Journal of Thoracic Oncology:
The IASLC Lung Cancer Staging Project: Proposals Regarding the Relevance of TNM in the Pathologic Staging of Small Cell Lung Cancer in the Forthcoming (Seventh) Edition of the TNM Classification for Lung Cancer
Vallières, Eric MD, FRCSC*; Shepherd, Frances A. MD, FRCPC†; Crowley, John PhD‡; Van Houtte, Paul MD§; Postmus, Pieter E. MD, PhD∥; Carney, Desmond MD, PhD¶; Chansky, Kari MS‡; Shaikh, Zeba BSc#; Goldstraw, Peter FRCS#; on Behalf of the International Association for the Study of Lung Cancer International Staging Committee and Participating Institutions
*Section of Thoracic and Foregut Surgery of the Swedish Cancer Institute, Seattle, Washington; †Department of Medicine, Division of Medical Oncology and Hematology of the University Health Network, Princess Margaret Hospital and the University of Toronto, Toronto, Canada; ‡Cancer Research And Biostatistics, Seattle, Washington; §Department of Radiation Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Belgium; ∥Department of Pulmonary Diseases, Vrije Universiteit University Medical Center, Amsterdam, the Netherlands; ¶Department of Medical Oncology, Mater University Hospital, Dublin, Ireland; and #Royal Brompton Hospital, Imperial College, London, United Kingdom.
Disclosure: The authors declare no conflicts of interest.
Address for correspondence: Eric Vallières, MD, FRCS(C), Swedish Cancer Institute, 1101 Madison, Suite 850, Seattle, WA 98104. E-mail: firstname.lastname@example.org
The project was supported by the AJCC grant “Improving AJCC/UICC TNM Cancer Staging.” Eli Lilly and Company provided funding to support the International Association for the Study of Lung Cancer (IASLC) Staging Committee’s work to establish a database and to suggest revisions to the 6th edition of the TNM classification for Lung Cancer (staging) through a restricted grant.
Eli Lilly and Company had no input into the committee’s analysis of the data or in their suggestions for revisions to the staging system.
Introduction: For more than 50 years, small cell lung cancer (SCLC) has been staged mainly as either limited or extensive stage disease. Small published series of resected SCLC have suggested that the tumor, node, metastases (TNM) pathologic staging correlates with the survival of resected patients. Recent analysis of the 8088 cases of SCLC in the International Association for the Study of Lung Cancer (IASLC) database demonstrated the usefulness of clinical TNM staging in this malignancy. The IASLC data bank contains an unprecedented number of resected SCLC cases with pathologic staging information. This analysis was undertaken to examine the impact of the TNM system on the pathologic staging of SCLC and to assess the new IASLC proposals in this subtype of lung cancer.
Methods: Using the IASLC database, survival analyses were performed for resected patients with SCLC. Prognostic groups were compared, and the new IASLC TNM proposals were applied to this population and to the Surveillance, Epidemiology, and End Results (SEER) database.
Results: The IASLC database contained 349 cases of resected SCLC where pathologic TNM staging was available. Survival after resection correlated with both T and N category with nodal status having a stronger influence on survival. Stage groupings using the 6th edition of TNM clearly identify patient subgroups with different prognoses. The IASLC proposals for the 7th edition of TNM classification also apply to this population and to the SEER database.
Conclusion: This analysis further strengthens our previous recommendation to use TNM staging for all SCLC cases.
Lung cancer is the leading cause of cancer-related mortality in the Western World with recent statistics showing that globally, it accounts for more than 1,000,000 deaths each year.1 Small cell lung cancer (SCLC) represents approximately 15% of lung cancers overall, with incidence rates declining in men, but continuing to rise in women in most countries.2 Nevertheless, by itself, SCLC is the fifth leading cause of cancer mortality in the United States when it is considered independently from non-SCLC (NSCLC).3 SCLC is distinguished by its rapid growth rate, early dissemination to regional lymph nodes and distant sites, and its sensitivity to chemotherapy and radiotherapy.4 The introduction of chemotherapy to the treatment of SCLC led to significant improvements in median and 5-year survival rates between the 1970s and the 1990s,5 but recently, survival seems to have reached a plateau for both localized and advanced SCLC.
