bluuebunny/crossref_metadata_2025_split huggingface dataset:
The incidence and clinical impact of bone metastases in non-small cell lung cancer.
Authors: Kuchuk Michael , Kuchuk Iryna , Hutton Brian , Clemons Mark , Wheatley-Price Paul 
Published: March 2020

e19024 Background: Non-small cell lung cancer (NSCLC) is the leading global cause of cancer death. Bone metastases (BM) in NSCLC are a common cause of morbidity, but use of bone targeted agents (BTA) is variable. We investigated the incidence and impact of BM in an unselected NSCLC population. Methods: With ethics approval, we performed a retrospective chart review of all patients (pts) with NSCLC seen at our institution in 2007. Baseline demographics, stage and initial treatment goals were recorded. In pts with advanced disease (mNSCLC) metastatic sites were identified. In BM pts, skeletal related events (SRE), interventions and outcomes were recorded. Results: In total, 374 pts were identified. Median age was 68 years (IQR 60-76), 54% female. Histological subtypes were adenocarcinoma (36%), squamous (18%), and other (46%). Overall 91% were current or ex-smokers. At initial diagnosis 37% had stage I-IIIa, 18% IIIb and 46% stage IV disease. A total of 160 pts (43%) were treated with curative intent; 211 (56%) were considered palliative. Of the 160 curative therapy pts, 90 (56%) subsequently relapsed, with a median time from diagnosis to relapse of 14.9 months. Of the 301 pts with mNSCLC, common sites of metastasis were lung/pleura (80%), mediastinal lymph nodes (69%), bone (39%), brain (30%), and liver (24%). In total 116 pts had BM; a higher incidence was observed in pts ≤70 years than pts >70 (36% vs 23%). SREs were observed in 69 pts (59%), the median number of SREs per BM pt was 1 (0-16). The incidence of SREs was radiotherapy (63%), fractures (22%), spinal cord compression (6%) and surgery to bone (5%). Factors associated with ≥2 SREs were smoking status (28% never smokers vs 9% ex/current smoker) and younger age (15% vs 5%). In BM pts, 64% required opioid analgesia, only 6% received BTA. Overall survival (OS) in pts with mNSCLC was 7.3 months (IQR 3.1-20.5). Pts with BM had significantly shorter OS compared to those without BM (5.5 vs. 9.9 months, p=0.02). Median OS in pts with or without SRE were 5.5 and 6.4 months (p=0.58). Conclusions: BM in NSCLC pts are common, and most pts will develop an SRE and/or require opioids. In mNSCLC, the presence of BM is associated with significantly shorter survival, which raises challenging questions around the use of BTA.
Clinical validation of mutational analysis of EGFR and KRAS in fine needle aspiration and small core needle biopsies using a real-time PCR method.
