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Toubat O, Ding L, Ding K, Wightman SC, Atay SM, Harano T, Kim AW, David EA. Benefit of adjuvant chemotherapy for resected pathologic N1 non-small cell lung cancer is unrecognized: A subgroup analysis of the JBR10 trial. Semin Thorac Cardiovasc Surg 2022; 36:261-270. [PMID: 36272526 DOI: 10.1053/j.semtcvs.2022.10.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 10/13/2022] [Indexed: 11/09/2022]
Abstract
Adjuvant chemotherapy is underutilized in clinical practice, in part, because its anticipated survival benefit is limited. We evaluated the impact of AC on overall and recurrence-free survival among completely resected pN1 NSCLC patients enrolled in the North American Intergroup phase III (JBR10) trial. A post-hoc subgroup analysis of pN1 NSCLC patients was performed. Participants were randomized to cisplatin+vinorelbine (AC) (n = 118) or observation (n = 116) following complete resection. The primary endpoint was overall survival (OS). The secondary endpoint was recurrence free survival (RFS). Kaplan-Meier methods were used to compare OS and RFS between the two treatment groups. Cox regression was used to identify factors associated with OS and RFS endpoints. Both groups had similar baseline characteristics. AC patients had improved 5-year OS (AC 61.4% vs observation 41.0%, log-rank p = .008) and 5-year RFS (AC 56.2% vs observation 39.9%, log-rank p = .011) rates compared to observation. Cox regression analyses confirmed the OS (HR 0.583, 95% CI 0.402-0.846, p = .005) and RFS (HR 0.573, 95% CI 0.395-0.830, p = .003) benefit associated with AC. AC was associated with a lower risk (HR 0.648, 95% CI 0.435-0.965, p = .0326) and a lower cumulative incidence (Subdistribution Hazard Ratio [SHR], 0.67, 95% CI 0.449-0.999, p = .0498) of lung cancer deaths. In the JBR10 trial, treatment with AC conferred a significant OS and RFS advantage over observation for pN1 NSCLC patients. These data suggest that pN1 NSCLC patients may experience a disproportionately greater clinical benefit from AC than the 6% survival advantage estimated by the LACE meta-analysis.
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Affiliation(s)
- Omar Toubat
- Division of Thoracic Surgery, Department of Surgery, Keck School of Medicine of USC, Los Angeles, California
| | - Li Ding
- Department of Population and Public Health Sciences, Keck School of Medicine of USC, Los Angeles, California
| | - Keyue Ding
- Department of Public Health Sciences, Canadian Cancer Trials Group, Queen's University, Kingston, Ontario, Canada
| | - Sean C Wightman
- Division of Thoracic Surgery, Department of Surgery, Keck School of Medicine of USC, Los Angeles, California
| | - Scott M Atay
- Division of Thoracic Surgery, Department of Surgery, Keck School of Medicine of USC, Los Angeles, California
| | - Takashi Harano
- Division of Thoracic Surgery, Department of Surgery, Keck School of Medicine of USC, Los Angeles, California
| | - Anthony W Kim
- Division of Thoracic Surgery, Department of Surgery, Keck School of Medicine of USC, Los Angeles, California
| | - Elizabeth A David
- Division of Cardiothoracic Surgery, Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado.
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Wang Z, Yang H, Hao X, Zhou J, Chen N, Pu Q, Liu L. Prognostic significance of the N1 classification pattern: a meta-analysis of different subclassification methods. Eur J Cardiothorac Surg 2021; 59:545-553. [PMID: 33253363 DOI: 10.1093/ejcts/ezaa388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 08/28/2020] [Accepted: 08/29/2020] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVES The number of positive lymph node stations has been viewed as a subclassification in the N1 category in the new revision of tumour node metastasis (TNM) staging. However, the survival curve of these patients overlapped with that of some patients in the N2 categories. Our study focused on the prognostic significance of different subclassifications for N1 patients. METHODS We systematically searched PubMed, Ovid, Web of Science and the Cochrane Library on the topic of N1 lymph node dissection. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were used to assess the prognostic significance of N1 metastases. I2 statistics was used to evaluate heterogeneity among the studies: If significant heterogeneity existed (P ≤ 0.10; I2 >50%), a random effect model was adopted. RESULTS After a careful investigation, a total of 17 articles were included in the analysis. The results showed that patients with non-small-cell lung cancer with multistation N1 disease have worse survival compared with those with single-station N1 disease (HR 1.53, 95% CI 1.32-1.77; P < 0.001; I2 = 5.1%). No significant difference was observed between groups when we assessed the number of positive lymph nodes (single or multiple) (HR 1.25, 95% CI 0.96-1.64; P = 0.097; I2 = 72.5%). Patients with positive hilar zone lymph nodes had poorer survival than those limited to the intrapulmonary zone (HR 1.80, 95% CI 1.57-2.07; P < 0.001; I2 = 0%). A subgroup analysis conducted according to the different validated lymph node maps showed a stable result. CONCLUSIONS Our result confirmed the prognostic significance of the N1 subclassification based on station number. Meanwhile, location-based classifications, especially zone-based, were also identified as prognostically significant, which may need further confirmation and validation in the staged population.
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Affiliation(s)
- Zihuai Wang
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.,West China School of Medicine, Sichuan University, Chengdu, China
| | - Hanle Yang
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Xiaohu Hao
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.,West China School of Medicine, Sichuan University, Chengdu, China
| | - Jian Zhou
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.,West China School of Medicine, Sichuan University, Chengdu, China
| | - Nan Chen
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Qiang Pu
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Lunxu Liu
- West China School of Medicine, Sichuan University, Chengdu, China
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ÇEVİK ERGÖNÜL AG, FAZLIOĞLU M, KOCATÜRK C, TURNA A, BEDİRHAN MA. Rezeke edilen erken evre küçük hücreli dışı akciğer karsinomunda prognostik faktörler ve 10 yıllık sağ kalım. EGE TIP DERGISI 2020. [DOI: 10.19161/etd.756265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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Prognostic factor and treatment strategy for clinical N1 non-small cell lung cancer. Gen Thorac Cardiovasc Surg 2019; 68:261-265. [PMID: 31535276 DOI: 10.1007/s11748-019-01205-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2019] [Accepted: 09/05/2019] [Indexed: 10/26/2022]
Abstract
OBJECTIVES The aim of this study is to evaluate the surgical results of clinical N1 disease and to clarify the high-risk clinical N1 subgroup. METHODS Between 1990 and 2012, 137 patients who were clinically diagnosed as having N1 disease were enrolled. Their medical records were reviewed to assess clinical characteristics, radiologic findings, pathologic results, postoperative outcomes, recurrence patterns, and survival. Logistic regression analysis was used to identify independent predictive factors for pathologic N2 upstaging. To determine which factors were significantly associated with survival, a multivariate analysis using a Cox proportional hazards model was performed. RESULTS More cases were pathological N2 in adenocarcinoma than squamous cell carcinoma (p = 0.039). The overall survival rates at 5 years were 54.9%, 36.7% in group upper lobe, middle and lower lobe, respectively (p = 0.013). Logistic regression analyses revealed that #10 positive (p = 0.002, HR 4.625) and adenocarcinoma (p = 0.029, HR 1.544) were significant predictor of pathologic N2 disease. Multivariate analyses revealed that pathologic N2 (p = 0.007, HR 4.186), middle and lower lobe (p = 0.009, HR 2.045) and presence of #10 (p = 0.024, HR 1.871) were independent prognostic factors. Patients with upper lobe and absence of #10 showed a significantly higher 5-year survival rate than patients with middle and lower lobe and presence of #10 (62.1 vs 25.9%: p < 0.0001). CONCLUSIONS Among patients with cN1, pathological N2 disease, tumor in middle and lower lobe and clinical #10 lymph node positive were high-risk subgroup. Further analyses using larger numbers of patients with N1 disease from multiple centers are necessary.
