bluuebunny/crossref_metadata_2025_split huggingface dataset:
NY-ESO-1 as a predictive and prognostic marker in NSCLC.
Authors: John Tom , Russell Prudence , Barnett Stephen , Wainer Zoe , White Shane , Mitchell Paul , Walkiewicz Marzena , Boutros Paul C , Starmans Maud HW , Chen Yao-Tseng , Wright Gavin , Knight Simon , Cebon Jonathan S. 
Published: March 2020

e17539 Background: Cancer-testis antigens (CTAgs) have previously been shown to be markers of poor prognosis and to be associated with chemoresistance in short interference RNA screens. In contradistinction, we recently reported the CTAg NY-ESO-1 predicted improved responses to neoadjuvant chemotherapy in pathological stage IIIA NSCLC. Despite this, no significant survival benefit was seen in NY-ESO-1 positive (NY-ESO-1+) patients. Given that tissues available for staining in the neoadjuvant setting were limited, we investigated a retrospective cohort of patients who underwent curative surgery for pathological N2 disease. As some of these patients were operated on prior to the broad acceptance of adjuvant chemotherapy (ACT), half did not receive chemotherapy. We investigated NY-ESO-1 as a prognostic and/or predictive marker in these patients. Methods: Formalin fixed paraffin embedded tissues were reviewed and stained using standard methods for a panel of CTAgs including NY-ESO-1 by immunohistochemistry. Tumors were categorized as NY-ESO-1+ or NY-ESO-1-. Isolated DNA was subjected to mutation profiling using Sequenom’s MassArray platform. Molecular markers were correlated with clinicopathological features and survival. Results: NY-ESO-1 stained 26/104 (25%) samples, including 15 cases that received ACT and 11 that did not. NY-ESO-1+ tumors were enriched for squamous cell carcinomas over adenocarcinomas (12/29 vs. 8/57; p = 0.01). They also lacked EGFR mutants and were enriched for KRAS mutants amongst adenocarcinomas relative to NY-ESO-1- tumors (5/8 vs. 9/49; p=0.02). NY-ESO-1+ patients who did not receive ACT had significantly worse outcome than NY-ESO-1- patients who did not receive ACT (HR 2.66 1.2-5.86, p=0.01). Median survival favored NY-ESO-1+ patients who received chemotherapy (37.7 months) compared to NY-ESO-1- patients regardless of chemotherapy (28.2 ACT vs 15.7 No ACT; p= 0.25) and NY-ESO-1+ patients who did not receive ACT (7.75). Conclusions: In this dataset, NY-ESO-1 was poorly prognostic but also predictive for more favorable outcomes with chemotherapy. These data support our previous observation of increased responses to chemotherapy in NY-ESO-1+ N2 patients and warrant further study.
Prognostic impact of c-Met/phospho-Met, and topoisomerase I in small cell lung cancer.
Authors: Ikeda Hideko , Koba Hayato , Kurokawa Koji , Nishikawa Shingo , Araya Tomoyuki , Tambo Yuichi , Sakai Asao , Sone Takashi , Fukuoka Junya , Kasahara Kazuo 
Published: March 2020

e17540 Background: The hepatocyte growth factor/MET pathway has been shown to cause tumor progression in several types of carcinomas. We reported that c-Met up-regulated topoisomease I (Topo I) in non-small cell lung cancer cell lines (submitted for publication). The aims of this study were 1) to examine the prognostic influence of c-MET/phospho-MET (p-Met), or Topo I expression and 2) to elucidate correlation between c-Met/p-Met expression and Topo I expression in small cell lung cancer (SCLC). Methods: This retrospective study included 72 SCLC patients (pts) with available tumor tissue from primary lung tumor or metastatic lesions and clinical data including survival. We performed immunohistochemistry to detect c-MET/phospho-MET and Topo I expression. Results: Tumor tissues were obtained from 72 SCLC pts. Sixty-six pts, (51 male, 15 female, median age 67.5 range 43-91, LD/ED 38/28, PS0,1/2,3,4 57/9) were evaluated. c-Met overexpression was seen in 40.9%, p-Met in 74.2%, and Topo I expression in 59.1%, respectively. High expression of Topo I associated with lower response rate (RR) (96.7% in low group vs 78.4% in high group, p=0.029) and shorter progression-free survival (PFS) (65W vs 39W, p=0.040) but did not correlate with overall survival (OS). Phosphorylation of Met protein did not correlate with RR, PFS or OS. Interestingly, intensity of p-Met significantly correlated with Topo I expression (p=0.048). High expression of c-Met protein did not associated with RR or PFS but significantly associated with shorter OS (high 53W, low 95W, p=0.018). Multivariate analysis which included c-Met, stage, PS, and age resulted that c-Met was an independent prognostic factor for OS of pts with SCLC (HR; 2.144, 95% confidence interval 1.162-3.956, p=0.015). Conclusions: This study suggested c-Met high expression was an independent prognostic factor, and Topo I was up-regulated by Met in SCLC.
