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M.R. Mueller
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OA12 - SBRT and Other Issues in Early Stage NSCLC (ID 383)
- Event: WCLC 2016
- Type: Oral Session
- Track: Early Stage NSCLC
- Presentations: 8
- Moderators:D. De Ruysscher, M.R. Mueller
- Coordinates: 12/06/2016, 11:00 - 12:30, Strauss 2
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OA12.01 - Phase II Randomized Study of 2 SBRT Regimens for Medically Inoperable Patients with Node Negative Peripheral NSCLC (ID 4342)
11:00 - 11:10 | Author(s): J.A. Gomez Suescun, G.M.M. Videtic, K. Stephans, J. Bogart, L. Tian, A. Groman, A.K. Singh
- Abstract
- Presentation
Background:
This phase II, multi-institutional (Roswell Park Cancer Institute, Cleveland Clinic, and Upstate Medical Center) randomized study was conducted to compare incidence of RTOG grade 3 or higher adverse events (AEs) associated with 2 different, established SBRT regimens for NSCLC
Methods:
Patients with documented baseline medical conditions precluding lobectomy and biopsy-proven peripheral (greater than 2 cm from the central bronchial tree) T1/T2, N0 (clinically node negative by PET), M0 tumors were eligible. Patients were randomized to receive either 30 Gy in one fraction (arm 1) or 60 Gy in 3 fractions (arm 2) over at least 8 days. Heterogeneity corrections were not used. Randomization was stratified by treatment center and Karnofsky performance status (100, 90, 80 and below.) The study was designed to detect whether psAEs rate > 17% at a 5% significance level (1-sided) and 81% power. Secondary endpoints included: local control, greater than 1 year toxicity, overall survival (OS) and progression-free survival (PFS).
Results:
The study opened in September 2008, was suspended between April 2010 to June 2010 as well as October 2010 to April 2011 while RTOG 0915 was open, and closed on April 15, 2015 after accruing a total of 98 patients. All patients received planned SBRT treatment. Median follow-up was 27 months. In follow-up, 10 patients were lost to follow-up; 1 was in arm 1 and 9 in arm 2. Baseline patient and tumor characteristics were balanced between both arms. On arm 1, 13 (27%) patients and 16 (33%) patients on arm 2 experienced RTOG grade 3 AEs, there were no grade 4 AEs. Thoracic grade 3 AEs were experienced by 8 (16%) patients on arm 1 and 6 (12%) patients on arm 2. There were no differences in OS or PFS survival, logrank p= 0.44 and 0.99 respectively. OS at 2 years was 71% (95% CI, 55-82%) for arm 1 and 61% (95% CI, 44-78%) for arm 2. PFS at 1 year was 63% (95% CI, 46-75%) for arm 1 and 51% (95% CI, 34-65%) for arm 2.
Conclusion:
This randomized phase II study demonstrated that 30 Gy in one fraction was equivalent to 60 Gy in three fractions in terms of toxicity, progression free survival and overall survival. Acknowledgment: Supported by Roswell Park Alliance Foundation grant
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OA12.02 - Excellent Survival Achieved by Stereotactic Body Radiotherapy for Medically Operable and Young (< 75 Years) Patients with Stage I Lung Cancer (ID 5019)
11:10 - 11:20 | Author(s): H. Onishi, Y. Shioyama, Y. Matsumoto, K. Takayama, Y. Matsuo, A. Miyakawa, H. Yamashita, H. Matsushita, M. Aoki, K. Nihei
- Abstract
- Presentation
Background:
Stereotactic body radiotherapy (SBRT) has been sometimes used as a curative treatment for both of medically operable patients with stage I non-small cell lung cancer (NSCLC). However, most of these patients are comparatively high-aged and not similar to the patients cohort generally operated with surgery. So, the purpose of this study was to collect results of SBRT for operable and young (70 years old or younger) patients with stage I NSCLC from multiple Japanese institutions.
Methods:
We organized a multi-institutional SBRT study group in Japanese Radiological Society (JRS-SBRTSG) and conducted a study for SBRT for stage I non-small cell lung cancer (NSCLC). This is a retrospective analysis to review 252 patients (male 168, female 84) who were medically operable and 70 years old or younger (range,40-74; median, 67 years) with stage I (IA 211, IB 41) NSCLC treated with curative intent by SBRT in 20 institutions of JRS-SBRTSG. Histology was proven in 177 patients (adenocarcinoma 121, squamous cell carcinoma 41, others 15), and the others were diagnosed clinically. Median tumor size was 22mm (range, 5-49mm). A total dose of 40 -70 Gy mainly was prescribed in 4-10fractions. Median calculated biological effective dose (BED) was 107 Gy (range, 75-134 Gy) based on alpha/beta = 10Gy).