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Lim CH, Hyun SH, Moon SH, Cho YS, Choi JY, Lee KH. Comparison of prognostic values of primary tumor and nodal 18F-fluorodeoxyglucose uptake in non-small cell lung cancer with N1 disease. Eur Radiol 2019; 29:5288-5297. [PMID: 30899978 DOI: 10.1007/s00330-019-06128-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Revised: 01/23/2019] [Accepted: 02/25/2019] [Indexed: 12/25/2022]
Abstract
INTRODUCTION We hypothesized that, in non-small cell lung cancer (NSCLC) with N1 metastasis, N1 nodal 18F-fluorodeoxyglucose (FDG) status offers independent and incremental prognostic value. METHODS We enrolled 106 NSCLC patients with pathology-confirmed N1 metastasis. N1 node FDG positivity, primary tumor maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured. Kaplan-Meier method and Cox regression analyses were performed for cancer-specific survival (CSS) and disease-free survival (DFS). RESULTS Subjects were 67 males and 39 females (61.9 ± 9.4 years). Eighty-one (76.4%) and 25 (23.6%) had pathologic stage IIB and IIIA NSCLC, respectively. All underwent complete tumor resection. FDG-positive N1 nodes were larger and had higher primary tumor SUVmax. During a follow-up of 42 months, there were 56 recurrences and 31 cancer deaths. Significant univariate predictors were stage, no adjuvant therapy, and FDG-positive nodes for DFS, and stage, no adjuvant therapy, node size, tumor MTV, TLG, and SUVmax, and FDG-positive nodes for CSS. Independent predictors on multivariate analyses were FDG-positive nodes (HR = 3.071, p = 0.003), greater tumor TLG (HR = 3.224, p = 0.002), and no adjuvant therapy (HR = 3.631, p < 0.001) for poor CSS, and FDG-positive nodes (HR = 1.771, p = 0.040) and no adjuvant therapy (HR = 2.666, p = 0.002) for poor DFS. Harrell's concordance and net reclassification improvement tests showed that CSS prediction was significantly improved by the addition of N1 FDG status to a model containing tumor TLG. CONCLUSION N1 node FDG status can be useful for predicting the outcome of NSCLC patients with N1 metastasis beyond that provided by other prognostic variables. KEY POINTS • In NSCLC with N1 disease, N1 node FDG status is useful as a prognostic predictor. • FDG-positive N1 nodes provide additional prognostic value beyond TLG of primary tumor. • Combining TLG of primary tumor and N1 node uptake can stratify the survival of patients.
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Affiliation(s)
- Chae Hong Lim
- Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Seung Hyup Hyun
- Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Seung Hwan Moon
- Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Young Seok Cho
- Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Joon Young Choi
- Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Kyung-Han Lee
- Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea.
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Ludovini V, Pistola L, Gregorc V, Floriani I, Rulli E, Di Carlo L, Semeraro A, Daddi G, Darwish S, Stocchi L, Tofanetti FR, Bellezza G, Sidoni A, Tognellini R, Crinò L, Tonato M. Biological Markers and DNA Flow Cytometric Analysis in Radically Resected Patients with Non-Small Cell Lung Cancer. A Study of the Perugia Multidisciplinary Team for Thoracic Tumors. TUMORI JOURNAL 2018; 94:398-405. [DOI: 10.1177/030089160809400317] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Aims and Background The aim of this study was to evaluate the relationship between a panel of biological markers (p53, Bcl-2, HER-2, Ki67, DNA ploidy and S-phase fraction) and clinical-pathological parameters and its impact on outcome in non-small cell lung cancer (NSCLC). Methods and Study Design Tumor tissue specimens obtained after surgical resection were collected from consecutive patients with NSCLC. We used an immunocytochemical technique for p53, Bcl-2, HER-2 and Ki67 analysis in fine-needle aspirates obtained from surgical samples that were also evaluated by flow cytometric DNA analysis using a FACScan flow cytometer. Results From April 2000 to December 2005, 136 patients with radically resected NSCLC were recruited. Median age was 66 years (range, 31–84 years), male/female ratio 117/19, ECOG performance status 0/1 127/4, stage I/II/III 76/25/35, squamous/adenocarcinoma/large-cell/mixed histology 62/49/17/8, smokers yes/no 121/11. Positivity of p53, Bcl-2, HER-2 and Ki67 was detected in 51.4%, 27.9%, 25.0% and 55.8% of the samples, respectively; 82.9% of the cases revealed aneuploid DNA histograms and 56.7% presented an S-phase fraction of more than 12%. Statistically significant associations between high Ki67 and poorly differentiated tumors (P = 0.016) and a smoking history (P = 0.053); p53 positivity and high Ki67 (P = 0.002); HER-2 positivity and adenocarcinoma subtype (P = 0.015) and presence of lymph node involvement (P = 0.006); and Bcl-2 positivity and squamous cell carcinoma subtype (P = 0.058) were observed. At univariate analysis, high Ki67 proved to be the only marker associated with disease-free survival (P = 0.047). After adjusting for stage, none of the examined immunocytochemical markers emerged as an independent factor for disease-free and overall survival; only pathological stage was identified as an independent prognostic factor for disease-free survival (P = 0.0001) and overall survival (P = 0.0001). In the group of 76 patients classified as TNM stage I, high Ki67 was the only marker associated with recurrence of disease (P = 0.05). Conclusions Our data do not support a relevant prognostic role of immunocytochemical markers in NSCLC, even if the Ki67 index might have particular relevance to identify patients with more aggressive tumors who are at high risk for disease relapse.
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Affiliation(s)
| | | | - Vanesa Gregorc
- Department of Oncology, San Raffaele Scientific Institute University Hospital, Milan
| | - Irene Floriani
- Oncology Department, Istituto di Ricerche Farmacologiche “Mario Negri”, Milan
| | - Eliana Rulli
- Oncology Department, Istituto di Ricerche Farmacologiche “Mario Negri”, Milan
| | | | | | - Giuliano Daddi
- Department of Thoracic Surgery, Azienda Ospedaliera, Perugia
| | | | | | | | - Guido Bellezza
- Institute of Pathological Anatomy and Histology Division of Cancer Research, University of Perugia, Perugia
| | - Angelo Sidoni
- Institute of Pathological Anatomy and Histology Division of Cancer Research, University of Perugia, Perugia
| | - Rita Tognellini
- Transplant Reference Center, Azienda Ospedaliera, Perugia, Italy
| | - Lucio Crinò
- Medical Oncology, Azienda Ospedaliera, Perugia
| | - Maurizio Tonato
- Regional Oncology Center, Azienda Ospedaliera, Perugia, Italy
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Li Q, Zhan P, Yuan D, Lv T, Krupnick AS, Passaro A, Brunelli A, Smeltzer MP, Osarogiagbon RU, Song Y. Prognostic value of lymph node ratio in patients with pathological N1 non-small cell lung cancer: a systematic review with meta-analysis. Transl Lung Cancer Res 2016; 5:258-64. [PMID: 27413707 DOI: 10.21037/tlcr.2016.06.13] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND Non-small cell lung cancer (NSCLC) patients with N1 disease have variable outcomes, and additional prognostic factors are needed. The number of positive lymph nodes (LNs) has been proposed as a prognostic indicator. However, the number of positive LNs depends on the number of LNs examined from the resection specimen. The lymph node ratio (LNR) can circumvent this limitation. The purpose of this study is to evaluate LNR as a predictor of survival and recurrence in patients with pathologic N1 NSCLC. METHODS We systematically reviewed studies published before March 17, 2016, on the prognostic value of LNR in patients with pathologic N1 NSCLC. The hazard ratios (HRs) and their 95% confidence intervals (CIs) were used to combine the data. We also evaluated heterogeneity and publication bias. RESULTS Five studies published between 2010 and 2014 were eligible for this systematic review with meta-analysis. The total number of patients included was 6,130 ranging from 75 to 4,004 patients per study. The combined HR for all eligible studies evaluating the overall survival (OS) and disease-free survival (DFS) of N1 LNR in patients with pathologic N1 NSCLC was 1.53 (95% CI: 1.22-1.85) and 1.64 (95% CI: 1.19-2.09), respectively. We found no heterogeneity and publication bias between the reports. CONCLUSIONS LNR is a worthy predictor of survival and cancer recurrence in patients with pathological N1 NSCLC.
