bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maintenance chemotherapy with pemetrexed in epiteliomorfe malignant pleural mesothelioma.
Authors: Nacci Angelo , Lotesoriere Claudio , Montrone Michele , Pisconti Salvatore , Orlando Laura , Fedele Palma , Rizzo Pietro , Calvani Nicola , Mazzoni Enrica , Cinefra Margherita , Marino Antonella , Sponziello Francesco , Cinieri Saverio 
Published: March 2020

e18545 Background: Maintenance chemotherapy with pemetrexed is not the standard treatment of choice in patients with locally advanced or metastatic epiteliomorfe malignant pleural mesothelioma (EMPM). We would assess the safety and efficacy of a treatment with pemetrexed until progression disease after 4 or 6 cycles of induction therapy with or without platin. Methods: From July 2008 to September 2012, 21 patients (18 males and 3 females with a median age of 67 years range 58-84) with locally advanced or metastatic epiteliomorfe malignant pleural mesothelioma (EMPM) were enrolled. In all patients histology was epiteliomorfe malignant mesothelioma. Only 15 patients (71,4%) had a PS 0 whereas 6 (28,6%) had a PS 1. All patients received an induction therapy with or without platin. Each patient received an average of 5,6 cycles of induction chemotherapy. Then all patients received a maintenance chemotherapy with pemetrexed 500 mg/mq intavenously over 10 minutes every 3 weeks. Each patient received an average of 7,3 cycles of maintenance chemotherapy. All patients received folic acid and vitamin B12 supplementation to improve safety. Results: At the time of analysis all patients were evaluable for response. Fourteen patients (66,6 %) had a partial response and two of these underwent surgery and obtained a complete response. Six patients (28,5%) had a stable disease. The median overall survival was 13 months, while median progression-free survival was 11 months. Grade 2-3 of WHO haematological toxicities (anemia and neutropenia) occurred in 4 patient (19%). We also observed grade 2-3 of WHO gastrointestinal toxicities (diarrhea, nausea and vomiting) in 2 patient (9.5%). Grade 2 of lack of appetite and asthenia occurred in 3 patients (14.3%). Conclusions: Our data show that a maintenance chemotherapy with pemetrexed in EMPM resulted in a moderate overall survival (13 months). These results indicate that patients with EMPM could benefit from a maintenance treatment with pemetrexed.
Concordance between formalin-fixed paraffin-embedded biopsy samples and surgically resected snap-frozen samples in multiplexed molecular profiling of lung cancers.
Authors: Kenmotsu Hirotsugu , Serizawa Masakuni , Koh Yasuhiro , Isaka Mitsuhiro , Takahashi Toshiaki , Murakami Haruyasu , Naito Tateaki , Taira Tetsuhiko , Shukuya Takehito , Ono Akira , Akamatsu Hiroaki , Imai Hisao , Mori Keita , Endo Masahiro , Nakajima Takashi , Ohde Yasuhisa , Yamamoto Nobuyuki 
Published: March 2020

e18556 Background: The results of comprehensive genome-wide characterization of lung cancer have recently been reported. However, the concordance of driver mutations between formalin-fixed paraffin-embedded (FFPE) and surgically resected snap-frozen samples is unclear. We conducted the Shizuoka Lung Cancer Mutation Study to analyze driver mutations in patients with lung cancer. Methods: Based on the biobanking system in conjunction with the clinic including the pathology lab, we developed a multiplexed mutational panel designed to assess 23 mutations in 9 genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN and HER2), EGFR, MET, PIK3CA, FGFR1 and FGFR2 amplifications, and EML4-ALK translocations, using pyrosequencing plus capillary electrophoresis, qRT-PCR, and RT-PCR, respectively.DNA concentration in FFPE samples was analyzed by measuring absorbance at 260 nm (A260) in a spectrophotometer. Results: Between July 2011 and July 2012, sixty-five lung cancer patients with both FFPE and snap-frozen samples were included in this study. Patient characteristics were as follows: median age (range) 70 (38-92) years; female 68%; never-smoker 34%; histology adenocarcinoma/squamous cell carcinoma/small cell carcinoma/other 52/29/6/13 %. FFPE samples included 64 transbronchial biopsies and one pleural biopsy. We detected driver mutations in 58% of all cases. Mutations found: EGFR 28%, KRAS 12%, PIK3CA 6%, NRAS 2%, HER2 5%, EGFR amplification 5%, PIK3CA amplification 12%, FGFR1amplification 2%. Complete concordance of driver mutations between FFPE and snap-frozen samples was shown in 65%. Median DNA concentration in FFPE samples was 72.7 ng/ul (range; 2.4 - 472.4 ng/ul). Exploratory analyses using an ROC curve, done to evaluate the useful cutoff of DNA concentration in FFPE samples, showed low AUC (AUC; 0.5326). Conclusions: These results suggest that the rate of complete concordance of driver mutations between FFPE and snap-frozen samples might be acceptable, and DNA concentration in FFPE samples might not be correlated with concordance.
The effect of front-line chemotherapy on overall survival in patients with malignant pleural mesothelioma.
Authors: Elkiran Emin Tamer , Sevinc Alper , Harputluoglu Hakan 
Published: March 2020