Results:
The median follow-up period for all patients was 37 months. Overall survival rate (OS) at three and five year was 83.3% and 76.6%, respectively. Radiation pneumonitis of grade 3 or more was noted in 0.8% of the total patients. In the total patients, local control rate (LC) at three year was 89.5%, and LC was significantly better in the subgroup of adenocarcinoma than that of squamous cell carcinoma. According to univariate analysis, female, adenocarcinoma, no emphysema, and no pulmonary interstitial change were better prognostic factors for OS. According to multivariate analysis, pulmonary interstitial change was only a worse survival factor for OS. OS at three and five year in the subgroup of patients without pulmonary interstitial change was 89.7% and 84.0%, respectively.
Conclusion:
The outcomes of SBRT for the medically operable and young (75 years or younger) patients with stage I NSCLC in the Japanese large database of practice level was excellent and the overall survival rate would be comparable to that of surgery. The results will support a rationale of applying SBRT for younger and operable patients with operable stage I NSCLC.
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OA12.03 - Percutaneous Cryoablation for Lung Cancer Patients for Whom Surgery or Radiotherapy is Contraindicated Due to Idiopathic Pulmonary Fibrosis (ID 3830)
11:20 - 11:30 | Author(s): T. Ohtsuka, K. Asakura, K. Masai, K. Kaseda, I. Kamiyama, M. Inoue, S. Nakatsuka, H. Asamura
- Abstract
- Presentation
Background:
Interstitial lung disease, such as idiopathic pulmonary fibrosis (IPF), have been widely known to be associated with lung cancer. Lung cancer patients concomitant with IPF sometimes develop a life-threatening acute exacerbation after surgery or radiotherapy. Percutaneous cryoablation is evolving as a potentially less invasive local treatment for lung cancer. The purpose of this study is to retrospectively analyze the outcomes of cryoablation for clinical T1N0M0 non-small cell lung cancer (NSCLC) patients for whom surgery or radiotherapy is contraindicated because of IPF.
Methods:
Between December 2003 to March 2016, 210 patients underwent computer tomography guided percutaneous cryoablation for lung tumors at our institution. Of these, 11 histologically proven clinical T1N0M0 NSCLC patients, for whom surgery or radiotherapy was considered contraindicated because of severe IPF, were retrospectively reviewed. Complications, local progression-free survival and clinicopathological factors were evaluated.
Results:
The cohort was composed of 11 men with a mean age of 74 years (range: 68 to 82). The median follow-up time was 20 months (range: 6 to 55 months). The mean Krebs von den Lungen-6 (KL-6) level was 1608 ±1025 U/mL. The mean tumor size was 24 ± 7mm. The mean percentage of predicted diffusing capacity for carbon monoxide (DLCO) was 37±27%. Thirty and 90-day mortality was 0 and 18%, respectively. Two patients required chest tube drainage because of severe pneumothorax. Acute exacerbation of IPF occurred in two patients (18%). The use of oral steroids and need for chest tube drainage were predictors of higher mortality (p < 0.05) and higher incidence of acute exacerbation of IPF (p < 0.05). However, higher level of KL-6 and low percentage of DLCO were not significant risk factors of mortality or acute exacerbation of IPF. Local progression-free survival at 1, 2 and 3 year was 51, 41 and 31%, respectively.
Conclusion:
Percutaneous cryoablation for lung cancer patients with IPF provoked acute exacerbation of IPF in 18% of patients. The use of oral steroids and need for chest tube drainage were predictors of higher mortality and higher incidence of acute exacerbation of IPF.
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OA12.04 - Discussant for OA12.01, OA12.02, OA12.03 (ID 7070)
11:30 - 11:45 | Author(s): M. Guckenberger
- Abstract
- Presentation
Abstract not provided
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- Abstract
- Presentation
Background:
CT screening programs frequently detect early stage lung adenocarcinoma. Recent studies show that distinct subtypes of lung adenocarcinoma are associated with different prognosis and suggest that treatment should be tailored to histological subtypes as identified in the new WHO Lung Tumor Classification. To develop this personalized approach, it is important to have reliable tools to diagnose tumors before treatment, preferably non-invasively through image analysis. We have developed a CT-image analysis system (iBiopsy) that uses computerized deep learning and artificial intelligence. To validate the accuracy of a noninvasive CT-based image biopsy system (iBiopsy) in differentiating early stage lung adenocarcinoma subtypes of atypical adenomatous hyperplasia (AAH), adenocaricnoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC).