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Affiliation(s)
- Qian Li
- 1 Department of Respiratory and Critical Care Medicine, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China ; 2 Division of Cardiothoracic Surgery, Washington University in St. Louis, St. Louis, USA ; 3 Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy ; 4 Department of Thoracic Surgery, St. James's University Hospital in Leeds, UK ; 5 School of Public Health, University of Memphis, Memphis, TN, USA ; 6 Thoracic Oncology Research Group, Baptist Cancer Center, Memphis, TN, USA
| | - Ping Zhan
- 1 Department of Respiratory and Critical Care Medicine, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China ; 2 Division of Cardiothoracic Surgery, Washington University in St. Louis, St. Louis, USA ; 3 Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy ; 4 Department of Thoracic Surgery, St. James's University Hospital in Leeds, UK ; 5 School of Public Health, University of Memphis, Memphis, TN, USA ; 6 Thoracic Oncology Research Group, Baptist Cancer Center, Memphis, TN, USA
| | - Dongmei Yuan
- 1 Department of Respiratory and Critical Care Medicine, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China ; 2 Division of Cardiothoracic Surgery, Washington University in St. Louis, St. Louis, USA ; 3 Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy ; 4 Department of Thoracic Surgery, St. James's University Hospital in Leeds, UK ; 5 School of Public Health, University of Memphis, Memphis, TN, USA ; 6 Thoracic Oncology Research Group, Baptist Cancer Center, Memphis, TN, USA
| | - Tangfeng Lv
- 1 Department of Respiratory and Critical Care Medicine, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China ; 2 Division of Cardiothoracic Surgery, Washington University in St. Louis, St. Louis, USA ; 3 Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy ; 4 Department of Thoracic Surgery, St. James's University Hospital in Leeds, UK ; 5 School of Public Health, University of Memphis, Memphis, TN, USA ; 6 Thoracic Oncology Research Group, Baptist Cancer Center, Memphis, TN, USA
| | - Alexander Sasha Krupnick
- 1 Department of Respiratory and Critical Care Medicine, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China ; 2 Division of Cardiothoracic Surgery, Washington University in St. Louis, St. Louis, USA ; 3 Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy ; 4 Department of Thoracic Surgery, St. James's University Hospital in Leeds, UK ; 5 School of Public Health, University of Memphis, Memphis, TN, USA ; 6 Thoracic Oncology Research Group, Baptist Cancer Center, Memphis, TN, USA
| | - Antonio Passaro
- 1 Department of Respiratory and Critical Care Medicine, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China ; 2 Division of Cardiothoracic Surgery, Washington University in St. Louis, St. Louis, USA ; 3 Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy ; 4 Department of Thoracic Surgery, St. James's University Hospital in Leeds, UK ; 5 School of Public Health, University of Memphis, Memphis, TN, USA ; 6 Thoracic Oncology Research Group, Baptist Cancer Center, Memphis, TN, USA
| | - Alessandro Brunelli
- 1 Department of Respiratory and Critical Care Medicine, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China ; 2 Division of Cardiothoracic Surgery, Washington University in St. Louis, St. Louis, USA ; 3 Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy ; 4 Department of Thoracic Surgery, St. James's University Hospital in Leeds, UK ; 5 School of Public Health, University of Memphis, Memphis, TN, USA ; 6 Thoracic Oncology Research Group, Baptist Cancer Center, Memphis, TN, USA
| | - Matthew P Smeltzer
- 1 Department of Respiratory and Critical Care Medicine, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China ; 2 Division of Cardiothoracic Surgery, Washington University in St. Louis, St. Louis, USA ; 3 Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy ; 4 Department of Thoracic Surgery, St. James's University Hospital in Leeds, UK ; 5 School of Public Health, University of Memphis, Memphis, TN, USA ; 6 Thoracic Oncology Research Group, Baptist Cancer Center, Memphis, TN, USA
| | - Raymond U Osarogiagbon
- 1 Department of Respiratory and Critical Care Medicine, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China ; 2 Division of Cardiothoracic Surgery, Washington University in St. Louis, St. Louis, USA ; 3 Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy ; 4 Department of Thoracic Surgery, St. James's University Hospital in Leeds, UK ; 5 School of Public Health, University of Memphis, Memphis, TN, USA ; 6 Thoracic Oncology Research Group, Baptist Cancer Center, Memphis, TN, USA
| | - Yong Song
- 1 Department of Respiratory and Critical Care Medicine, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China ; 2 Division of Cardiothoracic Surgery, Washington University in St. Louis, St. Louis, USA ; 3 Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy ; 4 Department of Thoracic Surgery, St. James's University Hospital in Leeds, UK ; 5 School of Public Health, University of Memphis, Memphis, TN, USA ; 6 Thoracic Oncology Research Group, Baptist Cancer Center, Memphis, TN, USA
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Rena O, Boldorini R, Papalia E, Turello D, Massera F, Davoli F, Roncon A, Baietto G, Casadio C. Metastasis to Subsegmental and Segmental Lymph Nodes in Patients Resected for Non-Small Cell Lung Cancer: Prognostic Impact. Ann Thorac Surg 2014; 97:987-92. [DOI: 10.1016/j.athoracsur.2013.11.051] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2013] [Revised: 11/12/2013] [Accepted: 11/19/2013] [Indexed: 11/27/2022]
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Li ZM, Ding ZP, Luo QQ, Wu CX, Liao ML, Zhen Y, Chen ZW, Lu S. Prognostic significance of the extent of lymph node involvement in stage II-N1 non-small cell lung cancer. Chest 2014; 144:1253-1260. [PMID: 23744276 DOI: 10.1378/chest.13-0073] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
BACKGROUND The non-small cell lung cancer (NSCLC) staging system (published in 2009 in the seventh edition of the cancer staging manuals of the Union for International Cancer Control and American Joint Commission on Cancer) did not include any changes to current N descriptors for NSCLC. However, the prognostic significance of the extent of lymph node (LN) involvement (including the LN zones involved [hilar/interlobar or peripheral], cancer-involved LN ratios [LNRs], and the number of involved LNs) remains unknown. The aim of this report is to evaluate the extent of LN involvement and other prognostic factors in predicting outcome after definitive surgery among Chinese patients with stage II-N1 NSCLC. METHODS We retrospectively reviewed the clinicopathologic characteristics of 206 patients with stage II (T1a-T2bN1M0) NSCLC who had undergone complete surgical resection at Shanghai Chest Hospital from June 1999 to June 2009. Overall survival (OS) and disease-free survival (DFS) were compared using Kaplan-Meier statistical analysis. Stratified and Cox regression analyses were used to evaluate the relationship between the LN involvement and survival. RESULTS Peripheral zone LN involvement, cancer-involved LNR, smaller tumor size, and squamous cell carcinoma were shown to be statistically significant indicators of higher OS and DFS by univariate analyses. Visceral pleural involvement was also shown to share a statistically significant relationship with DFS by univariate analyses. Multivariate analyses showed that tumor size and zone of LN involvement were significant predictors of OS. CONCLUSIONS Zone of N1 LN, LN ratios, and tumor size were found to provide independent prognostic information in patients with stage II NSCLC. This information may be used to stratify patients into groups by risk for recurrence.
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Affiliation(s)
- Zi-Ming Li
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Zheng-Ping Ding
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Qing-Quan Luo
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Chun-Xiao Wu
- Shanghai Municipal Center for Disease Control & Prevention, Shanghai, China
| | - Mei-Lin Liao
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Ying Zhen
- Shanghai Municipal Center for Disease Control & Prevention, Shanghai, China
| | - Zhi-Wei Chen
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Shun Lu
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
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Haney JC, Hanna JM, Berry MF, Harpole DH, D'Amico TA, Tong BC, Onaitis MW. Differential prognostic significance of extralobar and intralobar nodal metastases in patients with surgically resected stage II non-small cell lung cancer. J Thorac Cardiovasc Surg 2014; 147:1164-8. [PMID: 24507984 DOI: 10.1016/j.jtcvs.2013.12.015] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2013] [Revised: 10/11/2013] [Accepted: 12/09/2013] [Indexed: 11/19/2022]
Abstract
OBJECTIVES We sought to determine the prognostic significance of extralobar nodal metastases versus intralobar nodal metastases in patients with lung cancer and pathologic stage N1 disease. METHODS A retrospective review of a prospectively maintained lung resection database identified 230 patients with pathologic stage II, N1 non-small cell lung cancer from 1997 to 2011. The surgical pathology reports were reviewed to identify the involved N1 stations. The outcome variables included recurrence and death. Univariate and multivariate analyses were performed using the R statistical software package. RESULTS A total of 122 patients had extralobar nodal metastases (level 10 or 11); 108 patients were identified with intralobar nodal disease (levels 12-14). The median follow-up was 111 months. The baseline characteristics were similar in both groups. No significant differences were noted in the surgical approach, anatomic resections performed, or adjuvant therapy rates between the 2 groups. Overall, 80 patients developed recurrence during follow-up: 33 (30%) of 108 in the intralobar and 47 (38%) of 122 in the extralobar cohort. The median overall survival was 46.9 months for the intralobar cohort and 24.4 months for the extralobar cohort (P < .001). In a multivariate Cox proportional hazard model that included the presence of extralobar nodal disease, age, tumor size, tumor histologic type, and number of positive lymph nodes, extralobar nodal disease independently predicted both recurrence-free and overall survival (hazard ratio, 1.96; 95% confidence interval, 1.36-2.81; P = .001). CONCLUSIONS In patients who underwent surgical resection for stage II non-small cell lung cancer, the presence of extralobar nodal metastases at level 10 or 11 predicted significantly poorer outcomes than did nodal metastases at stations 12 to 14. This finding has prognostic importance and implications for adjuvant therapy and surveillance strategies for patients within the heterogeneous stage II (N1) category.
