bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amenorrhea in lung cancer patients.
Authors: Cathcart-Rake Elizabeth Jane , Ruddy Kathryn Jean , Gupta Ruchi , Partridge Ann , Stewart Elizabeth A. , Vachon Celine , Yang Ping 
Published: September 2018

e20092 Background: More than 5,000 premenopausal women are diagnosed (dx’d) with lung cancer annually in the United States. Improvements in treatment are contributing to a growing population of young survivors. Limited data exist regarding the risk of treatment-related amenorrhea, a surrogate for infertility and early menopause, after systemic therapies for lung cancer. Methods: Since 1997, we mailed annual surveys to patients seen at Mayo Clinic for lung cancer who consented to join a research cohort. Surveys queried menopausal status and age of menopause. Those who were dx’d under age 50, who were treated with curative intent, and who reported that they were premenopausal at the time of the cancer dx were included in this analysis. “Immediate” treatment-related menopause was defined as reporting age of menopause as the same as the age at diagnosis or 1 year (yr) older. Results: Of 182 survey respondents to date (mean time from dx to 1st survey: 26 mos, SD 24 mos, range 12-202 mos), 85 (mean age 44 yrs, SD 5, range 34-48) received chemo during the yr after diagnosis, 26 of whom also received targeted therapy during that yr. Lung cancer dx occurred 1958-2016. Platinum drugs, taxanes, and etoposide were the most common chemotherapies. 46% of chemo recipients (mean age 47, SD 2, range 41-49) experienced immediate menopause, 9% (mean age 43 yrs, SD 5, range 35-48) experienced menopause at least 2 yrs after the age of dx, and 45% (mean age 40 yrs, SD 5, range 25-48) remained pre- or peri-menopausal at their final survey (on average 3 years after dx, SD 2, range 1-10). Only 3 patients received targeted therapy alone, and the remaining 94 (mean age 42 yrs, SD 6 years) received no systemic therapy within a year of diagnosis. 15% of these 94 (mean age 45 yrs, SD 3, range 41-49) experienced immediate menopause, 16% (mean age 43 yrs, SD 4, range 36-49) experienced menopause 2+ yrs after the age of diagnosis, and 69% (mean age 41 yrs, SD 7, range 20-49) remained pre- or perimenopausal at their final survey (on average 4 yrs after dx, SD 3, range 1-10). Conclusions: Chemotherapy for lung cancer causes amenorrhea in a substantial proportion of women dx’d with lung cancer while premenopausal. Further research on fertility and menopausal symptoms after lung cancer treatment, and on differences between regimens, is warranted.
Efficacy of PD-1 inhibitors in patients with metastatic non-small cell lung cancer (NSCLC) with KRAS or EGFR T790M mutations.
Authors: Sharma Nitika , Stroud Chipman Robert Geoffrey , Walker Paul R. , Cherukuri Sulochana Devi , Muzaffar Mahvish , Cherry Cynthia R. , Parent Teresa , Hardin Jessica 
Published: September 2018

e20513 Background: Immune checkpoint blockade(ICB) has revolutionized the treatment of progressive NSCLC with its durable benefit when compared to cytotoxic agents. In the era of personalized medicine, there is a need to identify effective predictive biomarkers to detect exceptional responders to ICB. Immune modulating interventions with cytotoxic or biologic agents can maximize clinical responses from ICB in poorly immunogenic tumors. KRAS mutations are a negative prognostic factor for survival and generally lack targeted therapies. The T790M mutation in EGFR is the most common cause of acquired resistance to first line TKIs. As a group, patients with EGFR mutations generally do not derive clinical benefit from ICB versus cytotoxic chemotherapy. Preclinical data suggests that mutations like T790 m are associated with higher immunogenicity leading to avid stimulation of antigen specific T-cells (Ofuzi et al, 2014) and better response to ICB (Yamada, 2013). However, the efficacy of ICB by specific molecular mutations remains poorly defined. Methods: We reviewed data for 83 pts with recurrent or progressive metastatic lung cancer treated with nivolumab from June 2015-Dec 2016. All pts were treated with ICB as a second or subsequent line of treatment. The patients were assessed for pathology, mutational status and overall survival. Mutational status was checked on either tissue biopsy or serum samples submitted for proteomic veristrat/genestrat (Biodesix Inc., Boulder, CO, USA) assay. Results: Of the 83 patients treated with nivolumab, 65 patients were found to have NSCLC. Eleven pts were found to have KRAS mutation which was further subdivided as: 6 pts with KRAS G12C, 4 with KRAS G12V, 1 with KRAS G12D. Two pts were found to have T790M mutation. 81%(9/11) pts with KRAS mutation died. Median survival in pts with KRAS G12C mutation was 10 weeks and KRAS G12V was 12 weeks (p = 0.17). Median survival was not reached for patients with T790M mutation. Conclusions: KRAS mutations tend to have a shorter overall survival with ICB as compared to patients with EGFR T790M mutations. Further studies are necessary to isolate poorly immunogenic subtypes of NSCLC and develop novel treatment approaches to optimize outcomes.
Differences in survival between usual practice and clinical trial participants in advanced NSCLC by age.
Authors: Ortega Granados Ana Laura , Cárdenas Quesada Nuria , de la Torre Cabrera Capilla , Fernández Navarro Mónica , Ruiz Sanjuan María , Marin Pozo Juan Francisco , Millán García Rosa , García Verdejo Francisco José , Luque Caro Natalia , Fernández Garay David , Plata Fernández Yessica , López Leiva Pedro , Navarro Pérez Victor , Martínez Ortega Esther , Dueñas García Rosario , Lomas Garrido Maria , Álamo de la Gala Maria Carmen , Jaén Morago Ana , Moreno Jimenez Miguel Angel , Sánchez Rovira Pedro 
Published: September 2018

