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H. Asamura
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MINI 32 - Topics in Localized Lung Cancer (ID 166)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:D. Boffa, T. D'Amico
- Coordinates: 9/09/2015, 18:30 - 20:00, 201+203
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MINI32.06 - Clinical Impacts of Tumor Hypoxia Imaging with FAZA and ATSM PET in NSCLC (ID 182)
19:00 - 19:05 | Author(s): H. Asamura
- Abstract
- Presentation
Background:
The noninvasive dynamic characterization of hypoxia using molecular imaging approaches is supportive for evaluation of malignant tumor. In this study, we evaluated the clinicopathological impact of newly developed tumor hypoxia PET tests for localized non-small cell lung cancer (NSCLC).
Methods:
Forty-nine patients with localized NSCLC were enrolled[F1] [木下智成2] . They underwent chest hypoxia PET tests, namely [18]F-fluoroazomycin arabinoside (FAZA) and/or [62]Cu-diacetyl-bis (N4)-methylsemithiocarbazone (ATSM) PET in addition to routine whole-body [18]F-fluorodeoxyglucose (FDG) PET before treatment. Uptake of hypoxic tracers was quantified by calculating maximum standard uptake values (SUVmax) and tumor muscle ratios (TMR).
Results:
The uptake of [18]F-FAZA were in positive proportion to that of [62]Cu-ATSM (P < 0.05). Neutrophil lymphocyte ratio and tumor size were significantly correlated with uptake both in [18]F-FAZA (P < 0.01) and [62]Cu-ATSM (P < 0.05 in [18]F-FAZA and [62]Cu-ATSM). Pathologically, the case with vascular or pleural invasion, which indicate tumor malignancy, had higher uptake of [18]F-FAZA (P < 0.05). Those accumulations increased according to advanced TNM staging (P < 0.05). The patient with higher uptake of these tracers significantly had a poorer overall survival (P < 0.01 in [18]F-FAZA and P < 0.05 in [62]Cu-ATSM), and progression-free survival (P < 0.01 in [18]F-FAZA and P < 0.05 in [62]Cu-ATSM).
Conclusion:
[18]F-FAZA and [62]Cu-ATSM can provide useful information on tumor malignancy and prognosis, and might contribute toward guiding individualization of treatment of localized NSCLC. Figure 1Figure 2
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MS 10 - Management of Screening Detected Lung Cancer (ID 28)
- Event: WCLC 2015
- Type: Mini Symposium
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:N. Ikeda, B. Park, P. Goldstraw, L.E. Raez
- Coordinates: 9/07/2015, 14:15 - 15:45, Mile High Ballroom 2c-3c
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MS10.05 - Rationale for Sublobar Resection for Early Cancer (ID 1893)
15:00 - 15:10 | Author(s): H. Asamura
- Abstract
- Presentation
Abstract:
THE oncological appropriateness of the limited, sublobar resection (segmentectomy or wide wedge resection) for lung cancer has been again discussed in the thoracic surgical community, although the previous randomized trial definitively showed the prognostic advantage of the lobectomy over sublobar, limited resection. Generally, the operative modes used for pulmonary parenchymal resection have been classified into pneumonectomy, bi-lobectomy, lobectomy, segmentectomy, and wedge resection according to the volume of the resected lung parenchyma. From a technical viewpoint, these can be divided into non-anatomic (wedge resection) and anatomic (all the others) resections. In anatomic resections, all vessels and bronchi are divided at the hilum to ensure the resection of the whole lung area related to the divided bronchus. The term, “limited resection”, is also used as opposed to “standard resection”, which is essentially at least lobectomy with hilar and mediastinal lymph node sampling/dissection as of now. Therefore, the present-day “limited” resection inevitably indicates “sublobar” resections. There are several important landmark articles in the surgical evolution for lung cancer. In 1930s, Churchill and Belsey originally introduced segmentectomy for the treatment of bronchiectasis of the lingular segment, and it was termed as “segmental pneumonectomy” [1]. In 1970’s, Jensik reported a 5-year survival rate at 56% and local recurrence rate at 10% after segmentectomy for T1 lung cancer. He suggested that anatomic segmentectomy could be effectively applied to small primary lung cancers when the surgical margins were sufficient [2]. After these, many non-randomized, case series came out, and suggested the prognostic equivalence between lobectomy and segmentectomy for T1 lung cancer. To definitively answer the question regarding the prognoses after lobectomy and limited resection, a prospective, randomized trial was conducted by the North American Lung Cancer Study Group (LCSG) [3]. Segmentectomy and wide wedge resection were compared with lobectomy for stage IA lung cancer with regard to the postoperative prognosis and pulmonary function. A three-fold increase in local recurrence rate and 30% increase in overall death rate were shown for limited