling and Monte Carlo simulation confirmed significant overall differences between 5-year survival (P<0.05) and life span (P<0.001) of LCP with N1-2 in group A with respect to group C or B; however, 5-year survival of LCP for N0 in groups A, B and C were not significantly different.

5
UI - 12135861
AU - Hasbini A; Ozanne F; Ammarguellat H; Crequit J; Dolige T; Bouchaert E;
TI - Dutel JL; Durdux C [Radio-chemotherapy combinations in non operable localized non small cell lung carcinoma: updates and perspectives]
SO - Bull Cancer 2002 Jun;89(6):599-611
AD - Service de radiotherapie-oncologie, Centre hospitalier, avenue Leon-Blum, 60021 Beauvais Cedex, France.
Optimal treatment of non operable localized non small cell lung carcinoma (NSCLC) continues to evolve. Increasing overall survival must evolute through improving local tumoral control and eradication of probable occult metastasis. Historically, median survival varies between 7 and 10 months with a standard conventional fractionated radiotherapy (RT). Induction chemotherapy (CT) followed by RT has demonstrated its superiority over RT alone, modality which is widely utilised. Other studies revealed best results with decreasing metastatic relapses. Three independent meta-analysis confirmed benefit obtained with cisplatin based CT followed by RT that allowed to consider this association as a gold standard. Other authors demonstrated an improvement of local control and survival with concomitant RT-CT or hyperfractionated accelerated RT. Results of all of these new therapeutic modalities still poor. Implication of new CT drugs has conducted for an emergence of new studies finding to demonstrate more encouraging results. Randomized trials are conducted in this way.

6
UI - 8777165
AU - Sorensen JB; Hansen HH
TI - More power to trials for non-small-cell lung cancer.
SO - Ann Oncol 1996 Feb;7(2):119-20

7
UI - 8777169
AU - Planting A; Helle P; Drings P; Dalesio O; Kirkpatrick A; McVie G;
TI - Giaccone G A randomized study of high-dose split course radiotherapy preceded by high-dose chemotherapy versus high-dose radiotherapy only in locally advanced non-small-cell lung cancer. An EORTC Lung Cancer Cooperative Group trial.
SO - Ann Oncol 1996 Feb;7(2):139-44
AD - Department of Medical Oncology, Rotterdam Cancer Institute/Daniel den Hoed Kliniek, The Netherlands.
BACKGROUND: The treatment results of radiotherapy in stage III non-small-cell lung cancer are very poor. Several phase II studies showed that neoadjuvant chemotherapy followed by radiotherapy was feasible in this patient group and suggested that treatment outcome might improve. A randomized phase II study was performed addressing the response rate and morbidity of high-dose split course radiotherapy (RT) versus the same radiotherapy preceded by high-dose chemotherapy (CT) in patients with stage III non-small-cell lung cancer. PATIENTS AND METHODS: Seventy eligible patients were randomized in this study. CT consisted of cisplatin 100 mg/m2 days 1 and 22, and vindesine 3 mg/m2 on days 1, 8, 22 and 29. Radiotherapy started on day 43 in the combined arm and immediately in the RT-only arm. The primary tumour and the regional nodes were treated by 30 Gy/10 fractions/2 weeks and after the split by a second course of 25 Gy/10 fractions/2 weeks. In the combined arm a third CT cycle was planned during the split between RT courses. RESULTS: In the CT + RT arm 34 patients were evaluable for response and toxicity and 30 patients in the RT only arm. After completion of treatment 7 patients had a complete response (2 in the CT plus RT arm, 5 in the RT alone arm) and 26 patients a partial response (13 in the CT plus RT arm, 13 in the RT alone arm) for an overall response rate of 52% (95% CI 39%-65%). Acute toxicity was worse in the combined treatment arm with grade 4 leucocytopenia in 8 patients and thrombocytopenia grade 4 in one patient. Three patients had reversible renal toxicity grade 2. There was one toxic death in the RT plus CT arm. There was no enhancement of acute or late radiation pulmonary or oesophageal toxicity. Time to progressive disease (median 30 vs. 35 weeks) and overall survival time (median 12 months) were equal in both treatment arms. CONCLUSION: High-dose radiotherapy preceded by high-dose chemotherapy was more toxic than radiotherapy alone and did not result in this study in any benefit in terms of response rate, time to progressive disease and overall survival.

