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H. Decaluwe
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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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P2.02-055 - 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): H. Decaluwe
- 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.
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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
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SC01.01 - The Importance of Mediastinal Down-Staging During Induction Therapy of N2 Disease (ID 6598)
11:00 - 11:20 | Author(s): H. Decaluwe
- 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.