In lung cancer, the anatomic extent of disease or stage is second in importance only to the pathologic determination of cell type. Accurate staging provides prognostic information and stage aids in the planning of treatment strategies for all types of lung cancer. The first staging system for SCLC was introduced in the 1950s by the Veterans’ Administration Lung Study Group for use in their randomized clinical trials.6 This simple system divided SCLC into two disease subgroups termed “Limited” and “Extensive” Disease. Limited Disease (LD) was characterized by tumors confined to one hemithorax, although local extension and ipsilateral, supraclavicular nodes could also be present if they could be encompassed in the same radiation portal as the primary tumor. No extrathoracic metastases were allowed in the LD category. All other patients were classified as extensive disease (ED).
In 1989, the International Association for the Study of Lung Cancer (IASLC) issued a consensus report7 that, for the first time in 30 years, introduced changes to the Veterans’ Administration Lung Study Group staging system but maintained the limited and ED classification.
The tumor, node, metastasis (TNM) staging systems of the American Joint Committee on Cancer Staging (AJCC)8 and the Union Internationale Contre le Cancer (UICC)9 are also applicable to SCLC, but they are used less frequently in clinical practice because these two staging systems have relied historically on surgical confirmation for their accuracy, and patients with SCLC seldom present at a stage for which surgery is appropriate. Nevertheless, in small surgical series of patients with SCLC, the TNM staging system has been shown to be prognostic of outcome.10–33
The IASLC has established a database containing staging, treatment, and follow-up data for more than 100,000 patients with lung cancer from around the world, presenting between 1990 and the end of 2000. Among these are more than 12,000 cases of SCLC, including 349 cases treated by surgery. This represents the largest series of surgically resected SCLC cases to be analyzed in the modern era of staging using computed tomographic and magnetic resonance scanning and treatment with cisplatin-based chemotherapy regimens. The IASLC database was established to assess the current stage categories as defined by the AJCC8 and the UICC, 6th edition,9 with the goal of redefining and regrouping the T, N, and M descriptors and to make recommendations for change if and where appropriate. These analyses were performed initially on the large 67,725 case NSCLC database34–37 and then applied to the smaller SCLC cohort. Proposed changes for the UICC, 7th edition, for NSCLC that are relevant for SCLC are mainly those that result in changes to T categories. It has been recommended to subclassify T1 as T1a (≤2cm) and T1b (>2cm but ≤3 cm), to subclassify T2 as T2a (>3 cm to ≤5 cm or T2 by other factor and ≤5 cm) or T2b (>5 cm to ≤7 cm) and that large sized tumors >7 cm become T3; additional nodules within the same lobe as the primary tumor also become T3; ipsilateral intrapulmonary nodules in other lobes become T4 and malignant pleural and pericardial effusions become M1.34,36
Clinically staged SCLC cases were analyzed first,38 as these represent the majority of SCLC cases. We now report our analysis of pathologic TNM staging for SCLC using the current 6th edition TNM staging system for lung cancer and compare this to the IASLC proposals for the forthcoming 7th edition, which were based on analyses in NSCLC.
The database on which these analyses are based was created by the IASLC to inform revisions for the 7th edition of the UICC TNM classification of malignant tumors staging manual in lung cancer due to be published early in May 2009. To be eligible for inclusion in the IASLC database, cases were required to have a new diagnosis of either SCLC or NSCLC, an initial presentation during the time frame of 1990 to the end of 2000, adequate staging information at baseline, details of treatment(s) and proper follow-up for survival. There were no minimum requirements for staging procedures for inclusion in the database, and details of staging procedures were not generally analyzed. For surgical cases, reporting on the use of adjuvant treatment(s) was encouraged but not mandated.
TNM stage groupings for NSCLC were developed based on recommendations made by the individual T, N, and M subcommittees for changes to their respective components. Using these modified categories, a small number of candidate stage grouping schemes were developed initially using a recursive partitioning and amalgamation algorithm.39 This analysis grouped cases based on best stage (pathologic if available, otherwise clinical) after determination of best-split points based on overall survival on indicator variables for the newly proposed T/M categories and an ordered variable for N category. The analysis was performed on a randomly selected training set comprising two thirds of the available data that met the requirements for conversion to the newly proposed TNM categories (N = 17,726), reserving 9133 cases for later validation. The random selection process was stratified by type of database submission and time period of case entry (1990–1995 versus 1995–2000). Selection of a final stage grouping proposal from among the candidate schemes was based on its statistical properties in the training set and its relevance to clinical practice and was arrived at by consensus.
