; 55. Diagnosis and treatment of lung cancer
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55. Diagnosis and treatment of lung cancer


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									Oral Presentation                                                                                                                          Room Lehár 1-2 - 10:45-12:45

                                                              S UNDAY, S EPTEMBER 13 TH 2009

                                                                                               Aim: To provide histologic sample from minimally invasive bronchoscopic TBNA
                                                                                               cytologic aspirates.
                                                                                               Methods: Routine TBNA aspirate of suspected lymph node mets & parenchymal
                                                                                               lung masses with 22 ga cytology needles guided by Endobronchial Ultrasound is
                                                                                               processed to yield histologic sample by a coagulum clot technique. Studies include
                                                                                               immunostains for cancer markers, distinguish squam Vs non-sq for NSCLC, EGFR
                                                                                               & KRAS by PCR.

                                                                                               Results: 23 patients studied over 6 mos period. 12 with previous ca. 14 cancers
                                                                                               dx: 9 NSCLC with EGFR/KRAS studied in 6 from needle clots, other 3 squams
                                                                                               studied for KRAS only, 2/9 with KRAS mutation by PCR, noEGFR. 2 other squam
                                                                                               equivocal H&N mets Vs lung primary. 3 metastatic cancers. 5 true benign LNs,
                                                                                               4 TBNA samples quantity insufficient. Immunostains include AE1/3, CAM5.2,
                                                                                               CK5/6, CK7, CK20, TTF1, CDX2, DPC4; EGFR & KRAS by microdissection
                                                                                               for PCR.
                                                                                               Conclusion: Careful preparation of cytologic needle aspirates can yield sample
                                                                                               for cancer dx & analysis of predictive markers for molecular targeted therapy.

                                                                                               The relation of fluorine-18 fluorodeoxyglucose positron emission tomography
                                                                                               imaging to chemosensitivity for platinum doublet chemotherapy in patients
                                                                                               with advanced stage non small cell lung cancer
                                                                                               Nobuaki Kobayashi 1 , Yuji Watanuki 1 , Naoki Miyazawa 1 , Satoshi Inoue 1 ,
                                                                                               Makoto Kudo 1 , Takashi Sato 1 , Kei Mishina 1 , Takeshi Kaneko 1 ,
                                                                                               Yoshiaki Ishigatsubo 2 . 1 Department of Respiratory Medicine, Yokohama City
                                                                                               University Hospital, Yokohama, Kanagawa, Japan; 2 Department of Internal
                                                                                               Medicine and Clinical Immunology, Yokohama City University Graduate School
                                                                                               of Medicine, Yokohama, Kanagawa, Japan

                                                                                               Background: The findings by fluorine-18 fluorodeoxyglucose Positron Emission
                                                                                               Tomography (FDG-PET) may indicate biological features of tumors in patients
                                                                                               with non small cell lung cancer (NSCLC). The aim of this study was to evaluate
                                                                                               the predictive value of FDG-PET imaging for platinum doublet chemotherapy in
                                                                                               Japanese advanced NSCLC patients.
                                                                                               Method: Patients with advanced stage NSCLC (Stage IIIA, IIIB, and IV) estimated
                                                                                               by FDG-PET before treatment and treated with platinum doublet chemotherapy
                                                                                               were eligible in this study. Progression free survival (PFS), overall survival (OS),
                                                                                               and clinical backgrounds were statistically analyzed according to the maximum
                                                                                               standardized up take value (SUVmax) in the primary tumor.
                                                                                               Result: Forty-two patients were analyzed in this study. The patients were divided
                                                                                               into the high (SUVmax >7.35) and low (SUVmax <7.35) FDG uptake group
                                                                                               by median SUVmax. There were no difference in PFS (153 days for high SU-
                                                                                               Vmax versus 152 days for low SUVmax; P=0.519) and OS (526 days for high
                                                                                               SUVmax versus 386 days for low SUVmax; P=0.325). Moreover, the clinical
                                                                                               features associated with epidermal growth factor receptor gene mutations were
                                                                                               also analyzed. Seven of these patients met the criteria for the clinical features
                                                                                               (female, adenocarcinoma, and never smoker). The SUVmax among these patients
                                                                                               tended to be lower than that of others (5.66±3.22 versus 8.02±3.08; P=0.074),
                                                                                               however, there were no difference in PFS and OS.
                                                                                               Conclusion: Pretreatment SUVmax of the primary tumor in patients with an
                                                                                               advanced NSCLC does not predict the chemosensitivity for platinum based

