bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome of KRAS mutated (m) non-small cell lung cancer (NSCLC) patients (pts) treated with immune checkpoint inhibitors (immuneCI).
Authors: Pardo Aranda Nuria , Viaplana Cristina , Remon Jordi , Martinez Marti Alex , Cedres Perez Susana , Navarro Alejandro , Martinez de Castro Ana Maria , Villacampa Guillermo , Carbonell LLuisa , Hernando Alberto , Vivancos Ana , Dienstmann Rodrigo , Felip Enriqueta 
Published: September 2018

e20526 Background: The most frequent genetic alteration in advanced NSCLC is KRASm in ~25% of tumors. This event associates with smoking pattern and high mutational burden, which correlate with the efficacy of CI in NSCLC. There is in silico evidence that coexisting KRASm and TP53m positively impact immuneCI benefit , but this association needs clinical validation. Methods: We retrospectively assess the efficacy of PD-1/PDL-1 CI (atezolizumab, pembrolizumab, nivolumab or durvalumab) in a cohort of NSCLC patients whose tumors were KRASm (with or without coexisting TP53m) as assessed by a next-generation sequencing test. Endpoints were clinical benefit rate (CBR), defined as partial response or stable disease > 4 months (m), and time to progression (TTP) on immuneCI. Fisher-exact test and log-rank test P values are described. Results: 25 pacients were identified, 68% female, median age 54 y (33-75), 95% former/current smoker; 95% adenocarcinoma; 59% with 2 or more metastatic sites; 36% immuneCI as third-line or beyond (median time from first-line to immuneCI of 7.5 m). 20 tumors had KRASm in codon 12, 3 codon 13 and 2 in codon 61. Overall, CBR was 36% (CI95% 19%-57%) and median TTP was 3.7 m (CI95% 2.2-NA). Coexisting KRASm/ TP53m (n = 11) did not associate with higher CB (27% vs 50%, p = 0.56). A trend for lower TTP in the KRASm/ TP53m vs TP53 wild-type was observed (2.1 vs 5.6 m, HR 0.3; p = 0.11). Conclusions: NSCLC patients whose tumors are KRASm can have substantial benefit with immuneCI. In our series, the population with KRASm/ TP53m tumors did not derive higher clinical benefit from this therapeutic intervention
Apatinib plus icotinib in treating advanced non-small-cell lung cancer after icotinib treatment failure.
Authors: Xu Jianping , Liu Xiaoyan , Yang Sheng , Zhang Xiangru , Shi Yuankai 
Published: September 2018

e20528 Background: Icotinib, a small-molecule EGFR TKI, has been approved as the first-line therapy for treating advanced non-small-cell lung cancer (NSCLC) in China. However, treatment failures frequently occurred in NSCLC patients with EGFR-sensitizing mutations. A phase II clinical trial has reported the beneficial survival of apatinib, a new small-molecular VEGFR TKI, in treating NSCLC (Zhang et al. 2012 ASCO, 7548). This retrospective study tried to investigate the efficacy and safety of apatinib plus icotinib as second- or third-line treatment in patients with advanced NSCLC. Methods: This study comprised 27 patients diagnosed with advanced NSCLC and treated with icotinib and apatinib as the second- or third-line therapy. Patients received oral icotinib (125 mg, tid), alone initially. When disease progressed, they received icotinib plus apatinib (500 mg, qd, orally). Treatment was continued until disease progression or unacceptable toxic effects. Efficacy was evaluated based on RECIST version 1.0 and toxic effects were assessed using the NCI-CTC version 2.0. Results: Followed up to December, 2016, the median time of apatinib treatment was 7.47 months, and 8 of 27 patients were dead. The median overall survival had not reached and the median progression-free survival (PFS) was 5.33 months (95% CI 3.63-7.03 months). Moreover, the objective response rate (ORR) was 11.1% and the disease control rate (DCR) was 81.5%. Fourteen patients received icotinib and apatinib as the second-line treatment, and the RR and DCR were 7.1% and 78.6%. The remaining 13 patients received drugs as the third-line treatment, with an ORR and a DCR of 15.4% and 84.6%. Additionally, 11 patients experienced icotinib monotherapy failure within 6 months with median PFS of 7.37 months (95% CI 4.17-8.57 months) and 16 patients experienced icotinib monotherapy failure after 6 months with median PFS of 2.60 months (95% CI 0.00-8.54 months). The common drug-related toxic effects included hypertension (44.4%), fatigue (37.0%) and hand-foot syndromes (18.5%). Conclusions: Apatinib plus icotinib is efficacious in treating patients with advanced NSCLC after icotinib treatment failure, with acceptable toxic effects.
