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D.P. Steinfort
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MINI 20 - Surgery (ID 137)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:G. Veronesi, R. Flores
- Coordinates: 9/08/2015, 16:45 - 18:15, 201+203
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MINI20.13 - A Prospective Comparison of FDG-PET & EBUS for Determining the Extent of Mediastinal Lymph Node Involvement in NSCLC (ID 2323)
17:55 - 18:00 | Author(s): D.P. Steinfort
- Abstract
- Presentation
Background:
Non-small cell lung cancer (NSCLC) may be treated with curative intent using radiotherapy, either as single modality or in combination with systemic chemotherapy. Most commonly, radiation treatment is planned based on findings at 18-Fluorodeoxyglucose Positron Emission Tomography (PET), following pathologic confirmation of involvement at a single mediastinal site. We hypothesized that systematic mediastinal evaluation with EBUS-TBNA in NSCLC patients considered for radical radiation therapy may identify disease extent discrepant with that indicated by PET-CT.
Methods:
This prospective ethics board-approved multi-centre cohort study in three Austrailan tertiary centres consented patients prior to mediastinal evaluation with Endobronchial Ultrasound-guided Transbronchial Needle Aspiration (EBUS-TBNA) for NSCLC,where non-invasive imaging indicated the likely treatment modality would include radical radiotherapy. EBUS evaluation was performed systematically with sampling of any lymph node (LN) exceeding 6mm diameter.
Results:
Thirty eligible patients with NSCLC form the basis of this report. No procedural complications occurred during performance of EBUS-TBNA. LN sampling was performed from a mean 2.5 lymph node stations per patient (median 3,range 1–5). Adequate samples were obtained from all sites examined by EBUS-TBNA. Mean long-axis size of sampled LN was 16+7.8mm (median 13mm,range 5–36mm). 24% of sampled LN were 10mm or less. Discordant findings were observed in 10 of 30 patients (33%) (Figure 1) EBUS-TBNA identified a greater extent of mediastinal involvement than PET in four patients, with invasive sampling resulting in upstaging in three patients. In one further patient, extent of disease was greater than noted on PET due to more proximal involvement of LN disease not resulting in stage advancement. Median size of LN upstaged by EBUS was 7.5mm (range 7–9). In eleven mediastinal LN in six patients, EBUS identified a lesser extent of mediastinal disease than PET, including two patients down-staged from N3 à N2. Median size of LN down-staged by EBUS was 12mm (range 6–21). FIGURE 1. Flowchart of patients Figure 1
Conclusion:
Our findings demonstrate clinically significant discrepancy between two modalities frequently used to stage mediastinal disease extent in NSCLC patients being considered for radiotherapy. PET-based radiotherapy planning alone may not be appropriate given the risk of excessively large, or insufficiently large, radiation fields where planning is not based on invasive LN sampling. These results suggest minimally invasive comprehensive/systematic mediastinal staging should be considered for all patients prior to radiotherapy to accurately assess pathologic stage and extent of disease, and to ensure treatment fields most accurately encompass all sites of disease.
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ORAL 36 - Translational Science/Radiation (ID 151)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:E. Vokes, B. Kavanagh
- Coordinates: 9/09/2015, 16:45 - 18:15, Mile High Ballroom 2c-3c
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ORAL36.06 - 4D-VQ-PET/CT Imaging Allows Strong Correlation Between Radiotherapy Dose and Change in Lung Ventilation, Perfusion and Density (ID 211)
17:39 - 17:50 | Author(s): D.P. Steinfort
- Abstract
- Presentation
Background:
[68]Ga-V/Q PET/CT is a novel imaging modality for assessment of perfusion(Q), ventilation(V) and lung density changes in the context of radiotherapy (RT) for non-small cell lung cancer.
Methods:
In a prospective clinical trial, 20 patients underwent 4D-V/Q PET/CT before treatment, 4 weeks into treatment and 3 months after definitive lung RT. Eligible patients were prescribed 60 Gy in 30 fractions with or without concurrent chemotherapy. Functional images were registered to the RT planning 4D-CT and isodose volumes averaged into 10 Gy bins. Within each dose bin, relative loss in SUV was recorded for ventilation and perfusion, and loss in air-filled fraction was recorded to assess RT-induced lung fibrosis. A dose-effect relationship was described using both linear and 2-parameter logistic fit models and goodness of fit assessed using Akaike Information Criterion (AIC).
Results:
A total of 179 imaging datasets were available for analysis (1 scan unrecoverable). An almost perfectly linear dose-response relationship was observed for perfusion and air-filled fraction (r[2] = 0.99, p < 0.01), with ventilation also strongly linear (r[2] = 0.95, p < 0.01) [Figure]. Logistic models did not provide a better fit as evaluated by AIC [Table]. Perfusion, ventilation and the air-filled fraction changed by -7.5% ± 0.3%, -7.1% ± 0.6% and 4.9% ± 0.02% per 10 Gy, respectively. Within high-dose regions, higher baseline SUV was associated with greater rate of loss. At 50Gy and 60Gy the rate of loss was 1.35% (p = 0.07) and 1.73% (p = 0.05) per SUV, respectively. Of 8/20 patients with peri-tumoral reperfusion / re-ventilation during treatment, 7/8 did not sustain this effect post-treatment. Figure 1 Figure 2
Conclusion:
RT induced regional lung functional deficits occur in a dose dependent manner and can be estimated using simple linear models with 4D-V/Q PET/CT imaging. These findings may inform functional lung sparing by planning RT using this novel imaging technology.