e18560 Background: Malignant pleural mesothelioma (MPM) is a relatively rare, but aggressive tumor that causes high mortality. The major risk factor involved in the etiology is environmental and occupational exposure to asbestos. The optimal modality of therapy is controversial. Methods: The present study retrospectively evaluated the 141 patients from the database. Results: There were 80 males and 61 females with a mean age of 56 ± 1.07 years. The median survival in patients who were administered front-line chemotherapy was 17 months (95% CI: 13.19-20.81). 106 patients were administered pemetrexed-platinum combination and 35 patients were administered gemcitabine-platinum combination as front-line chemotherapy. For the patients who received pemetrexed-platinum regimen, a median of 6 cycles of chemotherapy was administered and 50 patients (47.2%) were able to receive all 6 cycles as planned. For the patients who received gemcitabine-platinum regimen, a median of 6 cycles of chemotherapy was administered and 19 patients (54.3%) were able to receive all 6 cycles. Median survival was found 16 months in the pemetrexed-platinum regimen and 26 months in the gemcitabine- platinum regimen. There was no statistically significant difference between the patients who received pemetrexed-platinum and gemcitabine-platinum regimens in terms of the median overall survival (p = 0.15). Conclusions: Results of our study suggest that chemotherapy prolongs overall survival. Survival rates in patients who received combining platinum analogues with pemetrexed or gemcitabine as front-line chemotherapy were found to be similar.
A clinical prognostic model to predict survival and efficacy in advanced or metastatic non-small cell lung cancer patients who received first-line chemotherapy: A retrospective analysis of 236 patients in northeast China.
Authors: Qu Xiujuan , Gong Jing , Hu Xuejun , Jin Bo , Zhao Mingfang , Yu Ping , Liu Yunpeng 
Published: March 2020

e19004 Background: This study was aimed to build a prognostic model for survival and predict efficacy in patients undergoing first-line chemotherapy in advanced or metastatic non-small cell lung cancer. Methods: Sixteen pretreatment clinical and biological variables were analyzed in 236 NSCLC patients who received first-line chemotherapy in our hospital. The prognostic model was calculated according to the results of multivariate Cox model, and the survival in different score groups were estimated by the Kaplan-Meier method and Long-rank tests. Results: Sixteen factors (smoking history, performance status, gender, disease stage, histological type, LDH, fibrinogen, WBC count, granulocyte count, lymphocyte count, hemoglobin, albumin, FBG, PLT, TP, β2-MG) were analyzed in univariate model for overall survival. The result showed PS=1 (HR=1.85, p<0.001), elevated fibrinogen (HR=1.63, p=0.008), elevated LDH (HR=1.78, p=0.002), granulocyte count >4.85×109/L (median) (HR=1.65, p=0.004) and increased PLT (HR=1.78, p=0.004) were poor prognostic factors. Then these five factors were enrolled in multivariate analysis. The result showed that PS=1 (HR=1.93, p<0.001), elevated LDH (HR=2.22, p<0.001) and increased PLT (HR=1.71, p=0.04) were independent prognostic factors. The patients were separated to low risk group (no adverse factor), intermediate risk group (1 adverse factor) and high risk group (2-3 adverse factors) according to the number of adverse factors. Median overall survival for these groups were 22.7, 14.5, and 7.5 months at a p value of <0.001. Kruskal-Wallis analysis revealed that the differences of efficacy in these three groups were statistically significant different (p=0.016). Conclusions: Prognostic model using PS=1, elevated LDH and increased PLT might be applied to predict survival and efficacy in advanced or metastatic NSCLC patients undergoing first-line chemotherapy. The model constituted by these three economic and easily acquired parameters may provide a tool in clinical decision making and therapy selection.
Early use of home health care on health care utilization for patients with advanced lung cancer.
Authors: Rousey Steven , Lassi Kiran Krishan , Wieczorek Jodi , Essler James , Brown Marie , Haroldson Sylvia , Sheppard Sue , Olson Kari , O'Brien Michelle , Wang Yunfei 
Published: March 2020