MUC4 expression in non-small cell lung cancer.
Authors: Ganti Apar Kishor , Kaur Sukhwinder , West William W , Dhangada Majhi Prabin , Lakshmanan Imayavarambam , Smith Lynette , Rolle Cleo E , Carey George , Sharma Poonam , Salgia Ravi , Batra Surinder 
Published: March 2020

e17549 Background: MUC4 has been shown to play a key role in breast and pancreatic cancer. MUC4 expression is seen in the normal bronchial epithelium, but its role in non-small cell lung cancer (NSCLC) is unclear. Here we study the association between MUC4 overexpression and clinical features of NSCLC. Methods: The diagnosis of lung cancer was confirmed in H&E sections. MUC4 level was semi-quantified by immunohistochemistry. Each sample was given a composite score based on intensity and extent of staining. The intensity was graded on a 4 point scale: – (0), + (1), ++ (2), and +++ (3). The extent of staining too was graded on a 4 point scale: 1 (1-25%), 2 (26-50%), 3 (51-75%), and 4 (76-100%). The composite score was obtained by multiplying the two values, with possible scores of 0-12. Poisson mixed effects models were used to compare the score between groups. Kaplan-Meier method was used to estimate survival distributions and the log-rank test was used to compare them. Wilcoxon sign rank test was used to compare the difference in score between lung tissue and corresponding lymph node. P value <0.05 was considered to be statistically significant. Results: 167 samples from 54 non-metastatic NSCLC patients were analyzed. Of these, 13 (25%) patients had stage I, 33 (63%) had stage II and 6 (12%) patients had stage III disease. Distribution of the composite score differed significantly by stage (p=0.0043). A higher proportion of patients with stage I NSCLC had a score of 12 (77%) compared to stage II (18%) and stage III (57%) (p=0.0001). When patients who had data for both the primary tumor and corresponding metastatic lymph node were analyzed, MUC4 expression was higher in the primary tumor compared to the metastasis (p=0.05). The effect of MUC4 expression on survival was analyzed in 29 patients with survival data. Of these, 16 had a composite score of 12, while 13 had a score <12. Patients with a score <12 had significantly worse survival than those with a score of 12 (p<0.045). Conclusions: MUC4 expression is more common in early stage NSCLC and appears to be associated with a better outcome in patients with non-metastatic NSCLC. The therapeutic implications of this finding need to be investigated further.
Neoadjuvant concurrent chemoradiation therapy followed by surgical resection in patients with non-small cell lung cancer invading chest wall.