Radiographic features of metastatic brain tumors from non-small cell lung cancer with ALK rearrangement.
Authors: Chu Li , Li Ruimin , Yang Xi , Xia Fan , Zhu Zhengfei 
Published: September 2018

e20533 Background: Approximately 5% of Non-Small Cell Lung Cancer (NSCLCs) have ALK rearrangement, in which brain metastases are common. The radiographic features of metastatic brain tumors have not been previously studied. Finding the features of brain metastasis could help establishing the treatment pattern for the ALK-rearranged NSCLC patients. Methods: All NSCLC patients with ALK rearrangement (132 patients) were detected from March 2008 through December 2016. The metastatic brain tumors (34 patients) detected from July 2014 through December 2016 were divided into metachronous brain metastasis (MBM) and synchronous brain metastasis (SBM) groups according to the diagnosis time. All patients were followed up using brain magnetic resonance imaging (MRI). The number of brain tumors, size of the largest brain tumors, and size of peritumoral brain edema were compared between the two groups. Results: Thirty-four patients were observed.The number of brain tumors in ALK-rearranged NSCLC patients is 4.6 with 41.07mm Peritumoral Brain Edema Size (PBES). Only one patient has the military brain metastases. All patients were divided into two groups: metachronous (15 patients) and synchronous (19 patients). The two groups had rare active and former smoker. The SBM group had more female patients. The SBM group had larger number of brain tumors (6.1 VS 2.8), but there was no significant difference ( P= 0.0672). The MBM group had smaller brain tumors (14.2mm vs 20.9mm, P= 0.0798) with smaller PBES (25.7mm vs 53.2mm, P= 0.0018) and Peritumoral Brain Edema Index (PBEI) (0.9 vs 1.9, P= 0.0201) than the SBM group. Conclusions: Only one patient in SBM group has the military brain metastases. The SBM group has larger brain tumors with larger peritumoral brain edema and PBEI. The MBM patients have smaller ones. Our studies show that ALK-rearranged NSCLC patients have a small number brain tumors and relatively large PBES.
Combination of anti-PD-1/PD-L1 antibodies with chemotherapy or CTL4 antibodies for first-line treatment of advanced lung cancer.