e20515 Background: It is known that outcome of patients included in clinical trials have a better outcome than patients treated with standard therapy. This is a retrospective case-control study of outcome of patients with stage III and IV non-small cell lung cáncer (NSCLC) recruited in clinical trials vs advanced NSCLC patients in usual clinical practice in our institution. Methods: We performed a case-control study matching all patients participating in trials with chemotherapy and/or TKis (immunotherapy was not included) in a 5 year period (January 2010-November 2014) in 1st line setting, matching them in a ratio 1:2 with individuals in usual clinical practice. There were 36 patients in trials and 72 patients treated by our protocol. Cases were matched by age ( < 65 and > 65), histology (adenocarcinoma and squamous), EGFR status (mutated and wild-type). All patients were WHO performance status 0-1. Results: Patients in each group were matched for stage, histological subtype, previous surgery and systemic therapy. Median follow up for patients treated on a trial was 3.3 years, compared with 2.9 years for matched patients who received standard 1st line therapy. Median overall survival for patients included a trial was 19.6 months, and 15.7 months for control group. The difference between groups was not significant (Log rank test, HR 0.81, 95% CI: 0.42 to 1.30, p = 0.53). Median overall survival in younger patients in trials ( < 65) was 19.3 months, and in elderly patients was 19.8 months. The median progression-free survival in the two groups was 6.8 and 5.5 months respectively (HR 0.72, 95% CI 0.30 to 1.43, p = 0.21). Conclusions: In our institution, we didn’t found significant differences for overall survival or progression-free survival, but there is a trend for a better outcome for those items. Benefit seems to be similar in younger patients than in older patients, so this encourages recruiting of selected elderly patients.
Targeted gene sequencing panel for identifying actionable genomic alterations in Taiwanese lung cancer patients.
Authors: Lu Yen-Jung , Tan Kien Thiam , Chen Chun-Jung , Jhou Ren-Shiang , Yang Yi-Ting , Chen Chien-Hung , Chen Hua-Chien , Chen Shu-Jen , Chung David T. 
Published: September 2018

e20522 Background: Lung cancer boasts an arsenal of targeted therapies directed at various molecular aberrations such as EGFR mutations and fusion genes. Simultaneous assessment for genetic alterations provides biomarkers to assist clinicians in their treatment selections. Methods: A total of 43 FFPE (formalin-fixed, paraffin-embedded) samples obtained from lung cancer patients in Taiwan were subjected to next-generation sequencing (NGS), using a compact panel encompassing 17 potentially actionable, lung cancer-associated genes. NGS was performed on the Ion Torrent PGM or Proton System with a targeted average depth of > 800x. Genomic alterations detected were categorized as single nucleotide variants (SNV) or chromosomal copy number alterations (CNA). Results: A total of 74 putatively actionable genomic alterations were detected across 38 patients (88.4%), which may predict sensitivity or resistance to established and/or therapies that are still in clinical development. 19 patients (44.2%) had tumors harboring activating EGFR mutations in the tyrosine kinase (TK) domain – L858R substitution or exon 19 deletion, which may suggest clinical benefit to first- and second-generation EGFR TK inhibitors (TKIs). Three patients (7.0%) whose tumor had acquired the EGFR T790M mutation were advised to switch to third-generation EGFR TKI. Possible resistance mechanisms to EGFR TKIs via increased copy number of EGFR (14.0%, n = 6) and MET (11.6%, n = 5) were observed. Deletion or loss of CDKN2A gene were detected in 14 patients (32.6%), which may confer sensitivity to CDK4/6 inhibitors. Inhibition of downstream effectors in the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways were suggested for patients whose tumor harbored PIK3CA and/or KRAS oncogenic mutations. Conclusions: Next-generation sequencing using a compact panel of genes may be sufficient to identify biomarkers for targeted therapies selection for most lung cancer patients in Taiwan.
The first- or second-line use of pemetrexed sequentially with EGFR-TKI did not differ in PFS for advanced NSCLC patients harboring EGFR-mutant tumors.
Authors: Ding Zhen-Yu , Chen Yue-Yun 
Published: September 2018

