Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
included 10 women, median age was 56.5 years and had 3 never smokers. All
patients received prior platinum-based chemotherapy and were receiving
>1 st line systemic treatment while awaiting NGS results. The minimum tumor
content for successful NGS was 20%. The median turnaround time from
sample collection to report was 27 days (range 21-38). Average strexome
coverage was 420X (tumor), 200X (germline), with an average of 277 million
RNA reads generated for tumors. All patients had ³2 clinically actionable
targets identified (associated with a commercially available, FDA-approved
drug by predefined rules), median 4 targets (range 2-8). Three patients
received treatment identified by NGS. One has continuing partial response
by RECIST 1.1 >8 months on a clinical trial involving PD-1 inhibitor+irinotecan
(MLH1 mutation); treatment linked to NGS was already initiated prior to the
report becoming available. One is too early to evaluate on olaparib (PARP1
mutation), and one had disease progression on dasatinib (KIT overexpression)
as best overall response. One patient has not yet received NGS recommended
therapy, and the remaining 8 evaluable patients had clinical deterioration
or died before NGS recommended therapy was initiated. Conclusion: SCLC
after 1 st line therapy tends to have more rapid progression and deterioration
making NGS application for systemic therapy challenging. Either applying
NGS earlier in the earlier stages of disease course or further improvements in
turnaround time may better address these challenges.
Keywords: small cell lung cancer, clinical trials, whole transcriptome
sequencing, next-generation sequencing
MA11: NOVEL APPROACHES IN SCLC AND NEUROENDOCRINE TUMORS
TUESDAY, DECEMBER 6, 2016 - 14:15-15:45
MA11.11 IS HIPPOCAMPAL AVOIDANCE DURING WHOLE BRAIN
RADIOTHERAPY RISKY FOR SMALL CELL LUNG CANCER PATIENTS?
Esra Kirakli 1 , Ozgur Oztekin 2
1 Radiation Oncology, Dr. Suat Seren Göğüs Hastalıkları Ve Cerrahisi Eğitim Ve
Araştırma Hastanesi, Izmir/Turkey, 2 Diagnostic Radiology, Tepecik Education and
Research Hospital, Izmir/Turkey
Background: Hippocampal avoidance (HA) during whole brain radiotherapy
(WBRT) is performed to prevent neural stem-cell injury causing decreased
neurocognitive function. Nevertheless, the estimated risk for metastases in
HA area in small cell lung cancer (SCLC) patients is unknown. The current study
aimed to characterize the metastatic distribution within the brain relative to
the hippocampus and estimate the incidence of hippocampal metastasis in
SCLC patients and also identify clinical and radiographic variables that may be
associated with the presence of metastases within the HA area. Methods:
SCLC patients treated with WBRT between January 2010 and December 2015
were reviewed. T1-wighted, post-contrast axial MRI (1.5 or 3 Tesla) images
obtained just before therapeutic cranial irradiation were retrieved and
reviewed for each patient. The HA area was generated by expanding the
hippocampal contour by 5 mm volumetrically to account for necessary dose
fall-off between the hippocampus (HP) and the whole brain planning target
volume. Metastatic lesions within HP or HA area were defined as HP
metastasis. HP metastasis rate was evaluated and characteristics of patients
with HP metastasis were analyzed and compared to patients without HP
metastasis. Results: 54 patients evaluated with cranial MRI were enrolled. HP
metastasis rate was 32% (17 patients). 4.4% of all metastases involved the HP
and HA area (2.2% of metastases each)
1.1-137.4, p=0.045) and being younger than 65 years of age (OR: 4.8, 95% CI:
1-23.2, p=0.049) were found to be independent risk factors for HP metastasis.
Conclusion: HP metastasis might be more common in SCLC patients. Reducing
the dose to the HP by HA-WBRT plan in SCLC may be risky for the development
of HP metastasis compared with other malignant solid tumors.