e19015 Background: Patients with advanced lung cancer historically have required significant use of health care resources including hospitalizations, ICU admissions and emergency room visits which are often related to inadequately controlled symptoms. Most patients with advanced lung cancer prefer to remain in their own home as much as possible and are willing to work with home nursing resources, if available. The purpose of this pilot study was to determine the effect of early use of home health care on health care utilization for patients with advanced lung cancer. Methods: Betweem May 2011 and May 2012, 18 patients were enrolled in a pilot program to explore early use of home care for individuals with advanced lung cancer. Inclusion criteria consisted of a diagnosis of stage III/IV lung cancer (any histology) and home care eligibility using Medicare criteria. The endpoints were hospitalization rate, number of ICU admissions and emergency room visits. The results were compared to an historical control group (562 patients with advanced lung cancer diagnosed between 2006 and 2011). Binomial confidence interval (CI) was used to estimate the 95% CIs and Fisher's exact test was used to assess the p-values. Results: Results at one year showed the hospitalization rates for the pilot group and the control group were 44% (95% CI, 22-69) and 78% (95% CI, 74-81), respectively (p<0.01) and the ER visit rate was 17% (95% CI, 4-41) and 41% (95% CI, 37-45), respectively (p=0.049). The ICU admission rates were 0% and 11% in the two groups, respectively, and this difference was not statistically significant. Home care visits ranged from 1-77 with an average of 12 visits per patient. The estimated cost of the home care program for the duration of enrollment was $2,330 per patient. Conclusions: Early use of home health care for patients with advanced lung cancer appears to reduce the rates of hospitalization and emergency room visits when compared with historical controls, and though the results were not statistically significant, none of the 18 patients in the pilot group were admitted to the ICU. A larger multi-institutional study will examine the potential of this simple intervention for cost saving, enhanced care quality and improved patient satisfaction.
Clinical results of recombinant adenoviral human p53 gene in treatment of malignant pleural effusions caused by advanced lung cancers.
Authors: He Yong 
Published: March 2020

e19026 Background: Management of the malignant pleural effusion caused by advanced or recurrent lung cancer is a big challenge for clinicians due to multiple reasons: patients’ poor conditions, resistance to chemo- or radio-therapy, intolerance to an aggressive treatment, et al. This report presents a new safe treatment for controlling this type of tough conditions. Methods: Fifty-six patients, 39 males and 17 females with an average age of 64.2 years old were included in this study. All these patients had either a lung cancer in advanced stage or a recurrent cancer after a radical tumorectomy, with malignant pleural effusion. After draining most of the effusion fluid, the patients received intra-cavity infusion of rAed-p53 once per week for 4 weeks, at dose of 2×1012 viral particles (VP) diluted into 300 ml of saline solution. The complete response is defined as the complete disappearance of pleural or peritoneal fluid and negative cytologic findings for >4 weeks, and the partial response is defined as a decrease over 50% of the fluid without the need of drainage and negative cytologic findings for >4 weeks. Results: Participants were followed up for a median time of 15 month. Fifty patients (26.8%) achieved a complete response (CR) and 23 (41.1%) achieved a partial response (PR). The overall response rate is 67.9%. Patients’ quality of life, assessed by using Karnofsky performance scale (KPS) scores, was improved by an average of 27.2. The one-year of overall survival rate was 48.2% with a median survival time of 11.0 months. There were no serious side effects observed except for self-limited fever found in 82.6% of the cases. Conclusions: Intra-cavity infusion of rAd-p53 is a safe and effective method for controlling the malignant pleural effusion for patients with advanced lung cancer and in a poor condition, especially for those who can’t tolerate the standard treatments.
Are sarcomatoid lung cancers resistant tumors to conventional chemotherapy?
Authors: Wislez Marie , Vieira Thibault , Ung Mony , Antoine Martine , Monnet Isabelle , Bonnette Pierre , Cazes Aurelie , Duruisseaux Michael , Belmont Laure , Mazieres Julien , Cadranel Jacques , Girard Nicolas 
Published: March 2020