e20531 Background: Both EGFR-TKI and pemetrexed doublet chemotherapy (P) are two effective therapies in advanced NSCLC patients with EGFR mutant tumors. But which one should be used in first-line remains controversial. Methods: This was a retrospective study where patients prescribed with EGFR-TKI (gefitinib or icotinib) from Jan 2013 to Jan 2016 were screened. Patients must have metastastic diseases harboring TKI-sensitizing EGFR mutation. They must be older than 18 years, and have evaluable target lesions. Whether TKI or P was used in the first line, it must be switched to the other in the second line. PFS in both first line (PFS1) and second line (PFS2) was collected. Results: We screened totally 550 patients (gefitinib n = 455, icotinib n = 95) to enroll a cohort of 36 patients. They were all adenocarcinoma except 1 adenosquamous carcinoma. Gender (M or F), PS (0 or 1), mutation type (Exon19Ddel or other) were equally distributed. The median age was 50.5 years. For the whole cohort, the total PFS (PFS1+PFS2) was 18.1 m (95%CI: 15.2-21.1 m). For those (n = 24) receiving first-line TKI, PFS1, PFS2, and total PFS were 10.3 m, 6.6 m, and 19.2 m. And for those receiving first-line P (n = 12), they were were 3.4 m, 11.5 m, and 16.5m. The total PFS in both groups did not differ significantly (p = 0.548). Conclusions: Our results argued the sequential usage of TKI and P achieve a comparable PFS irrespective of the sequence.
Short course pembrolizumab in complete responders with advanced non-small cell lung cancer.
Authors: Chan Daniel Boon Yeow 
Published: September 2018

e20537 Background: Pembrolizumab has been available in Singapore since October 2014 for clinical use. All clinical trial protocols of Pembrolizumab in patients with advanced non-small cell lung cancer (NSCLC) require a 2 year period of treatment in responders, even in complete responders. It is not known if shorter treatment durations in complete responders can afford reasonable progression free interval (PFS). Such abbreviated treatment in complete responders would result in significant cost savings and lesser side effects. Methods: A single physician practising at a single private medical oncology center in Singapore collated consecutive cases of advanced NSCLC seen by him and treated with Pembrolizumab from October 2014 till December 2016. All were smokers except for 2 patients. All patients were biopsy and imaging proven to have advanced NSCLC. 46 patients were treated with Pembrolizumab 2mg/kg body weight 3 weekly and observed with sequential imaging every 3-6 months with the first assessment scan after Cycle 4. All complete responders by imaging stopped treatment after 4 cycles of Pembrolizumab by mutual consent. PD-L1 IHC testing by DAKO 22C3 was not done on any of the patients’ tumours as the test has only been available in Singapore since December 2016. Results: Cut-off date for analysis of data was 1 Feb 2017. 4 out of 46 patients (9%) achieved a complete metabolic response on FDG PET by irRC and/or CT scans by RECIST 1.1. All 4 patients with complete response (CR) (except Patient #3) were smokers. All 4 patients remain in CR with ECOG Performance Status (PS) 0 without any further treatment. Conclusions: Real world clinical usage of Pembrolizumab in advanced NSCLC can afford long PFS in complete responders in spite of abbreviated treatment of 4 cycles. Clinical trials should be designed to address this issue due to its impact on health care costs. [Table: see text]
Impact of primary tumor resection in oligometastatic non-small cell lung cancer: Experience of a resource-limited cancer center in southern Brazil.
Authors: Nunes Filho Paulo Ricardo Santos , da Silva Caroline Albuquerque Moreira , Tsukazan Maria Teresa Ruiz , Fay Andre Poisl , Barrios Carlos H. , Debiasi Marcio 
Published: September 2018