Methods:
We retrospectively identified 365 eligible patients from Zhongshan Hopsital Fudan University, diagnosed with AAH, AIS, MIA or IAC by surgical pathological diagnosis. The last high definition CT scan prior to the surgery of the lesion was analyzed using the iBiopsy system, blinded to pathological result. Based on a pulmonary nodule image feature set (PNIFS) in combination with classified pattern models, such as R-SVM, all the pulmonary nodules were classified into four groups. For diagnosis efficacy, area under the curve (AUC) of Precision-Recall score (PRS), receiver operating characteristic (ROC) of a classification model were calculated in each group.
Results:
365 patients were included in the analysis. The classification recognition rate of the PNIFS was 80.03%. The average value of PRS is 0.92, the mean of ROC is 0.95, and it is more than 0.80 for the cross validation value.
Conclusion:
iBiopsy system allows the non-invasive imaged based stratification of pulmonary adenocarcinoma nodules into four groups, from AAH to IAC. Our result suggest that iBiopsy system could ultimate facilitate the diagnosis and precision management of pulmonary nodules.
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OA12.06 - A Retrospective Analysis of Patients with Small Lung Adenocarcinoma (≤2cm) by New World Health Organization Classification (ID 5844)
11:55 - 12:05 | Author(s): K. Nakao, J. Nitadori, S. Morita, H. Kuwano, K. Nagayama, M. Anraku, A. Shinozaki-Ushiku, M. Sato, M. Fukayama, J. Nakajima
- Abstract
- Presentation
Background:
We have recently demonstrated that the presence of the Spread Through Air Spaces (STAS) and the variety of histologic subtypes increase the risk of recurrence after resection for small lung adenocarcinoma (ADC). Currently, the new World Health Organization classification of lung cancers was revised and newly prescribed to describe the presence of each histologic subtypes and STAS. The purpose of this study is to examine the risk factor for recurrence other than TNM staging analyzing clinical information retrospectively.
Methods:
All available tumor slides from patients with clinical stage I, therapy-naive, surgically resected solitary lung ADC ≤2 cm in size (1998-2015) were reviewed. Each tumor was evaluated by comprehensive histologic subtyping, and the percentage of each histologic component was recorded in 5% increments. STAS was defined as the spread of tumor cells into air spaces in the lung parenchyma adjacent to the main tumor according to the WHO classification. Recurrence-free probability (RFP) was estimated using the Kaplan-Meier method.
Results:
354 patients met inclusion criteria (52.3% men; median age: 67yrs; median tumor size: 1.3cm; 325 stage IA/ 29 stage IB; 91 partial resection/ 22 segmentectomy / 241 lobectomy or pneumonectomy). The prognosis didn’t differ significantly between sublobar resection group and lobectomy or pneumonectomy group (5-year RFP: 88.4% (N=113) vs. 91.9% (N=241), P=.162). Presence of STAS was identified in 74 cases (20.9%) (36 Micropapillary pattern / 55 Solid pattern / 15 Single cells). STAS was significantly associated with recurrence (5-year RFP: 94.3% vs. 76.2%, P < .0001). Histologic subtypes were 62 adenocarcinoma in situ (18%), 110 minimally invasive adenocarcinoma (31%) and 182 invasive adenocarcinoma (51%). The recurrence after sublobar resection was seen in 13 cases (1 partial resection (4.5%) / 12 segmentectomy (13%), 5 STAS (+)/ 8 STAS (-), 6 solid predominant / 5 acinar predominant / 2 lepedic predominant, 5 pulmonary recurrence / 4 lymph node recurrence / 2 local recurrence / 2 others). Patients with solid component had significantly worse prognosis (5-year RFP: 71.7% (N=83) vs. 96.3% (N=271), P<.0001). Among them, patients with sublobar resection had significantly more recurrence than with lobectomy or pneumonectomy (5-year RFP: 51.4% (N=19) vs. 77.7% (N=64), P=.0021).
Conclusion:
The patients of small ADC with STAS or solid component had worse prognosis. The patients after sublobar resection with solid component should be made follow-up closely. We propose that the presence of those features should be considered a factor to upgrade the pathologically defined T stage.