Authors: Lozano Maria D. , Labiano Tania , Echeveste Jose Ignacio , Montanana Myriam , Gomez Nerea , Aguirre Mercedes , Shieh Felice , Ramos Teresa , Zulueta Javier , Gurpide Alfonso , Perez-Gracia Jose Luis , Martin-Algarra Salvador 
Published: March 2020

e19027 Background: About 75% of NSCLC is diagnosed at an advanced stage, thus analysis is often performed from small samples. There is a growing need for multiple biomarker testing when tissue is limited. We evaluated two real-time PCR based assays to assess EGFR and KRAS mutation status in limited tissue specimens and compared results to a lab validated method. Methods: 117 NSCLC patient samples (46 CNB, 71 FNA) were tested for EGFR and KRAS mutations using a single section. DNA was extracted directly from one stained smear in FNA samples (without pre-processing) and one 5-micron section in CNB using the cobas DNA Sample Preparation Kit. Sixty samples were also analyzed for both genes by direct sequencing using the same DNA. Eleven patients had matched CNB and FNA samples. Results: We tested 68 ADCs, 38 SqCCs, 8 NSCLC-NOS, 2 ADCs in situ non-mucinous, and 1 large cell carcinoma (Table). Median DNA concentrations for CNB and FNA were 14.17 ng/ul and 3.75 ng/ul. The failure rate for the cobas were 1.7% (EGFR), 6.8 % (KRAS) in FNA samples, and 0% for CNB. The failure rate for EGFR sequencing was 13.1% (FNA), 16.4% (CNB), and 0% for KRAS. The 11 patients with FNA and CNB showed concordant results between cobas and sequencing. One patient had two mutations; one (L782F) was detected only by sequencing. No discordant findings were seen other than invalid results comparing both systems. Conclusions: Assessment of mutations in limited tissue samples of CNB and FNA using a single section performed on the cobas EGFR and KRAS test is feasible and reliable. There was a lower invalid rate for EGFR testing on cobas test compared to Sanger sequencing. The cobas tests have rapid turnaround time to results, require limited input DNA, and are easier to use compared to sequencing. Still, it is mandatory that pathologists maintain careful quality control of the samples. [Table: see text]
Comparison of the effects of bevacizumab (BV) in combination with chemotherapy (CT) and CT alone on the incidence of brain metastases (BM) in non-small cell lung cancer (NSCLC): A retrospective clinical analysis.
Authors: Du Nan , Li Fang , Jiao Shunchang , Fu Yan , Li Xiaosong , Zhao Hui 
Published: March 2020

e19044 Background: The incidence of BM of advanced NSCLC is 20-40%, and there's a lack of effective treatment. This study aims to investigate the value of the angiogenesis marker VEGF in predicting the risk of BM in patients (pts) with NSCLC receiving CT+BV or CT alone and to explore the cumulative risk of BM of NSCLC with high VEGF expression that treated with BV. Methods: Pts with stage IIIB/IV NSCLC underwent CT and/or targeted therapy from 2008-1 to 2010-12 were included. Semi-quantitative detection of VEGF expression was carried out using conventional immunohistochemical staining of lung tissue specimens. Pts experienced BM prior to treatment were excluded. Pts underwent gemcitabine /carboplatin (GC) + BV treatment were included in observation group; pts underwent GC were included in control group. The cumulative risk of BM was calculated using death as a competing risk. Results: 177 pts were included (118 in BV+CT group; 59 in CT group). The median follow-up duration was 18.7 months. Up to 2012-12-31, BM occurred in 15 cases in BV+CT group and 17 in CT group (12.71% vs. 28.81%). 4 cases (33.89%) in BV+CT group survived, and 11 (18.64%) in CT group survived. In BV+CT group, the cumulative risks of BM at 6, 12, and 24 months were 0.86%, 7.52%, and 13.01%, respectively, and 6.74%, 18.88%, and 28.85% in CT group, respectively (P < 0.001). HR of BM in BV+CT group was 0.048 (95% CI: 0.171-0.994) compared to CT group. In BV+CT group, the 6-, 12-, and 24-month cumulative risks of BM were 1.6%, 7.97%, and 12.63% in pts with VEGF(+) and 0, 7.24%, and 12.71% in pts with VEGF(-), respectively; in CT group, the 6-, 12-, and 24-month cumulative risks of BM were 9.35%, 27.04%, and 37.5% in pts with VEGF(+) and 3.52%, 10.71%, and 18.05% in pts with VEGF(-), respectively; there was no significant difference between them. Conclusions: BV+CT can effectively reduce the incidence of BM in pts with advanced NSCLC and improve their prognosis. This small data sample suggests that pts with VEGF(+) are more prone to BM than pts with VEGF(-). The incidence of BM in pts with VEGF(+) is reduced after BV treatment, though its specific mechanism still requires further study.
Retreatment with pemetrexed-based chemotherapy in advanced nonsquamous NSCLC patients.