8
UI - 10192341
AU - Sawyer TE; Bonner JA; Gould PM; Garces YI; Foote RL; Lange CM; Li H
TI - Predictors of subclinical nodal involvement in clinical stages I and II non-small cell lung cancer: implications in the inoperable and three-dimensional dose-escalation settings.
SO - Int J Radiat Oncol Biol Phys 1999 Mar 15;43(5):965-70
AD - Division of Radiation Oncology, Mayo Clinic and Mayo Foundation, Rochester, MN, USA.
PURPOSE: When mediastinal lymph nodes are clinically uninvolved in the setting of inoperable non-small cell lung cancer, whether conventional radiation techniques or three-dimensional dose-escalation techniques are used, the benefit of elective nodal irradiation is unclear. Inclusion of the clinically negative mediastinum in the radiation portals increases the risk of lung toxicity and limits the ability to escalate dose. This analysis represents an attempt to use clinical characteristics to estimate the risk of subclinical nodal involvement, which may help determine which patients are most likely to benefit from elective nodal irradiation. METHODS: From 1987 to 1990, 346 patients undergoing complete resection of non-small cell lung cancer underwent a preoperative computed tomographic scan revealing no clinical evidence of N2/N3 involvement. Multivariate regression and regression tree analyses attempted to define which patients were at highest risk for subclinical mediastinal involvement (N2) and which patients were at highest risk for subclinical N1 and/or N2 involvement (N1/N2). Immunohistochemical data suggest that the conventional histopathologic techniques used during this study somewhat underestimate the true degree of lymph node involvement; therefore, a third end point was also evaluated: N1 involvement and/or N2 involvement and/or local-regional recurrence (N1/N2/LRR). RESULTS: Regression analyses revealed that the following factors were independently associated with a high risk of more advanced disease: positive preoperative bronchoscopy (N2, p = 0.02; N1/N2, p < 0.0001; N1/N2/LRR, p < 0.001) and tumor grade 3/4 (N1/N2/LRR, p < 0.01). A regression tree analysis was then used to separate patients into risk groups with respect to N1/N2/LRR. CONCLUSION: In inoperable non-small cell lung cancer, the patients for whom mediastinal radiation therapy may most likely be indicated are those with a positive preoperative bronchoscopy, especially with large (> 3 cm) primary tumors.

9
UI - 10924977
AU - Nestle U; Nieder C; Walter K; Abel U; Ukena D; Sybrecht GW; Schnabel K
TI - A palliative accelerated irradiation regimen for advanced non-small-cell lung cancer vs. conventionally fractionated 60 GY: results of a randomized equivalence study.
SO - Int J Radiat Oncol Biol Phys 2000 Aug 1;48(1):95-103
AD - Department of Radiotherapy, Saarland University Medical Center, Homburg/Saar, Germany. raunes@med-rz.uni-sb.de
PURPOSE: Radiation oncologists are often faced with patients with advanced non-small-cell lung cancer (NSCLC), who are not suitable candidates for state-of-the-art radical treatment, but who also are not judged to have a very short life expectancy. Some physicians treat these patients palliatively, whereas others advocate more intensive treatment. To find out if there is a substantial difference in outcome between these approaches, we performed a randomized prospective study. METHODS AND MATERIALS: Between 1994 and 1998, 152 eligible patients with advanced NSCLC Stage III (n = 121) or minimal Stage IV (n = 31) were randomized to receive conventionally fractionated (cf; A: 60 Gy, 6 weeks, n = 79) or short-term treatment (PAIR; B: 32 Gy, 2 Gy b.i.d.; n = 73) of tumor and mediastinum. RESULTS: One-year survival rate for all patients was 37% with no significant difference between the two treatment arms (A: 36%; B: 38%; p = 0.76). As far as can be judged from limited data available, palliation was adequate and similar for the two treatment arms. Apart from expected differences in the time course of esophagitis, acute side effects were moderate and equally distributed. No severe late effects were observed. CONCLUSIONS: In the present randomized trial, survival and available data on palliation were not different after cf to 60 Gy compared to the palliative PAIR regimen. Therefore, for patients who are not suitable for radical treatment approaches, the prescription of a palliative short-term irradiation appears preferable compared to cf over several weeks.