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- Abstract
- Presentation
Background:
The newly proposed International Association for the Study of Lung Cancer (IASLC) staging system reclassified T2aN0M0 tumors greater than 4 cm as stage IIA instead of stage IB. This study investigated the role of adjuvant chemotherapy in pathologic stage IB non-small cell lung cancer (NSCLC).
Methods:
The patients with pathologic T2aN0M0 NSCLC who underwent complete resection between 2001 and 2013 were identified from prospectively maintained databases, and classified into three groups based on tumor size: A (≤3.0 cm, n = 205), B (3.1-4.0 cm, n = 264), and C (>4.0 cm, n = 254). After propensity score matching, overall survival (OS) and freedom from recurrence (FFR) were compared between each group of paired patients who received platinum-based adjuvant chemotherapy and those who did not.
Results:
Among the 723 patients, 134 patients (18.5%) received adjuvant chemotherapy: Group A, 38 (18.5%) patients; Group B, 47 (17.8%); and Group C, 49 (19.3%). Matching based on propensity scored produced 38, 47, and 49 paired patients in Group A, B, and C, respectively. In Group A and B, there was no significant difference in OS and FFR between patients who received adjuvant chemotherapy and those who did not. In Group C, patients who received adjuvant chemotherapy experienced less recurrence and higher survival than those who did not. The 5-year FFR was 79.0% in in patients who received adjuvant chemotherapy and 66.1% in patients with surgery alone (p = 0.090). The 5-year OS was 95.8% in patients who received adjuvant chemotherapy and 68.9% in patients with surgery alone (p < 0.001). Figure 1
Conclusion:
Adjuvant chemotherapy was related with reduced recurrence and improved survival in patients with T2a tumors exceeding 4 cm. In considering the next upcoming 8[th ]edition of the TNM classification, adjuvant chemotherapy is a worthwhile and justified treatment for tumors greater than 4 cm with early stage disease.
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OA12.08 - Discussant for OA12.05, OA12.06, OA12.07 (ID 6987)
12:15 - 12:30 | Author(s): R. Waseda
- Abstract
- Presentation
Abstract not provided
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Author of
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ED08 - Early-Stage NSCLC: State-of-the-Art Treatment and Perspectives (ID 276)
- Event: WCLC 2016
- Type: Education Session
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:T. Le Chevalier, M. Tsuboi
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall C2
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ED08.01 - Surgery of Early-Stage NSCLC (ID 6469)
14:30 - 14:50 | Author(s): M.R. Mueller
- Abstract
- Presentation
Abstract:
General considerations Early stage lung cancer - a term in transition Generally early stage lung cancer is understood as stage I and stage II non-small lung cancer. An alternative understanding of early stage lung cancer is resectable disease. However, both definitions are imprecise and subject to development and Expertise. 1. Defining early stage lung cancer as resectable disease depends on regional philosophies and local expertise and therefore is the most unreliable and variable definition. The term resectability focuses on the T factor of the tumour and describes the ability of the surgeon to achieve radical resection. In contrast operability includes any potential regional and systemic spread and focuses more on the N and M descriptors. 2. Defining early stage lung cancer based on mediastinal nodal involvement neglects the fact, that single station N2 (N2a) is associated with the same five-year survival as multistation N1 (N1b). This touches on the term locally advanced disease, which in fact also means different things for different people. For the oncologist locally advanced disease usually means N2 involvement with the consequent call for chemotherapy. For the surgeon locally advanced disease primarily addresses the T factor and is used for T3 or T4 tumours, indicating more extended resections in the absence of N2 disease. In summary, terms like early stage, locally advanced stage or advanced stage should be avoided since they do not properly describe a clinical situation nor are they guiding therapy. If the term early stage lung cancer should be maintained for any reason, there is need for revisions. The five-year survival of stage I and stage II non-small lung cancer is a range of less than 30 to more than 90% and the survival expectedly mainly depends on nodal involvement. The estimated median five-year survival of patients with Screening detected T1N0 NSCLC is a reported 92%. Even nodal negativeT3 tumours are associated with almost 60% five year survival following radical resection. On the other hand involvement of multiple N1 lymph nodes results in a much worse prognosis of about 35%. However, for this presentation the current definition of stage I and stage II non-small lung cancer was used. Preoperative staging Resectability of lung cancer for technical reasons in general, and in early stage lung cancer in particular, very rarely is an issue. Oncological