Authors: Zhuo Minglei , Wang Jie , An Tongtong , Wang Zhijie , Zhao Jun , Wu Meina , Duan Jianchun , Wang Yuyan , Bai Hua , Wang Shuhang 
Published: March 2020

e19061^ Background: Retreatment of pemetrexed based chemotherapy (PBC) has been reported in MPM previously, but it is not investigated in non-squamous NSCLC (NS-NSCLC). Methods: We retrospectively enrolled 26 advanced NS-NSCLC patients who had received retreatment of PBC when their response to initial PBC were PR or SD. Chemotherapy regimens administered as retreatment were single pemetrexed (500 mg/m2every 3 weeks) or pemetrexed with a platinum. Response was evaluated according to RECIST. Toxicity was evaluated according to NCI-CTC version 3.0. PFS and OS were computed by Kaplan-Meier. Statistical analyses were performed with SPSS13.0. Results: In retreatment, most adverse effects (AE) were tolerable but doublet regimen was associated with higher AE including bone marrow depression and fatigue. In patients who received retreatment of PBC, objective response rate (ORR) and disease control rate (DCR) was 12% (3/26) and 73% (19/26) respectively. Patient with PFS≥10 months in initial PBC therapy would have a longer PFS in retreatment comparing with those PFS <10 months (6.0 vs 3.1 month, p = 0.004); patients with therapy-free interval (TFI) ≥6 months after initial PBC therapy also have a longer PFS in retreatment comparing with those interval <6 months (7.0 vs 3.0 month, p = 0.001). The OS also tend to be longer but not reach statistic significance. The response of first round PBC therapy (PR vs. SD) was not a factor affecting the PFS in retreatment. Conclusions: Patients with PFS over 10 months or TFI over 6 months after first round of PBC could benefit from retreatment of PBC.
Confirmation of non-small cell lung cancer (NSCLC) diagnosis using ALK testing and genetic profiling in patients presenting with carcinoma of unknown primary site (CUP).
Authors: Penley William Charles , Spigel David R. , Greco F Anthony , Hainsworth John D. 
Published: March 2020

e19062 Background: Emerging data suggest real-time reverse transcriptase-polymerase chain reaction (RT-PCR) tumor profiling can predict the primary site in CUP. We report on CUP patients (pts) predicted to have NSCLC by RT-PCR, in whom detection of ALK rearrangements provided further diagnostic support. Methods: 4 pts were diagnosed with CUP based on standard clinical, radiographic, pathologic evaluation with immunohistochemistry (IHC), and bronchoscopy/endoscopy where indicated. All pts had a RT-PCR assay (CancerTYPE ID, bioTheranostics, Inc.) performed on tumor specimens for the purpose of predicting a primary site. Tissue was also tested for ALK by FISH using a break-apart probe. Results: Pt characteristics are shown (Table). RT-PCR results prompted ALK testing in Pts 2 and 3. ALK testing and RT-PCR testing were performed concurrently in Pts 1 and 4. Each specimen was diagnosed as lung adenocarcinoma (AC) by RT-PCR gene profiling, and also tested positive for an EML4-ALKrearrangement. All pts are being followed for clinical outcome. Conclusions: Gene expression profiling in CUP diagnosed lung AC in 4 pts who also had ALK rearrangements supporting the diagnosis. Identifying ALK-positive NSCLC among pts who present with CUP improves the site-specific treatment options. [Table: see text]
EGFR mutation testing, from bench to practice: A single Irish institute experience.