10
UI - 10969647
AU - Asaph JW; Handy JR Jr; Grunkemeier GL; Douville EC; Tsen AC; Rogers RC;
TI - Keppel JF Median sternotomy versus thoracotomy to resect primary lung cancer: analysis of 815 cases.
SO - Ann Thorac Surg 2000 Aug;70(2):373-9
AD - The Oregon Clinic, PC, Earle A Chiles Research Institute, and Medical Data Research Center, Providence Health System, Portland, Oregon 97213, USA.
BACKGROUND: We sought to determine if median sternotomy (MS) is an equivalent incision to thoracotomy (TH) in the treatment of primary pulmonary carcinoma. METHODS: We followed 801 patients undergoing 815 operations for primary lung carcinoma in a computer registry; 447 had MS, 368 had TH. RESULTS: Both groups were similar in preoperative risk assessment. Complete staging lymph node dissections were performed in 42% of MS patients and 17% of TH patients. Operative mortality (3.8% for MS, 3.3% for TH) and postoperative complications were similar. MS patients had a shorter postoperative hospital stay (7.5 days vs. 8.2 days). One hundred thirty-nine underwent pneumonectomy. Operative mortality was 12.5% for MS and 10.4% for TS (p = NS). Five hundred eighty-one underwent lobectomy with an operative mortality of 2.1% for MS and 2.0% for TH. Mean length of stay for MS lobectomy was 7.5 days compared with 8.5 days for TH (p = 0.06). Follow-up was 89% through 1998, comprising 1,339 MS and 1,463 TH patient-years. Survival for stage I at 5 and 10 years, respectively, was 51% and 34% for MS vs 54% and 32% for TH (p = NS). Survival for other stages was also similar. CONCLUSIONS: Median sternotomy provides more complete staging, shorter postoperative hospitalization, and better patient acceptance with equivalent operative and long-term survival when compared with thoracotomy. Concerns regarding increased wound infections in MS patients appear unfounded.

11
UI - 11395236
AU - Rosenzweig KE; Sim SE; Mychalczak B; Braban LE; Schindelheim R; Leibel
TI - SA Elective nodal irradiation in the treatment of non-small-cell lung cancer with three-dimensional conformal radiation therapy.
SO - Int J Radiat Oncol Biol Phys 2001 Jul 1;50(3):681-5
AD - Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
PURPOSE: Dose escalation using three-dimensional conformal radiation therapy (3D-CRT) has been investigated as a means to improve local control. However, with higher doses, the risk of toxicity increases. Early in our experience, we ceased treating elective nodal areas (lymph node stations without evidence of tumor involvement) in an effort to decrease toxicity while treating the gross tumor to higher doses. This report measures the rate of regional failure without elective radiation therapy to uninvolved lymph nodes. METHODS AND MATERIALS: A total of 171 patients with non-small-cell lung cancer treated with 3D-CRT at Memorial Sloan-Kettering Cancer Center between 1991 and 1998 were reviewed. Only lymph node regions initially involved with tumor either by biopsy (55%) or radiographic criteria (node > or =15 mm in the short axis on CT) were included in the clinical target volume. Elective nodal failure was defined as a recurrence in an initially uninvolved lymph node in the absence of local failure. RESULTS: Only 11 patients (6.4%) with elective nodal failure were identified. With a median follow-up of 21 months in survivors, the 2-year actuarial rates of elective nodal control and primary tumor control were 91% and 38%, respectively. In patients who were locally controlled, the 2-year rate of elective nodal control was 85%. The median time to elective nodal failure was 4 months (range, 1-19 months). Most patients failed in multiple lymph node regions simultaneously. CONCLUSION: Local control remains one of the biggest challenges in the treatment of non-small-cell lung cancer. Most patients in our series developed local failure within 2 years of radiation therapy. The omission of elective nodal treatment did not cause a significant amount of failure in lymph node regions not included in the clinical target volume. Therefore, we will continue our policy of treating mediastinal lymph node regions only if they are clinically involved with tumor.