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Affiliation(s)
- John C Haney
- Division of Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC
| | - Jennifer M Hanna
- Division of Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC
| | - Mark F Berry
- Division of Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC
| | - David H Harpole
- Division of Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC
| | - Thomas A D'Amico
- Division of Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC
| | - Betty C Tong
- Division of Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC
| | - Mark W Onaitis
- Division of Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC.
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Rivera C, Falcoz PE, Rami-Porta R, Velly JF, Begueret H, Roques X, Dahan M, Jougon J. Mediastinal lymphadenectomy in elderly patients with non-small-cell lung cancer. Eur J Cardiothorac Surg 2012; 44:88-92. [PMID: 23171938 DOI: 10.1093/ejcts/ezs586] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVES The progressive ageing of the population is accompanied by an increasing incidence of cancer. Our objective was to compare mediastinal lymphadenectomy performed in the surgical treatment of non-small-cell lung cancer (NSCLC) patients between ≥ 70 and <70. METHODS We performed a retrospective single-centre case-control study, including 80 patients ≥ 70 years of age, surgically treated for NSCLC between January 2008 and December 2010, matched 1:1 to 80 younger controls on gender, American Society of Anesthesia score, performance status and histological subtype of the tumour. The number and type of dissected hilar/intrapulmonary and mediastinal lymph node stations as well as the number of resected lymph nodes were compared between the two age groups. RESULTS The type of pulmonary resection was significantly different between the two groups (P = 0.03): pneumonectomy 6% (n = 5) for patients ≥ 70 vs 12% (n = 10) for patients <70, lobectomy 85 (n = 68) vs 65% (n = 52), bilobectomy 1 (n = 1) vs 2% (n = 2) and sub-lobar resection 7 (n = 6) vs 20% (n = 16). There was no significant difference in type of mediastinal lymphadenectomy (radical vs sampling; P = 0.6). Elderly patients presented a more advanced N status of lymph node invasion than younger controls (P = 0.02). The number and type of dissected lymph node stations and the number of lymph nodes were not significantly different between the two age groups (P = 0.66 and 0.25, respectively). The mean number of metastatic lymph nodes was higher in patients ≥ 70 (2.3 vs 1.3 in patients <70; P = 0.002). Lymph node ratio between metastatic and resected lymph nodes was higher in elderly patients (0.11 vs 0.07 in younger controls; P = 0.009). CONCLUSIONS Lymph node involvement in surgically treated NSCLC was more significant in elderly patients ≥ 70 than in younger patients presenting comparable clinical and histopathological characteristics, and undergoing a similar lymphadenectomy.
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Affiliation(s)
- Caroline Rivera
- Department of Thoracic Surgery, Haut Lévêque Hospital, University of Bordeaux, Bordeaux, France.
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12
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Ciancio N, Galasso MG, Campisi R, Bivona L, Migliore M, Di Maria GU. Prognostic value of p53 and Ki67 expression in fiberoptic bronchial biopsies of patients with non small cell lung cancer. Multidiscip Respir Med 2012; 7:29. [PMID: 22978804 PMCID: PMC3537558 DOI: 10.1186/2049-6958-7-29] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2012] [Accepted: 08/27/2012] [Indexed: 01/15/2023] Open
Abstract
Background Overexpression of the tumor suppressor gene p53 and the marker for cellular proliferation Ki67 in open lung biopsies are indicated as predictor factors of survival of patients with lung cancer. However, the prognostic value of p53 and Ki67 in fiberoptic bronchial biopsies (FBB) has not been fully investigated. We evaluated p53 and Ki67 immunostaining in FBB from 19 with Non Small-Cell Lung Cancer (NSCLC: 12 adenocarcinomas, 5 squamous cell carcinomas and 2 NSCLC-NOS). Methods FBB specimens were fixed in formalin, embedded in paraffin, and immunostained using anti-p53 and anti-Ki67 antibodies. Slides were reviewed by two independent observers and classified as positive (+ve) when the number of cells with stained nuclei exceeded 15% for p53 or when >25% positive cells were observed throughout each section for Ki67. Results Positive (+ve) immunostaining was found in 9 patients for p53 (47.37%) and 8 patients for Ki67 (42.10%). We examined overall survival curves of the patients with Mantel's logrank test, both p53 -ve and Ki67 -ve patients had significantly higher survival rates than p53 + ve (p < 0.005) and Ki67 + ve (p < 0,0001), respectively. Conclusion This study suggests that negative immunostaining of fiberoptic bronchial biopsies for p53 and Ki67 could represent a better prognostic factor for patients with NSCLC.
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Affiliation(s)
- Nicola Ciancio
- Pneumology Unit, University of Catania, Vittorio Emanuele Hospital, Catania, Italy.
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Maeshima AM, Tsuta K, Asamura H, Tsuda H. Prognostic implication of metastasis limited to segmental (level 13) and/or subsegmental (level 14) lymph nodes in patients with surgically resected nonsmall cell lung carcinoma and pathologic N1 lymph node status. Cancer 2012; 118:4512-8. [DOI: 10.1002/cncr.27424] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2011] [Revised: 12/15/2011] [Accepted: 12/16/2011] [Indexed: 11/11/2022]
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Maeda R, Yoshida J, Ishii G, Hishida T, Nishimura M, Nagai K. Risk Factors for Tumor Recurrence in Patients With Early-Stage (Stage I and II) Non-small Cell Lung Cancer. Chest 2011; 140:1494-1502. [DOI: 10.1378/chest.10-3279] [Citation(s) in RCA: 65] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
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Prognostic stratification of patients with T3N1M0 non-small cell lung cancer: which phase should it be? Med Oncol 2011; 29:607-13. [PMID: 21431959 DOI: 10.1007/s12032-011-9907-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2010] [Accepted: 03/09/2011] [Indexed: 10/18/2022]
Abstract
In the 1997 revision of the TNM staging system for lung cancer, patients with T3N0M0 disease were moved from stage IIIA to stage IIB since these patients have a better prognosis. Despite this modification, the local lymph node metastasis remained the most important prognostic factor in patients with lung cancer. The present study aimed to evaluate the prognosis of patients with T3N1 disease as compared with that of patients with stages IIIA and IIB disease. During 7-year period, 313 patients with non-small cell lung cancer (297 men, 16 women) who had resection were enrolled. The patients were staged according the 2007 revision of Lung Cancer Staging by American Joint Committee on Cancer. The Kaplan-Meier statistics was used for survival analysis, and comparisons were made using Cox proportional hazard method. The 5-year survival of patients with stage IIIA disease excluding T3N1 patients was 40%, whereas the survival of the patients with stage IIB disease was 66% at 5 years. The 5-year survival rates of stage III T3N1 patients (single-station N1) was found to be higher than those of patients with stage IIIA disease (excluding pT3N1 patients, P = 0.04), while those were found to be similar with those of patients with stage IIB disease (P = 0.4). Survival of the present cohort of patients with T3N1M0 disease represented the survival of IIB disease rather than IIIA non-small cell lung cancer. Further studies are needed to suggest further revisions in the recent staging system regarding T3N1MO disease.
