Virtual Library
Start Your Search
C. Dooms
Author of
-
+
P2.02 - Poster Session with Presenters Present (ID 462)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P2.02-045 - Prognostic Value of Metabolic FDG-PET Response in Locally Advanced NSCLC: A Literature Review (ID 4781)
14:30 - 14:30 | Author(s): C. Dooms
- Abstract
Background:
It is still a matter of debate whether metrics of metabolic imaging by [18]F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) predict clinical outcome in non-small cell lung cancer (NSCLC). Pretreatment FDG uptake in the primary tumor has been shown to be a prognostic factor for survival. The prognostic role of FDG-PET in the evaluation of tumor response remains unclear and controversial. Hence, we conducted a comprehensive literature review to assess the prognostic value of FDG-PET/CT response monitoring along multimodality treatment in patients with locally advanced NSCLC.
Methods:
A systematic search of studies published in PubMed was performed using the keywords "positron emission tomography" or “PET”, "non-small cell lung cancer", and “response” or "outcome". References from adequate articles were checked for studies not retrieved by the search strategy. Inclusion criteria were: studies limited to locally advanced NSCLC containing >60% stage III patients, studies in which response monitoring with FDG-PET or PET/CT was performed, and studies that reported survival data.
Results:
Twenty-two studies (median 47 patients, range 15-545) published between 1998 and 2016 were included in the analysis. Ten studies used PET alone while recent trials used integrated PET/CT. PET based response evaluation was performed either after neoadjuvant chemotherapy prior to surgery or radiotherapy either after radical treatment consisting of (chemo)radiotherapy. Eight studies specifically addressed the prognostic value of early metabolic response measurement, either during induction chemo(radio)therapy (n=2) either early in the course of radical (chemo)radiotherapy (n=6). A heterogeneity between the studies was observed regarding timing of the repeat PET, thresholds to define metabolic response, and metrics of metabolic FDG imaging such as MRglu (metabolic rate of glucose), Total Lesion Glycolysis (TLG), Standardized Uptake Value (SUV), SUVmax, SUVpeak, SUVmean or Metabolic Tumor Volume (MTV). All studies showed a significant correlation between either the change in FDG uptake or the residual FDG uptake within the primary tumor and survival.
Conclusion:
Posttreatment FDG-PET/CT has been considered as a useful tool in determining prognosis and guiding therapy for patients with locally advanced NSCLC. Before implementation in routine clinical practice, there is however a need for standardization of PET data acquisition and analysis and a validation of a single definition for metabolic tumor response.
-
+
P2.02-055 - Pathologic Mediastinal Nodal and Metabolic Tumor Response to Predict Overall Survival in Stage IIIA-N2 NSCLC after Neoadjuvant Chemotherapy (ID 5098)
14:30 - 14:30 | Author(s): C. Dooms
- Abstract
Background:
Neoadjuvant chemotherapy (NCT) is a therapeutic option that is used in patients with resectable stage IIIA-N2 NSCLC. We previously hypothesized that combined major histopathological mediastinal nodal response (≤10% residual tumor cells in nodal tissue) and metabolic FDG-PET response (ΔSUVmax ≥60%) on the primary tumor could be regarded as a powerful surrogate of overall survival (OS) in stage IIIA-N2 NSCLC given NCT and confirmed mediastinal nodal disease at diagnosis. This phase II prospective multicenter study aimed to validate the predictive power for OS of our restaging algorithm.
Methods:
Patients with resectable stage IIIA-N2 NSCLC having mediastinal nodal disease proven by endosonography and primary tumor SUVmax at least 2.5 were eligible. All patients were scheduled for 3 cycles of NCT followed by video-assisted mediastinoscopy (VAM). A standardized PET/CT was performed at baseline, after one and three cycles. The primary endpoint was the predictive power for longer OS of a major histopathological mediastinal nodal response at VAM combined with a pre-defined primary tumor SUVmax ≥60% at PET (good prognosis group) compared to all other situations (poor prognosis group). Under an assumption of a 2-year OS of 80% compared to 30% for the good versus poor prognosis group, respectively, 48 patients were required to have 80% power with 2-sided alpha of 0.05.
Results:
We enrolled 32 patients between 2009 and 2014. Two patients demonstrated stage IV at PET/CT after cycle one. All 3 cycles were given to 30 patients of whom 29 underwent VAM and 22 underwent surgical resection. Objective response rate (RECIST 1.1) was 44%. Complete pathological response occurred in 2 patients. Median OS was 26 months (all 2-year events occurred). In ITT, combined major histopathologic nodal and metabolic tumor response was associated with a trend towards longer OS (HR 0.29, 95%CI 0.14-1.09, P=0.07). Major histopathologic mediastinal nodal response was significantly associated with longer OS (HR 0.25, 95%CI 0.02-0.51, P=0.006), while metabolic ΔSUVmax ≥60% primary tumor response was only associated with a trend towards better OS (HR 0.41, 95%CI 0.17-1.27, P=0.14).