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P1.02 - Poster Session/ Treatment of Localized Disease – NSCLC (ID 209)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.02-023 - The Role of Selective EBUS-TBNA Mediastinal Sampling in Early Lung Cancer (ID 542)
09:30 - 09:30 | Author(s): D.P. Steinfort
- Abstract
Background:
Accurate pre-operative staging of the mediastinum in lung cancer is essential to determine the type of treatment. The commonly used investigations are CT scan, PET scan, EBUS-TBNA (Endobronchial ultrasound-guided transbronchial needle aspiration) and mediastinoscopy, and often these tests complement each other to increase the accuracy of staging. With advances in technology and increased experience, EBUS has the potential to replace mediastinoscopy to stage the mediastinum. Surgical mediastinal dissection, though commonly performed, has not been convincingly proven to have a therapeutic value. We postulate that if the mediastinum can be staged accurately with EBUS-TBNA (a low morbid procedure) then a surgical staging of the mediastinum (mediastinoscopy and / or dissection) can be avoided and therefore, avoid the morbidity associated with these procedures. We have studied the use of selective EBUS-TBNA which is sampling abnormal nodes on imaging (CT, PET scan) and compared it with the mediastinal dissection done surgically.
Methods:
This is a retrospective study of patients who underwent surgery (lobectomy/pneumonectomy + mediastinal lymphnode dissection) for early stage lung cancer (stage I/II).Patients who had negative N2 lymph nodes on EBUS-TBNA evaluation were included in the study. All patients had CT and PET scans which assisted the EBUS study. The results of EBUS-TBNA were compared with that of the surgical mediastinal lymph node dissection.
Results:
A total of 86 patients were included in the study. EBUS-TBNA correctly staged the mediastinum in 78 patients (90.7%, negative predictive value (NPV) = 0.90). Eight patients had false negative (FN) evaluation by EBUS-TBNA. On review, two of these patients had a sampling error. Three patients had incomplete evaluation of the mediastinum. All these 3 patients had left lung cancer whose level 5 lymph nodes could not be sampled, and surgical sampling displayed these nodes to be involved with extracapsular spread. There were three other patients with FN results, and they had mediastinal nodes biopsied by EBUS which with surgical removal showed metastasis. Two of these patients had metastatic deposits < 3mm in size. We feel that diligent and systematic EBUS would have avoided the FN result in most of the above patients except for sampling of level 5 nodes which may not be technically accessible by EBUS. The NPV for right lung cancers, especially right upper lobe (NPV=0.96) was higher as compared to left sided cancers.
Conclusion:
This study shows that selective EBUS-TBNA mediastinal staging in early lung cancer is feasible, has an acceptable NPV and provides evidence to facilitate studies on systematic EBUS. This study draws attention thorough the identified 8 FNs to the real and potentially avoidable limitations of selective EBUS mediastinal lymphnode sampling. The accuracy of systematic EBUS evaluation should be superior to a selective study and can therefore potentially avoid a surgical staging of the mediastinum and its associated complications.
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-051 - Molecular Testing on Cell Blocks Formed From Bronchial Brush Tip Washings (ID 2334)
09:30 - 09:30 | Author(s): D.P. Steinfort
- Abstract
Background:
With the rapid growth of genotype guided targeted therapies, molecular testing is increasingly important for the routine work up in lung cancer. This testing is traditionally performed on biopsy specimens. Bronchoscopy is commonly performed for diagnosis of suspected lung cancer; and multiple sampling modalities are often combined to maximize diagnostic yield. Bronchial brushings are frequently reported to have the highest sensitivity, though the cytology smears generated from these brushings are rarely used for molecular analysis. The aim of this study was to assess the feasibility and accuracy of molecular testing performed on cell blocks (CB) formed from a brush tip wash (BTW).
Methods:
We retrospectively reviewed molecular testing performed on CB from BTW in patients undergoing investigation of peripheral lung lesions between January 2014 and March 2015. During bronchoscopy, brushings were performed and smears created. Following this, the brush tip was then washed in normal saline. This was repeated each time the peripheral lesion was sampled with the bronchial cytology brush. The fluid from the BTW was then processed into a formalin fixed paraffin embedded CB. Patients were included in the study cohort if molecular testing was attempted on the CB created from BTW. The CB specimens underwent molecular testing targeting regions on BRAF (exon 15), KRAS (exon 2,3,4), NRAS (exon 2,3,4), PIK3CA (exon 9. 20) and EGFR (exon 18, 19, 20, 21) genes by amplicon-based parallel sequencing using an Illumina MiSeq.
Results:
There were 22 patients in whom BTW CB was subjected to molecular testing. Results are summarized in figure 1. Figure 1 Figure 1. Results of molecular analysis In fifteen cases (68%) a CB was generated, and was successfully subject to molecular testing. Fourteen of these were adenocarcinomas, in which the frequency of detecting a mutation in any of the five assayed genes was 57% (8/14). This is similar to previous reports of molecular testing on adenocarcinoma from other sampling modalities, and suggests that BTW CB generally contain adequate tumour cells for testing. In seven cases, there was no diagnosis obtained from transbronchial lung biopsy, meaning BTW was the sole specimen available for molecular testing.
Conclusion:
Our results demonstrate that molecular studies can successfully be performed on cell blocks obtained from brush tip wash and that this may be the only sample that has adequate material for analysis. We suggest that brush tip washings be routinely created during bronchoscopy to maximize the likelihood of successful molecular testing.