Authors: Fan Yun , Xu Xiaoling 
Published: September 2018

e20538 Background: Checkpoint inhibitors showed satisfactory efficacy in treating lung cancer. We conducted this meta-analysis to explore the therapeutic efficacy and safety of anti-PD-1/PD-L1 antibodies combine with chemotherapy or CTL4 antibodies as first-line treatment on advanced lung cancer. Methods: A quantitative meta-analysis was performed through a systematic search in PubMed, Web of Science, the conference abstracts and so on. The pooled ORR, 6-month progression-free survival rate (PFSR6m), and 1-year overall survival rate (OSR1y) were calculated and compared. 9 trials were included in this meta-analysis. Results: Our analyses demonstrated the pooled ORR and DCR of anti-PD-1/PD-L1 antibodies combine with chemotherapy for non-small-cell lung cancer were 48.0% (40.2–56.0 %) and 84.8 % (78.1– 89.7%), respectively. The pooled OR and DCR of anti-PD-1/PD-L1 antibodies combine with chemotherapy for small-cell lung cancer were 42.9% (18.5–71.2 %) and 73.6 % (32.8–94.1%), respectively. The pooled PFSR6m of anti-PD-1/PD-L1 antibodies combine with chemotherapy for NSCLC and SCLC were 62.9% (46.3–79.6%) and 27.6 % (18.9–36.2 %), respectively. The OSR1y of anti-PD-1/PD-L1 antibodies combine with chemotherapy for NSCLC and SCLC were 70.1 % (57.4%-82.8 %) and 32.0 % (25.2–38.9 %). In addition, the pooled ORR and DCR for anti-PD-1/PD-L1 antibodies plus CTL4 antibodies treatment group was 29.6% (11.4%-657.8%) and 48.7% (16.8%-81.7%), respectively. Conclusions: Anti-PD-1/PD-L1 antibody plus chemotherapy can serve as a promising treatment option for lung cancer. While patients treated anti-PD-1/PD-L1 antibodies plus CTL4 antibodies may benefit less compare with anti-PD-1/PD-L1 antibodies combine with chemotherapy. Encouraging activity with tolerable adverse effect was observed.
Long-term clinical outcomes of ALK inhibitors in patients with ALK-positive advanced non-small cell lung cancer.
Authors: Murakami Haruyasu , Ono Akira , Nakashima Kazuhisa , Omori Shota , Wakuda Kazushige , Kenmotsu Hirotsugu , Naito Tateaki , Takahashi Toshiaki 
Published: September 2018

e20542 Background: Anaplastic lymphoma kinase (ALK) inhibitors show high clinical efficacy in patients with ALK-positive advanced non-small cell lung cancer (NSCLC). However, the long-term clinical outcomes remain unknown. Methods: We retrospectively reviewed medical records of patients with ALK inhibitor-naïve ALK-positive advanced NSCLC who initiated alectinib or crizotinib therapy at the Shizuoka Cancer Center between June 2010 and December 2011. Results: This retrospective study included 14 patients (male/female, 5/9; PS 0/1, 6/8; adenocarcinoma/adenosquamous carcinoma, 13/1; smoker/never smoker, 8/6; brain metastasis presence/absence, 5/9; number of prior chemotherapy regimens 0/1/≥2, 1/7/6; alectinib/crizotinib, 4/10) with a median age of 55 years (range, 28-71). At the data cut-off (January 16, 2017), three patients were still receiving first ALK inhibitors (alectinib in two patients and crizotinib in one). One patient requested the discontinuation of alectinib therapy after five years. One patient discontinued crizotinib therapy due to unacceptable toxicity. Nine patients discontinued first ALK inhibitors due to disease progression. The overall response rate was 78.6% with complete response in two patients (14.3%), partial response in nine (64.3%), stable disease in one (7.1%), and progressive disease in two (14.3%). The median progression-free survival (PFS) for all 14 patients was 15.3 months, and the five-year PFS rate was 35.7%. The five-year PFS rates in patients treated with alectinib and crizotinib were 75.0% and 20.0%, respectively. The median overall survival (OS) for all 14 patients was 36.8 months, and the five-year OS rate was 42.9%. The five-year OS rates in patients treated with alectinib and crizotinib were 75.0% and 30.0%, respectively. Conclusions: ALK inhibitors showed favorable long-term clinical outcomes in patients with ALK inhibitor-naïve ALK-positive advanced NSCLC, especially in patients treated with alectinib.
Real-life use of nivolumab in non-small cell lung cancer: A multicentric cohort to determine its clinical efficacy and predictive factors of early progression.