Authors: Yamaguchi Yoko , Yoh Kiyotaka , Hishida Tomoyuki , Ohmatsu Hironobu , Goto Koichi , Niho Seiji , Umemura Shigeki , Ishii Genichiro , Akimoto Tetsuo , Nagai Kanji , Ohe Yuichiro 
Published: March 2020

e17554 Background: The treatment approach of patients with non-small-cell lung cancer (NSCLC) invading the chest wall (stage T3N0M0) is still controversial. The clinical outcome of NSCLC patients with chest wall invasion has remained poor. The purpose of this study was to determine the efficacy and safety of neoadjuvant concurrent chemoradiation therapy followed by surgical resection in NSCLC patients with chest wall invasion. Methods: We retrospectively reviewed medical records of 19 patients with NSCLC invading chest wall (T3N0M0 or T4N0M0), who underwent neoadjuvant concurrent chemoradiation therapy followed by surgical resection between April 2003 and October 2009. Neoadjuvant chemotherapy was administered intravenously at cisplatin 80 mg/m2 on day 1 and vinorelbine 20 mg/m2 on days 1 and 8, q4w, with a maximum of 2 cycles. Radiotherapy directed at the primary tumor invading chest wall was started in cycle 1, at the total dose of 45Gy in 25 fractions. Surgical resection of the tumor was performed 4 to 8 weeks after the completion of neoadjuvant therapy. Results: Patient characteristics included: median age 61 years (range 43-68); Male/Female=17/2; and stage T3N0M0/T4N0M0=18/1. Six patients (32%) had superior sulcus tumors. Neoadjuvant chemoradiation therapy was generally well tolerated. All patients underwent surgical resection, and complete resection was achieved in 18 patients (95%). There were 10 (53%) patients with pathologic complete response. There were no treatment-related deaths. The 3-year disease-free and overall survival rates for all patients were 58% and 81%, respectively, with a median follow-up of 37 months. The 3-year disease-free survival rate was 78% for patients with a pathologic complete response compared with 25% for those who did not achieve a pathologic complete response. Disease progression occurred mainly in distant sites. Conclusions: Neoadjuvant chemotherapy consists of cisplatin-vinorelbine and radiotherapy followed by surgical resection is effective and tolerable in patients with NSCLC invading chest wall (T3N0M0). This treatment approach produces high rates of pathologic complete response.
Modern imaging technique assessment of small cell lung cancer doubling time.
Authors: Mohd Sharial Mohd Syahizul Nuhairy , Teo MinYuen , Doherty Mark , McDermott Raymond S. , Walshe Janice Maria 
Published: March 2020

e17561 Background: Doubling time in non-SCLC tumors has been well studied, but this is less so in SCLC. We aim to study in vivo doubling time in SCLC using modern imaging techniques. Methods: Patients (pts) with SCLC with both diagnostic computed tomography (CT) and subsequent staging Positron Emission Tomography (PET)/CT were identified from institutional database. Primary lesion and nodal disease on the initial CT scan and on the CT component of PET/CT scan was measured. Diameter Doubling Time (D-DT) = [(dt)*log 2] / [3(log D2 – log D1)], where dt was time interval between scans, D2 and D1 are diameters of lesion on second and first scan respectively. Volume Doubling Time (V-DT) = [(dt)*log 2] / (log V2 – log V1), where V2 and V1 are volume of 2nd and 1st CT. Results: 18 eligible pts were identified. 61% were males, median age 63. Primary lesion was assessable in 14 pts and nodal disease in 17. Mean interval between scans was 19.7 days (range: 6 – 67). Mean diameter of primary lesion on 1st and 2nd scans: 4.17 cm +/- 2.11 and 4.63 cm +/- 2.26. Mean diameter of lymph nodes on 1st and 2nd scans: 4.24 cm +/- 1.72 and 4.78 cm +/- 1.81. Mean volume of primary lesion on 1st and 2nd scans: 35.56 cm3 (=/- 43.34) and 45.52 cm3 (+/- 55.66). Mean volume of nodal disease on 1st and 2nd scans: 32.77 cm3 (+/- 44.52) and 44.16 cm3 (+/- 55.06). For primary tumor, mean D-DT was 70.0 days +/- 16.4, with mean V-DT 60.5 days +/- 11.8, p=.64. There is a significant correlation between D-DT and V-DT with Pearson rho of 0.7691 (p=0.0013). For nodal disease, mean D-DT = 51.1 days +/- 15.1 and mean V-DT 42.2 days +/- 9.3, p= .62, with correlation between D-DT and V-DT, Pearson rho of 0.7609, p=.0004. There was higher doubling time in extensive stage (ES) SCLC primary tumors compared with limited stage (LS), with mean D-DT 24.0 days vs 97.6 days, p=.046. When all lesions analyzed collectively, mean D-DT = 59.6 days, 95% CI 37.1 – 82.2 and mean V-DT = 50.5 days, 95% CI 35.3 – 65.7. Conclusions: Our data demonstrate more rapid doubling time of SCLC compared to historical data. The differential in growth between LS and ES points to a biologic dichotomy. This has a significant impact in the timely management of SCLC, and potential avenues for therapeutic development.