Analyses focusing on 6th edition TNM were applied to the whole subset of resected SCLC cases for which complete pathologic TNM stage was provided. The newly proposed TNM stage groupings were applied to the smaller set of SCLC cases that had sufficient descriptors to reclassify according to the IASLC proposals for the 7th edition of TNM.
Survival was measured from the date of entry (date of diagnosis for registries and the date of registration for protocols) and was estimated by the Kaplan-Meier method. Prognostic groups were compared formally by Cox proportional hazards regression analysis, using the SAS System for Windows Version 9.0 PHREG procedure. In regression analyses, stage categories were modeled categorically using indicator variables.
Of the 100,869 cases submitted to the IASLC database, 13,290 cases of SCLC met the initial screening requirements of having a new diagnosis rather than recurrent diagnosis, presentation between 1990 and 2000, adequate follow-up for survival, and adequate baseline staging information. From the 13,290 SCLC cases meeting the initial screen criteria, 670 with mixed histology or with conflicts between TNM and extent of disease were excluded, to yield 12,620 eligible cases of small cell histology. Of the 12,620 eligible SCLC cases, 349 had undergone complete R0 surgical resection and thus had pathologic TNM staging information, including 10 patients with M1 disease. These 349 cases originated from three global regions: Asia and Australia (57%), Europe (36%), and North America (7%). Median age of the patients was 66 years, ranging from 26 to 88 years. Adequate details of TNM stage allowing application of the IASLC proposals for the forthcoming (7th) edition of the TNM classification for lung cancer were available for 262 patients (Table 1). A complete listing of data contributors is given in Appendix.
Comparing Clinical with Pathologic Staging
Clinical TNM staging was available in 218 of the 349 pathologically staged cases of SCLC (Table 2). Clinical T category had a reasonable concordance with pathologic T category, the exception being cT3, which only predicted pT3 in 44% of cT3 cases. As expected, clinical nodal category was not as accurate. Of the 144 cN0 cases analyzed, 14% (20/144) were upstaged to pN2 or above after resection. Conversely, clinical N2 (n = 47) was downstaged to pN1 or less in 32% of cN2 cases resected. The overall concordance between clinical and pathologic TNM staging was 58% When grouping clinical stages I and II together, 19.7% of the 157 cases were upstaged to stage pIIIA or above after resection. An even larger proportion (30%) of clinical stages III (A and B) were downstaged to pathologic stage II or less after resection.
Survival by Pathologic T, N, and M Categories According to 6th Edition of the TNM Classification for Lung Cancer, Derived from the IASLC Database
As shown in Figure 1A, for the 339 patients without evidence of systemic involvement (M0), increasing pathologic T category, using the 6th edition TNM staging system trended with progressively lower survival. A statistically significant difference in 5-year survival rates was observed favoring T1 lesions over T2 (hazard ratio [HR] 1.46, p = 0.01). As would be expected from a surgical SCLC series, most patients had pT1 and pT2 tumors (285/339, 84%) with only 23 and 31 patients having pT3 and pT4 lesions, respectively. The better survival seen with T4 tumors over that of T3 (HR 0.9, p = 0.73) is not significant and furthermore may be a reflection of these small numbers and the highly selective nature of such cases undergoing surgical treatment. Both T3 and T4 groups had similar proportions of patients with nodal involvement (61% and 65%, respectively). Tumors were defined as T4 for the following reasons: involvement of “T4” structures (52%), separate nodules in the same lobe (29%), and malignant pleural effusion (3%). The details for T4 status were not provided in 16% of cases. When correcting with the proposed revisions of the T3 and 4 descriptors for the 7th edition of TNM,34 the survival of the T3 group, however, was better than that of the T4 group (18-month median survival versus 9-month median survival for cases that could be staged according to proposed version 7). Comparisons between T categories and 1 and 5-year survival rates are shown in Table 3.
Half of the patients in this surgical series had pN0 disease (179/339, 51%). As shown in Figure 1B and Table 4, increasing pathologic N category was associated with progressively lower survival with significant differences for each progressive N category from N0 to N3.
Survival for each pathologic N category within pathologic T categories T1–4 is shown in Figure 2 and shows the strong influence of nodal involvement in every T category.