12
UI - 9602259
AU - Vansteenkiste JF; De Leyn PR; Deneffe GJ; Lievens YN; Nackaerts KL; Van
TI - Raemdonck DE; van der Schueren E; Lerut TE; Demedts MG Vindesine-ifosfamide-platinum (VIP) induction chemotherapy in surgically staged IIIA-N2 non-small-cell lung cancer: a prospective study. Leuven Lung Cancer Group.
SO - Ann Oncol 1998 Mar;9(3):261-7
AD - Department of Pulmonology, University Hospital Gasthuisberg, Belgium. johan.vansteenkiste@uz.kuleuven.ac.be
PURPOSE: In the pioneer data from the Memorial-Sloan-Kettering group, preoperative mitomycin-C-vindesine-platinum (MVP) induction chemotherapy in N2-NSCLC was accompanied with substantial pulmonary toxicity. In this study, the efficacy and toxicity of three-drug VIP induction chemotherapy, the pathologic response in resection specimens, the early survival and relapse patterns are examined. PATIENTS AND METHODS: proven N2-NSCLC were treated with three cycles of VIP induction, followed by definitive locoregional treatment (resection and mediastinal dissection or radical radiotherapy). Several patients had unfavorable prognostic characteristics with respect to clinical and biological findings, tumor location and bulk of disease. RESULTS: The response rate to chemotherapy was 59% (95% Confidence Interval 34-75). Twenty-three responding patients had radical locoregional treatment: radical radiotherapy in four, resection in 19. Downstaging was present in nine of the 19 resection specimens, with two pathologic complete responses. The median survival time (MST) of all patients is 19 months, with a projected two-year survival of 49%. In patients responsive to chemotherapy who received definitive local treatment, the MST is not yet reached, and the projected two-year survival is 57%. Relapses were mainly distant, with isolated brain relapse as a disturbing finding. The main toxicity's were leukopenia and vomiting, but they were manageable. In contrast with MVP, no severe pulmonary toxicity occurred. CONCLUSIONS: VIP is a suitable induction regimen for N2-NSCLC, demonstrating a good activity and very acceptable toxicity.

13
UI - 12050682
AU - Esik O; Horvath A; Bajcsay A; Hideghety K; Agocs L; Piko B; Lengyel Z;
TI - Petranyi A; Pisch J [Principles of radiotherapy of non-small cell lung cancer]
SO - Magy Onkol 2002;46(1):51-85
AD - Sugarterapias Osztaly, Orszagos Onkologiai Intezet, Budapest, Hungary. esik@oncol.hu
The long-term survival probability for Hungarian lung cancer patients is 10% worse than the best results published in the most highly developed countries (the mean 5-year survival probability in Hungary is 5%, in contrast with the 15% survival probability in the USA). On the basis of the international recommendations and personal experience, an attempt was made to formulate the guidelines for radiotherapy as one of the fundamental non-small cell lung cancer (NSCLC) treatment modalities for national use. An expert panel was set up comprising physicians from 6 radiotherapeutic centers (the National Institute of Oncology / Semmelweis University, Budapest; the Beth Israel Medical Center, New York; the University of Kaposvar; the University of Essen; the University of Debrecen; and the County Hospital of Gyula). Experts in two important medical fields closely related to radiotherapy (surgery and diagnostic imaging) were also engaged in the elaboration of the manuscript. Discussion of the most important principles of the radiotherapy and an overview of the prognostic factors was followed by a critical analysis of the protocols applied in the radiotherapy of Hungarian NSCLC patients during recent decades. The new guidelines suggested for the radiotherapy of NSCLC are presented separately for the postoperative period, marginally resectable tumors, and the aggressive or non-aggressive radiotherapy of inoperable tumors. Detailed accounts are given of the techniques of external irradiation and brachytherapy, and of the acute and late radiation-induced damage of normal tissues. The authors believe that this document may be instrumental in improving the survival index of Hungarian NSCLC patients in the near future.

14
UI - 11891025
AU - Wu Y; Huang ZF; Wang SY; Yang XN; Ou W
TI - A randomized trial of systematic nodal dissection in resectable non-small cell lung cancer.
SO - Lung Cancer 2002 Apr;36(1):1-6
AD - Lung Cancer Research Center, 3rd University Hospital, Sun Yat-sen University of Medical Sciences, Guangzhou 510630, PR China. gzyilong@public.guangzhou.gd.cn
PURPOSE: We conducted a randomized trial to investigate whether systematic nodal dissection (SND) is superior to mediastinal lymph nodal sampling (MLS) in surgical treatment of non-small cell lung cancer (NSCLC). METHODS: The patients resectable clinical Stage I-IIIA NSCLC were randomly assigned to lung resection combined with SND or lung resection combined with MLS. After postoperative pathological Kaplan-Meier method was used for survival analysis. COX proportional hazards model was used for prognostic analysis. RESULTS: Of the 532 patients who were enrolled in the study, 268 patients were assigned to lung resection combined with SND and 264 were assigned to lung resection combined with MLS. After surgical restaging only 471 cases were eligible for follow-up. The median survival was 59 months in the group given SND and 34 months in the group given MLS (P=0.0000 by the log rank test). There was significant difference in survival in Stage I (5-year survival 82.16 vs. 57.49%) and Stage IIIA (26.98 vs. 6.18%) by the log rank test and Breslow test. There was no significant yet marginal difference in survival by log rank test (10-year survival 32.04 vs. 26.92%, P=0.0523) but significant difference in survival by Breslow test (5-year survival 50.42 vs. 34.05%, P=0.0284) in Stage II. Types of mediastinal lymph node dissection, pTNM stage, tumor size and number of lymph node metastasis were four factors that influenced long-term survival rate by multivariate analysis. CONCLUSIONS: As compared with MLS, lobectomy (pneumonectomy) combined with SND can improve survival in resectable NSCLC.