Brain metastasis in a series of NSCLC: Egyptian experience.
Authors: Elmesidy Salah Eldeen , Abdelsalam Mahmoud , Zawam Husam 
Published: March 2020

e18001 Background: Incidence of cerebral metastasis is increasing among lung cancer patients. Many factors have been reported associated with increase risk of brain metastasis. The aim of this retrospective analysis is to investigate the predictive factors for the development of brain metastasis in lung cancer patients. Methods: We retrospectively analyzed histologically proven lung cancer patients radiologically diagnosed of having brain metastases who presented to Kasr Al-Eini Center for Oncology (NEMROCK) in the period from 2004 till 2010, with follow up period of 6 months at least. The following factors were analyzed: age, gender, PS, smoking history, tumor size & grade preceding development of brain metastasis. Results: Our study included 403 patients. 67 patients (16.6%) experienced brain metastasis during the course of their disease. 40 (10%) patients had brain metastasis among other sites of distant spread at first presentation which represent 88.9% of patients presented with metastatic disease. In a median follow-up of 17.1 months (6-77) the time to develop brain metastasis (TTBM) for the whole group was 5 months (range 2-22 months) (95% CI : 4.3-7.7). The most important factor affecting the TTBM was the use of chemotherapy before developing brain metastasis with a median TTBM of 5.9 months (95%CI : 3.2-6.8) among those who received chemotherapy compared to 2 months among the patients who didn't receive chemotherapy (P= <0.0001). The second factor was PS at time of initial diagnosis (P= 0.027). The median OS after brain metastasis was 6 months (95% CI : 4.26-7.74). On univariate analysis, PS and use of chemotherapy after developing brain metastases showed statistically significant difference affecting OS. Conclusions: We concluded that PS as well as use of chemotherapy are the 2 main factors associated with shorter time to develop brain metastasis. PS and use of chemotherapy after developing brain metastases showed longer OS after developing brain metastases. Keywords: NSCLC, Brain metastasis, Egypt
What factors affect long-term survival after responding to gefitinib in advanced non-small cell lung cancer? Real-world evidence.