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Hubbs JL, Boyd JA, Hollis D, Chino JP, Saynak M, Kelsey CR. Factors associated with the development of brain metastases: analysis of 975 patients with early stage nonsmall cell lung cancer. Cancer 2010; 116:5038-46. [PMID: 20629035 DOI: 10.1002/cncr.25254] [Citation(s) in RCA: 102] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
BACKGROUND The risk of developing brain metastases after definitive treatment of locally advanced nonsmall cell lung cancer (NSCLC) is approximately 30%-50%. The risk for patients with early stage disease is less defined. The authors sought to investigate this further and to study potential risk factors. METHODS The records of all patients who underwent surgery for T1-T2 N0-N1 NSCLC at Duke University between the years 1995 and 2005 were reviewed. The cumulative incidence of brain metastases and distant metastases was estimated by using the Kaplan-Meier method. A multivariate analysis assessed factors associated with the development of brain metastases. RESULTS Of 975 consecutive patients, 85% were stage I, and 15% were stage II. Adjuvant chemotherapy was given to 7%. The 5-year actuarial risk of developing brain metastases and distant metastases was 10%(95% confidence interval [CI], 8-13) and 34%(95% CI, 30-39), respectively. Of patients developing brain metastases, the brain was the sole site of failure in 43%. On multivariate analysis, younger age (hazard ratio [HR], 1.03 per year), larger tumor size (HR, 1.26 per cm), lymphovascular space invasion (HR, 1.87), and hilar lymph node involvement (HR, 1.18) were associated with an increased risk of developing brain metastases. CONCLUSIONS In this large series of patients treated surgically for early stage NSCLC, the 5-year actuarial risk of developing brain metastases was 10%. A better understanding of predictive factors and biological susceptibility is needed to identify the subset of patients with early stage NSCLC who are at particularly high risk.
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Affiliation(s)
- Jessica L Hubbs
- Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina, USA
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Wisnivesky JP, Arciniega J, Mhango G, Mandeli J, Halm EA. Lymph node ratio as a prognostic factor in elderly patients with pathological N1 non-small cell lung cancer. Thorax 2010; 66:287-93. [PMID: 21131298 DOI: 10.1136/thx.2010.148601] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
BACKGROUND Lymph node (LN) metastasis is an important predictor of survival for patients with non-small cell lung cancer (NSCLC). However, the prognostic significance of the extent of LN involvement among patients with N1 disease remains unknown. A study was undertaken to evaluate whether involvement of a higher number of N1 LNs is associated with worse survival independent of known prognostic factors. METHODS Using the Surveillance, Epidemiology and End Results-Medicare database, 1682 resected patients with N1 NSCLC diagnosed between 1992 and 2005 were identified. As the number of positive LNs is confounded by the total number of LNs sampled, the cases were classified into three groups according to the ratio of positive to total number of LNs removed (LN ratio (LNR)): ≤0.15, 0.16-0.5 and >0.5. Lung cancer-specific and overall survival was compared between these groups using Kaplan-Meier curves. Stratified and Cox regression analyses were used to evaluate the relationship between the LNR and survival after adjusting for potential confounders. RESULTS Lung cancer-specific and overall survival was lower among patients with a high LNR (p<0.0001 for both comparisons). Median lung cancer-specific survival was 47 months, 37 months and 21 months for patients in the ≤0.15, 0.16-0.5 and >0.5 LNR groups, respectively. In stratified and adjusted analyses, a higher LNR was also associated with worse lung cancer-specific and overall survival. CONCLUSIONS The extent of LN involvement provides independent prognostic information in patients with N1 NSCLC. This information may be used to identify patients at high risk of recurrence who may benefit from aggressive postoperative therapy.
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Affiliation(s)
- Juan P Wisnivesky
- Department of Medicine, Mount Sinai School of Medicine, One Gustave L Levy Place, Box 1087, New York, NY 10029, USA.
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Relapse in resected lung cancer revisited: does intensified follow up really matter? A prospective study. World J Surg Oncol 2009; 7:87. [PMID: 19909550 PMCID: PMC2784765 DOI: 10.1186/1477-7819-7-87] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2009] [Accepted: 11/12/2009] [Indexed: 12/01/2022] Open
Abstract
Background beside the well known predominance of distant vs. loco-regional relapse, several aspects of the relapse pattern still have not been fully elucidated. Methods prospective, controlled study on 88 patients operated for non-small cell lung cancer (NSCLC) in a 15 months period. Stage IIIA existed in 35(39.8%) patients, whilst stages IB, IIA and IIB existed in 10.2%, 4.5% and 45.5% patients respectively. Inclusion criteria: stage I-IIIA, complete resection, systematic lymphadenectomy with at least 6 lymph node groups examined, no neoadjuvant therapy, exact data of all aspects of relapse, exact data about the outcome of the treatment. Results postoperative lung cancer relapse occurred in 50(56.8%) patients. Locoregional, distant and both types of relapse occurred in 26%, 70% and 4% patients respectively. Postoperative cancer relapse occurred in 27/35(77.1%) pts. in the stage IIIA and in 21/40(52.55) pts in the stage IIB. In none of four pts. in the stage IIA cancer relapse occurred, unlike 22.22% pts. with relapse in the stage IB. The mean disease free interval in the analysed group was 34.38 ± 3.26 months. The mean local relapse free and distant relapse free intervals were 55 ± 3.32 and 41.62 ± 3.47 months respectively Among 30 pts. with the relapse onset inside the first 12 month after the lung resection, in 20(66.6%) pts. either T3 tumours or N2 lesions existed. In patients with N0, N1 and N2 lesions, cancer relapse occurred in 30%, 55.6% and 70.8% patients respectively Radiographic aspect T stage, N stage and extent of resection were found as significant in terms of survival. Related to the relapse occurrence, although radiographic aspect and extent of resection followed the same trend as in the survival analysis, only T stage and N stage were found as significant in the same sense as for survival. On multivariate, only T and N stage were found as significant in terms of survival. Specific oncological treatment of relapse was possible in 27/50(54%) patients. Conclusion the intensified follow up did not increase either the proportion of patients detected with asymptomatic relapse or the number of patients with specific oncological treatment of relapse.
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Impact of main bronchial lymph node involvement in pathological T1-2N1M0 non-small-cell lung cancer: multi-institutional survey by the Japan National Hospital Study Group for Lung Cancer. Gen Thorac Cardiovasc Surg 2009; 57:599-604. [DOI: 10.1007/s11748-009-0451-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2009] [Accepted: 04/07/2009] [Indexed: 10/20/2022]
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Demir A, Turna A, Kocaturk C, Gunluoglu MZ, Aydogmus U, Urer N, Bedirhan MA, Gurses A, Dincer SI. Prognostic significance of surgical-pathologic N1 lymph node involvement in non-small cell lung cancer. Ann Thorac Surg 2009; 87:1014-22. [PMID: 19324121 DOI: 10.1016/j.athoracsur.2008.12.053] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2008] [Revised: 12/06/2008] [Accepted: 12/12/2008] [Indexed: 11/20/2022]
Abstract
BACKGROUND Patients with N1 non-small cell lung cancer represent a heterogeneous population with varying long-term survival. To better define the importance of N1 disease and its subgroups in non-small cell lung cancer staging, we analyzed patients with N1 disease using the sixth edition and proposed seventh edition TNM classifications. METHODS From January 1995 to November 2006, 540 patients with N1 non-small cell lung cancer who had at least lobectomy with systematic mediastinal lymphadenectomy were analyzed retrospectively. RESULTS For completely resected patients, the median survival rate and 5-year survival rate were 63 months and 50.3%, respectively. The 5-year survival rates for patients with hilar N1 (station 10), interlobar (station 11), and peripheral N1 (stations 12 to 14) involvement were 39%, 51%, and 53%, respectively. Patients with hilar lymph node metastasis showed a shorter survival period than patients with peripheral lymph node involvement (p = 0.02). Patients with hilar zone N1 (stations 10 and 11) involvement tended to show poorer survival than patients with peripheral zone N1 (12 to 14) metastasis (p = 0.08). Multiple-station lymph node metastasis indicated a poorer prognosis than single-station involvement (5-year survival 39% versus 51%, respectively, p = 0.01). Patients with multiple-zone N1 involvement showed poorer survival than patients with single-zone N1 metastasis (p = 0.04). A significant survival difference was observed between N1 patients with T1a versus T1b tumors (p = 0.02). Multivariate analysis revealed that only multiple-station lymph node metastasis was predictive of poor prognosis (p = 0.05). CONCLUSIONS Multiple-station versus single-station N1 disease and multiple-zone versus single-zone N1 involvement indicate poorer survival rate. Patients with hilar lymph node involvement had lower survival rates than patients with peripheral N1. The impact of T factor seemed to be veiled by the heterogenous nature of N1 disease. Further studies of adjusted postoperative strategies for different N1 subgroups are warranted.
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Affiliation(s)
- Adalet Demir
- Department of Thoracic Surgery, Yedikule Teaching Hospital for Chest Diseases and Thoracic Surgery, Istanbul, Turkey.