Authors: Corny Jennifer , Costantini Adrien , Renet Sophie , Fallet Vincent , Jouveshomme Stephane , Giroux Leprieur Etienne , Duchemann Boris , Selvarathnam Shobanya , Beaussier Hélène , Brosseau Solenn , Hajouiji Linda , Taillade Laurent , Doucet Ludovic , Zalcman Gerard , Friard Sylvie , Tredaniel Jean , Wislez Marie , Jardin Meryam , Cadranel Jacques 
Published: September 2018

e20543 Background: Nivolumab (NIV) is now widely used in ≥ 2ndline of advanced non-small cell lung cancer (NSCLC). The aims of this real-life study were (1) to evaluate its efficacy, (2) to identify predictive factors of worsening under NIV. Methods: This retrospective multicentric study (8 Thoracic Oncology regional centers) included all patients treated by NIV in 2015 (follow-up until 2016, June 30th). Demographics and tumor characteristics were extracted. Objective tumor response was assessed by computerized tomography (RECIST v1.1). Median NIV treatment duration and overall survival (OS) were calculated. Clinical and biological factors evaluated as predictive markers of earlyprogression (discontinuation before 1stevaluation) were: NSCLC histology, PS, smoking-history, number of previous chemotherapy received and initial albumine (alb), C-reactive protein (CRP) and lactate dehydrogenase (LDH) serum levels. For these factors, patients quickly worsened and responders were compared (Student’s t-test, Chi-2 test). Results: Our cohort included 297 patients (non-squamous NSCLC n = 181 [61%]; PS > 1 n = 66 [22%]). At first evaluation, partial response was observed in 16% (n = 47), stable disease in 18% (n = 54) and progression in 49% (n = 144). A total of 45 patients (15%) were early progressors and no evaluation could be performed. Median NIV duration of treatment was 2.8 months [0-15], OS 6.9 months [0-16] (n = 146 still alive on June 30th, 2016). Early progressor patients were PS > 1 in 42% versus (vs) 21% for responders (mean PS 1.7 vs 1.0 for responders (p < 0.001)) and an alb level of 29.9 g/L vs 33.6 (p = 0.03). Mean CRP (p = 0.06) and LDH (p = 0.08) serum levels, NSCLC histology (p = 0.64), smoking-history (p = 0.08), number of previous chemotherapy (p = 0.90) were non-significant. Conclusions: This study confirms that NIV may be effective in NSCLC, with a 16% objective response rate. However early progression observed in 15% of patients was associated with a lower initial alb level and a higher PS. Missing data for LDH and CRP levels may have influenced their non-significance. Further studies must be realized to determine the interest of these factors as predictive markers.
Impact of early progression on prognosis for non-small cell lung cancer patients with EGFR mutation.
Authors: Yoshitsugu Kanako , Kenmotsu Hirotsugu , Omae Katsuhiro , Omori Shota , Nakashima Kazuhisa , Wakuda Kazushige , Ono Akira , Naito Tateaki , Murakami Haruyasu , Takahashi Toshiaki 
Published: September 2018

e20570 Background: For epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) patients, EGFR-tyrosine kinase inhibitors (TKIs) improve progression free survival compared with cytotoxic chemotherapy. However, some patients show early progression (EP) in first-line EGFR-TKI treatment, and their prognosis is still unclear. This study aimed to examine the implications of EP for prognosis of EGFR mutant NSCLC patients. Methods: Advanced EGFR mutant NSCLC patients treated with gefitinib (GEF) as first-line between 2005 and 2015 at Shizuoka Cancer Center were retrospectively reviewed. EP on GEF was defined as disease progression before 180 days according to the Jackman criteria. Results: Forty-five of 198 patients treated with GEF as first-line, showed EP. Patient characteristics was as follows (with EP/ without EP) : median age (range), 69 (32-88)/ 70 (35-92) years; male, 40/ 28%; ECOG performance status (PS) 0-1, 64/ 79%; deletion in exon 19 (del 19), 36/ 53%; L858R in exon 21, 53/ 43%; never smoker, 44/ 65%; liver metastasis, 27/ 12%; brain metastasis, 44/ 37%. The median overall survival was 395 days (95% CI: 267-547 days) for patients with EP and 979 days (95% CI: 808-1124 days) for those without EP. Post progression survival after treatment with GEF was significantly shorter in patients with EP (median: 254 days vs. 420 days, HR: 0.55 (95% CI: 0.39-0.79), P < 0.05). Among patients with EP, 56% received subsequent chemotherapy (patients without EP: 71%). In univariate analysis, EP was significantly associated with four factors; liver metastasis, smoking history, PS 2-4, absence of del 19. In multivariate analysis, smoking history (OR: 0.38, 95% CI: 0.18-0.80), PS 2-4 (OR: 0.43, 95% CI: 0.19-0.98), and del 19 (OR: 2.15, 95% CI: 1.04-4.45) were significantly correlated (P < 0.05) with EP. Conclusions: Patients with EP during first-line GEF therapy for advanced EGFR mutant NSCLC showed poor prognosis. Since smokers, patients with PS 2-4, or absence of del 19 tend to show EP, improving first-line treatment is necessary to improve their prognosis.