resection, and therefore, this study solidified lobectomy as the procedure of choice for the treatment of T1N0 lung cancer. This is still the only completed, randomized trial that directly compared limited resection with lobectomy, and therefore, the gold standard for lung cancer still remains as lobectomy as of now. However, there has been a surge of the interest in the sublobar resection among thoracic surgeons recently, since many earlier, smaller cases are being found owing to the improved technology in CT image and the introduction of the CT screening programs. [4] Among the lesions that are specifically found in this context, the non-solid lesion that is referred to as ground glass opacity (GGO) is a newly established clinical entity that may be a candidate for limited pulmonary resection. The understandings of pathobiological nature of such earlier lesions have progressed [5]. New proposal for the classification of adenocarcinoma was also promulgated, in which the earlier forms of adenocarcinoma were newly defined as AIS (adenocarcinoma in situ) or MIA (minimally invasive adenocarcinoma) [6]. In the face of this situation, it is not surprising that questions have arisen as to whether it might be possible to manage smaller, earlier lung cancers by sublobar resections. Moreover, it has been more than 20 years since the LCSG randomized clinical trial was conducted in the 1980s. Given this situation, randomized clinical trials with peripheral lung cancers no more than 2 cm in diameter as the target lesions were begun in the United States (CALGB 140503) and Japan (JCOG 0802) at almost the same time [7]. JCOG0802/WJOG4607L trial is a prospective, randomized, multi-institutional study which intends to compare the prognosis and postoperative pulmonary function between patients with non-small lung cancer 2 cm or less in diameter undergoing either lobectomy or segmentectomy. The target number of patient accrual is 1,100, and as of the end of June, 2015, accrual is over in full and the data maturation is awaited. The important fact is that the candidate lesions of this trial are supposed to be invasive adenocarcinomas pathologically with solid part in ground glass opacity (GGO) on the CT images. As a selection criterion, a consolidation/tumor ratio has been employed as 25 to 100% to define invasive adenocarcinomas preoperatively. This study is coupled with JCOG0804/WJOG4507L trial, which deals with the non-invasive or minimally invasive adenocarcinomas (adenocarcinoma in situ, AIS/minimally invasive adenocarcinoma, MIA) with CT images as pure GGO with/without minimal solid part. They are treated with limited, sublobar resection (segmentectomy or wide wedge resection). This study is a prospective, but non-randomized, single-arm study because no death is expected for these tumors despite surgical modes. Target accrual is 330, and the registration was already closed, waiting for data maturation. The present-day selection of the surgical mode for lung cancer should be based upon the solid data which demonstrate the overt advantage over the standard mode of resection (lobectomy). We need another some years until getting the definitive conclusion as to the appropriateness of sublobar resection for early stage lung cancer. Until then, surgeons should be prudent in performing a sublobar resection as a radical resection for lung cancer.[8] Figure 1 SEGMENTECTOMY OF THE ANTERIOR SEGMENT OF THE RIGHT UPPER LOBE (from "Asamura's Operative Thoracic Surgery") [References] 1. Churchill ED, Belsey R. Segmental pneumonectomy in bronchiectasis: the lingular segment of the left of the left upper lobe. Ann Surg 1939;109:481-99 2. Jensik RJ. Faber LP, Milloy FJ, Monson DO. Segmental resection for lung cancer. A fifteen-year experience. J Thorac Cardiovasc Surg 1973;66:563-72 3. Lung Cancer Study Group, Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1N0 non-small cell lung cancer. Ann Thorac Surg 1995;60:615-23 4. El-Sherif A, Gooding WE, Santos R, et al. Outcome of sublobar resection versus lobectomy for stage I non-small cell lung cancer: a 13-year analysis. Ann Thorac Surg 2006;82:408-16 5. Asamura H, Hishida T, Suzuki K, et al. Japan Clinical Oncology Group Lung Cancer Surgical Study Group. Radiographically determined noninvasive adenocarcinoma of the lung: Survival outcomes of Japan Clinical Oncology Group 0201. J Thorac Cardiovasc Surg 2013;146:24-30 6. Travis WD, Brambilla E, Noguchi M, et al. International association for the study of lung cancer/American thoracic society/European respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 2011;6:244-85 7. Nakamura K, Saji H, Nakajima R, et al.. A phase III randomized trial of lobectomy versus limited resection for small-sized peripheral non-small cell lung cancer (JCOG0802/WJOG4607L). Jpn J Clin Oncol 2010;40:271-4 8. Asamura H. Role of limited sublobar resection for early-stage lung cancer: steady progress. J Clin Oncol. 2014;32(23):2403-4.