Authors: Shikhrakab Hassan , O'Brien Cathal , Osman Nemer , O'Byrne Kenneth John 
Published: March 2020

e19064 Background: Epidermal growth factor receptor (EGFR) gene mutations determine the treatment and prognosis in lung adenocarcinoma. Exon 19 and exon 21 (L858R) deletions represent the most common recognised mutations detected. To date, no figures regarding the prevalence of EGFR mutations in the Irish population have been published. Methods: The prevalence of EGFR mutations was retrospectively analysed for all patient samples tested since the introduction of EGFR testing routinely (Mar to Dec 2012) in a single Irish institute. The presence of 41 known treatment linked EGFR mutations in exons 18, 19, 20 and 21 of the EGFR gene was tested in 209 Irish patients. Resection, core biopsy or FNA samples were analysed using a commercially available CE-IVD marked multiplex real-time PCR assay. Samples were included from patients of curative and palliative treatment intent. Results: 30 out of 209 patients with lung adenocarcinoma tested had an EGFR mutation (13%, 95% CI 8.4-17.6%). Of the mutations detected relative frequency was as follows: exon 19 deletion 63.3% (n=19, 95% CI 46.1-80.6%), exon 21 (p.L858R) 16.7% (n=5, 95% CI 3.3-30.0%), exon 20 insertions 13.3% (n=4, 95% CI 1.2-25.5%) and exon 18 (p.G719X) and exon 20 (p.T790M) both at 3.3% (n=1, 95% CI 0-9.8%). Of those patients tested 51.2% were male (n=107) and 48.8% (n=102) female. The incidence of mutations was higher in females than in males; 63.3% of those with an EGFR mutation were female (n=19, 95% CI 46.1-80.6%). Reciprocally, the male percentage was 36.7% (n=11, 95% CI 19.4-53.9). The mean age at testing was 67 years. Complete smoking data was unavailable for this study. All samples tested were formalin fixed paraffin embedded tissue or cell preparations. Turn around time (TAT) for EGFR mutation processing substantially improved over ten month period, from over five weeks to less than four working days. Conclusions: This group of patients represent the largest cohort of patients tested for EGFR mutation in a single institute in Ireland in less than 12 months. The incidence of EGFR mutations in this patient population is comparable to current European estimates. The gender bias was notable amongst those tested, with female patients being nearly twice as likely to harbour an EGFR mutation.
Paclitaxel/carboplatin (PC) intercalated with gefitinib or paclitaxel/carboplatin (PC) for advanced non-small cell lung cancer (NSCLC) in selected population who were smoker or wild-type EGFR: Randomized phase II study.
Authors: Choi Yoon Ji , Kim Sang-We , Lee Dae Ho , Choi Chang-Min , Lee Jung Shin 
Published: March 2020

e19079 Background: The introduction of EGFR inhibitors to standard chemotherapy is an attractive approach to improved outcome. However, the tumor cells which were driven to G0/G1 phase by gefitinib may not sensitive to cytotoxic chemotherapy which is active to G2M arrested tumor cells. This randomized phase II study compared the efficacy of PC intercalated with gefitinib versus PC, as first-line treatment in a clinically selected population of advanced NSCLC patients. Methods: Eligible patients were chemotherapy-naïve advanced NSCLC patients with good ECOG PS of 0 or 1. Non-smoking patients with adenocarcinoma or patients with activating EGFR mutation were excluded because they could benefit from gefitinib alone. They were randomized to either one of the treatments; standard chemotherapy alone (control arm, 46 pts) of paclitaxel (175 mg/m2) and carboplatin (AUC 5) on day 1; or the same chemotherapy plus gefitinib 250 mg/day on day 2 through 15 (study arm, 44 pts). The treatment was repeated every 3 weeks for maximum 4 cycles without maintenance. The primary endpoint included the response rate (RR), and the secondary endpoints were progression-free survival (PFS) and overall survival (OS). Results: A total of 90 patients (male 85.6%, median age 59, adenocarcinoma 63.3%, smoker 90.0%, wild-type EGFR 24.4%, unknown EGFR status 75.6%) were included. There was no difference in terms of RR (the study arm, 40.9% [95% CI 27.3-56.8%] vs. the control arm, 37.0% [95% CI 23.8-51.2%], p=0.701). There was also not difference in terms of PFS (the median PFS; 4.13 vs. 4.13, HR=0.941 [95% CI 0.61-1.45], p=0.781) and OS (the median OS; 9.33 vs. 10.53, HR=0.95 [95% CI 0.58-1.54], p=0.827). Safety analyses showed a similar incidence of drug-related grade 3/4 toxicity in study group (20.9%) compared with control group (23.3%), while mild rash (58% vs. 9%) and diarrhea (14% vs. 7%) were more common in the study arm. Conclusions: PC chemotherapy intercalated with gefitinib did not improved RR, PFS, and OS compared to PC chemotherapy alone in clinically selected population of advanced NSCLC patients who were smoker or wild-type EGFR. Clinical trial information: NCT01196234.