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Santos PARD, Rocha RSD, Pipkin M, Silveira MLD, Cypel M, Rios JO, Pinto JALDF. [Concordance between clinical and pathological staging in patients with stages I or II non-small cell lung cancer subjected to surgical treatment]. J Bras Pneumol 2008; 33:647-54. [PMID: 18200364 DOI: 10.1590/s1806-37132007000600007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2006] [Accepted: 04/03/2007] [Indexed: 11/22/2022] Open
Abstract
OBJECTIVE To compare clinical and pathological staging in patients with non-small cell lung cancer submitted to surgical treatment, as well as to identify the causes of discordance. METHODS Data related to patients treated at the Department of Thoracic Surgery of the Pontifical Catholic University of Rio Grande do Sul São Lucas Hospital were analyzed retrospectively. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for clinical stages IA, IB, and IIB. The kappa index was used to determine the concordance between clinical and pathological staging. RESULTS Of the 92 patients studied, 33.7% were classified as clinical stage IA, 50% as IB, and 16.3% as IIB. The concordance between clinical and pathological staging was 67.5% for stage IA, 54.3% for IB, and 66.6% for IIB. The accuracy of the clinical staging was greater for stage IA, and a kappa of 0.74, in this case, confirmed a substantial association with pathological staging. The difficulty in evaluating nodal metastatic disease is responsible for the low concordance in patients with clinical stage IB. CONCLUSIONS The concordance between clinical and pathological staging is low, and patients are frequently understaged (in the present study, only one case was overstaged). Strategies are necessary to improve clinical staging and, consequently, the treatment and prognosis of patients with non-small cell lung cancer.
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Affiliation(s)
- Pedro Augusto Reck Dos Santos
- Serviço de Cirurgia Torácica, Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brasil.
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Lung Neoplasms. Surgery 2008. [DOI: 10.1007/978-0-387-68113-9_72] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Prognostic Factors in Patients with Pathologic T1-2N1M0 Disease in Non-small Cell Carcinoma of the Lung. J Thorac Oncol 2007; 2:1098-102. [DOI: 10.1097/jto.0b013e31815ba227] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Fukai R, Sakao Y, Sakuraba M, Oh S, Shiomi K, Sonobe S, Saitoh Y, Miyamoto H. The prognostic value of carcinoembryonic antigen in T1N1M0 and T2N1M0 non-small cell carcinoma of the lung. Eur J Cardiothorac Surg 2007; 32:440-4. [PMID: 17643308 DOI: 10.1016/j.ejcts.2007.06.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2007] [Revised: 06/05/2007] [Accepted: 06/11/2007] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVE To evaluate the significance of preoperative clinicopathological factors, including serum carcinoembryonic antigen (CEA), as well as postoperative clinicopathological factors in T1-2N1M0 patients with non-small cell lung cancer who underwent curative pulmonary resection. METHODS Twenty T1N1M0 disease patients and 25 T2N1M0 patients underwent standard surgical procedures between September 1996 and December 2005, and were found to have non-small lung cancer. As prognostic factors, we retrospectively investigated age, sex, Brinkman index, histologic type, primary site, tumor diameter, clinical T factor, clinical N factor, pathological T factor, preoperative serum CEA levels, surgical procedure, visceral pleural involvement, and the status of lymph node involvement (level and number). RESULTS The overall 5-year survival rate of all patients was 59.6%. In univariate analysis, survival was related to age (<70/>or=70 years, p=0.0079), site (peripheral/central, p=0.043), and CEA level (<5.0/>or=5.0 ng/ml, p=0.0015). However, in multivariate analysis, CEA (<5.0/>or=5.0 ng/ml) was the only independent prognostic factor; the 5-year survival of the patients with an elevated serum CEA level (>or=5.0 ng/ml) was only 33.2% compared to 79.9% in patients with a lower serum CEA level (<5.0 ng/ml). CONCLUSIONS An elevated serum CEA level (>or=5.0 ng/ml) was an independent predictor of survival in pN1 patients except for T3 and T4 cases. Therefore, even in completely resected pN1 non-small cell lung cancer, patients with a high CEA level might be candidates for multimodal therapy.
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Affiliation(s)
- Ryuta Fukai
- Department of General Thoracic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8431, Japan.
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Cerfolio RJ, Bryant AS. Predictors of Survival and Disease-Free Survival in Patients With Resected N1 Non-Small Cell Lung Cancer. Ann Thorac Surg 2007; 84:182-8; discussion 189-90. [PMID: 17588408 DOI: 10.1016/j.athoracsur.2007.03.030] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2006] [Revised: 03/08/2007] [Accepted: 03/12/2007] [Indexed: 11/17/2022]
Abstract
BACKGROUND Factors that predict poor survival or increased risk of recurrence for patients with N1 disease may be dependent on tumor characteristics. METHODS This study was a retrospective review of a prospective database of consecutive patients who had clinical or pathologic N1 non-small cell lung cancer (NSCLC) who underwent preoperative 2-[18F] fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) scans and complete resection with thoracic lymphadenectomy. RESULTS There were 135 patients (88 men). The 5-year disease-free rate was 55%. Kaplan-Meier analysis showed that poor differentiation (p = 0.036), multiple N1 stations (p = 0.010), and the lack of adjuvant chemotherapy (p = 0.039) were all associated with a shorter 5-year disease-free rate. Multivariate disease-free analysis demonstrated that only multiple stations (p = 0.002) were independently associated with recurrence. The overall 5-year survival was 48%. Univariate analysis showed that multiple nodes within one station (p = 0.016), multiple station involvement (p = 0.041), and lack of adjuvant chemotherapy (p = 0.039) and moderate-to-poor tumor differentiation (p = 0.046) were associated with decreased survival. Multivariate analysis found that multiple stations, multiple nodes, and lack of adjuvant chemotherapy were independent predictors of poor survival. Integrated PET-computed tomography (CT) was significantly more sensitive for staging N1 disease than dedicated FDG-PET (p = 0.032). Neoadjuvant chemotherapy given to 48 nonrandomized patients did not seem to impact disease recurrence or overall 5-year survival rates (p = 0.349). CONCLUSIONS Factors that predict a poor outcome in patients with resected N1 NSCLC are the involvement of multiple N1 stations, multiple N1 nodes, and the lack of adjuvant chemotherapy. Integrated PET-CT is more sensitive for detecting N1 disease then dedicated PET. These data may influence preoperative or postoperative therapy, or both.
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Affiliation(s)
- Robert J Cerfolio
- Division of Cardiothoracic Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
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Fujimoto T, Cassivi SD, Yang P, Barnes SA, Nichols FC, Deschamps C, Allen MS, Pairolero PC. Completely resected N1 non–small cell lung cancer: Factors affecting recurrence and long-term survival. J Thorac Cardiovasc Surg 2006; 132:499-506. [PMID: 16935101 DOI: 10.1016/j.jtcvs.2006.04.019] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2005] [Revised: 04/12/2006] [Accepted: 04/20/2006] [Indexed: 11/22/2022]
Abstract
OBJECTIVE N1 disease in non-small cell lung cancer represents a heterogeneous patient subgroup with a 5-year survival of approximately 40%. Few reports have evaluated the correlation between N1 disease and tumor recurrence or which subgroup of patients would most benefit from adjuvant chemotherapy. METHODS From 1997 through 2002, all patients with pathologic T1-4 N1 M0 non-small cell lung cancer who had a complete resection with systematic mediastinal lymphadenectomy were retrospectively analyzed and evaluated for factors associated with recurrence and long-term survival. RESULTS One hundred eighty patients with N1 disease were evaluated. Sixty-six (37%) patients had either locoregional recurrence (n = 39 [22%]), distant metastasis (n = 41 [23%]), or both during follow-up. Univariate analysis demonstrated that visceral pleural invasion and age were associated with locoregional recurrence, whereas visceral pleural invasion, distinct N1 metastasis (as opposed to direct N1 invasion by the primary tumor), and multistation lymph node involvement were associated with distant metastasis (P < .05). Multivariable analysis demonstrated that visceral pleural invasion, multistation N1 involvement, and distinct N1 metastasis were the only independent predisposing factors for locoregional recurrence and distant metastasis. Overall 5-year survival was 42.5%. Survival was significantly decreased by advanced pathologic T classification (P = .015), visceral pleural invasion (P < .0001), and higher tumor grade (P = .014). CONCLUSIONS In patients with N1-positive non-small cell lung cancer, visceral pleural invasion, multistation N1 disease, and distinct N1 metastasis are independent predictors of subsequent locoregional recurrence and distant metastasis. Advanced T classification, visceral pleural invasion, and higher tumor grade were predictors of poor survival. These patients represent a subgroup of patients with N1 disease who might benefit from additional therapy, including adjuvant chemotherapy.