15
UI - 11891041
AU - Atagi S; Kawahara M; Hosoe S; Ogawara M; Kawaguchi T; Okishio K; Naka N;
TI - Sunami T; Mitsuoka S; Akira M A phase II study of continuous concurrent thoracic radiotherapy in combination with mitomycin, vindesine and cisplatin in unresectable stage III non-small cell lung cancer.
SO - Lung Cancer 2002 Apr;36(1):105-11
AD - Department of Internal Medicine, National Kinki Central Hospital for Chest Diseases, 1180 Nagasone, Sakai, Osaka 591-8555, Japan. s-atagi@kch.hosp.go.jp
The split-course concurrent thoracic radiation therapy (TRT) and full-dose chemotherapy for unresectable stage III non-small cell lung cancer (NSCLC) has produced promising results by comparison with the sequential approach. Instead of split-course radiation, we conducted a phase II study to investigate the feasibility of continuous concurrent TRT and chemotherapy. Twenty-two patients with unresectable NSCLC were enrolled onto a phase II study of continuous concurrent radiotherapy and chemotherapy. Treatment consisted of two courses of cisplatin (80 mg/m(2) on days 1 and 29), vindesine (3 mg/m(2) on days 1, 8, 29 and 36), and mitomycin (8 mg/m(2) on days 1 and 29). TRT began on day 2 at a dose of 60 Gy (2 Gy per fraction and 5 fractions per week for a total of 30 fractions). Of 22 patients assessable for response, none achieved a CR and 17 (77.3%) achieved a PR with an overall response rate of 77.3% (95% confidence interval, 54.6-92.2%). Grade 3 or 4 leukopenia was observed in 5/13 (81.8%) patients. Six patients (27.3%) experienced > or = grade 3 thrombocytopenia. Non-hematological toxicity was relatively mild. The overall median survival time was 19.0 months and the 1- and 2-year survival rates were 84.8 and 34.5%, respectively. It was possible to administer two courses of chemotherapy in 18 patients (81.8%) as planned. Nineteen (86.4%) of the 22 patients received the planned 60 Gy radiation. It seems to be difficult to administer the planned treatment without any interruption for the majority of patients. However, in the selected patients who completed the 60 Gy TRT, nearly half of the patients completed TRT without interruption. This combination regimen is considered to be feasible on condition that the stopping rule of the treatment is followed. We recommend administering radiotherapy continuously as far as possible.

16
UI - 11891032
AU - Padilla J; Calvo V; Penalver JC; Zarza AG; Pastor J; Blasco E; Paris F
TI - Survival and risk model for stage IB non-small cell lung cancer.
SO - Lung Cancer 2002 Apr;36(1):43-8
AD - Servicio de Cirugia Toracica, Hospital Universitario La Fe, Avda. de Campanar 21, 46009 Valencia, Spain. jpadilla@comv.es
BACKGROUND: The aim of this work is to estimate the prognostic value of a set of clinical-pathological factors in patients resected for non-small cell lung cancer (NSCLC) and classified as stage IB, in order to create a prognostic model for establishing risk groups, and to validate that model. METHODS: Among 637 patients resected and classified as stage IB, we analyzed sex, age, symptoms, location, type of resection, cell type, histology, and tumor size. The Kaplan-Meier method was used to estimate the survival. The results were compared using the log-rank test. All the significant variables from this univariable method were then included in a multivariable method of estimation of the proportional risk for survival data developed by Cox, using the variables selected, a regression model was developed for accurately predicting survival. To validate the predictive capability of the regression model, we randomly divided our patients into training and test subsets, containing 322 and 315 cases, respectively. RESULTS: The overall 5-year survival rate of the series was 60%. The cell type, the squamous or non-squamous and the tumor size showed a significant influence on survival in the univariable analysis, while, according to the Cox model, only the tumor size and the squamous or non-squamous type entered into regression. Hazard rates were calculated for each patient. The mean risk was 0.87 +/- 0.25 (range 30-1.94). The series was divided into three risk groups (low, intermediate, and high risk) according to the fitted hazard rates, using cut-off points (one standard deviation from the mean). The 5-year survival rates were 85, 59, and 44%, respectively. To validate the model, we repeated the analysis for training and test subsets. Only the tumor size had a significant influence on survival in the univariable analysis. Using the Cox model, also the tumor size entered into regression. The mean risk was 0.79 +/- 0.29 (range 0.09-2.12). Cut-off points were 0.50 and 1.08 for the low, intermediate, and high-risk groups. The 5-year survival rates were 83, 58, and 40%, respectively. We validated the regression model obtained in the training subset by demonstrating its capacity in identifying risk groups in the test subset. The 5-year survival rates were 83, 61, and 49.5% for the low, intermediate, and high-risk groups, respectively (P = 0.0104). CONCLUSIONS: Stage IB does not succeed in configuring a group of patients with a homogeneous prognosis, as there is a wide variability in a 5-year survival. The estimation of prognosis derived from a multivariable analysis can obviate the limitations of the actual staging system for NSCLC.