Conclusion:
Complete pathological response to NCT in stage IIIA-N2 NSCLC is infrequent and therefore not useful as a surrogate for OS. Combined major pathologic nodal and metabolic tumor response was associated with a trend towards longer OS. By contrast, a major histopathologic mediastinal nodal response with ≤10% residual tumor cells at VAM is well suited to be adopted as a surrogate of OS.
-
+
PC01 - Pro Con Session: Invasive Mediastinal Staging for N2 Disease (ID 323)
- Event: WCLC 2016
- Type: Pro Con
- Track: Radiology/Staging/Screening
- Presentations: 1
-
+
PC01.02 - Invasive Staging and Restaging (ID 6594)
14:40 - 15:00 | Author(s): C. Dooms
- Abstract
- Presentation
Abstract:
The aim of mediastinal staging is to exclude with the highest certainty and the lowest morbidity patients with mediastinal nodal disease. The concepts of decision analysis and Bayes’ theorem form the basis for a mediastinal staging strategy. The goal of the clinical staging strategy is to lower the post-test probability sufficiently so that it falls below a testing threshold, which ascertains the clinician that the result is accurate. The ESTS working group considers a rate of unforeseen mediastinal nodal disease at the time of anatomic resection with lymph node dissection less than 10% as acceptable.[1] Contrast-enhanced multi-detector CT (computed tomography) scanning has an excellent spatial resolution but is an imperfect means of staging the mediastinum. A Cochrane review evaluated integrated positron emission tomography (PET) - CT for assessing mediastinal lymph node involvement in NSCLC.[2] The review showed that the accuracy of PET-CT is insufficient to allow management on PET-CT alone, but PET-CT can be used to guide clinicians in the next step (either a biopsy or direct to surgery). The suboptimal specificity of mediastinal lymph nodes positive on PET-CT requires a tissue confirmation. There are conditions where invasive staging is also mandatory despite a normal mediastinum on PET-CT as the prevalence of N2/N3 disease remains significant. These conditions include a primary tumour >3 cm, any central primary tumour, PET/CT hilar N1 disease, or low FDG uptake in the primary tumour.[1] Cervical Mediastinoscopy. A conventional cervical mediastinoscopy through a pretracheal suprasternal incision was introduced in 1959 and for decades considered the gold standard for invasive mediastinal nodal staging. Recently, a very large (N=721 patients; prevalence of mediastinal nodal disease 47 %) retrospective single center study reported on safety and efficacy of cervical mediastinoscopy performed by general thoracic surgeons.[3] There was no mortality, a low perioperative complication rate at 1.3 %, and an unexpected hospital (re)admission rate of 0.46 %. The sensitivity, negative predictive value and post-test probability were 0.90 (95% CI 0.87-0.92), 0.92 (95% CI 0.90-0.94), and 0.09 (95% CI 0.07-0.11), respectively. It is performed under general anesthesia and allows a full mapping of the ipsilateral and contralateral superior mediastinal lymph nodes. Since 1995, the use of video techniques has been introduced leading to video-assisted mediastinoscopy (VAM) clearly improving visualization and teaching. In addition, VAM allows bimanual dissection with possibilities to perform nodal dissection and removal rather than sampling or biopsy. The ESTS working group recommends performing VAM.[1] Endoscopic ultrasonography (EUS) en endobronchial ultrasonography (EBUS). In the last decade, the predominant role of cervical mediastinoscopy has been challenged by EUS and EBUS using a convex probe. When mediastinal nodal staging is required, systematic nodal sampling seems feasible but some primary choices have to be made. At least mediastinal nodal stations 4R, 4L and 7 should be sought. To avoid contamination, the order of sampling should begin at the level of N3 stations followed by N2 stations before N1. There is no evidence to suggest that sampling of all visible nodes in each nodal station is superior to a systematic nodal sampling of the largest measuring ≥5 mm or PET-positive node in each station. It must be stressed that EBUS cannot access the prevascular nodes (station 3a), the subaortic and para-aortic nodes (stations 5 and 6) as well as the paraesophageal and pulmonary ligament nodes (stations 8 and 9). Some of these nodes (stations 8 and 9) can however be reached from the esophagus. Therefore the use of the EBUS scope is extended to an esophageal exploration with EUS-B sampling of stations 4L, 7, 8 and 9. In terms of safety, EBUS and EUS have a low complication or serious adverse event rate of 1.4 and 0.3%, respectively.[4,5] The two staging strategies, surgical staging alone on the one hand and combined EUS/EBUS followed by surgical staging whenever endosonography was negative on the other hand, were compared in a pivotal randomized controlled trial (RCT).