                                                                                               Mesenchymal stem cells reduce lung metastases by controlled targeted
     55. Diagnosis and treatment of lung cancer                                                delivery of TNF-related apoptosis-inducing ligand (TRAIL)
                                                                                               M.R. Loebinger, S.M. Janes. Centre for Respiratory Research, University College
                                                                                               London, London, United Kingdom

379                                                                                            Background: Bone marrow mesenchymal stem cells (MSCs) can incorpo-
Routine analysis of diagnostic,prognostic and predictive cancer markers from                   rate within tumors. We hypothesised MSCs engineered to deliver TNF-related
transbronchial (TBna) cytology needle aspiration samples                                       apoptosis-inducing ligand (TRAIL), which causes selective apoptosis of tumor
Rex Yung 1 , Ola Abdelrehim 1 , Kay Li 2 , Peter Illei 2 . 1 Pulmonary & Critical Care         cells, would home to and kill cancer cells in a lung metastatic cancer model.
Medicine, Johns Hopkins University, Baltimore, MD, United States of America;                   Methods: TRAIL and GFP, under the control of a Tet-promoter, were cloned into
  Pathology, Johns Hopkins University, Baltimore, MD, United States of America                 a lentivirus before transducing MSCs. Transgene activation was demonstrated by
                                                                                               flow cytometry, Western blot, ELISA. Apoptotic function of MSCs expressing
Introduction: Accurate Tissue Diagnosis & Staging of Thoracic Malignancies is                  TRAIL was established in co-culture with cancer cells (Hela, MDAMB231, A549)
key to treatment planning. With molecular medicine, simply diagnosing cancer                   using Annexin V flow cytometry. MSC homing was shown with chemotaxis assays
as primary lung,either Small Cell & NSCLC is insufficient. Predictive markers                   and in vivo cell tracking. SCID mice were used for in vivo subcutaneous and
of response require distinction of squamous Vs non-squam, plus EGFR & KRAS                     metastatic lung cancer models (MDAMB231).
mutation status,studies that have required surgical biopsies.                                  Results: MSCs were transduced with 80% efficiency and expressed TRAIL under

                      Abstract printing supported by Chiesi Farmaceutici SpA. Visit Chiesi Farmaceutici SpA. at Stand B.40
Oral Presentation                                                                                                                            Room Lehár 1-2 - 10:45-12:45