Authors: Takeuchi Yoshiko , Imamura Fumio , Morita Satoshi , Mori Masahide , Komuta Kiyoshi , Kijima Takashi , Namba Yoshinobu , Nishino Kazumi , Yamamoto Suguru , Takahashi Ryo , Nakazawa Yukie , Minami Seigo , Ogata Yoshitaka , Kumanogoh Atsushi 
Published: March 2020

e18007 Background: After gefitinib was approved in July 2002, we experience long-term surviving patients in the actual clinical setting. However, it is not clear how the factors or treatment strategy are contributing to the long-term surviving patients.We evaluated the effects of clinical backgrounds and treatment histories on overall survival (OS). Methods: We extracted information on advanced NSCLC patients with the following inclusion criteria from the medical records: 1) Patients who were diagnosed by October 2010 and treated with gefitinib after July 2002: 2) Performance status (PS) 0 – 2, 3) PR, CR, or long SD (6 months or more) by gefitinib treatment : 4) Patients who had not received curative surgical operation or curative radiation therapy. Primary objective is to evaluate survival time of the patients who responded to gefitinib and clarify the relationship between clinical factors and survival time. We also conducted “Dynamic Treatment Regimen Analysis (DTRA)” to explore key treatment regimen and sequence of regimens contributing to long-term survival. Results: The medical records of total of 275 patients were extracted. 44% (122/275) were EGFR mutation examined and 93% (114/122) has shown the EGFR mutation positive. The mean age was 65 years, 72% (198/275) were women, 66% (182/275) were non-smokers, and 90% (247/275) had adenocarcinoma histology. 20% (54/275) and 21% (58/275) underwent re-administration and beyond PD administration of gefitinib respectively. Median survival time (MST) was 615 day (95% C.I; 519-691). 10% patients survived for more than 5 years. The multivariate Cox analysis demonstrated that sex (p=0.0108) and gefitinib re-administration (p=0.0012) were significant independent factors for long-term OS. Grade 3/4 interstitial lung disease, skin, diarrhea, and liver dysfunction were observed in 1.5%, 4.4%, 1.1%, and 13.1% of the patients, respectively. Conclusions: This study suggests that sex and gefitinib re-administration, may have significant affects on OS in long survivors after responding gefitinib treatment.
Analysis of neuroendocrine marker synaptophysin and stem-cell related marker CD133 on circulating tumor cells (CTC) in patients with metastatic non-small cellular lung cancer (NSCLC).
Authors: Kuemmerlen Verena , Puggina Anna , Fusi Alberto , Keilholz Ulrich 
Published: March 2020

e18010 Background: In NSCLC heterogeneity or switch to neuroendocrine phenotype and the expression of stem-cell related markers have been associated with higher tumor aggressiveness. We evaluated the presence of CTC bearing stem cell-related marker CD133+ and the neuroendocrine marker synaptophysin (SYP) in patients with metastatic non small cellular lung cancer (NSCLC). Methods: Forty-four blood samples (20 mL) were collected after informed consent from 16 consecutive patients (pts) with metastatic NSCLC before and during chemotherapy at our Institution. Blood was enriched for tumor cells by CD45 depletion using a magnetic bead separation technique and potential CTC were identified by flow cytometry. CTC were defined as EpCAM+ CK7/8 + CD45-CD53-. Multiparameter cytometry assessed surface expression of the combinations of CD133 and SYP. Results: CTC phenotype: Twenty-five of all 44 samples (57%) were found positive for presence of at least 1 CTC. The median number of CTC was 4 (range: 1-9) / 10mL blood. Twelve samples (27%) showed to be positive for the cancer putative stem cell marker CD133. The median number of CD133+ CTC was 2 (range: 1-7) / 10mL. Seventeen samples (38%) were positive for SYP with a median number of 2 SYN+ CTC (range: 1-6 ) /10ml. Eleven samples (25%) resulted double positive for CD133 and SYP. Tumor heterogeneity: Twelve of the 16 patients (75%) had at least one sample positive for CTC. In 3 pts (25%) CTC expressed only SYP, in 5 pts (42%) both the markers and in 4 pts (33%) neither CD133 nor SYP were expressed. Conclusions: A higher rate of CD133-SYP-double positive CTC compared to the single positive CTC was observed. This suggests that the switch to the neuroendocrine phenotype might occur concomitantly with a stem-cell like more resistant and aggressive phenotype. It needs to be clarified, whether the presence of stem-cell like and neuroendocrine CTC may be a predictive factor for treatment response and outcome in patients with metastatic NSCLC.
Prospective study into the necessity of hemogram on day 8 in oral vinorelbine and cisplatin regimen.