17
UI - 11891039
AU - Veronesi G; Solli PG; Leo F; D'Aiuto M; Pelosi G; Leon ME; De Braud F;
TI - Spaggiari L; Pastorino U Low morbidity of bronchoplastic procedures after chemotherapy for lung cancer.
SO - Lung Cancer 2002 Apr;36(1):91-7
AD - Division of Thoracic Surgery, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy. giulia.veronesi@ieo.it
OBJECTIVE: To evaluate if induction chemotherapy, with or without irradiation, represents an additional risk factor for early and late morbidity and perioperative mortality in bronchoplastic procedures for underwent a bronchial sleeve resection after induction treatment at the European Institute of Oncology in Milan. They represent 7% of lung cancer resections (387) and 27% of those performed after neoadjuvant treatment (100 cases). Histology was: 17 epidermoid carcinoma, 8 adenocarcinoma and 2 SCLC. Twenty-four patients (89%) received a preoperative cisplatin based polichemotherapy, and three cases (11%) a chemo-radiation therapy. A right sleeve lobectomy or bilobectomy was undertaken in 21 patients (78%) and a left lobectomy in 6 (22%). A resection of tracheal carina was associated in three cases and a vascular resection in 10 (five vena cava and five pulmonary artery). Twelve patients (44%) received adjuvant mediastinal irradiation. Perioperative morbidity of the study group (group 1) was compared with that of patients submitted to sleeve resection without neoadjuvant treatment (group 2), or standard pneumonectomy after induction treatment (group 3). RESULTS: There were no postoperative deaths. A major perioperative complication occurred in two patients (7%) of group 1, one patient of group 2 (3.5%), and four in group 3 (17%). Among patients of the study group, no anastomotic dehiscence or pleural empyema were observed. Only one late anastomotic stricture occurred after postoperative radiation treatment. No significant difference in early and late complication rate was found between the three groups of patients. High rate of complete resection was achieved (93%) in patients of the study group and extent of nodal dissection was similar between sleeve resections and pneumonectomy patients. CONCLUSIONS: Preoperative chemotherapy or combination of chemo-radio therapy is not associated with an additional risk of anastomotic complications in bronco and angioplastic procedures. Parenchyma sparing resection is a valid option for selected patients with locally advanced lung cancer after induction treatment. A longer follow up is necessary to evaluate efficacy of the procedure in term of survival and local control.

