Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
Comprehensive Cancer Network (NCCN) member institutions consider
surgery to be indicated in stage IIIA patients with involvement of a single
N2 lymph node station smaller than 3 cm who have undergone induction
chemotherapy. However, there is no agreement among institutions regarding
treatment for other manifestations of stage IIIA-N2 involvement (e.g.,
multi-station or bulky disease) and both NCCN and European Society of
Medical Oncology (ESMO) guidelines recommend that the role of surgery be
discussed in a multidisciplinary tumor board setting. The use of induction
chemotherapy vs induction chemoradiotherapy is currently of great interest
worldwide, and the use of the latter is still common despite the results of
numerous clinical trials and meta-analysis. The lack of consensus regarding
treatment strategies for stage III NSCLC is in part due to the relatively low
number of randomized studies available to guide decision-making, as well
as institutional biases despite evidence. One important issue is the role and
methods of restaging after induction therapy for patients with potentially
resectable Stage IIIA (N2) disease. While all would agree that pathologic
confirmation of N2 disease prior to induction chemotherapy is mandatory,
using EBUS or mediastinoscopy, not all surgeons believe that restaging after
induction therapy to confirm response to chemotherapy is necessary, despite
evidence that the overall and cancer-specific survival of non-responders
is quite low. There are 2 dominant strategies for staging and restaging
patients with N2 disease: EBUS prior to induction therapy and restaging
with videomediastinoscopy or mediastinoscopy prior to induction therapy
and restaging with thoracoscopy or repeat mediastinoscopy. There may be
a role for each strategy depending on individual patient characteristics.
Advantages of thoracoscopic restaging after induction therapy include the
ability to resect all ipsilateral nodes to most accurately assess response and
the resection of nodal tissue at thoracoscopy is the first step in thoracoscopic
resection and thus greatly facilitates the procedure. The role of thoracoscopic
restaging after induction therapy will be reviewed, and the technical aspects
for successful restaging and thoracoscopic lobectomy after induction therapy
are demonstrated in videos.References 1. Martins RG, D’Amico TA, Loo BW, Jr.,
et al. The management of patients with stage IIIA non-small cell lung cancer
with N2 mediastinal node involvement. Journal of the National Comprehensive
Cancer Network : JNCCN. 2012;10(5):599-613. 2. Vansteenkiste J, De Ruysscher,
D, Eberhardt WEE, Lim E, Senan S, Felip E, Peters s. Early-Stage and Locally
Advanced (non-metastatic) Non-Small-Cell Lung Cancer: ESMO Clinical
Practice Guidelines. Annals of Oncology. 2013;24((suppl 6)):vi 89-98. 3.
Ettinger DS, Wood DE, Akerley W, et al. Non-small cell lung cancer, version
6.2015. Journal of the National Comprehensive Cancer Network : JNCCN.
2015;13(5):515-524. 4. Weeks JC, Uno H, Taback N, et al. Interinstitutional
variation in management decisions for treatment of 4 common types of
cancer: A multi-institutional cohort study. Annals of internal medicine.
2014;161(1):20-30. 5. Pless M, Stupp R, Ris HB, et al. Induction chemoradiation
in stage IIIA/N2 non-small-cell lung cancer: a phase 3 randomised trial. Lancet.
2015;386(9998):1049-1056. 6. Katakami N, Tada H, Mitsudomi T, et al. A
phase 3 study of induction treatment with concurrent chemoradiotherapy
versus chemotherapy before surgery in patients with pathologically
confirmed N2 stage IIIA nonsmall cell lung cancer (WJTOG9903). Cancer.
2012;118(24):6126-6135. 7. Girard N, Mornex F, Douillard JY, et al. Is neoadjuvant
chemoradiotherapy a feasible strategy for stage IIIA-N2 non-small cell lung
cancer? Mature results of the randomized IFCT-0101 phase II trial. Lung
Cancer. 2010;69(1):86-93. 8 Jaklitsch MT, Gu L, Harpole DH, D’Amico TA, et al.
Prospective phase II trial of pre-resection thoracoscopic restaging following
neoadjuvant therapy for IIIA(N2) non-small cell lung cancer: Results of CALGB
39803. J Thorac Cardiovasc Surg 2013;146: 9-16 9. Yang CF, Gulack BC, Gu L, et
al. Adding radiation to induction chemotherapy does not improve survival
of patients with operable clinical N2 non-small cell lung cancer. The Journal
of thoracic and cardiovascular surgery. 2015;150(6):1484-1492; discussion
1492-1483. 10. Shah AA, Berry MF, Tzao C, et al. Induction chemoradiation is
not superior to induction chemotherapy alone in stage IIIA lung cancer. Ann
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Keywords: lung cancer surgery, minimally invasive surgery, stage IIIA
SESSION SC02: MULTIFOCAL LUNG CANCER
MONDAY, DECEMBER 5, 2016 - 11:00-12:30
SC02.01 MULTIPLE PRIMARY LUNG CANCERS VERSUS LUNG
METASTASES: PATHOLOGICAL DIFFERENTIAL DIAGNOSIS
Erik Thunnissen
VU University Medical Center, Amsterdam/Netherlands
Introduction The pathological differential diagnosis of in a patient with
synchronous multiple tumors has a similar thought process for classic
morphology as for DNA analysis. Metachronous multiple lung cancers are not
discussed here, as the provided title implies a clinical situation at moment in
time. In the end of the text the usefulness of clinical context is mentioned. 1–5
Morphology In the setting of obvious metastatic dissemination, histologic
appearance is generally conserved. This implies that most metastases look
alike and in most instances also have a similar morphologic appearance as the
primary tumor. However, dedifferentiation occasionally occurs in metastases.
