Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
Hospitals NHS Foundation Trust, Sheffield/United Kingdom, 3 The Christie,
Manchester/United Kingdom
Background: Worldwide lung cancer is the biggest cause of cancer mortality
(Cancer Research UK, 2012) and is the UK’s second most commonly diagnosed
malignancy (Macmillan Cancer Support, 2013). Early detection and treatment
significantly improves five year survival rates but curative treatments can
impact on patients’ health and wellbeing. To date little research has been
conducted to establish the support needs and recovery patterns of health
and wellbeing among lung cancer patients treated with curative intent
radiotherapy. This limits our ability to identify those most at risk of poorer
health and wellbeing outcomes and target services effectively to support
patients better. This study assesses the feasibility of collecting patient
reported outcomes measures (PROMs) and clinical details to understand
recovery after curative intent radiotherapy treatment for lung cancer.
Methods: This mixed methods study used a prospective, longitudinal cohort
design. Eligible patients awaiting curative intent radiotherapy were recruited
from six UK sites between October 2015 and June 2016. Questionnaires
were completed before undergoing radiotherapy and 3 months later. The
questionnaires included validated patient reported outcome measures,
including quality of life, symptoms, social support, wellbeing and sociodemographic
details. Participants’ medical details were collected by
healthcare professionals (HCPs) including cancer type, stage, treatment,
and comorbid conditions. Study procedures were evaluated in a qualitative
process evaluation. Results: Of 229 eligible patients, 136 consented to the
study with 73% uptake of those approached. A further 13 patients provided
reduced consent to collect demographic and medical information only.
Preliminary results: response rates 76% at baseline and 65% at 3 months.
Of baseline responders: 59% were male; the median age was 70 years; 29%
lived alone; 61% were home owner-occupiers and 20% were current smokers.
Baseline EORTC-QLQ-C30 results showed a mean global health status score
of 56.6 and patients were most affected by dyspnoea and fatigue with
mean scores of 48.8 and 45.0. These are in line with expected scores based
on reference data. To date 9 HCPs, 7 patients and 2 stakeholders have been
interviewed as part of the process evaluation, study processes and procedures
are deemed acceptable to participants. Conclusion: This study demonstrates
it is feasible to recruit a cohort of lung cancer patients prospectively to
assess wellbeing and patterns of recovery following radiotherapy. This novel
approach to understanding lung cancer patients’ experiences of survival will
enhance our ability to target appropriate and timely support to those most at
risk of poorer health and wellbeing.
Keywords: quality of life, Feasibility, Radiotherapy
SESSION MA14: IMMUNOTHERAPY IN ADVANCED NSCLC:
BIOMARKERS AND COSTS
TUESDAY, DECEMBER 6, 2016 - 16:00-17:30
MA14.01 UPDATED DATASET ASSESSING TUMOR MUTATION
BURDEN (TMB) AS A BIOMARKER FOR RESPONSE TO PD-1/PD-L1
TARGETED THERAPIES IN LUNG CANCER (LC)
Alexa Schrock 1 , Neelesh Sharma 2 , Nir Peled 3 , Jose Bufill 4 , Gordan Srkalovic 5 ,
David Spigel 6 , David Fabrizio 1 , Garrett Frampton 1 , Caitlin Connelly 1 , Mary Beth
Lipka 2 , Anna Belilovski 3 , Jun Lo 1 , Yali Li 1 , James Sun 1 , Kyle Gowen 1 , Gregory
Kalemkerian 7 , Luis Raez 8 , Sai-Hong Ou 9 , Jeffrey Ross 1 , Philip Stephens 1 , Siraj
Ali 1 , Vincent Miller 1
1 Foundation Medicine, Cambridge/United States of America, 2 Hematology
and Oncology, University Hospitals, Cleveland/OH/United States of America,
3 Davidoff Cancer Center, Petach Tikva/Israel, 4 Michiana Hematology-Oncology,
Pc, Mishawaka/IN/United States of America, 5 Sparrow Regional Cancer Center,
Lansing/AL/United States of America, 6 Sarah Cannon Research Institute, Nashville/
United States of America, 7 University of Michigan Cancer Center, Ann Arbor/MI/
United States of America, 8 Memorial Cancer Institute, Miami/FL/United States of
America, 9 University of California Irvine School of Medicine, Orange County/CA/
United States of America
Background: Immune checkpoint inhibitors (ICPIs) nivolumab and
pembrolizumab have been FDA-approved in non-small cell LC (NSCLC). Current
IHC based diagnostics are challenged by assay and slide scoring issues and
modest predictive value, and more robust and comprehensive biomarkers
of ICPI efficacy are needed. A discovery set of 64 NSCLCs treated with ICPIs
suggested that high TMB (≥15 mutations/Mb) significantly correlated with
longer time on drug (Spigel et al., ASCO 2016, Abstract:9017). Methods:
Comprehensive genomic profiling (CGP) was performed during the course
of clinical care. TMB was assessed as the number of somatic, coding, base
substitution and indels per Mb of genome. Microsatellite instability-high
(MSI-H) or stable (MSS) status was determined using a proprietary algorithm.
Results: 15,529 LCs: 66% adenocarcinoma, 1% sarcomatoid, 14% NSCLC NOS,
11% squamous, 5% small cell, and 2% large cell were assessed. TMB was similar
across all lung histologies (median: 6.3, 8.1, 9.0, 9.9, 9.9, and 10.8); the median
was 7.6 for all LC cases (TMB ≥15 in 24% of cases), compared to 4.5 for 80,000+
samples of diverse tumor types in the database. Of LCs assessed 0.3% were
MSI-H, of which 30/31 were TMB-high; however, 24% of MSS-stable cases
were also TMB-high. PD-L1 amplification and DNA repair pathway mutation
(MLH1, MSH2, POLE) were found in 1.0% and 1.1% of LC cases analyzed,
respectively. Tumors harboring known drivers (ALK, ROS1, EGFR, BRAF V600E,
MET splice) had low TMB (median: 2.5, 3.6, 3.8, 3.8, 4.5), whereas tumors with
KRAS mutation, non-V600E BRAF mutation, PD-L1 amplification, or DNA
repair alterations were more likely to be TMB-high (median: 9.0, 10.8, 14.4,
21.6). Conclusion: High TMB may be a predictive biomarker of response to
ICPIs. Several factors including lack of a known driver, MSI-H status, PD-L1
amplification, and DNA repair mutation correlated with high TMB (P