Ten patients with M1 involvement underwent resection: one had tumor in another ipsilateral lobe, one in the contralateral lung, four were described as distant “not otherwise specified,” and four were listed without description. Half of this highly selected small cohort was alive at 1 year, 30% at 5 years (Table 5). These numbers are obviously too small from which to derive any meaningful conclusion.
Survival by Pathologic Stage Grouping According to 6th Edition of the TNM Stage Classification for Lung Cancer Derived from the IASLC Database (n = 349)
Survival by pathologic TNM stage based on the 6th edition for the 349 patients is shown in Figure 1C and Table 5. The similarity of survival for patients with IIB disease compared with those with IIA may be a reflection of the fact that all of the IIA cases had N1 disease whereas only 25/34 (74%) of the IIB cases were N1, the rest being T3 N0 cases. Median survivals for patients with IIIA and IIIB tumors were 14 and 17 months, respectively (HR 0.68, p = 0.089). This may be explained by the fact that 93% (71/76) of patients with IIIA cancers had N2 disease combined with the observation that 33% (11/33) of patients with IIIB disease were T4N0. Pairwise comparisons among adjacent stage groupings are shown in Table 5. There were no significant differences with the exception of the difference between IIIA and IIB (HR 2.03, p = 0.002).
Comparing Survival by Pathologic Stage Grouping Between the 6th Edition of the TNM Classification and that Proposed for the 7th Edition
Comparisons Using the IASLC Database (n = 262)
It was not possible to classify all 339 surgical M0 SCLC cases according to the proposed IASLC stage groupings: 26 T1 tumors has incomplete size data to reclassify as T1a or T1b, 46 T2 tumors were without size data and 5 T4 lesions had inadequate T4 descriptor information. Figure 3A and Table 6 show the survival according to the TNM stage 6th edition for the smaller cohort of patients with full T descriptor data (n = 262). The difference in 5-year survival rates noted between IIIA and IIB remains significant (HR 2.49, p = 0.0006). The apparent superior survival of IIIB disease compared with IIIB disease (HR 0.58, p = 0.03) must be interpreted with caution in view of the small numbers in each group. Figure 3B and Table 6 show survival of these same 262 resected patients with SCLC using the IASLC stage groupings proposed for the UICC, 7th edition. The application of the proposed TNM classification for the 7th edition seems to predict survival more accurately than the 6th edition with progressively lower survival seen with increasing stage. The apparent superiority of the proposed changes is most evident when looking at survivals of stages IIIA and IIIB. (HR 1.96, p = 0.035).
Comparisons Using the Surveillance, Epidemiology and End Results Database (n = 232)
The same comparison using the Surveillance, Epidemiology and End Results (SEER) database of the National Cancer Institute for cases registered with an initial diagnosis of SCLC during the years 1998–2002 are shown in Figures 4A, (Supplemental Digital Content 1, http://links.lww.com/JTO/A3) and 4B (Supplemental Digital Content 2, http://links.lww.com/JTO/A4) and Table 7 (Supplemental Digital Content 3, http://links.lww.com/JTO/A5).
In both our data set and the SEER database, the proposed IASLC system works well with increasing stage being associated with decreasing survival.
Approximately 15% of all primary lung cancers are small cell carcinomas.40 As most of patients with SCLC have evidence of advanced disease at presentation, SCLC represents less than 5% of cases in reported large surgical series. In our IASLC database, surgically treated SCLC cases represented only 1.3% (349/26, 526) of all resected cases where sufficient pT and pN descriptors were available. These 349 cases represented only 2.8% of all SCLC cases in the database.