Clinical profile, pathological characteristics, mutational profile and disease outcome of non-small cell lung cancer patients treated at the Benavides Cancer Institute-University of Santo Tomas Hospital : A five-year study.
Authors: Bautista Maria Diana Aileen Chua , Caguioa Priscilla B. 
Published: September 2018

e20580 Background: Lung cancer is the most commonly diagnosed cancer worldwide and its incidence continues to grow. Lung cancer mortality and survival rates vary markedly by race and ethnicity resulting into a public health burden that differs by population subgroups. This study determined the association of the clinical profile, pathological characteristics and mutational profile with the disease outcome of Non Small Cell Lung Cancer patients at the Benavides Cancer Institute – University of Santo Tomas Hospital from January 1, 2007 to December 31, 2011. Methods: This is a retrospective descriptive study. Medical records of all of patients diagnosed with non-small cell lung cancer were included. Results: A total of 80 patients with non small cell lung cancer were treated, 78.75% (63) were adenocarcinoma and 13.75% (11) were squamous cell carcinoma. Overall 5-year survival rate was at 5%. The 1 year, 2-year, 3-year survival rates were 38.75%, 21.25% and 12.5% respectively with the mean survival time of 1.6 years. The mean survival time of patients who received adjuvant treatment was 26 months, while for metastatic patients was 18 months. Only the stage at time of diagnosis was correlated with overall survival. Age, gender, family history, smoking history, number of pack years smoking history, histologic subtype, response after first line of treatment and sites of metastases were not associated with overall survival. EGFR mutational analysis was not performed in this study since it was not the standard of care and had limited availability in low to middle income countries at the time of the study period. Conclusions: Similar to global incidence, adenocarcinoma remains the most common type of lung cancer in our center. Stage at diagnosis predicts overall survival among lung cancer patients. There is a need for molecular immunotyping to further characterize patients and response to treatment.
Association of KRAS mutations detected via liquid biopsy in metastatic non-small cell lung cancer patients with high levels of FDG-PET SUV.
Authors: Kim Seo-Hyun , Karo Ammar , Buckingham Lela , Basu Sanjib , Borgia Jeffrey Allen , Bonomi Philip , Batus Marta , Fidler Mary J. 