A practical decision-making strategy based on clinical triple features for EGFR-TKIs to treat advanced non-small cell lung cancer patients with unknown EGFR mutation status.
Authors: Zheng Di , Wang Jiying , Lu Bing 
Published: March 2020

e19082 Background: EGFR mutated lung cancers are strongly associated with clinical characteristics of never- smoking history and adenocarcinoma histology type, and tended to develop multiple pulmonary metastases.Whether multiple pulmonary metastatic lung adenocarcinomas with never-smoking history would respond to EGFR-TKIs as those harboring EGFR active mutation remains unclear. Methods: 223 consecutive metastatic non-small cell lung cancer (NSCLC) patients with unknown EGFR status who received EGFR-TKIs as salvage therapy after failure of previous platinum-based chemotherapy in Shanghai Pulmonary hospital between 2009 and 2011 were included to the study. Available CT scans, routinely performed at baseline and one month after the start of EGFR-TKIs therapy, were reviewed independently by two investigators. For the purposes of this study, diffuse pulmonary metastatic nodules were defined as multiple nodules distributed diffusely throughout the whole lung with at least 20 nodules within the unilateral lung field. Paraffin embedded tissues were available for 45 of 223 patients for EGFR gene mutation test. Results: Of 134 never-smokers with lung adenocarcinoma,70 patients responded to EGFR-TKIs with an objective response rate (ORR) of 52.2% (70/134), and the ORR for the 62 patients with diffuse pulmonary metastatic nodules was 79% (49/62). Among the 20 patients with confirmed EGFR mutation (based on the available 45 archived specimen), the ORR was 75% (15/20). The multivariate analyses showed that the presence of diffused multiple pulmonary metastatic nodules, activating EGFR mutation and female are independent predictive factors of the response to EGFR-TKIs. Conclusions: Patient selection based on specific clinical features to recieve EGFR-TKI treatment yield high response rate comparable to that selected by EGFR mutation status. It is practical to consider EGFR-TKI as salvage therapy in non-smoking patients with lung adenocarcinoma characterized by diffuse pulmonary nodules when EGFR mutation testing is a challenge.
Tyrosine kinase inhibitors (TKI) treatment of non-small cell lung cancer (NSCLC) patients (p) based on EGFR mutations (m) status in serum only.