e19036 Background: Pulmonary sarcomatoid carcinomas (SC) account for about 0.4% of non-small cell lung carcinoma. These tumors have a poor prognosis due to high aggressiveness and maybe chemotherapy (CT) resistance. Methods: From 1995 to 2012, all consecutive patients with SC from 7 French hospitals and who underwent a 1st-line chemotherapy were included. Clinical characteristics and effect of CT (best response by RECIST 1.1 and progression-free survival [PFS]) as well as overall survival (OS) were collected. Results: Ninety-seven patients were included. Mean age was 62±1 years, 70% were men, 84% smokers, 84% symptomatic, 25% had a stage III and 75% a stage IV disease. At 1st-line, 73% received a platinum-based CT and 27% received a non-platinum-based CT. Progression (PR), stable disease (SD) and response (RR) rates were 69, 14.5 and 16.5%, respectively. For patients with platinum-based CT, PR, SD and RR rates were 69, 11 and 20%, respectively. RR rate was higher for platinum- than for non-platinum-based CT (p=0.018). Median PFS and OS were 2.0 mo [1.8 ; 2.3] and 6.7 mo [5.1 ; 8.2], respectively. No statistical difference in PFS (p=0.264) and OS (p=0.096) was observed between platinum and non-platinum based CT. In multivariate analysis, factors associated with better OS were disease control (HR=0.36 [0.21;0.59]), platinum-based CT (HR=0.92 [0.85;0.99]) and tobacco status (HR=0.92 [0.85 ; 0.99]). Conclusions: Two-thirds of patients with SC had early progression during 1st-line CT. Platinum-based regimen increased response rate for a few and was an independent factor for better OS with a 8% decreased risk of death. Overall, SC appear to be chemoresistant suggesting that new therapeutic strategies based on a better knowledge of its carcinogenesis should be tested for these patients.
Clinical outcome of treatment with pemetrexed/cisplatin in patients with EGFR-mutation negative (EGFR–) metastatic non-small cell lung cancer (NSCLC).
Authors: Storozhakova Anna E , Vladimirova Liubov Yu , Kit Oleg Ivanovich 
Published: March 2020

e19047 Background: Althogh some improvements of the treatment of NSCLC were achieved recently the results of therapy in patients with EGFR– adenocarcinoma are still poor. The purpose of the study was to evaluate the effectiveness and toxicity of the treatment in these patients. Methods: Pts with EGFR– adenocarcinoma were recruited in 2010-2011. Key elegibility criteria included measurable EGFR– adenocarcinoma, confirmed stage IV, ECOG ≤2, adequate organ function, CT-naïve pts. Pemetrexed/cisplatin was administered 500/75 mg/ m² 1 day q3w up to 6 cycles. Treatment was continued until progression or unacceptable toxicity. A total of 94 cycles were estimated. Endpoints include response rate, OS, PFS and safety. Results: 16 pts (12 male and 4 female) were recruited. Mean age was 56.6±5.6. Infiltrative EGFR– adenocarcinoma was found in 93.75%, adenocarcinoma mixed with squamous cancer – 6.25% (1pt). All the pts had ≥2 disease sites: lung 16 (100%), lymph nodes 16 (100%), bones 5 (31.25%), liver 7 (43.75%), brain 1 (6.25%). Mean number of disease sites = 2.8. Overall RR was 43.75% (7) including 2 CR (12.5%), 3 PR (18.75%) and 2 SD (12.5%). Med OS = 16.1 mo ±1.5, Med PFS = 7.4 mo ±0.8. 6 pts (37.5%) are alive till the abstract submission. Most common adverse events in 94 cycles were neutropenia 1/2 Gd. -30.85, 3/4 Gd. -6.4%, thrombocytopenia 1/2 Gd .-2.1% cycles. Nonhematological toxicity included nausea 1/2 Gd.- 74.5%, 3/4 Gd.- 12.7%, vomiting 1/2 Gd.- 43.6%, 3/4 Gd.- 6.4%, hyperthermia 2 Gd. –6.4%, fatigue 1/2 Gd.-15.95%, hiccough 2 Gd.-2.1%. No treatment-related mortality occurred. Conclusions: Pemetrexed/cisplatin combination had a satisfactory efficacy and controlled toxicity as well in patients with EGFR-mutation negative (EGFR–) metastatic NSCLC. The favorable PFS and OS allow to use it in clinical setting widely.
Development and clinical validation of an adeno/squamous multiplexed diagnostic assay for NSCLC.
Authors: Hembrough Todd A. , Liao Wei-Li , Thyparambil Sheeno , Erickson Heidi S. , Carey George , Guiel Thomas , Heaton Robert B. , Krizman David , Wistuba Ignacio Ivan , Salgia Ravi , Burrows Jon 
Published: March 2020