Published: September 2018

e20594 Background: We had previously evaluated the relationship between FDG-PET SUV with TP53 and KRAS mutations in formalin fixed paraffin embedded tissue (FFPE) in non-small cell lung cancers (NSCLC) in which genomic profiling had been performed. Considering FDG-PET SUV as a surrogate of glycolysis, we found TP53 and KRAS mutations were associated with increased glycolytic activity. The aim for this study was to evaluate KRAS and TP53 in circulating tumor DNA (ctDNA) in relation to FDG-PET SUV in a different cohort of NSCLCs in which genomic profiling was performed on peripheral blood. Methods: All stage IV NSCLC patients with genomic analysis from ctDNA and baseline FDG-PET scans between December 2014 and November 2016 were included. Associations between KRAS and TP53 mutations and maximal standard uptake value (SUVmax) were assessed using the Mann-Whitney and Kruskal-Wallis test. A subset analysis studying all KRAS positive patients from FFPE and ctDNA was performed based on the specific KRAS mutation. Results:122 patients had FDG-PET scans and genomic analyses of their circulating tumor cells. 62 (51%) patients had a TP53 mutation, 20 (17%) patients had a KRAS mutation, and 13 (11%) patients had both TP53 and KRAS mutations. Patients with a KRAS mutation had a higher SUVmax with a mean of 12.32 (p = 0.019). The presence of TP53 alone or concurrent TP53/KRAS was not significantly related to SUVmax. Analyzing 48 patients with KRAS mutation from FFPE and ctDNA assay, 16 patients had mutations of G12C and 9 patients had G12V. The presence of the G12C mutation was particularly highly correlated with higher SUVmax with a mean of 17.68 (p = 0.0006). Conclusions: In analyzing ctDNA, a larger cohort, mutations in KRAS had the strongest correlation with increased SUVmax. Targeting glycolysis and cellular metabolism could be a potential therapeutic strategy for patients with KRAS mutations. Although individual numbers are small, KRAS subtype analysis showed the presence of the G12C mutation might have the strongest relationship with SUV max and increased glycolysis.
Expanded molecular routine testing for targetable mutations in non-small cell lung cancer to reveal frequent co-occuring mutations.
Authors: Kostenko Anna , Fassunke Jana , Steinhauser Susanne , Scheffler Matthias , Merkelbach-Bruse Sabine , Michels Sebastian Yves Friedrich , Fischer Rieke Nila , Nogova Lucia , Hellmich Martin , Zander Thomas , Buettner Reinhard , Wolf Juergen ,   For the Network Genomic Medicine
Published: September 2018

e20596 Background: Using next-gen sequencing of predefined gene panels in routine clinical diagnostics of lung cancer allows, in contrast to single-gene assays, assessment of co-occuring mutations, which might underly heterogeneity of response to targeted drugs and survival. The Network Genomic Medicine (NGM) performs high sensitive next generation sequencing (NGS) based routine molecular diagnostics on a central platform for about 5000 inoperable lung cancer patients (pts) annually in Germany. Methods: NGS panel used in NGM consists of 17 genes to cover potentially targetable aberrations. Mutation analyses were run on an Illumina (MySeq) platform, while FISH analyses were performed separately. In 2016, we have started the evaluation of all NGM pts with available clinical data who had received NGS-based molecular diagnostics. In particular, we have focused on non-squamous (non-sq) and squamous (sq) NSCLC pts with co-occurring mutations: their frequency, significance and impact on overall survival. Results: From 2014 molecular genotyping was performed for 7,893 NGM pts (n = 7,246 NSCLC (5,667 non-sq and 1,487 sq pts) and n = 489 SCLC) with eligible clinical data. Genetic alterations in transformation-associated pathways were found in 79 % of all NSCLC pts. Furthermore, co-occurring mutations were detected in 39 % of these pts: 40 % in non-sq and 37 % in sq NSCLC. 11 % of pts had more than 2 co-occurring mutations. 1 % of all pts had 5 co-occurring mutations. The most frequent paired mutations were KRAS, EGFR and MET each with TP53 in non-sq and FRGF1 and TP53 in sq NSCLC. The incidences and significance of 3, 4 and 5 co-mutations as well as the impact of these co-occurring mutations on overall survival will be presented. Conclusions: Frequent occurrence of co-occuring mutations in transformation – associated pathways underlines the genetic heterogeneity also of lung cancer with classical driver mutation and the impact of co-occurring mutations on survival. This work confirms the use of molecular multiplex testing in routine molecular diagnostics of NSCLC. Assessment of co-occuring mutations will help to further specify genetically defined subgroups of lung cancer with therapeutic relevance.