Authors: Capdevila Laia , Carcereny Enric , de Aguirre Itziar , Cros Sara , Queralt Cristina , Moran Teresa , Buges Cristina , Mijangos Erika , Pardo Nuria , Rosell Rafael 
Published: March 2020

e19088 Background: Treatment of EGFR mutated NSCLC p with EGFR TKIs in phase III trials has shown improved efficacy to standard chemotherapy. However, it can be difficult to obtain sufficient tumor tissue for analysis of EGFR m status in a large proportion of p. Nevertheless, so far, no data exists for NSCLC p treated according to EGFR m status in serum alone. Methods: We reviewed our database to identify EGFR mutated p, excluding those for whom status was available in both serum and tissue. We analyzed p treated with an EGFR TKI for whom EGFR m status was known in serum only (status in tissue unknown due to insufficient material). At the same time, we reviewed p in whom EGFR m status in tissue was available over the same period in order to compare clinical characteristics and efficacy parameters: PFS, ORR and overall survival (OS). EGFR m analysis was performed in cell free circulating DNA (cfDNA)isolated from serum and plasma using the QIAmp DNA blood mini kit. Results: 9 p with EGFR m detected in serum and 33 p with EGFR m in tissue were included. In EGFR mutated p in serum, median age 63; male 55.6%; non-smokers 33.3%; former smokers 44.4%; ECOG PS 0-1 66.7%; adenocarcinoma 77.8%; deletion19 33.3%, L858R 66.7%; EGFR TKI treatment in 1st line 44.4%; 2nd or 3rd line 55.6%. ORR: complete response (CR) 22.2%; partial response (PR) 22.2%; stable disease (SD) 22.2%; progressive disease (PD) 11.1%. 2p had poor PS and died prior to evaluation. mPFS 4.7 months (mo). mOS 18 mo. In p with EGFR m in tissue, median age 61; male 36.4%; non-smokers 75.8%; former smokers 24.2%; adenocarcinoma 87.9%; deletion19 75.8%; L858R 24.2%; 1st line 54.5%; 2nd or 3rd line 45.5%. ORR: CR 15.2%; PR 57.6%; SD 12.1%; PD 15.2%. mPFS 8.9 mo. mOS 32.7 mo. The multivariate analysis for OS considering EGFR m in serum differed according to PS (PS 0-1 16.6 mo vs PS > 2 5.2 mo). Conclusions: Obtaining sufficient tissue from NSCLC p for analysis of EGFR m status and other molecular alterations can be difficult. Determination of EGFR m in serum alone is feasible, yields similar results to mutation status in tissue, and could permit us to take treatment decisions.
Predicting significance of EGFR mutation existing in tissues and plasma concuurrently or alone to EGFR–tyrosine kinase inhibitors (EGFR-TKIs) for advanced non-small cell lung cancer.
Authors: Wang Yuyan , Wang Jie , Bai Hua , Wang Zhijie , Duan Jianchun , An Tongtong , Zhao Jun , Zhuo Minglei , Wu Meina , Wang Shuhang 
Published: March 2020

e19091 Background: To investigate predicting significance of EGFR mutations existing in tissues couples with plasma or either sample alone to EGFR–tyrosine kinase inhibitors (EGFR-TKIs) treatment for advanced non–small-cell lung cancer (A-NSCLC). Methods: Two hundred-eighty-seven A-NSCLC patients met following criteria were included into this study: 1) had received EGFR-TKIs as first- or second-line therapy; 2) had sufficient tissue and plasma samples for EGFR mutation analysis. All patients were divided into four subgroups which were wild-type EGFR in both of specimens (B-/T-), mutated in both of specimens (B+/T+), mutated only in one specimen (B+/T- and B-/T+). EGFR mutation was screened by denaturing high performance liquid chromatograph (DHPLC) and confirmed by ARMS. Objective response rate (ORR) and progression-free survival (PFS) were compared among four subgroups. Results: Of all 287 patients, 101 patients carried EGFR mutation both in tissue and plasma, 103 patients carried mutation only in tissue (65 cases) or plasma (38 cases). Median PFS was 9.2 months (95% CI, 6.3 to 12.1) and 2.0 months (95% CI, 1.3 to 2.7) in B+/T+ and B-/T- group, respectively. For single mutated group, mPFS were 7.87 month for B-/T+ group (95% CI, 5.1 to 10.6) and 11.87 months for B+/T- group (95% CI, 3.3 to 20.5) (P=0.001). For ORR, 53.0% for B+/T+ group, 15.8% for B-/T- group, 40.0% for B-/T+ group and 28.9% for B+/T- group (P=0.000). EGFR-TKIs therapeutic line could not change trend which B+/T- or B+/T+ group had better PFS than B-/T+ group. Conclusions: Detection of EGFR mutation in tissue and plasma may have different significance in predicting response of EGFR-TKIs.