                                                               S UNDAY, S EPTEMBER 13 TH 2009

Tet-control. Transduced MSCs caused tumor cell apoptosis in co-culture (p<                    384
0.001). This was maintained at low (1:16) MSC/Tumor ratios (p< 0.001) and                     Prior noninvasive ventilation is a bad prognostic factor in mechanically
reduced by a TRAIL neutralising antibody (p< 0.001). Tumor cells expressing                   ventilated cancer patients
dominant negative Fas-associated death domain showed TRAIL-induced death was                  Anne-Pascale Meert 1 , Thierry Berghmans 1 , Marianne Paesmans 2 ,
via the extrinsic apoptotic pathway (p< 0.001). Homing of MSCs to tumours was                 Nathalie Nayer 1 , Jean-Paul Sculier 1 . 1 Thoracic Oncology and Intensive Care,
demonstrated by transwell migration (p< 0.001) and in vivo engraftment of DiI-                Institut Jules Bordet, Brussels, Belgium; 2 Data Centre, Institut Jules Bordet,
labeled MSCs. TRAIL-MSCs reduced tumor growth in subcutaneous xenograft                       Brussels, Belgium
models (p< 0.001). Systemically injected MDAMB231 cells produced lung metas-
tases in all untreated mice. The metastases were cleared completely in 38% of                 Background: in cancer patients, invasive mechanical ventilation (IMV) is a life
mice with intravenous TRAIL-MSCs (p=0.03).                                                    supporting technique associated with a very high mortality rate. Non invasive
Conclusions: This is the first study to show significant tumor reduction with                   ventilation (NIV) is increasingly used for the management of acute respiratory
TRAIL-expressing MSCs.                                                                        failure and has modified IMV indications.
                                                                                              Objectives: to assess the indications and results of IMV in a general cancer
                                                                                              population in the NIV era and to study mortality rates and factors predicting
382                                                                                           mechanical ventilation (MV) success.
Combined endoesophageal-endobronchial ultrasound-guided, fine-needle                           Method: retrospective study
aspiration of mediastinal lymph nodes through a single bronchoscope in 150                    Results: 164 patients were eligible: 106 with solid tumours, 58 with haemato-
patients with suspected lung cancer                                                           logical malignancies and 42 initially treated by NIV before further IMV. The
Felix J.F. Herth 1 , Armin Ernst 2 , Mark Krasnik 3 , Ralf Eberhardt 1 . 1 Pneumology         main indications for MV were sepsis/shock (35%), acute respiratory failure (33%),
and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Heidelberg,               cardiopulmonary resuscitation (16%) and neurologic disease (10%). Respectively,
Germany; 2 Interventional Pulmonology, Beth Israel Deaconess Medical Center,                  35%, 28% and 24% of the patients were extubated, discharged from the ICU and
Harvard Medical School, Boston, MA, United States of America; 3 Thoracic                      from the hospital. For patients initially treated with NIV, the values were 22%, 17%
Surgery, Gentofte Hospital, Copenhagen, Denmark                                               and 10%, respectively. In multivariate analysis, 3 variables were independently
                                                                                              associated with decreased probability of being discharged from the hospital: NIV
Background: Mediastinal lymph nodes must often be biopsied to accurately stage                use before IMV (OR=0.30, 95% CI: 0.09-0.95; p=0.04); leucopenia (OR=0.21,
lung cancer. Endobronchial ultrasound-guided, transbronchial needle aspiration                95% CI: 0.06-0.77; p=0.02) and bilirubinemia > 1.1 mg/dl (OR=0.38, 95% CI:
(EBUS-TBNA) allows real-time guidance in sampling paratracheal, subcarinal,                   0.16-0.94; p=0.04). Median survival time was 8 days and one year survival was
and hilar lymph nodes, and esophageal, ultrasound-guided-guided fine-needle as-                9% (IC 95%: 4%-14%).
piration (EUS-FNA) can sample mediastinal lymph nodes located adjacent to the                 Conclusion: NIV before IMV is associated with a worse outcome in cancer
esophagus. Mediastinal nodes can be sampled and staged more completely by                     patients.
combining these procedures, but to date, use of two different endoscopes has been
required. We examined whether both procedures could be performed with a single
EBUS bronchoscope.                                                                            385
Patients and methods: Consecutive patients with presumptive evidence of NSCLC                 Is there any survival benefit of surgery after neoadjuvant chemoradiotherapy
underwent staging by EBUS-TBNA and EUS-FNA through a single linear                            and persisting pn2/3 in stage III NSCLC?
ultrasound- bronchoscope. Surgical confirmation and clinical follow-up was the                 Volker Steger 1 , Thorsten Walles 1 , Bora Kosan 1 , Tobias Walker 2 , Stefanie Veit 1 ,
reference standard when indicated.                                                            Thomas Kyriss 1 , Godehard Friedel 1 . 1 Thoracic Surgery, Schillerhoehe Hospital,
Results: Among 150 evaluated patients, 139 (91%; 83 male; 56 female; mean                     Gerlingen, Germany; 2 Thoracic-, Cardiac- and Vascular Surgery, Tuebingen
age 57.6 y) were diagnosed with NSCLC. In these 139 patients, 619 nodes were                  University, Tuebingen, Germany
endoscopically biopsied: 229 by EUS-FNA and 390 by EBUS-TBNA. Sensitivity
was 92% for EUS-FNA and 89% for EBUS-TBNA. The combined approach had                          Background and objectives: Several authors advocate denying surgery after
a sensitivity of 96% and negative predictive value (95%), values higher than either           neoadjuvant therapy in stage III NSCLC if persisting mediastinal affection is
approach alone. No complications occurred.                                                    confirmed because of significant worse outcome.
