Abstract
BackgroundPatients newly diagnosed with lung adenocarcinoma with bone metastases (LABM) have poor survival rates after treatment with conventional therapies. To improve outcomes, we retrospectively investigated whether the application of a more comprehensive genetic test of tumor biopsies samples from LABM patients could provide the basis for treatment with more effective tyrosine kinase inhibitors (TKIs) regimens.MethodsFine needle biopsies were taken from the primary tumor (PT) and a secondary bone metastasis (BM) of 17 LABM patients before treatment. Simple genetic profiles for selecting therapies were initially obtained using an ARMS-PCR test for EGFR and ALK fusion mutations. More detailed genetic profiles of somatic exon SNVs and CNVs in 457 cancer-related genes were retrospectively derived using capture single molecule amplification and resequencing technology (capSMART).ResultsARMS-PCR identified 14 EGFR positive, 3 EGFR negative and 1 ALK fusion positive patient. A therapy regimen incorporating TKIs Gefitinib and Crizotinib was offered to the EGFR and ALK fusion positive patients, respectively. With the exception of two patients, molecular profiling of matching PT and BM biopsies identified a highly shared somatic variant fingerprint, although the BMs exhibited additional genomic instability. In six of 13 EGFR positive patients and in all three EGFR negative patients, examination of the genetic profiles identified additional clinically significant mutations that are known or experimental drug targets for treatment of lung cancer.ConclusionOur findings firstly suggest that treatment regimens based on comprehensive genetic assessment of newly diagnosed LABM patients should target both the PT and secondary BMs, including rogue clones with potential to form new BMs. Second, the additional information gained should allow clinicians to design and implement more personalized treatment regimens and potentially improve outcomes for LABM patients.
Highlights
Patients newly diagnosed with lung adenocarcinoma with bone metastases (LABM) have poor survival rates after treatment with conventional therapies
With the exception of P11, P14 and P17, the tumor purity of the formalin fixed and paraffin-embedded (FFPE) sections was relatively similar between matching primary tumor (PT) and bone metastases (BM) biopsies (Fig. 2)
Treatment outcomes for LABM patients Based on disease severity, tumor assessments and genetic evaluation, the managing clinicians initiated personalized treatment regimens for each patient (Table 1, Supplementary Table 1)
Summary
Patients newly diagnosed with lung adenocarcinoma with bone metastases (LABM) have poor survival rates after treatment with conventional therapies. In China, lung cancer ranks first for morbidity and mortality (Chen et al 2016) with approximately 30–40% patients presenting with metastatic disease. Radiotherapy, chemotherapy and targeted therapy comprise the treatment regimens available to treat LABM patients but even after clinical treatment, the median survival time is still only 6–10 months and, at 1 year, the survival rate is only 40–50% (Bender 2014; Hess et al 2006; Tas et al 1999)
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