Accurate staging provides prognostic information and stage aids in the planning of treatment strategies for all types of lung cancer, NSCLC and SCLC. The use of TNM descriptors has been the basis of the NSCLC staging system since 1973,41 but these descriptors are seldom used in the staging of SCLC. Instead, most clinicians have used a two-group staging system for SCLC describing the extent of disease as being either limited or extensive.6,7The TNM staging systems of the AJCC8 and the UICC9 also are applicable to SCLC, but they are seldom used in clinical practice because these systems have relied historically on surgical confirmation for their accuracy, and, as stated earlier, patients with SCLC seldom present at a stage for which surgery is appropriate. Nevertheless, in small surgical series of patients with SCLC, the TNM staging system has been shown to be prognostic of outcome, particularly in the era of adjuvant systemic chemotherapy.10–33 Of historical interest, in 1978, Mountain published a series of 368 resected cases of SCLC. Without adjuvant chemotherapy, only one patient survived longer than 1 year and more importantly, neither the size of the primary cancer nor its nodal status had any influence on survival.42
In 1982, Shields et al.10 were the first to suggest the importance of TNM staging in SCLC, an observation made in a subset analysis of 148 patients with SCLC of 3133 men (4.7%) who had participated in adjuvant chemotherapy trials completed by the Veterans Administration Surgical Oncology Group over 25 years. Applying the pathologic TNM classification and criteria of the 1979 version of the AJCC, they reported the following 5-year survivals: T1N0M0 59.5%, T1N1M0 31.3%, T2N0M0 27.9%, T2N1M0 9.0%, and any T3 or N2 3.6%. In an analysis of histologically verified TNM stage in treated SCLC published in 1985, Meyer et al.43 stated that: “Contrary to general usage, TNM staging of patients with SCLC promises to correlate closely with the probability of long disease-free survival.” The University of Toronto Lung Oncology Group, in reviewing their experience with surgery and adjuvant chemotherapy in SCLC, also suggested that the simplified staging of limited or ED in SCLC was inadequate to identify patients with “very limited” disease who might benefit from surgery.13,44 Others have since reported on the usefulness of the TNM classification in series that included patients with SCLC who had received preoperative or adjuvant chemotherapy.11–33 Table 8 (Supplemental Digital Content 4, http://links.lww.com/JTO/A6) lists modern day series of at least 50 patients treated by surgery and chemotherapy and published over the last 10 years.23–27,29,30,32
Since the introduction of chemotherapy to the treatment of SCLC, the present IASLC series is by far the largest cohort of pathologically staged SCLC reported to date. Nevertheless, the surgical population we studied was likely highly selected. The majority of patients had T1 and T2 tumors (84%) with less than 55 patients having T3 or T4 tumors. Similarly, 51% of the entire population was found to have N0 disease after resection. In this population of patients without apparent systemic disease, the survival of patients varied inversely with the pT and also the pN categories. For each T category, nodal status had the strongest influence on survival. Akin to what we have demonstrated with clinical TNM staging in our larger data set of predominantly nonsurgical SCLC cases,38 pTNM staging is applicable to the staging of resected SCLC. Furthermore, the proposed modifications for the UICC TNM, 7th edition, seem to correlate even more closely with the survival of SCLC by stage, particularly in stage III. The results of this analysis confirm that TNM staging clearly identifies patients with different prognoses and is applicable to the staging of resected SCLC.
In this large data set, we observed 5-year survival rates of 35 to 53% for patients with stage IIB disease or less initially treated by surgical resection (Table 5). Unfortunately, our database does not include reliable data on postoperative or adjuvant therapy for most patients in the cohort analyzed. Nevertheless, we believe that it is likely that most of these patients did receive postoperative chemotherapy as all cases in this series were diagnosed and treated between 1990 and 2000, long after multiagent platinum-based chemotherapy became the cornerstone of treatment of SCLC, and after several publications suggested a beneficial role for adjuvant chemotherapy.45 As well, the 35 to 43% 5-year survival rate we report for patients with stage II disease (9 T3N0 and 62 T1-2N1) in this series compares favorably to the survival noted by others who reported on the use of surgery followed by adjuvant chemotherapy in treating pathologic stage II SCLC.30,32 Similarly, the survival rates reported recently by Lewinski et al.46 and Eberhardt et al.47 who evaluated the role of induction chemotherapy alone or induction chemoradiation therapy in surgical SCLC parallel those in this series, once again suggesting that systemic chemotherapy likely was administered to many of the patients in the IASLC cohort.