operability has to be defined preoperatively along international guidelines. The European Society of Thoracic Surgeons (ESTS) recently has ublished revised guidelines for preoperative mediastinal lymph nodes staging for non-small cell lung cancer. Only one selected group of patients with tumours of less than 3 cm in diameter (cT1) in the outer third of the lung without signs of nodal involvement at CT scan, PET scan or PET CT (cN0) may directly undergo surgical resection. All other clinical situations require invasive preoperative staging by bronchoscopy plus EBUS/EUS. If the absence of nodal involvement is verified by EBUS/EUS this patient may also directly undergo surgery. In the presence of radiologically suspect mediastinal lymph nodes and negative EBUS/EUS further confirmation is recommended using mediastinoscopy or thoracoscopy. If mediastinal nodal involvement is histologically verified by any means the patient has to undergo multimodality treatment. All clinical findings are to be discussed in an interdisciplinary tumour board for proper therapy planning. [1] Surgical therapy of early stage NSCLC Surgery remains the cornerstone of treatment of early stage non-small lung cancer for patients willing to accept the procedure-related risks. Goal of any surgical intervention for early stage lung cancer is the complete resection of the primary tumour together with regional lymphatic nodes. The standard for any resection with curative intent is defined by anatomical lung resection. In early stage lung cancer the predominant type of resection is lobectomy or bilobectomy, sometimes along with bronchoplastic or angioplastic procedures or extended resections for locally invading T3 tumours. Pneumonectomy particularly in the treatment of early stage lung cancer is rarely used. Gold standard of surgical resection for lung cancer is lobectomy. This standard is based on a prospective multi-institutional randomized trial comparing limited resection with lobectomy for peripheral T1N0 non-small cell lung cancer published in 1995. [2 ]In the absence of more recent prospective randomised trials lobectomy still must be considered the surgical procedure of choice for patients with peripheral T1N0 non-small cell lung cancer. An extensive body of literature mainly composed of retrospective studies supports the use of radical anatomical segmentectomy for peripheral cT1N0M0 non-small lung cancer with less than 2 cm in diameter, certainly for older patients with limited cardiopulmonary function. However, caution should be taken to promote a widespread indication for intentional segmentectomy in young good surgical candidates until the results of the ongoing randomised controlled trials become available.[ 3,4] The role of minimally invasive surgery Minimally invasive anatomical resection for lung cancer carried out by means of video-assisted thoracic surgery (VATS) has been increasingly carried out during the past years. A systematic review and meta-analysis of randomized and nonrandomized trials published in 2009 reported an improved five-year survival and reduced systemic recurrences in patients who received VATS lobectomy. [5 ]A multicentric propensity-matched analysis of more than 1000 patients, of which 700 had undergone VATS lobectomy confirms, that thoracoscopic lobectomy is associated with lower morbidity as compared with thoracotomy. The positive impact of minimally invasive surgery in the treatment of lung cancer particularly applies to the elderly. [6] Regarding long-term survival after video-assisted thoracoscopic lobectomy a meta- showed a survival benefit in the favour of VATS with a difference in survival of 5% at five years. The reason for this observed survival benefit may be attributed to a less pronounced compromise of the immunocompetence after the surgical trauma. [7] The role of mediastinal lymph node dissection The rationale for a formal mediastinal lymph node dissection is multifold. The distribution pattern of mediastinal lymph node metastasis is not predictable and skip metastasis are seen in up to 30% of patients. Even small tumours may present with unexpected N2 disease with an incidence of 6-10%. The operative morbidity is not significantly influenced by a systematic mediastinal lymph node dissection. Recommended standard of mediastinal lymph node dissection is the removal of all mediastinal tissue containing lymph nodes in a systematic Approach within anatomical landmarks. The most recent randomized controlled trial published in 2011 did not find a survival benefit by complete mediastinal lymphadenectomy in patients with early stage lung cancer, but the results should not be generalized to patients staged only radiographically or those with higher stage tumours. The recommendation from this study is that a formal mediastinal en-bloc dissection may still affect survival and certainly optimally stages patients. In the subgroup analysis no difference between VATS and open lobectomy was observed for number of lymph nodes harvested and regarding long-term survival.