[6] It was concluded that invasive mediastinal nodal staging should start with combined linear endosonography, as the trial showed that a staging strategy starting with combined linear endosonography (EUS+EBUS) detected significantly (P=0.02) more mediastinal nodal N2/N3 disease compared to cervical mediastinoscopy alone, resulting in a significantly higher sensitivity of 0.94 (95%CI 0.85-0.98) compared to 0.79 (95%CI 0.66-0.88), respectively.[6] Another RCT suggested that EBUS-TBNA is the preferred primary procedure in combined linear endosonography for mediastinal nodal staging of resectable stage I-III lung cancer.[7] There is no RCT comparing combined EBUS-EUS(-B) to EBUS-TBNA alone for mediastinal nodal staging, but a recent meta-analysis suggested that the combined EBUS-EUS is more sensitive than EBUS-TBNA alone to detect mediastinal nodal disease.[8] The absolute increase in sensitivity of the combined approach compared to EBUS-TBNA alone depends on the quality of the EBUS-TBNA procedure, but published studies suggest an increase in sensitivity up to 10%. Overall, a confirmatory VAM is still warranted for the individual patient with a negative combined linear endosonography as this further lowers the post-test probability. This has been shown within ASTER for patients with clinical N2/3 disease on PET-CT (prevalence of mediastinal nodal disease 63%), as the post-test probability of a negative linear combined endosonography of 20% could be lowered to 5% by adding a cervical mediastinoscopy.[9] A recent prospective cohort study on clinical stage II lung cancer based on N1 disease on imaging (prevalence of mediastinal nodal disease 24%) showed that the post-test probability of a negative endosonography was 19%, which could be lowered to 9% by adding a cervical mediastinoscopy.[10] In conclusion, combined EBUS-EUS(-B) linear endosonography is the standard for initial baseline mediastinal nodal staging, but a VAM is still recommended after a negative (or incomplete) combined linear endosonography. Mediastinal restaging after induction therapy for locally advanced stage III NSCLC is an important prognostic factor. In the context of a 40-50% prevalence of residual mediastinal disease after induction therapy, a first cervical VAM as a restaging technique seems to be the most accurate method for nodal assessment.[1] Overall, limited literature reported a sensitivity and NPV for linear endosonography that is lower than for a first mediastinoscopy.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
SC01 - Staging Before and After Induction Therapy for N2 Disease (ID 325)
- Event: WCLC 2016
- Type: Science Session
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:G. Mostbeck, E. Fadel
- Coordinates: 12/05/2016, 11:00 - 12:30, Lehar 3-4
-
+
SC01.01 - The Importance of Mediastinal Down-Staging During Induction Therapy of N2 Disease (ID 6598)
11:00 - 11:20 | Author(s): C. Dooms
- Abstract
Abstract:
The importance of mediastinal downstaging during induction therapy of N2 disease P. De Leyn*, H. Decaluwe*, C. Dooms** and J. Vansteenkiste**. Department of Thoracic Surgery*, Department of Pneumology**, University Hospitals Leuven, Belgium Patients with preoperative pathological proven N2 disease have a dismal prognosis after surgery. Neoadjuvant chemotherapy or chemoradiotherapy is a therapeutic option that is used in patients with baseline resectable stage IIIA-N2 non-small cell lung cancer. Mediastinal downstaging is an important prognostic factor for long term survival. Different restaging techniques are available. The mediastinum can be restaged by CT scan, remediastinoscopy, VATS, PET-CT and EBUS-EUS fine needle aspiration. In primary staging, CT scan has proved to have a low accuracy. It is not surprising that the accuracy of CT scan in restaging the mediastinum is also low. In a Spanish study of 24 patients who underwent neoadjuvant chemotherapy for N2 non-small cell lung cancer, staging was performed by CT scan and remediastinoscopy (1). CT scan had a sensitivity of 41%, a specificity of 75% and an accuracy of 58%. In a prospective study of 93 patients who were restaged by integrated PET-CT after induction chemoradiotherapy, repeat PET-CT was found to be more accurate than CT alone for pathological stages. However, there were 20 false negative and 25 % false positive cases. So, in case of suspicion of residual mediastinal disease, nodal biopsies are still required (2). We evaluated in a prospective single center study repeat mediastinoscopy and PET-CT after induction chemotherapy for N2 disease. PET-CT had a sensitivity of 77% and a specificity of 88% (3). Repeat mediastinoscopy, technically much more difficult than the first procedure, offers