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ORAL 34 - Quality/Survival/Prognosis in Localized Lung Cancer (ID 153)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:B.C. Cho, R.L. Keith
- Coordinates: 9/09/2015, 16:45 - 18:15, 201+203
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ORAL34.03 - Prognostic Factors in Early Stage NSCLC: Analysis of the Placebo Group in the MAGRIT Study (ID 24)
17:07 - 17:18 | Author(s): H. Asamura
- Abstract
- Presentation
Background:
The MAGRIT study was a worldwide, multicenter, phase-3 double-blind, randomized trial evaluating efficacy of the MAGE-A3 Cancer Immunotherapeutic in resected non-small cell lung cancer (NSCLC) (www.clinicaltrials.gov NCT00480025). We examined baseline patient and disease characteristics associated with overall survival (OS) and disease-free survival (DFS) among patients assigned to placebo.
Methods:
Study participants were ≥18 years, with histologically proven, MAGE-A3-positive stage IB, II or IIIA NSCLC (AJCC 6.0). Participants had undergone complete anatomical resection of the tumor (lobectomy or pneumectomy) with mediastinal lymph node (LN) dissection or sampling according to standard of care. Up to four cycles of platinum-based adjuvant chemotherapy were allowed. Cox regression models were used to explore characteristics that could predict DFS and OS. Factors statistically significant in univariate analysis (p<0.05) were included in multivariate models using a stepwise approach (p<0.05 to enter/remain in the model).
Results:
There were 757 placebo patients in the total treated population; median age 63 years, 76% male, 53% with squamous cell carcinoma (SCC), 34% with adenocarcinoma, 98% with performance status 0-1, 52% had received adjuvant chemotherapy.In univariate analyses, SCC, lower N-category and earlier disease stage were associated with improved DFS. Lower N-category, earlier stage and smaller tumor size were associated with improved OS. In multivariate analysis, N-category (HR 1.34, 95%CI [1.16-1.55]) and histological type (HR for SCC vs non-SCC 0.64, 95%CI [0.51-0.81]) remained significant for DFS. N-category (HR 1.47, 95%CI [1.21-1.79]) and tumor size (HR by unit increase 1.08, 95%CI [1.01-1.15]) did so for OS. No association was found between DFS or OS and age, gender, race, region, baseline performance status, quantitative MAGE-A3 expression, chemotherapy administration or type of chemotherapy, smoking status or type of LN sampling (minimal/systematic). Among patients with SCC, univariate analysis identified increased number of chemotherapy cycles and operative technique (pneumectomy) as associated with improved DFS (p<0.05). Only operative technique remained in the multivariate model. When including N-category (p<0.10 in univariate analysis) in the multivariate model, N-category and number of chemotherapy cycles were also selected. Lower N-category and smaller tumor size were significantly associated with improved OS, in univariate and multivariate analyses. Among patients with non-SCC, univariate analysis identified younger age, being female, lower N-category and earlier disease stage with improved DFS, and lower N-category, earlier disease stage and region (East Asia) with improved OS. N-category and gender, and N-category and region remained significant in the multivariate analysis for DFS and OS, respectively.
Conclusion:
This is the first prognostic factor analysis in resected NSCLC performed on data from a large, prospective randomized study. It highlighted that in terms of DFS, SCC patients have a better prognosis than non-SCC patients. N-category plays a major role in determining prognosis. Operative technique (pneumectomy), number of chemotherapy cycles (SCC) and gender (non-SCC) are also associated with outcome. Variables predictive for OS are N-category and tumor size (all) and region (non-SCC). These results confirm retrospective studies done within the context of TNM classification, but add that histopathology subtype is a strong determinant for DFS in resected NSCLC.
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