Conclusions: The two procedures can easily be performed with a linear EBUS                    We verify this postulation on the basis of our results after trimodal therapy in
bronchoscope in one setting. They are complementary and provide better diagnos-               pN2/N3 NSCLC and persisting mediastinal affection after neoadjuvant chemora-
tic accuracy than either one alone. The combination may be able to replace more               diotherapy.
invasive methods.                                                                             Method: Between 1994 and 2005 we did neoadjuvant therapy in 167 patients of
                                                                                              whom 85 patients had histologically proven pN2/3 NSCLC. Outcome measure
                                                                                              for this retrospective study was survival calculated with Kaplan-Meier-Method.
383                                                                                           Risk factors were analyzed using univariate log rank test. Neoadjuvant protocol
Shox2, a biomarker for confirming malignancy in bronchial lavage from                          consisted of platin based polychemotherapy and radiation.
patients with suspected lung cancer and inconclusive cytology                                 Results: Pre-treatment distribution of T4/T3/T2/T1 was 39/12/29/5. 68 patients
Bernd Schmidt 1 , Volker Liebenberg 2 , Dimo Dietrich 2 , Christoph Kneip 2 ,                 had pN2 and 17 patients had pN3 resulting in 34 UICC IIIa, 49 UICC IIIb and
Thomas Schlegel 2 , Sabine Weickmann 1 , Anke Seegebarth 2 , Christian Witt 1 ,               2 patients with UICC IV with curative treated isolated brain metastasis. We did
Michael Fleischhacker 1 , Triantafillos Liloglou 3 , Olaide Raji 3 , John K. Field 3 .         44 pneumonectomies and 41 Lobectomies/Bilobectomies for 77 R0 and 8 R1/2
  Medizinische Klinik M.S. Infektiologie Und Pneumologie, Bereich Pneumologie                 resections. 35 patients had persisting pN2/3. Hospital mortality was 2.4% (2/85).
(Prof. Witt), Charité - Universitätsmedizin Berlin, Berlin, Germany; 2 Product                Mean and median overall survival rates were 52 and 31 months respectively.
Development, Epigenomics AG, Berlin, Germany; 3 Roy Castle Lung Cancer                        Persisting N2/3 was a significant negative factor for survival with p<0.001. In case
Research Programme, The University of Liverpool, School of Cancer Studies,                    of ypN2/3 mean and median survival rates were 32.5 and 21 months respectively.
Liverpool, United Kingdom                                                                     5 year survival rate in ypN2/3 was 14%.
                                                                                              Conclusion: We found that surgery after neoadjuvant therapy and persisting N2/3
Patients with suspected lung cancer usually have CT-scanning and bronchoscopy                 can offer superior survival rates than many multimodal therapy protocols without
to establish a diagnosis. Unless histology or cytology allow to confirm malignancy,            surgery. If hospital mortality remains low, global denying of surgery seems not
further diagnostic procedures need to be considered to establish a final diagnosis.            justified even in subgroups with bad prognosis.
This retrospective clinical study evaluated a recently developed assay detecting
methylation of the SHOX2 gene providing diagnostic information sufficiently
sensitive to avoid additional invasive procedures.                                            386
Bronchial lavage samples with inconclusive cytology results from patients with                A randomised prospective trial of concurrent chemoradiotherapy (CCRT)
suspected lung cancer were obtained by bronchoscopy at the Charite, Berlin. 77                with cisplatin and paclitaxel or docetaxel or gemcitabine in stage IIIB
patients had malignant and 74 had benign lung disease.                                        nonsmall cell lung cancer
SHOX2 gene copies were measured quantitatively. DNA with known methylation                    Hee-Jung Ban 1 , Byeong-Kab Yoon 1 , Su-Young Chi 1 , Yong-Soo Kwon 1 ,
status was used to normalize for lot-to-lot variability. A cutpoint from a previous           In-Jae Oh 1 , Kyu-Sik Kim 1 , Yu-il Kim 1 , Sung-Chul Lim 1 , Young-Chul Kim 1 ,
study was applied. Patients showing methylation above the cutpoint were called                Kyung-Ok Park 1 , Jong-Pil Jeong 2 , Young-Chun Ko 2 , Jun-Gwang Son 3 ,
SHOX2 positive.                                                                               Jung-Hwan Lim 4 , Jong-Chul Lim 5 . 1 Internal Medicine, Chonnam National
Results: Sensitivity, 53% of patients with lung cancer were found to be positive at           University Hopital, Gwangju, Republic of Korea; 2 Internal Medicine, Gwangju
a specificity of 99%. Detection rate of the major histological subtypes: small cell            Christian Hospital, Gwangju, Republic of Korea; 3 Internal Medicine, Gwangju
6/7, adenocarcinomas 15/35 and squamous cell carcinomas 8/13.                                 Samsung Hospital, Gwangju, Republic of Korea; 4 Internal Medicine, Saint
Conclusion: The described SHOX2 methylation assay measuring methylation of                    Carollo Hospital, Suncheon, Republic of Korea; 5 Internal Medicine, Gwangju
the SHOX2 gene holds great potential as a diagnostic tool in the workup of patients           Veterans Hospital, Gwangju, Republic of Korea
with suspected lung cancer especially when bronchoscopy is non-diagnostic. It
correctly identified more than half of the tumor patients.                                     Background: Concurrent chemoradiation (CCRT) is recommended as the
The assay can simplify and speed up the diagnostic process by identifying patients            evidence-based approach for the management of stage IIIB non-small cell lung
with malignant lung disease without requiring additional invasive procedures. A               cancer (NSCLC). This study aimed to compare the effects of concurrent radiation
prospective clinical trial for the evaluation of this marker is ongoing.                      and weekly cisplatin doublets with paclitaxel, or docetaxel, or gemcitabine.
                                                                                              Methods: Since March 2005, eligible patients were randomized into three