18
UI - 12171836
AU - Li WW; Lee TW; Lam SS; Ng CS; Sihoe AD; Wan IY; Yim AP
TI - Quality of life following lung cancer resection: video-assisted thoracic surgery vs thoracotomy.
SO - Chest 2002 Aug;122(2):584-9
AD - Division of Cardiothoracic Surgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China.
STUDY OBJECTIVES: Quality of life (QOL) following video-assisted thoracic surgery (VATS) major lung resection has not been systematically studied. This study was designed to evaluate the intermediate to long-term QOL in patients with lung cancer following resection, comparing VATS with thoracotomy. DESIGN: Cross-sectional study, telephone survey. METHODS: Of 136 disease-free surviving patients with non-small cell lung cancer operated on between 1994 and 2000, 45 patients were excluded because of large tumors (> 5 cm) or locally advanced disease, and another 27 patients were excluded because of adjuvant therapy, coexisting cancer from another source, or psychiatric illness. At the time of the survey, 13 patients were found to be either unsuitable or unwilling to participate. This left a total of 51 patients, with 27 patients in the VATS group and 24 patients in the thoracotomy group (open group), for the final analysis. QOL was assessed using Chinese versions of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and the EORTC QLQ-LC13, supplemented with nine self-developed surgery-related questions. RESULTS: Mean follow-up time was 33.5 months in the VATS group (median, 20.8 months; range, 6.0 to 84.2 months) and 39.4 months in the open group (median, 37.7 months; range, 7.0 to 75.1 months). Both groups had good QOL and high levels of functioning despite a fairly high incidence of symptoms. There was a trend for VATS patients to score higher on the QOL and functioning scales and to report fewer symptoms. However, these differences did not lead to statistical significance. CONCLUSIONS: This study showed that lung cancer patients with resectable disease following surgical treatment without recurrence have good QOL and high levels of functioning on intermediate to long-term follow-up, with no significant differences between the VATS and open groups.

19
UI - 12029226
AU - Conti B; Brega Massone PP; Lequaglie C; Magnani B; Cataldo I
TI - Major surgery in lung cancer in elderly patients? Risk factors analysis and long-term results.
SO - Minerva Chir 2002 Jun;57(3):317-21
AD - Department of Thoracic Surgery, Istituto Nazionale Tumori, Milan, Italy.
BACKGROUND: In the Oncological Thoracic Surgery Department of the Istituto Nazionale Tumori of Milan a retrospective study was performed on lung cancer patients 70 years old or more with the aim of evaluate the role of surgical treatment and to analyse long-term results. cancer patients 70 years old or more underwent surgery for lung cancer. One hundred and twenty-six of them (83%) were males and 25 were females (17%), the average age was 73.09+/-2.91 years (median: 77; range: 70-82). All the subjects were completely staged preoperatively. In order to establish operability criteria, we considered some selection parameters. Patients general conditions were evaluated using Karnofsky score accepting only the ones with 70% or more for surgery, all the cases performed cardio-respiratory functional evaluation. Patients with: a) FEV1 <60% of predicted value or FEV1 <1 l; b) PaO2 <60 mmHg e PaCO2 >40 mmHg were excluded from surgery. RESULTS: The operations performed were: 23 pneumonectomies, 6 bilobectomies, 93 lobectomies, 13 segmentectomies and 16 wedge resections. Eight cases were submitted to thoracectomy in association to pulmonary resection. Peroperative mortality was 3% and morbidity was 10%. Histological examination showed 69 adenocarcinomas, 65 squamous carcinomas, 4 large cells carcinomas, 4 typical carcinoids, 5 small cells carcinomas, 2 mucoepidermal carcinomas and 2 adenosquamous carcinomas. Eighty-six patients were classified at stage I, 38 at stage II, 24 at stage III and 3 at stage IV (multifocal disease). The actuarial 4-years global survival predicted with Kaplan Meier method was 40%, in particular it was 75% for stage I patients. CONCLUSIONS: In case of resectable primary pulmonary neoplasm, surgery represents the first choice therapy; patient's age doesn't seem to be an absolute contraindication, but it has to be evaluated with biological and not with age criteria. Using adequate selection criteria, it's possible to obtain, in patients older than 70 years, long-term survivals that don't seem to differ from global survivals.

20
UI - 12202311
AU - Hansen HH
TI - Treatment of advanced non-small cell lung cancer.
SO - BMJ 2002 Aug 31;325(7362):452-3

22
UI - 9918960
AU - Little AG; DeHoyos A; Kirgan DM; Arcomano TR; Murray KD
TI - Intraoperative lymphatic mapping for non-small cell lung cancer: the sentinel node technique.
SO - J Thorac Cardiovasc Surg 1999 Feb;117(2):220-4
AD - University of Nevada School of Medicine, Department of Surgery, Las Vegas, Nev., USA.
BACKGROUND: The purpose of the study was to determine the accuracy and role of the sentinel node technique in patients with non-small cell lung cancer. METHODS: This study was carried out on 36 consecutive patients undergoing lung resection. Peritumoral tissue was infiltrated with isosulfan blue dye and the first lymph node to stain was identified as a sentinel node. Sensitivity and specificity of the sentinel node in predicting the status of other lymph node stations were determined. RESULTS: Seventeen patients had sentinel lymph nodes. In 9 of these 17 cases neither the sentinel node nor any other lymph node contained metastatic carcinoma. In 5 cases the sentinel node was in the mediastinum and documented unexpected N2 disease. In 19 patients no sentinel node was found. Final lymph node statuses were N0 in 13 patients, N1 in 5, and N2 in 1. CONCLUSIONS: The use of isosulfan blue for intraoperative lymphatic mapping is feasible. The specificity in our experience was good; 9 of 9 patients with negative sentinel nodes were found to be N0 on the final pathology report. Unexpected N2 disease was found in 5 patients. The accumulation of further experience will determine the role of the sentinel node technique in patients with non-small cell lung cancer.