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Affiliation(s)
- Toshio Fujimoto
- Division of General Thoracic Surgery, Mayo Clinic College of Medicine, Rochester, Minn 55905, USA
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Maounis NF, Chorti M, Apostolakis E, Ellina E, Blana A, Aggelidou M, Dritsas I, Markidou S. Prognostic impact of Deoxyribonucleic acid (DNA) image analysis cytometry and immunohistochemical expression of Ki67 in surgically resected non-small cell lung cancers. ACTA ACUST UNITED AC 2006; 30:507-14. [PMID: 17113721 DOI: 10.1016/j.cdp.2006.07.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/14/2006] [Indexed: 11/21/2022]
Abstract
BACKGROUND The aim of the present study was to evaluate the prognostic significance of DNA ploidy and Ki67 expression in non-small cell lung carcinoma (NSCLC). METHODS This prospective study included 96 patients with stages I-IIIA NSCLC who underwent surgical excision. DNA image analysis cytometry was applied on imprints. Calculation of the DNA index (DI) and the 5c exceeding rate (5cER) was performed and the histograms were classified as peridiploid, peritetraploid, and x-ploid-multiploid. The Ki67 immunoreactivity was determined according to the avidin-biotin complex immunoperoxidase method. RESULTS DNA histogram classification disclosed 30 peridiploid cases, 15 peritetraploid and 51 x-ploid-multiploid. Forty-eight cases (50%) had 5cER > 5%. The Ki67 immunoreactivity was below 25% in 53 tumors (62.4%) and above 25% in 32 (32.6%). Our results revealed the existence of a statistically significant relationship of DNA ploidy with nodal status (p = 0.042) and grade (p = 0.005). Adenocarcinomas and large cell carcinomas were more frequently encountered in x-ploid-multiploid tumors as compared to squamous cell carcinomas, which were more frequently peridiploid (p = 0.003). 5cER showed statistically significant association with nodal status (p = 0.037). Univariate analysis with respect to survival revealed significant association with stage (p < 0.001), nodal status (p < 0.001), tumor status (p < 0.001), DNA ploidy (p = 0.008) and 5cER (p = 0.0124). Multivariate analysis revealed stage and ploidy status as independent factors: peridiploid tumors were associated with better survival as compared to x-ploid-multiploid tumors (p = 0.022). CONCLUSION Our results suggest that DNA ploidy, as determined by image analysis, provides an independent prognostic parameter for patients with NSCLC and thus, could be used to identify a subset of patients with more aggressive tumors.
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Affiliation(s)
- Nicoletta F Maounis
- Department of Cytology, Sismanoglion General Hospital, 1 Sismanogliou Str., Athens 151 26, Greece.
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Wisnivesky JP, Henschke C, McGinn T, Iannuzzi MC. Prognosis of Stage II non-small cell lung cancer according to tumor and nodal status at diagnosis. Lung Cancer 2005; 49:181-6. [PMID: 16022911 DOI: 10.1016/j.lungcan.2005.02.010] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2004] [Revised: 01/25/2005] [Accepted: 02/08/2005] [Indexed: 10/25/2022]
Abstract
PURPOSE To evaluate the prognostic significance of tumor and node status among patients with Stage II non-small cell lung cancer using a population-based national database. METHODS We identified all primary cases of Stage II non-small cell lung cancer diagnosed prior to autopsy from the Surveillance, Epidemiology and End Results (SEER) registry. Lung cancer-specific survival curves were obtained for the 5254 patients who had curative surgical resection, stratifying for tumor and node status (T1-2N1M0, T3N0M0). The 12.5-year Kaplan-Meier estimator of survival was used as a measure of lung cancer cure rate. The influence of gender, age, cell type, pathologic tumor status, nodal metastasis, surgical method, and post-operative radiation therapy were evaluated using Cox regression. RESULTS Survival was better for T1N1 cases during the first 3--4 years after diagnosis. Five-year survival for T1N1 and T3N0 cases however, was not significantly different (46% versus 48%, p=0.4) and the cure rate was somewhat higher for T3N0 cases (33% versus to 27%, p=0.10). T2N1 cases had the worst overall survival. Multivariate analysis revealed that gender, age, tumor and nodal status, and histology were independent prognostic factors. CONCLUSIONS Among Stage II cancers, T3N0 cases have the highest cure rate and an overall survival pattern that more closely resembles T1N1 tumors. Several clinico-pathologic characteristics are significantly associated with survival and may explain some of the heterogeneity in outcomes among Stage II patients. These results suggest that T3N0 cases may be better classified as Stage IIA disease.
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Affiliation(s)
- Juan P Wisnivesky
- Division of General Internal Medicine, Mount Sinai School of Medicine One Gustave L. Levy Place, Box 1087, NY 10029, USA.
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Rea F, Marulli G, Callegaro D, Zuin A, Gobbi T, Loy M, Sartori F. Prognostic significance of main bronchial lymph nodes involvement in non-small cell lung carcinoma: N1 or N2? Lung Cancer 2004; 45:215-20. [PMID: 15246193 DOI: 10.1016/j.lungcan.2004.01.017] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2003] [Revised: 01/15/2004] [Accepted: 01/20/2004] [Indexed: 10/26/2022]
Abstract
STUDY OBJECTIVES Accurate TNM staging is the basis to evaluate prognosis and to plan treatment of patients with non-small cell lung cancer. Exact definition of N status is fundamental and the boundary line between N1 and N2 stations is one of the most controversial issue. Purpose of this study is to evaluate the prognostic significance of main bronchus nodes, that we classified as station number 10 (N1). METHODS We reviewed retrospectively lymph node patterns and survival of 175 patients with N1 and 154 with N2 disease, that underwent surgical resection with hilar and mediastinal lymphadenectomy from January 1990 to December 2000. These two groups were subdivided in N1 without station number 10 involvement (N1-, n = 144), N1 with station number 10 involvement (N1+, n = 31), N2 single station (N2s, n = 107) and N2 multiple stations (N2m, n = 47), respectively. A univariate and multivariate analysis of prognostic factors predicting survival has been performed. RESULTS Overall 5-year survival rate for 175 N1 patients and 154 N2 patients was 42 and 13%, respectively and the difference was statistically significant (P < 0.001). The prognosis between N1-, N1+, N2 was compared: 5-year survival rate was 44, 31 and 13%, respectively and the difference reached a statistical value between N1+ and N2 (P < 0.05), but not between N1- and N1+. When the comparison was made with N1-, N1+, N2s and N2m, the difference was significant between N1- and N2s (P = 0.0003), between N1+ and N2m (P = 0.0001), but not between N1+ and N2s. CONCLUSIONS The aim of a uniform anatomical and clinical classification of nodal stations has not been thoroughly achieved, particularly regarding the boundary line between N1 and N2. Our study points out that the involvement of main bronchial nodes has a prognostic significance similar to that of N2 single station and should be considered as an early N2 disease.
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Affiliation(s)
- Federico Rea
- Division of Thoracic Surgery, University of Padua, Via Giustiniani, 2, 35128, Italy.
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Tanaka F, Yanagihara K, Otake Y, Kawano Y, Miyahara R, Takenaka K, Katakura H, Ishikawa S, Ito H, Wada H. Prognostic Factors in Resected Pathologic (p-) Stage IIIA-N2, Non-Small-Cell Lung Cancer. Ann Surg Oncol 2004; 11:612-8. [PMID: 15150069 DOI: 10.1245/aso.2004.07.013] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
BACKGROUND Postoperative prognosis for patients with pathologic (p-) stage IIIA-N2 non-small-cell lung cancer (NSCLC) is poor, and significant factors that influence the prognosis remain unclear. METHODS A total of 99 patients who underwent complete resection for p-stage IIIA-N2 NSCLC without any preoperative therapy were retrospectively reviewed. Biological features such as tumor angiogenesis (intratumoral microvessel density [IMVD]), proliferative activity (proliferative index [PI]), and p53 status were also evaluated immunohistochemically. RESULTS Univariate analysis revealed that the number of involved N2 stations was a significant prognostic factor; 5-year survival rates for a tumor with metastases in single N2 stations, tumor with metastases in two N2 stations, and tumor with metastases in 3 or more N2 stations were 41.6%, 35.3%, and 0.0%, respectively (P =.041) In addition, the 5-year survival rate for cN0-1 disease was significantly higher than that for cN2 disease (41.9% and 25.5%, respectively; P =.048) Tumor angiogenesis and proliferative activity were the most significant prognostic factors; 5-year survival rates for lower-IMDV tumor and higher-IMVD tumor were 53.6% and 15.9%, respectively (P =.002), and those for lower-PI tumor and higher-PI tumor were 47.0% and 20.4%, respectively (P =.019) There was no difference in the postoperative survival between tumor showing aberrant p53 expression and tumor showing no aberrant p53 expression. These results were confirmed by a multivariate analysis. CONCLUSIONS P-stage IIIA-N2 NSCLC cases represented a mixture of heterogeneous prognostic subgroups, and the number of involved N2 stations, cN status, PI, and IMVD were significant predictors of the survival.