Thus it is reasonable to conclude that lesions of different histological types,
e.g. squamous cell and adenocarcinoma, are two separate primary cancers.
Recently, it was suggested that differences in a comprehensive histologic
assessment may provide an argument for separate primary cancers. However,
resection specimen analysis is required for this assessment, making this
approach only useful in about 15-20% of the cases. Moreover, an evidence
based data set supporting comprehensive histologic assessment is currently
lacking. Reproducibility has to be taken into account. 6 In contrast to different
morphological types, in case of two tumors with similar morphology a
conclusion for same lineage (primary tumor- metastases relation) or different
lineage (two primary tumors) is not easy to reach. The reason for this is that
within an individual the genetic predisposition and etiologic factors are the
same and may lead to separate tumors with the same morphology, which
may still represent two lineages (thus two primary tumors) or alternatively,
the same morphology in metastatic setting is one lineage. In case of multiple
adenocarcinoma in-situ lesions, they are assumed to be separate primaries.
In summary , in comparing two tumors differences in morphologic types
is conclusive for second primary tumors, but demonstration of the same
morphology is not sufficient for lineage analysis. DNA changes Demonstration
of specific driver mutations by widely available PCR sequencing techniques
may have use in establishing lineage. 7 In case of different driver mutations
between two tumors, this obviously provides a strong argument for two
primary (lung) cancers. However the frequency of discordant driver mutations
is not so high. Noteworthy is that the demonstration of different passenger
mutations does not have any use for lineage determination. In case of equal
driver mutations a conclusion about lineage is not easy to reach. 8,9 Not only
because the genetic predisposition and etiologic factors are the same,
but also because in certain genes hotspot mutations occur. Thus simple
demonstration of the same mutation does not provide definite evidence
for lineage analysis. On this matter more research is needed with posterior
probability analysis involving a relevant number of similar mutations. A
detailed genetic assessment such as in comparative genomic hybridisation
(CGH) may have greater discriminative power but has been used in only
a few small studies. 10 In array CGH the number of data points is orders of
magnitude greater than in mutation analysis. Array CGH encompasses the
predisposition and etiologic factor related copy number variations (CNV) as
well as lineage specific CNV. In this sense comparison of exact breakpoints
in gene rearrangements is useful. Although the data are limited as the
assessment was in the past complex, nowadays arrayCGH in the form of
shallow sequencing can reliable be performed on small biopsies as well. To
which extend NGS with a large mutation panel may be useful remains to be
seen. In summary , different driver mutations is conclusive for second primary
tumors, but demonstration of the same driver mutation is not sufficient for
lineage analysis. Clinical context Adding clinical context provides interesting
arguments. 1) Imaging may show multiple ground glass opacities (mGGO)
and lack of enlarged lymph nodes. Although the morphology may be similar
(lepidic pattern with AIS, MIA, Invasive adenocarcinoma) the mGGO lesions
are considered to be separate primaries. In case of part solid component
the morphological equivalent is usually infarction (=benign) or invasive
cancer. 2) Imaging may show multiple consolidations (pneumonic type) with
mostly the morphological correlate of invasive mucinous adenocarcinoma.
3) Abundance of nodular lesions, provides an argument for metastases
(although rare exceptions exist, e.g. DIPNECH, Carney’s triad), while lack of
nodal or systemic metastases provides an argument of two primary lung
cancers. 4) Clinical follow-up is in hindsight only partly useful: lack of nodal or
systemic metastases provides an argument of two primary lung cancers, while
presence of local and/or distant metastases may be due to one of the two or
both lung cancers. Conclusion If morphological and/or DNA analysis provides
differences between two tumors it is relatively easy to establish that these
pulmonary foci of cancer are separate primary tumors. Many commonly used
characteristics are associated with a substantial rate of misclassification.
Careful review by a multidisciplinary tumor board, considering all available
information, is recommended.References 1. Detterbeck, F. C. et al. The IASLC
Lung Cancer Staging Project: Summary of Proposals for Revisions of the
Classification of Lung Cancers with Multiple Pulmonary Sites of Involvement
in the Forthcoming Eighth Edition of the TNM Classification. J. Thorac. Oncol.
11, 639–50 (2016). 2. Detterbeck, F. C. et al. The IASLC Lung Cancer Staging
Project: Background Data and Proposals for the Classification of Lung
Cancer with Separate Tumor Nodules in the Forthcoming Eighth Edition of
the TNM Classification for Lung Cancer. J. Thorac. Oncol. 11, 681–92 (2016). 3.
Detterbeck, F. C. et al. The IASLC Lung Cancer Staging Project: Background
Data and Proposals for the Application of TNM Staging Rules to Lung Cancer
Presenting as Multiple Nodules with Ground Glass or Lepidic Features or a
Pneumonic-Type of Involvement in the Forthcoming Eighth. J. Thorac. Oncol.
11, 666–680 (2016). 4. Kozower, B. D., Larner, J. M., Detterbeck, F. C. & Jones,
D. R. Special treatment issues in non-small cell lung cancer: Diagnosis and
management of lung cancer, 3rd ed: American College of Chest Physicians
evidence-based clinical practice guidelines. Chest 143, e369S–99S (2013). 5.
Detterbeck, F. C. et al. The IASLC Lung Cancer Staging Project: Background
Data and Proposed Criteria to Distinguish Separate Primary Lung Cancers
S38 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017