the advantage of providing histological evidence of response after induction therapy. Although some centers obtain good results (4), most surgeons will accept that remediastinoscopy is technically difficult and often incomplete. We performed a prospective study to evaluate the accuracy of remediastinoscopy and PET-CT in restaging the mediastinum after mediastinoscopy proven N2 disease (3). The first mediastinoscopy was thoroughly performed with a mean lymph node level of 3.6 per patient biopsied. In our experience, remediastinoscopy was technically feasible, but inaccurate due to severe adhesions and fibrosis. The sensitivity to detect residual mediastinal lymph nodes was only 28,6% with an accuracy of 58,3%. Minimally invasive endoscopic technique EUS and EBUS also obtain histological diagnosis. Their accuracy is very good in baseline mediastinal staging. In the study Herth et al (5) EBUS-FNA was performed for restaging after induction chemotherapy or chemoradiotherapy for N2 disease in 124 patients. The sensitivity was 76% but the negative predictive value was as low as 20%. The largest series in the literature is reported by Szlubowski (6). They combined EBUS-EUS FNA for restaging N2 disease in 106 patients. Sensitivity was 67% with a negative predictive value of 73%. Some recent smaller studies showed better results for EBUS-EUS to prove persistent nodal disease. Most of the new lesions that appear after induction chemotherapy on PET-CT are not malignant (7). We know that some patients with minimal persistent N2 disease (mainly single level) can have a good prognosis after surgical resection (8). In a study published by Dooms et al (9) patients with less than 10% viable tumor cells in mediastinal lymph node sampled at mediastinoscopy and s with more than 60% decrease of SUV~max~ of primary tumor had a five year survival of over 60%. Therefore, we believe that a new staging algorithm could be used to select patients for radical therapy after induction chemotherapy for N2 disease. At baseline staging, pathological N2 disease should be proved by EBUS-EUS fine needle aspiration. PET-CT should be done to exclude distant metastasis and to evaluate SUV~max~ of the primary tumor. At restaging, mediastinoscopy with nodal dissection should be performed. Also repeat PET-CT should be done. In patients with major pathological response in lymph nodes and a major SUV drop of the primary tumor, surgery can be performed with good outcome. References (1)Mateu-Navarro M, Rami-Porta R, Bastus-Oiulats R, Cirera-Noqueras L, Gonzalez-Pont G. Remediastinoscopy after induction chemotherapy in non-small cell lung cancer. Ann Thorac Surg 2000;70:391-5. (2)Cerfolio R, Bryant A, Ojha B. Restaging patients with N2 (stage IIIa) non-small cell lung cancer after neoadjuvant chemoradiotherapy: a prospective study. J Thorac Cardiovasc Surg 2006;131(6):1229-1235. (3)De Leyn P, Stoobants S, Vansteenkiste J, Dewever W, Lerut A.. Prospective study of accuracy of redo videomediastinoscopy and PET-CT in detecting residual mediastinal disease after induction chemotherapy for NSCLC. Lung Cancer 2005;49 Suppl 2 : S3. (4)Rami-Porta R, Call S. Invasive staging of mediastinal lymph nodes: mediastinoscopy and remediastinoscopy. Thorac Surg Clin 2012: 22:177-89. (5)Herth F, Annema J, Eberhardt R, Yasufuku K, Ernst A, Krasnik M, Rintoul R. Endobronchial ultrasound with transbronchial needle aspiration for restaging the mediastinum in lung cancer. J Clin Oncol 2008;26(20):3346-3350. (6)Szlubowski A, Zielinski M, Soja J, Filarecka A, Orzechowski S, Pankowski J, Obrochta A, Jakubiak M, Wegrzyn J, Cmiel A. Accurate and safe mediastinal restaging by combined endobronchial and endoscopic ultrasound-guided needle aspiration performed by single ultrasound bronchoscope. Eur J Cardiothor Surg 2014;46:262-266. (7)Collaud S, Lardinois D, Tischler V, Steinert H, Stahel R, Weder W. Significance of a new fluorodeoxyglucose-positive lesion on restaging positron emission tomography/computed tomography after induction therapy for non-small-cell lung cancer. Eur J Cardiothorac Surg 2012;41:612-616. (8)H. Decaluwé, P. De Leyn, J. Vansteenkiste, C. Dooms, D. Van Raemdonck, P. Nafteux, W. Coosemans, T. Lerut. Surgical multimodality treatment for baseline resectable stage IIIA-N2 non-small cell lung cancer. Degree of mediastinal lymph node involvement and impact on survival. Eur J Cardiothoracic Surg 2009 ;36 :433-9. (9)Dooms C, Verbeken E, Stroobants S, Nackaerts K, De Leyn P, Vansteenkiste J. Prognostic stratification of stage IIIA-N2 non-small-cell lung cancer after induction chemotherapy: a model based on the combination of morphometric-pathologic response in mediastinal nodes and primary tumor response on serial 18-fluoro-2-deoxy-glucose positron emission tomography. J Clin Oncol 2008;26(7):1128-1134.