                      Abstract printing supported by Chiesi Farmaceutici SpA. Visit Chiesi Farmaceutici SpA. at Stand B.40
Oral Presentation                                                                                          Room Lehár 1-2 - 10:45-12:45

                                                            S UNDAY, S EPTEMBER 13 TH 2009

arms: paclitaxel 45mg/m2 /week (TP), docetaxel 20mg/m2 /week (DP), gemcitabine
350mg/m2 /week (GP) in addition to cisplatin 20mg/m2 /week. Three-dimensional
conformal radiotherapy (3DCRT) was given once daily, 2-2.4Gy fraction to the
GTV, weekly 5 fractions and the total prescription dose was over 60 Gy. Four
weeks after the completion of CCRT, we proceeded to the three weekly consoli-
dation chemotherapy. The primary end-point was response rate and the secondary
end-points were survival and toxicity.
Results: For this preliminary analysis, we included the fifty-one patients (TP: 19,
DP: 14, GP: 18). Similar overall response rates are observed; TP: 94.7%, GP:
92.9%, DP: 94.4%, respectively (p=1.0). There is no significant difference in me-
dian survival; TP: not reached, GP: 13 months, DP: not reached (p=0.31). Radiation
esophagitis (≥grade 2) was noted in 5%(TP), 3%(DP), and 8%(GP, p=0.673) and
radiation pneumonitis (≥grade 2) was observed in 2%(TP), 0%(DP), and 6%(GP,
p=0.017). During the CCRT, both hematologic (p=0.31) and non-hematologic
toxicities (p=0.27) were not different in three arms.
Conclusions: Among the 3 arms, no significant difference in response rate and
survival is observed. Tendency of different toxicity profiles are being observed.

                     Abstract printing supported by Chiesi Farmaceutici SpA. Visit Chiesi Farmaceutici SpA. at Stand B.40

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