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D. De Ruysscher
Moderator of
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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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MA06 - Locally Advanced NSCLC: Risk Groups, Biological Factors and Treatment Choices (ID 379)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:P. Van Houtte, M. Zemanová
- Coordinates: 12/05/2016, 16:00 - 17:30, Strauss 2
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MA06.05 - Screening for Brain Metastases in Patients with Stage III NSCLC, MRI or CT? A Prospective Study (ID 5664)
16:30 - 16:36 | Author(s): D. De Ruysscher
- Abstract
- Presentation
Background:
In all current non-small cell lung cancer (NSCLC) guidelines it is advised to screen all stage III patients for brain metastases, preferably by magnetic resonance imaging (MRI), or otherwise a contrast-enhanced computed tomography (CE-CT). Access to MRI can be problematic and a dedicated brain CE-CT can be incorporated in the staging [18]Fluodeoxoglucose-positron-emission-tomography ([18]FDG-PET)-CT scan. The additive value of a brain MRI after a dedicated brain CE-CT scan is unknown.
Methods:
In this observational prospective multicentre study all consecutive stage III NSCLC patients scheduled for treatment with curative intent from three Dutch hospitals who underwent a dedicated brain CE-CT incorporated in the staging [18]FDG-PET and an additional brain MRI were included. Patients with another primary tumour within 2 years of NSCLC diagnosis were excluded. Data regarding patient characteristics and imaging results were collected. Primary endpoint was the percentage of patients diagnosed with brain metastases on MRI without suspect lesions on CE-CT. 118 patients were needed to show a clinically relevant considered difference of 2%.
Results:
Between December 14[th] 2012 and July 15[th] 2016, 264 consecutive patients had an extracranial stage III NSCLC based on [18]FDG-PET. 111 out of these 264 patients (42.0%) were excluded because of no dedicated brain CE-CT 57 (51.4%) had only a low dose CT for attenuation correction, 54 (48.6%) had a CE-CT but without dedicated brain imaging protocol). Fourty (26.1%) of the remaining 153 patients were excluded because of asymptomatic brain metastases on dedicated CE-CT brain (N=8), second primary (N=6) or no brain MRI (N=26). 113 stage III patients were included (updated results of 118 patients will be presented). 57.5% of the included patients were male; mean age was 67.0 years, 84.1% had WHO PS 0-1, 60.2% had stage IIIA (before MRI brain) and 42.5% had an adenocarcinoma. Median time (range) between [18]FDG-PET-CE-CT and MRI was 2.0 (0.0 -8.1) weeks. 5/113 (4.4%) patients had a solitary brain metastasis on MRI despite no suspect brain lesions on CE-CT. In retrospect, in one of these five patients a solitary brain metastasis could be identified on the [18]FDG-PET–CE-CT.
Conclusion:
Although asymptomatic brain metastasis were detected in staging CE-CT, MRI brain is in daily practice clinically relevant superior to a CE-CT in screening for brain metastases in stage III NSCLC
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MTE20 - Radiotherapy of Locally Advanced NCSLC: Selecting the Right Patient for the Right Radiotherapy (Ticketed Session) (ID 446)
- Event: WCLC 2016
- Type: Meet the Expert Session (Ticketed Session)
- Track: Radiotherapy
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 07:30 - 08:30, Stolz 2
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MTE20.01 - Radiotherapy of Locally Advance NCSLC: Selecting the Right Patient for the Right Radiotherapy (ID 6509)
07:30 - 08:30 | Author(s): D. De Ruysscher
- Abstract
- Presentation
Abstract not provided
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P2.02 - Poster Session with Presenters Present (ID 462)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.02-021 - Extracranial Progression (ePD) after Chemoradiotherapy (CRT) for Stage III NSCLC: Does the Chemotherapy Regimen Matter? (ID 4887)
14:30 - 14:30 | Author(s): D. De Ruysscher
- Abstract
Background:
In stage III NSCLC concurrent chemoradiation (cCRT) compares favourably to sequential CRT (sCRT). No superior chemotherapy regimen has been identified regarding (extracranial)PD. Previously we reported that the specific chemotherapy did not influence symptomatic brain metastases incidence. Here we analyse whether the specific chemotherapy influences occurrence of extracranialPD as first PD site (ePD~first~) after CRT.
Methods:
This retrospective multicenter study included all consecutive stage III NSCLC patients that completed CRT between 01-2006 and 06-2014. Primary endpoint was ePD~first ~(with/without cranial PD). Differences between regimens were assessed using logistic regression modelling including known relapse risk factors (age, gender, stage, histology) and the specific chemotherapy: cCRT versus sCRT. Within cCRT: daily low dose cisplatin (LDC) versus cyclic dose polychemotherapy (CDC); LDC versus (non-)taxane CDC; LDC versus subgroups of ≥50 CDC patients).
Results:
838 patients (737 cCRT, 101 sCRT) from 5 institutions were eligible. Median follow-up [95% CI] was 45.1 [42.3-47.8] months. 530 (63.2%) had PD, of which 463 (87.4%) had ePD~first. ~Median time to ePD~first~ was 16.6 [14.5-18.7] months. Patients with ePD~first~ had more often squamous histology (p=0.04). ePD~first~% or median time to ePD~first~ was not different for sCRT versus cCRT (table 1). 461 (62.6%) patients had PD after cCRT, of whom 401 (87.0%) had ePD~first~. ePD~first~% or median time to ePD~first~ did not differ between LDC and CDC. The chemotherapy regimen (cCRT versus sCRT) did not influence ePD~first~ on multivariate analysis: OR 0.81 [0.52-1.24] (p=0.33). LDC versus CDC cCRT did not differ: OR 0.96 [0.72-1.29] (p=0.80). Comparable results were found for LDC versus CDC non-taxane (N=277) and CDC taxane regimens (N=69) and for cCRT regimens with ≥50 patients (LDC versus cisplatin/etoposide (N=188), cisplatin/vinorelbin (N=65), weekly cisplatin/docetaxel (N=60)).Table1
concurrent N=737 sequential N=101 p-value PD N(%) 461 (62.6) 68 (68.3) 0.18 ePDfirst N(%) -patients with concomitant brain metastases 401 (87.0) -38 (9.5) 62 (89.9) -8 (12.9) 0.19 median time to ePD [95%CI] months 17.5 [15.0-20.0] 14.3 [11.9-16.7] 0.16 LDC N=391 cyclic dose N=346 p-value PD N(%) 245 (62.7) 216 (62.4) 0.33 ePDfirst N(%) -patients with concomitant brain metastases 211 (86.1) -17 (8.1) 190 (88.0) -21 (11.1) 0.80 median time to ePD [95%CI] months 17.4 [14.3-20.5] 18.3 [14.2-22.5] 0.59
Conclusion:
Sixty-three percent of stage III NSCLC patients developed PD, of whom 87% had ePD~first~. Incidence of ePD~first~ is independent of the specific chemotherapy regimen.