Keywords: hippocampal avoidance, small cell lung cancer
SESSION MA12: MISCELLANEOUS BIOLOGY/PATHOLOGY
TUESDAY, DECEMBER 6, 2016 - 14:15-15:45
MA12.01 NEXT GENERATION SEQUENCING BASED CLINICAL
FRAMEWORK FOR ANALYSES OF TREATMENT PREDICTIVE
MUTATIONS AND GENE FUSIONS IN LUNG CANCER
Kajsa Ericson Lindquist 1 , Anna Karlsson 2 , Per Levéen 1 , Hans Brunnström 1 ,
Christel Reuterswärd 2 , Karolina Holm 2 , Mats Jönsson 2 , Karin Annersten 2 ,
Frida Rosengren 2 , Karin Jirström 1 , Jaroslaw Kosieradzki 3 , Lars Ek 3 , Åke Borg 2 ,
Maria Planck 2 , Göran Jönsson 2 , Johan Staaf 2
1 Pathology, Regional Laboratories Region SkÅne, Lund/Sweden, 2 Oncology and
Pathology, Lund University, Lund/Sweden, 3 Department of Respiratory Medicine
and Allergology, Skane University Hospital, Lund/Sweden
Background: The use of new, emerging techniques in the search of tailored
patient therapies is rapidly becoming a reality. Here we describe the
optimization and implementation of next generation sequencing for
treatment predictive mutation screening in parallel with gene fusion
status of ALK, RET and ROS1 in non-small cell lung cancer (NSCLC) patients.
Methods: The Illumina TruSight tumor 26-gene NGS panel was validated
in 81 clinical routine FFPE or cytology specimens and implemented in 533
diagnostic NSCLCs during one year of clinical analysis. In parallel, a RNA-based
NanoString method was evaluated in 169 cases for gene fusion status of
ALK, RET and ROS1. Results: We have successfully established a streamlined
workflow with a 5-day turnaround time from specimen arrival to mutation
report. The concordance in the validation cohort was 99% for comparable
variants. In the 533 diagnostic samples, 1-2 variants were detected in 79% of
the cases. Most frequently mutated genes included TP53, KRAS, EGFR, STK11,
and BRAF, all with differences in mutational patterns between histological
subgroups. The RNA-based NanoString assay was successfully established
and validated. The success rate in the 169 cases was 80% and 10 gene fusions
were found (five ALK fusions, three RET fusions and two ROS1 fusions) all in
adenocarcinomas. Integration of mutation and gene fusion status revealed
that 68% of adenocarcinomas, 13% of SqCCs and 56% of NSCLC-NOS harbored
≥1 actionable alteration ALK, RET, ROS1, EGFR, KRAS, PIK3CA, BRAF, NRAS,
MAP2K1, ERBB2 or AKT1. Specifically, in 13.2% of the adenocarcinomas
where no EGFR or ALK alteration was detected emerging targeted therapy
may be considered in addition to the 15.3% of patients that was eligible for
EGFR or ALK inhibitors. The corresponding proportions for SqCCs were 5.5%
in addition to the 2.2%, and for NSCLC-NOS 2.5% in addition to the 11.2%
eligible for EGFR or ALK inhibitors. Conclusion: Next generation sequencing
in combination with the NanoString technology is time- and cost efficient
in the diagnostic routine for treatment predictive mutation screening and
gene fusion status detection. The techniques represent valuable tools for
pinpointing patients eligible to standard targeted therapies in addition to
new emerging therapies.
Keywords: NGS, clinical routine, mutation, personalized medicine
MA12: MISCELLANEOUS BIOLOGY/PATHOLOGY
TUESDAY, DECEMBER 6, 2016 - 14:15-15:45
MA12.02 MMP12 AND LMO7, TWO KEY PLAYERS ON OPPOSITE
SIDES OF EARLY LUNG SQUAMOUS CELL CARCINOMA
DEVELOPMENT
Angela Barrett 1 , Sofia Lourenco 1 , Krishna Kolluri 1 , Bernadette Carroll 2 , Mary
Falzon 2 , Elaine Borg 2 , Jeremy George 2 , Sam Janes 3 , Vitor Teixeira 1
1 Medicine, University College London, London/United Kingdom, 2 University College
London Hospital, London/United Kingdom, 3 Lungs for Living Research Centre, UCL
Respiratory, University College London, London/United Kingdom
. The most common location of metastasis was frontal lobe followed by
cerebellum and temporal lobe. Having diabetes mellitus (OR: 12.1, 95% CI:
Background: Our laboratory has a unique cohort of patients with pre-invasive
lung squamous cell carcinoma (SqCC) lesions, within which there is a clear
discrepancy between the prevalence of pre-invasive lesions and the incidence
of lung cancer, suggesting that not all pre-invasive lesions progress to cancer.
Using gene expression microarrays we identified 1846 genes significantly
differentially expressed between progressive and regressive pre-invasive
SqCC lesions. The macrophage metalloelastase MMP12 gene was found
to be highly expressed in progressive lesions, and we hypothesised that it
S208 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017