Authors: Provencio Mariano , Sánchez Antonio , Domine Manuel , Artal Angel , Garcia-Gomez Ramon , Constenla Manuel , Sanchez Torres Jose Miguel , Castro Javier , Vinolas Nuria , Huelves Miriam , Perez Javier , Sanchez-Hernandez Alfredo 
Published: March 2020

e18011 Background: One of the standard treatments for metastatic non-small-cell lung cancer patients is the combination of cisplatin plus vinorelbine. This regimen is associated with a high rate of severe neutropenia, and a hemogram is therefore routinely performed on day 8 before the administration of vinorelbine. However, no prospective study has ever examined the rate of neutropenia detected in this hemogram or the rate of discontinuation of chemotherapy as a result. Since one of the objectives in the treatment of advanced lung cancer is to maintain quality of life, we performed this prospective study of cisplatin plus vinorelbine to address the question of whether this hemogram on day 8 could be avoided, thus eliminating unnecessary venipunctures without endangering patient safety. Methods: We included 58 chemotherapy-naïve advanced NSCLC patients from 10 centers. They received intravenous doses of cisplatin on day 1 plus oral vinorelbine on days 1 and 8, every 3 weeks, for a maximum of six cycles. Median age was 61 years; 87% were males; ECOG 1: 66%. Results: Of 189 cycles analyzed, vinorelbine was administered on day 8 in 661 (97.8%), and the dose was reduced or canceled in 15 (2.2%; IC 95%: 0.5 - 5.45) due to hematological toxicity. Conclusions: The hemogram on day 8 could potentially be avoided in patients ECOG 0-1 while still maintaining an acceptable safety margin.
Serum CYFRA 21-1 as a biomarker of pemetrexed plus cisplatin treatment in nonsquamous non-small cell lung cancer.
Authors: Sakatani Toshio , Ohyanagi Fumiyoshi , Tanimoto Azusa , Kawano Yuko , Saito Ryota , Kaburaki Kyohei , Yanagitani Noriko , Kudo Keita , Horiike Atsushi , Hagiwara Sachiko , Horai Takeshi , Nishio Makoto 
Published: March 2020

e18014 Background: Pemetrexed (P) is a key drug in the treatment of advanced non-squamous (N-Sq) non-small cell lung cancer (NSCLC). Although differential efficacies of P between squamous (Sq) and N-sq subtypes have been reported, it is difficult to get a clear histological diagnosis from a small biopsy sample. Therefore, a more objective, yet simple, biomarker for histology-based treatment is needed. Previously, we reported that serum Cytokeratin fragment 21-1 (CYFRA) was related to the outcome of P monotherapy. In this study, we examined whether serum CYFRA could predict the efficacy of the cisplatin-pemetrexed (CP) combination regimen as well as it did for P monotherapy. Methods: Pre-treatment serum concentrations of CYFRA, carcinoembryonic antigen (CEA), squamous cell carcinoma (SCC) antigen, and sialyl Lewis X-I antigen (SLX) were measured in 50 N-sq NSCLC patients who were enrolled in a phase II study of C (75 mg/m2 and 500 mg/m2) against N-Sq NSCLC. Eligibility criteria consisted of histologically or cytologically confirmed recurrent or metastatic N-Sq NSCLC previously untreated with chemotherapy, ECOG performance status (PS) 0-1. The primary endpoint was response rate, which was evaluated with RECIST. The planned sample size was 50 patients. We analyzed possible associations between these NSCLC marker levels and the efficacy of the CP regimen. Results: From April 2010 to June 2011, 50 N-sq NSCLC patients (male/female, 34/16; median age 60 y (28-74 y)) were enrolled in this study. Patients’ histological characteristics were: adeno/large/not otherwise specified (NOS), 39/5/6; PS: 0/1, 31/19. In these 50 patients, elevated levels of serum CYFRA, CEA, SCC and SLX were found in 25, 32, 5 and 32 patients, respectively. CYFRA was significantly associated with progression-free survival (PFS) (median PFS: 5.53 vs. 3.29 months; p < 0.05), whereas no significant associations were observed between PFS and CEA, SCC or SLX. In addition, multivariate analysis showed that higher CYFRA and PS levels were significant factors associated with a shorter PFS. (p < 0.05) Conclusions: Serum CYFRA is related to the outcome of CP treatment; our results suggest that serum CYFRA is a promising predictive marker of CP therapy.