[8] As minimally invasive surgery along with unilateral mediastinal lymphadenectomy generally prolongs operation times and the requirement of single lung ventilation the advantages for the elderly population has to be questioned and discussed individually. An alternative to thoracoscopic unilateral lymphadenectomy is offered by video-assisted mediastinal lymphadenectomy through the neck (VAMLA). The approach is similar to transcervical mediastinoscopy and allows for a radical bloc dissection of all mediastinal lymph node stations. Besides the benefit of bilateral lung ventilation during this phase of the operation a bilateral mediastinal lymphadenectomy offers improved surgical radicality. Alternatives to surgical resection and the role of primary radiotherapy In patients unfit for surgery SABR is the treatment of choice for peripherally located stage I non-small cell lung cancer. If SABR is not available a hypofractionated radiotherapy is advocated. A systematic Review comparing outcomes of SABR and surgery in patients with severe COPD revealed a higher 30 day mortality following surgery but similar overall survival at one and three years. [9] In a meta-analysis of 19 out of 318 papers with the best evidence addressing a comparison of SABR and surgical wedge resection both methods proved as reasonable alternatives to lobectomy in high risk surgical patients. In this analysis SABR was associated with reduced local recurrence compared to wedge resection and should be considered when wedge resection is planned due to anatomical location and size of the primary tumour in a patient who is high risk for surgery. [10] Although local tumour control may be comparable or even superior to extra-anatomic surgical resection a quite high rate of late radiological changes after stereotactic ablative radiotherapy for early stage lung cancer has to be considered. At one year follow-up the predicted probability of having expected or pronounced radiological changes after SABR were 65 and 22%. These changes included phenomena like mass-like appearance, radiation fibrosis, and rib fractures, which sometimes are difficult to differentiate from tumour recurrence. Summary The ACCP guidelines address the question, who had to be considered a high risk candidate for surgery. With the advent of minimally invasive resection, the criteria to classify a patient as too ill to undergo an anatomic lung resection are being redefined. Surgical resection remains the primary and preferred approach to the treatment of stage I and II NSCLC in patients with good or low surgical risk. Primary radiation therapy remains the primary curative intent approach for patients who refuse surgical resection or are determined by a multidisciplinary team to be inoperable. [11] References 1. Revised ESTS guidelines for preoperative mediastinal lymph node staging for non-small-cell lung cancer. De Leyn P, Dooms C, Kuzdzal J, Lardinois D, Passlick B, Rami-Porta R, Turna A, Van Schil P, Venuta F, Waller D, Weder W, Zielinski M. Eur J Cardiothorac Surg. 2014 May;45(5):787-98 2. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ginsberg RJ; Rubinstein LV. Ann Thorac Surg. 1995; 60(3):615-22; discussion 622-3 3. Tsutani Y, Miyata Y, Nakayama H, et al. Oncologic outcomes of segmentectomy compared with lobectomy for clinical stage IA lung adenocarcinoma: propensity score-matched analysis in a multicenter study. J Thorac Cardiovasc Surg 2013;146:358-64. 4. Zhao X, Qian L, Luo Q, et al. Segmentectomy as a safe and equally effective surgical option under complete video-assisted thoracic surgery for patients of stage I non-small cell lung cancer. J Cardiothorac Surg 2013;8:116, 5. Yan TD, Black D, Bannon PG, McCaughan BC. Systematic review and metaanalysis of randomized and non-randomized Trials on safety and efficacy of videoassisted thoracic surgery lobectomy for early-stage non-small cell lung cancer. J Clin Oncol 2009; 27: 2553–2562 6. Thoracoscopic lobectomy is associated with lower morbidity compared with thoracotomy.Villamizar NR, Darrabie MD, Burfeind WR, Petersen RP, Onaitis MW, Toloza E, Harpole DH, D'Amico TA. J Thorac Cardiovasc Surg. 2009 Aug;138(2):419-25. 7. Long-term survival in video-assisted thoracoscopic lobectomy vs open lobectomy in lung-cancer patients: a meta-analysis. Taioli E, Lee DS, Lesser M, Flores R. Eur J Cardiothorac Surg. 2013 Feb 14. 8. Darling GE, et al. Randomized trial of m diastinal lymph node sampling versus complete lymphadenectomy during pulmonary resection in the patient with N0 or N1 less than hilar) non-small cell carcinoma. J Thorac Cardiovasc Surg 011;141:662-70 9. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, Treatment and follow-up. J. Vansteenkiste, D. De Ruysscher, W. E. E. Eberhardt, E. Lim, S. Senan, E. Felip & S. Peters, on behalf of the ESMO Guidelines Working Group 10. Mahmood S, Bilal H, Faivre-Finn C, Shah R. Is stereotactic ablative radiotherapy equivalent to sublobar resection in high-risk surgical patients with stage I non-small-cell lung cancer? Interact Cardiovasc Thorac Surg. 2013 Nov;17(5):845-53. 11. Treatment of stage I and II non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.Howington JA, Blum MG, Chang AC, Balekian AA, Murthy SC. Chest. 2013 May;143(5 Suppl)
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