e20552 Background: Stage IV non-small cell lung cancer (NSCLC) with low volume disease represents a more indolent phenotype within the biological spectrum of lung cancer. Recent data suggest that aggressive local therapy may impact clinical benefit in this subgroup of patients, with 5-year overall survival (OS) rate around 20%. Methods: We analyzed patients with oligometetastatic (≤3 metastasis) NSCLC treated with primary tumor resection at Hospital São Lucas da PUCRS. Clinico-pathological features and survival data were retrospectively collected using standard templates. The primary endpoint was OS. Survival was estimated using the Kaplan-Meier method and log-rank test was used to univariate analysis. Results: Between April 1991 and December 2015, 25 patients with oligometastatic NSCLC underwent surgery of the primary tumor. Clinico-pathological data are summarized in Table 1. Overall, median OS was 16 months (95% CI: 8.87-23.13 months) with a 5-years survival rate of 7%. Age less than 65 years old was associated with longer OS (HR 0.34 95%CI 0.13-0.92 p = 0.02). Patients with brain metastasis had a non-significant lower OS than those without (16 vs. 24 months, respectively). Conclusions: This analysis suggests that in a resource-limited center, where immunotherapies and targeted-therapies are not available, local therapy for oligometastatic NSCLC did not provide the same clinical benefit seen in the same population from high-income countries. See table. [Table: see text]
Impact on OS of 2nd and 3rd generation TKI in EGFR mt+ and ALK+ patients: Results of the NOWEL network.
Authors: Roeper Julia , Netchaeva Maria , Lueers Anne Christina , Stropiep Ursula , Hallas Cora , Tiemann Markus , Neemann Nicole , Heukamp Lukas C. , Falk Markus , Wiest Gunther , Wesseler Claas , Ukena Dieter , Sackmann Sandra , Griesinger Frank 
Published: September 2018

e20560 Background: Available clinical research data shows that early mutation testing for patients with NSCLC stage IV could lead to an effective choice of therapy for patients with proven mutations. Targeted therapies achieve a higher ORR, PFS, OS and a better quality of life than chemotherapy in mt+ patients. With the advent of 2nd and 3rd generation TKI´s effective in 1st generation TKI resistant tumors, we wanted to study the impact of these drugs on the outcome of patients in a real life setting in 3 lung cancer centers. Methods: 1383 patients from the three cancer centers diagnosed with NSCLC stage IV (UICC 7) were examined. Methods for the detection of mutations included Sanger Sequencing, hybridization based COBAS testing as well as hybrid cage next generation sequencing. Results: 880/1383 (64%) consecutive patients with non-squamous cell NSCLC from the cancer centers were studied for the presence of tumor mutations, especially for EGFR and ALK mutations. The EGFR mutation rate was 16.6% (141/880), and the ALK-translocation rate 3.8% (24/635). Median OS in EGFR mt+ patients was 31 (n = 78) vs. 32 (n = 38) vs. 16 (n = 14) months respectively (center 1 vs. center 2 vs. center 3). Median OS in ALK mt+ patients was 25 (n = 17) months in center 1 and 11 (n = 5) months in center 2 (p < 0.05). Use of 3rd generation TKI Osimertinib (n = 17) lead to a significantly higher OS (n = 17, median OS 67 mo) than the use of only 1st and 2nd generation TKI (n = 113, median OS 24 mo, p < 0.000). Similarly, use of 2nd and 3rd generation ALKi impacted significantly on median OS: Crizotinib alone n = 7, 17 months, Crizotinib followed by Ceritinib and/or Brigatinib (n = 9) median OS not reached, p < 0.001. Conclusions: Smalldifferences in OS were observed, depending on the treatment centers, but the use of multiple EGFR and ALK-I impacted highly significantly on the outcome of patients with EGFR and ALK-alterations in a real life setting.
The efficacy and safety of nivolumab in advanced non-small cell lung cancer in clinical practice in Japan: A multicenter analysis.
Authors: Kobayashi Keigo , Naoki Katsuhiko , Nakachi Ichiro , Oyamada Yoshitaka , Nakamura Morio , Inoue Takashi , Tateno Hiroki , Sakamaki Fumio , Sayama Koichi , Terashima Tsuyoshi , Ko Hidefumi , Nishino Makoto , Masuzawa Keita , Hasegawa Hanako , Manabe Tadashi , Arai Daisuke , Yasuda Hiroyuki , Kawada Ichiro , Soejima Kenzo , Betsuyaku Tomoko ,   Keio Lung Oncology Group
Published: September 2018