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Affiliation(s)
- Fumihiro Tanaka
- Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Shogoin-kawahara-cho 54, Sakyo-ku, Kyoto 606-8507, Japan.
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Khan OA, Fitzgerald JJ, Field ML, Soomro I, Beggs FD, Morgan WE, Duffy JP. Histological determinants of survival in completely resected T1-2N1M0 nonsmall cell cancer of the lung. Ann Thorac Surg 2004; 77:1173-8. [PMID: 15063229 DOI: 10.1016/j.athoracsur.2003.08.080] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/21/2003] [Indexed: 10/26/2022]
Abstract
BACKGROUND The histologic determinants of survival after surgical resection of stage II nonsmall cell lung cancer are poorly understood. We analyzed the prognostic significance of a number of histologic features after complete resection of T1-2N1M0 nonsmall cell cancer of the lung. METHODS The case notes and histology of all patients who underwent a potentially curative surgical resection for T1-2N1M0 nonsmall cell carcinoma of the lung between 1991 and 1997 were reviewed retrospectively. The following histologic factors were recorded: histologic type of tumor; number of nodes with metastatic deposits together with their nodal station; the presence of vascular invasion, visceral pleural involvement, and cellular necrosis; and grade of tumor. The results from 98 patients were analyzed. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS Univariate analysis showed that only three factors had a statistically significant correlation with a poor prognosis: vascular invasion (p = 0.002), nonsquamous histology (p = 0.005), and visceral pleural involvement (p = 0.002). Multivariate analysis revealed that all three factors were significant independent adverse prognostic indicators. CONCLUSIONS Visceral pleural involvement, nonsquamous histology, and vascular invasion are all significant adverse prognostic factors after surgical resection of T1-2N1M0 nonsmall cell cancer of the lung. These findings conflict with previously published reports, and we advocate a prospective, large-scale study in order to clarify the prognostic significance of histologic characteristics in stage II disease.
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Affiliation(s)
- Omar A Khan
- Thoracic Unit, Nottingham City Hospital, Nottingham, United Kingdom.
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Macdonald C, Michael A, Colston K, Mansi J. Heterogeneity of immunostaining for tumour markers in non-small cell lung carcinoma. Eur J Cancer 2004; 40:461-6. [PMID: 14746866 DOI: 10.1016/j.ejca.2003.10.019] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Lung carcinoma is a leading cause of death. However, there are few indicators that can aid in prediction and prognosis. Many tumour markers are available, but their reliability is questionable. For example, Ki-67 expression has been associated with increased as well as decreased survival or with no clinical significance. The varying results have been attributed to the methodology, relative intensity of staining, variety of marking and statistical methods. To determine whether differential expression of markers within tumours may be a contributory factor to this lack of agreement, we used two marking methods to evaluate the level of expression of Ki-67, p53 and bcl-2, in addition to the apoptotic index, in serial sections of non-small cell carcinoma. All stains exhibited a degree of heterogeneity. This small study highlights the importance of standardisation of marking methods and interpretation of results if tumour markers are to be used as predictive or prognostic factors.
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Affiliation(s)
- C Macdonald
- Division of Oncology, Gastroenterology and Metabolism, St. George's Hospital Medical School, London SW17 ORE, UK
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Poleri C, Morero JL, Nieva B, Vázquez MF, Rodríguez C, de Titto E, Rosenberg M. Risk of recurrence in patients with surgically resected stage I non-small cell lung carcinoma: histopathologic and immunohistochemical analysis. Chest 2003; 123:1858-67. [PMID: 12796161 DOI: 10.1378/chest.123.6.1858] [Citation(s) in RCA: 74] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
STUDY OBJECTIVE To evaluate the prognostic value of histopathologic variables and molecular markers in a group of patients with stage I non-small cell lung cancer (NSCLC). SETTING "María Ferrer" Hospital of Buenos Aires, Argentina. PATIENTS Pathologic stage IA and IB patients who underwent radical surgery and nonneoadjuvant therapy for NSCLC between January 1985 and December 1999. MEASUREMENTS AND RESULTS Fifty-three patients fulfilling the inclusion criteria were identified. The overall survival was 52.8%, and 28% of patients had recurrent disease. We found significant differences between squamous cell carcinoma (SCC) and adenocarcinoma in mitotic counting (p = 0.001) and lymphatic permeation (p = 0.01). SCCs showed higher proliferation (MIB-1 grades 2 and 3) [p = 0.001], Bcl-2 expression (p = 0.038), and CD44 expression (p = 0.019) than adenocarcinomas. The log-rank test showed that mitosis count, necrosis, MIB-1, and Bcl-2 were predictive factors for relapse. All of them were associated with increased relapse and a shorter time to recurrence. Multivariate analysis using the Cox proportional hazards regression model showed that mitosis count, Bcl-2 expression, and grade 3 of MIB-1 emerged as independent prognostic factors of recurrence. CONCLUSIONS We found that mitosis count and MIB-1 expression had significant value to predict recurrence, reflecting the aggressiveness of high-rate proliferative tumors. We could also show that patients with positive Bcl-2 tumors had a poor outcome, probably related to the uncontrolled cell growth that the expression of Bcl-2 promotes. Our observations are of potential interest for the development of rational postresection treatment strategies based on the estimated risk of recurrence of patients with NSCLC.
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Affiliation(s)
- Claudia Poleri
- Pathology Service, Hospital de Rehabilitación Respiratoria María Ferrer, Buenos Aires, Argentina.
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Daniels JMA, Eerenberg JP, Rijna H, Kummer JA, Broeckaert MAM, Paul MA, van Diest PJ, van Mourik JC. Mitotic index does not predict prognosis in stage IA non-small cell lung cancer. Lung Cancer 2002; 38:163-7. [PMID: 12399128 DOI: 10.1016/s0169-5002(02)00215-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Despite radical resection, many patients with stage IA non-small cell lung cancer (NSCLC) die of metastatic disease, showing that apparently there were already micrometastases at the time of surgery. To identify patients at risk for metastatic disease, accurate prognostic factors are needed. Because the mitotic activity index (MAI) is of good prognostic value in several other cancers, we assessed its value in stage IA NSCLC. We assessed the MAI in the sections of 133 patients with radically resected stage IA NSCLC. MAI, histologic subtype, age, sex, location of tumor, type of surgery and tumor diameter were correlated with survival. The mean MAI was 29, ranging from 0 to 89. MAI was not correlated to histologic tumor type or lymph node sample procedure, or any of the other clinicopathologic features. No correlation was found between MAI and survival. Univariate analysis showed that only age was a significant predictor of survival (P = 0.0007). This was confirmed by multivariate analysis. The mitotic index is not a predictor of prognosis in stage IA NSCLC. Therefore other prognostic factors have to be investigated.
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Affiliation(s)
- Johannes M A Daniels
- Department of Surgery, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
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Abstract
Despite complete resection of what seems to be all evident tumor, one third to three quarters of patients with stages I and II NSCLC ultimately succumb to this neoplasm. Patients who are cured of an original NSCLC or small cell cancer remain at risk for a new primary lung cancer. Although the importance of lifelong surveillance is clear, the extent and timing of optimal follow-up remain undefined. Although clinicians refer to the development after treatment of clinically discernible sites of tumor as "recurrence," it is probably more accurate to consider these foci as "persistence"--that is, the locoregional site was not sterilized by surgery, and the distant implants were present from the outset but undetected. Although data are sparse, induction and improved adjuvant therapy for early NSCLC may be helpful. Much further experience is needed. Further study and application of biologic indicators in addition to TNM staging likely will help identify patients at high risk for surgical failure who may benefit by combination treatment.
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Affiliation(s)
- Lynn T Tanoue
- Yale University School of Medicine, New Haven, Connecticut, USA
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