The population of patients we studied was highly selected, and the proportion of patients who may have been explored without resection during the same period of time is unknown. In offering possible resection to a patient with known SCLC, it is important to remember that clinical staging will often underestimate the extent of SCLC, as imaged by conventional radiology. The Toronto Group, in 1989, was the first to draw attention to the discrepancy between clinical and pathologic staging in SCLC.15 Others have since made similar observations.20,31,48 This poor concordance of clinical and pathologic TNM staging was once again demonstrated in our analysis of the 216 patients where both clinical and pathologic TNM stages were available. Between clinical stages I and II, 20% of our patients were upstaged to pIII stage or higher at resection. Nevertheless, conversely nearly one third of the patients clinically staged as having cIIIA or higher at presentation were downstaged to pII disease or less at resection. This degree of pathologic down-staging has not been reported previously in patients with SCLC who underwent surgical resection in the absence of induction therapy. Such data, once again, stress the importance of aggressively staging the mediastinum in patients with SCLC preoperatively and not relying solely on imaging to render therapeutic decisions. Nevertheless, it is possible that the more general use of FDG PET imaging in the evaluation of patients with SCLC will improve on clinical staging as reports of small published series have suggested.49–50
In summary, this analysis and the previously reported clinical analysis of the SCLC staging subcommittee of the IASLC Lung Cancer Staging Project38 together confirm that both clinical and pathologic TNM staging are important in the evaluation and reporting of SCLC. The proposals made by the IASLC for the forthcoming (7th) edition of the TNM system seem to be of relevance for SCLC. Stratification by stages I–III should be incorporated into all clinical trials for early-stage SCLC whether treatment is surgical or not and full details of TNM staging should be reported to evaluate and compare the results of various treatment modalities in future trials. We propose that TNM staging become the standard for all cases of SCLC and that the use of LD and ED staging be discouraged in the future. For tumor registries, the TNM designations should be recorded.
IASLC International Staging Committee
P. Goldstraw (Chairperson), Royal Brompton Hospital, Imperial College, London, UK; H. Asamura, National Cancer Centre Hospital, Tokyo, Japan; D. Ball, Peter MacCallum Cancer Centre, East Melbourne, Australia; V. Bolejack, Cancer Research And Biostatistics, Seattle, Washington; E. Brambilla, Laboratoire de Pathologie Cellulaire, Grenoble Cedex, France; P. A. Bunn, University of Colorado Health Sciences, Denver, Colorado; D. Carney, Mater Misericordiae Hospital, Dublin, Ireland; K. Chansky, Cancer Research And Biostatistics, Seattle, Washington; T. Le Chevalier (resigned), Institute Gustave Roussy, Villejuif, France; J. Crowley, Cancer Research And Biostatistics, Seattle, Washington; R. Ginsberg (deceased), Memorial Sloan-Kettering Cancer Center, New York; D. Giroux, Cancer Research and Biostatistics, Seattle, Washington; P. Groome, Queen’s Cancer Research Institute, Kingston, Ontario, Canada; H. H. Hansen (retired), National University Hospital, Copenhagen, Denmark; P. Van Houtte, Institute Jules Bordet, Bruxelles, Belgium; J. -G. Im, Seoul National University Hospital, Seoul, South Korea; J. R. Jett, Mayo Clinic, Rochester, Minnesota; H. Kato (retired), Tokyo Medical University, Tokyo Japan; C. Kennedy, University of Sydney, Sydney, Australia; H. Kondo, Shizuoka Cancer Centre, Sunto-gun, Japan; M. Krasnik, Gentofte Hospital, Copenhagen, Denmark; J. van Meerbeeck, University Hospital, Ghent, Belgium: T. Naruke, (deceased), Saiseikai Central Hospital, Tokyo, Japan; E. F. Patz, Duke University Medical Center, Durham, North Carolina; P. E Postmus, Vrije Universiteit Medical Center, Amsterdam, the Netherlands; R. Rami-Porta, Hospital Mutua de Terrassa, Terrassa, Spain; V. Rusch, Memorial Sloan-Kettering Cancer Center, New York; N. Saijo, National Cancer Centre East, Kashiwashi, Japan; J. P. Sculier, Institute Jules Bordet, Bruxelles, Belgium; F. A. Shepherd, University of Toronto, Toronto, Ontario, Canada; Y. Shimosato (retired), National Cancer Centre, Tokyo, Japan; L. Sobin, Armed Forces Institute of Pathology, Washington, DC; W. Travis, Memorial Sloan-Kettering Cancer Center, New York; M. Tsuboi, Tokyo Medical University, Tokyo, Japan; R. Tsuchiya (retired), National Cancer Centre, Tokyo, Japan; E. Vallieres, Swedish Cancer Institute, Seattle, Washington; J. Vansteenkiste, Leuven Lung Cancer Group, Belgium; Yoh Watanabe (deceased), Kanazawa Medical University, Uchinada, Japan and H. Yokomise (retired), Kagawa University, Kagawa, Japan.