23
UI - 11936523
AU - Egermann U; Jaeggi K; Habicht JM; Perruchoud AP; Dalquen P; Soler M
TI - Regular follow-up after curative resection of nonsmall cell lung cancer: a real benefit for patients?
SO - Eur Respir J 2002 Mar;19(3):464-8
AD - Dept of Internal Medicine, Institute of Pathology, University Hospital, Basel, Switzerland.
Even though complete resection is regarded as the only curative treatment for nonsmall cell lung cancer (NSCLC), >50% of resected patients die from a recurrence or a second primary tumour of the lung within 5 yrs. It remains unclear, whether follow-up in these patients is cost-effective and whether it can improve the outcome due to early detection of recurrent tumour. The benefit of regular follow-up in a consecutive series of 563 patients, who had undergone potentially curative resection for NSCLC at the University Hospital, was analysed. The follow-up consisted of clinical visits and chest radiography according to a standard protocol for up to 10 yrs. Survival rates were estimated using the Kaplan-Meier analysis method and the cost-effectiveness of the follow-up programme was assessed. A total of 23 patients (6.4% of the group with lobectomy) underwent further operation with curative intent for a second pulmonary malignancy. The regular follow-up over a 10-yr period provided the chance for a second curative treatment to 3.8% of all patients. The calculated costs per life-yr gained were 90,000 Swiss Francs. The cost-effectiveness of the follow-up protocol was far above those of comparable large-scale surveillance programmes. Based on these data, the intensity and duration of the follow-up was reduced.

24
UI - 12098006
AU - Spasova I; Petera J; Hytych V
TI - The role of neoadjuvant chemotherapy in marginally resectable or unresectable stage III non-small cell lung cancer.
SO - Neoplasma 2002;49(3):189-96
AD - Department of Pulmonary Medicine; University Hospital in Hradec Kralove, Hradec Kralove, 500 05 Czech Republic. spasova@fnhk.cz
The study was undertaken to test whether marginally resectable or unresectable stage IIIa-IIIb non-small cell lung cancer (NSCLC) patients could reach complete resectability after induction chemotherapy. Fifty six patients were included into the study and treated either by vinorelbine 35 mg/m2 day 1 and cisplatin 75 mg/m2 day 1 (n=28) or by vinorelbine 30 mg/m2 day 1 and 8 and cisplatin 80 mg/m2 day 1 (n=28). Cycles were repeated every 21 days. At the completion of induction therapy patients assessed to be resectable underwent thoracotomy. Radiation therapy was applicated in nonresected cases. The minimal follow up was 24 months. 32% of patients with marginally resectable or unresectable stage IIIa-IIIb NSCLC could reach a complete resectability after induction chemotherapy. Survival of patients stage IIIa was comparable to stage IIIb. Responders and resected patients survived significantly longer comparing to the patients with stable disease and progression, respectively to the incompletely resected plus nonresected patients. Perioperative complications were rare and there were no treatment-related deaths in our study. The main surgery-related complication was late bronchopleural fistula.

25
UI - 12103369
AU - Terzi A; Lonardoni A; Falezza G; Scanagatta P; Santo A; Furlan G;
TI - Calabro F Completion pneumonectomy for non-small cell lung cancer: experience with 59 cases.
SO - Eur J Cardiothorac Surg 2002 Jul;22(1):30-4
AD - Division of Thoracic Surgery, Ospedale Maggiore, Azienda Ospedaliera, Verona, Italy. aterzi@tiscalinet.it
OBJECTIVE: The objective of this study was to assess the results of completion pneumonectomy performed for non-small cell lung cancer, classified as second primary or recurrence/metastasis. METHODS: From 1982 to 2000, 59 patients underwent completion pneumonectomy for lung cancer, classified second primary or recurrence/metast

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