e20577 Background: Nivolumab, an immune checkpoint inhibitor, is now approved as standard treatment for pre-treated advanced non-small cell lung cancer (NSCLC) based on the results from mega clinical trials with carefully selected patients. We sought to clarify the real-world efficacy and safety of nivolumab and to identify the clinical factors influencing the efficacy. Methods: This study enrolled 142 patients with pre-treated advanced NSCLC who had been administered nivolumab (3mg/kg, Q2W) from January to July 2016 at Keio University and affiliated hospitals in Japan. We retrospectively evaluated objective responses, adverse events (AEs), and analysed clinical factors associated with the response. Results: The overall response rate and disease control rate were 17% and 62%, respectively. The rate of any grade AEs was 45%, while the rate of grade 3-4 AEs was 13%. Among patient’s clinical factors such as age, gender, ECOG performance status, types of carcinoma, epidermal growth factor receptor ( EGFR)/ anaplastic lymphoma receptor tyrosine kinase (ALK) mutation status, smoking status, number of previous treatment lines, presence of central nervous system (CNS) metastasis and presence of prior radiotherapy, “ EGFR/ALK mutation negative” and “administration of prior radiotherapy” were independently associated with the good response to nivolumab treatment by multivariate logistic regression analysis (OR NA/ p < 0.01, OR 5.4/ p < 0.01, respectively). None of the 19 EGFR/ALK mutation positive patients showed response. Although a significant difference was not recognized between “current, former smokers” and “never smokers” (chi-square test, p = 0.1), a subsequent analysis showed smoking pack years (PY) was significantly higher in responders than in non-responders ( t-test, p = 0.035). Conclusions: The objective responses and the profiles of AEs confirmed in our study were similar to those observed in Checkmate 057/017 trials. We can use nivolumab safely regardless of age or number of treatment lines. EGFR/ALK mutation and presence of prior radiotherapy were key clinical factors statistically associated with the nivolumab efficacy.
Comparative study of two PD-L1 expression assays in patients with non-small cell lung cancer (NSCLC).
Authors: Feng Zheng , Schlichting Michael , Helwig Christoph , Chand Vikram K. , Gelb Arnold , Jin Hulin , Grote Hans Juergen 
Published: September 2018

e20581 Background: Response to anti–PD-L1/PD-1 therapy in patients with NSCLC has been associated with tumor PD-L1 expression. Avelumab is a fully human anti‒PD-L1 IgG1 antibody that has shown antitumor activity in advanced NSCLC, with a trend for greater efficacy in patients with PD-L1+ vs PD-L1– NSCLC tumors, as assessed using a proprietary PD-L1 assay in development (Dako, Carpinteria, CA; based on antibody clone 73-10, Merck KGaA, Darmstadt, Germany). This study compares the analytical performance of the 73-10 assay with the FDA-approved PD-L1 IHC 22C3 pharmDx diagnostic assay (Dako) in NSCLC tumors. Methods: Formalin-fixed paraffin-embedded NSCLC tumor samples were obtained from a commercial source and from a study of first-line (1L) avelumab in patients with advanced NSCLC (NCT01772004). Tumor membrane PD-L1 expression was assessed with the 73-10 and 22C3 assays by immunohistochemistry. Correlation between assays was determined at different PD-L1 cut-off levels. Results: In initial staining of commercial NSCLC samples, the 73-10 assay showed a broad dynamic range. Of 148 commercial samples, the 73-10 assay with ≥1%, ≥50% and ≥80% cut-offs classified 64.2%, 36.5% and 23.6% of samples as PD-L1+, respectively, whereas 20.3% were PD-L1+ with the 22C3 assay at a pre-specified ≥50% cut-off. The overall percentage agreement between assays was 83.8% using the ≥50% cut-off for both assays, and 93.9% using the ≥80% cut-off for 73-10 and ≥50% for 22C3. In follow-up studies, 83 study samples from the 1L NSCLC cohort were evaluable with both assays. With the 73-10 assay at ≥1%, ≥50%, and ≥80% cut-offs, 79.5%, 45.8%, and 31.3% of study tumors, respectively, were PD-L1+; with the 22C3 assay at ≥1% and ≥50% cut-offs, 59.0% and 21.7% were PD-L1+. Conclusions: Using a high tumor cell PD-L1 staining cut-off, the 73-10 and 22C3 assays showed highly concordant staining of NSCLC samples, with similar sensitivity observed with an ≥80% cut-off for 73-10 and ≥50% for 22C3. Using a low frequency of tumor PD-L1 expression, data suggested that the 73-10 assay had greater sensitivity than the 22C3 assay. These results provide a rationale for additional studies using the 73-10 assay at various cut-offs within the avelumab trial program. Clinical trial information: NCT01772004.