Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
SCIENTIFIC SESSIONS
SESSION SC01: STAGING BEFORE AND AFTER INDUCTION
THERAPY FOR N2 DISEASE
MONDAY, DECEMBER 5, 2016 - 11:00-12:30
SC01.01 THE IMPORTANCE OF MEDIASTINAL DOWN-STAGING
DURING INDUCTION THERAPY OF N2 DISEASE
Paul De Leyn 1 , Herbert Decaluwe 1 , Christophe Dooms 2 , Johan Vansteenkiste 3
1 Thoracic Surgery, University Hospital Leuven, Leuven/Belgium, 2 Respiratory
Oncology, University Hospital KU Leuven, Leuven/Belgium, 3 Respiratory Oncology
Unit (Pneumology), University Hospital KU Leuven, 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) nonsmall
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-deoxyglucose
positron emission tomography. J Clin Oncol 2008;26(7):1128-1134.
Keywords: Mediastinal restaging, NSCLC, induction therapy
SC01: STAGING BEFORE AND AFTER INDUCTION THERAPY FOR N2 DISEASE
MONDAY, DECEMBER 5, 2016 - 11:00-12:30
SC01.02 PET-CT FOR RESPONSE ASSESSMENT DURING INDUCTION
THERAPY OF N2 NSCLC
Christoph Pöttgen, Martin Stuschke
West German Cancer Center, University of Duisburg-Essen, Essen/Germany
Approximately 30% of patients with non-small cell lung cancer (NSCLC) are
found to have locally advanced stage III tumours at initial diagnosis. For
these patients the curative therapeutic options include definitive high-dose
radiotherapy with concurrent chemotherapy or, alternatively, induction
treatment followed by surgery. Preoperative chemotherapy or combined
radiochemotherapy protocols followed by resection result in cure rates
of 25-35 percent at 3 years for locally advanced NSCLC. However, surgical
resection in patients with stage IIIa N2 remains an issue of controversy
depending on the extent of lymph node involvement. Neoadjuvant
chemo- or radiochemotherapy is being used to reduce disease burden in
the mediastinum before surgery since patients who are downstaged via
neoadjuvant therapy and then undergo resection experience a significantly
longer 5-year survival of 40% to 50% than those who are found to have
residual N2 disease at the time of surgery. Thus, identification of patients
who are N2 negative after completion of their neoadjuvant therapy is a
critical component for patient selection for thoracotomy. However, clinical
restaging in these patients often is challenging. Endoscopic ultrasound
guided biopsies (EUS/EBUS-FNA) have increasingly become available and
are currently preferred procedures for staging and restaging before surgery
due to their high diagnostic accuracy.(1) Serial PET-CT imaging captures
anatomical changes and additionally offers semiquantitative information
about morphometric and metabolic tissue changes during induction
treatment. Issues of PET-CT performance and quality assurance concerning
standardization have been clarified during recent years and the validity
of repeated measurements has been approved.(2) Successful induction
treatment regimes have been frequently found to reduce 18F-FDG uptake and
thus PET-CT allows to assess the therapeutic response. Reduction in FDGuptake
of mediastinal lymph nodes after induction therapy has been shown
to correlate well with histopathologic response (3), while postinduction
PET avidity taken alone was not consistently found to be associated with
pathological N2 involvement (4). In the direct comparison of EUS-FNA with
PET-CT for restaging after induction chemoradiotherapy, concordance
between findings of restaging EUS-FNA and metabolic response of lymph
node metastases was observed in 63% patients treated within a prospective
study but the diagnostic accuracy of PET-CT was limited.(5) Nevertheless,
serial FDG-uptake measurements seem to provide prognostic information
during induction therapy. Data collected in prospective trials suggest that
a decrease in SUV max
between 45% to 60% optimally separates between
responders and non-responders (6-9). In a recent large retrospective analysis,
a decrease in SUV max
greater than 60% in the involved mediastinal nodes was
the best predictor of overall survival, better than changes seen in the primary
tumour site. (10) An analysis of a randomized trial in potentially resectable
stage III NSCLC of induction treatment (including a hyperfractionated
accelerated radiotherapy phase) and definitive radiochemotherapy compared
with induction treatment followed by surgery confirmed that as early as
after two cycles of cisplatin-based induction chemotherapy percentage of
SUV max
remaining represents a significant prognostic parameter.(9) PETresponse
was of higher importance than all other clinical factors. Cut-off
levels between 0.45 and 0.55 were predictive for freedom from extracerebral
progression in all randomized patients. No important differences in the
predictive value were observed comparing resection versus definitive
radiochemotherapy. PET-response was closely related to extracerebral
S36 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017