O. Visser, Amsterdam Cancer Registry, Amsterdam, the Netherlands; R. Tsuchiya and T. Naruke (deceased), Japanese Joint Committee of Lung Cancer Registry; J. P. Van Meerbeeck, Flemish Lung Cancer Registry-VRGT, Brussels, Belgium; H. Βülzebruck, Thorax-klinik am Universitatsklinikum, Heidelberg, Germany; R. Allison and L. Tripcony, Queensland Radium Institute, Herston, Australia; X. Wang, D. Watson and J. Herndon, Cancer and Leukemia Group B (CALGB), USA; R. J. Stevens, Medical Research Council Clinical Trials Unit, London, England; A. Depierre, E. Quoix and Q. Tran, Intergroupe Francophone de Cancerologie Thoracique (IFCT), France; J. R. Jett and S. Mandrekar, North Central Cancer Treatment Group (NCCTG), USA; J. H. Schiller and R. J. Gray, Eastern Cooperative Oncology Group (ECOG), USA; J. L. Duque-Medina and A. Lopez- Encuentra, Bronchogenic Carcinoma Co-operative Group of the Spanish Society of Pneumology and Thoracic Surgery (GCCB-S), Spain; J. J. Crowley, Southwest Oncology Group (SWOG); J. J. Crowley and K. M. W. Pisters, Bimodality Lung Oncology Team (BLOT), USA; T. E. Strand, Cancer Registry of Norway; S. Swann and H. Choy, Radiation Therapy Oncology Group (RTOG), USA; R. Damhuis, Rotterdam Cancer Registry, The Netherlands; R. Komaki and P. K. Allen, MD Anderson Cancer Center- Radiation Therapy (MDACC-RT), Houston, Texas; J. P. Sculier and M. Paesmans, European Lung Cancer Working Party (ELCWP); Y. L. Wu, Guangdong Provincial People’s Hospital, Peoples Republic of China; M. Pesek and H. Krosnarova, Faculty Hospital Plzen, Czech Republic; T. Le Chevalier and A. Dunant, International Adjuvant Lung Cancer Trial (IALT), France; B. McCaughan and C. Kennedy, University of Sydney, Sydney, Australia; F. Shepherd and M. Whitehead, National Cancer Institute of Canada (NCIC); J. Jassem and W. Ryzman, Medical University of Gdansk, Poland; G. V. Scagliotti and P. Borasio, Universita’ Degli Studi di Torino, S Luigi Hospital, Orbassano, Italy; K. M. Fong and L. Passmore, Prince Charles Hospital, Brisbane, Australia; V. W. Rusch and B. J. Park, Memorial Sloan-Kettering Cancer Center, New York; H. J. Baek, Korea Cancer Centre Hospital, Seoul, South Korea; R. P. Perng, Taiwan Lung Cancer Society, Taiwan; R. C. Yung, A. Gramatikova, John Hopkins University, USA; J. Vansteenkiste, Leuven Lung Cancer Group (LLCG), Belgium; C. Brambilla and M. Colonna, Grenoble University Hospital-Isere Cancer Registry, France; J. Hunt and A. Park, Western Hospital, Melbourne Australia; J. P. Sculier and T. Berghmans, Institute of Jules Bordet, Brussels, Belgium; A. K. Cangir, Ankara University School of Medicine, Ankara, Turkey; D. Subotic, Clinical Centre of Serbia, Belgrade, Serbia; R. Rosell and V. Aberola, Spanish Lung Cancer Group (SLCG), Spain; A. A. Vaporciyan and A. M. Correa, MD Anderson Cancer Center-Thoracic and Cardiovascular Surgery (MDACC-TCVS), Houston, Texas; J. P. Pignon, T. Le Chevalier and R. Komaki, Institut Gustave Roussy (IGR), Paris, France; T. Orlowski, Institute of Lung Diseases, Warsaw, Poland; D. Ball and J. Matthews, Peter MacCallum Cancer Institute, East Melbourne, Australia; M. Tsao, Princess Margaret Hospital, Toronto, Ontario, Canada; S. Darwish, Policlinic of Perugia, Italy; H. I. Pass and T. Stevens, Karmanos Cancer Institute, Wayne State University, USA; G. Wright, St Vincent’s Hospital, Victoria, Australia; C. Legrand and J. P. van Meerbeeck, European Organisation for Research and Treatment of Cancer (EORTC), Brussels, Belgium. Cited Here...
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