e19057 Background: The diagnosis of adenocarcinoma (ADC) vs. squamous cell carcinoma (SCC) in NSCLC is critical since new therapies (e.g. pemetrexed) are restricted to non-squamous NSCLC. Most diagnoses are made based on histopathology, though IHC is often performed as well. Since IHC is not quantitative, interpretation of intensity is subjective, and reproducibility can be problematic. Using the Liquid Tissue-SRM mass spectrometry (MS) platform, we have developed a quantitative, multiplexed clinical diagnostic assay to measure the adeno/squamous markers TTF-1/CK7 (ADC) and K5 and p63/40 (SCC) in FFPE tissue. This proteomic assay is epitope independent, and highly reproducible. Methods: Recombinant K5, K7, TTF-1 and p63/p40, were subjected to trypsin digestion mapping to identify peptides for MS analysis. Heavy isotope labeled peptides were synthesized as positive control peptides for quantitation. The multiplexed assay was technically validated on cell lines, and human tumor tissues. Results: ADC/SCC proteomic analysis was performed on a training set of 39 NSCLC tissues from U. of Chicago (20 ADC and 19 SCC). Principal Component Analysis was used to define optimal quantitative cutoffs for each of the four markers for the two tumor subtypes. The ADC diagnosis was unequivocal for all 20 ADC samples, however within the 19 SCC’s, one sample appeared to be ADC and two samples had markers for both ADC and SCC. Proteomic analysis of a test set of 194 NSCLC tumors (98 ADC and 98 SCC based on pathology reports) from MD Anderson Cancer Center was consistent with the observations in the training set. 93/98 ADC cases were confirmed by proteomic analysis, four ADC cases showed mixed or SCC phenotypes. Proteomic analysis confirmed 58/98 SCC cases but identified 27 cases as mixed ADC SCC or ADC based on TTF1/K5 expression. Further studies are ongoing to determine the clinical utility of these findings. Conclusions: These data demonstrate that quantitative proteomic analysis can define cut offs for ADC and SCC Biomarkers profiles in NSCLC tumors. These profiles can determine ADC, SCC and mixed phenotypes and provide physicians with accurate information to help them stratify their patients to the right evidence based treatment therapy.
Patterns of presentation and management of non-small cell lung cancer in an Algerian cancer center.
Authors: Jamous Houda , Filali Taha 
Published: March 2020

e19063 Background: To evaluate the pattern of management and outcome of patients with NSCLC in our cancer center over the last 8 years. Methods: A retrospective study of all NSCLC patients seen between January 2005 and December 2012 in Medical Oncology Center, Constantine, Algeria. All demographic, clinical data, management and outcome were captured and analyzed. Results: 581 patients with NSCLC, male-female ratio 10:4, median age 59.7 years (21-85), 64.2% were smokers (0.8% were females), and 15% exposed to alcohol. Diagnostic specimens were obtained by CT scanguided biopsy in 62% of cases, bronchoscopy in 26.2%, and surgical biopsy in 9.6%. Median time to diagnosis was 6.1 months (0 months -6 years). During the study period, incidence of squamous cell carcinoma declined from 62.1% to 37.5% and adenocarcinoma incidence doubled(from 29.5% to 57.5%). Most of the patients had an advanced stage disease, 58.5% stage IV, 15.3% stage IIIB, 14.5% stage IIIA, stageIIB 4.1%, stage IIA 0.9%, stage IB 1.9%, and stage IA 0.9%. 8.6% underwent surgery, 13.9% received radiotherapy, 88.6% with PS≤ 2 received first-line chemotherapy which was platinum-based in 95.1% of the cases. 17.2% second-line, and 3.6% third-line. Most used chemotherapy regimens are: etoposide-cisplatin (EP) in 2005-2006, cisplatin-gemcitabine (P/GMZ) 2007-2009, taxotere-cisplatin (TP) 2010-2012. Outcome of these regimens ranged for response rate (RR) between 12.8% and 23.8% and overall disease control (ODC) ranged between 17.8% and 30.5%. Pemetrexed/platinum administered to 20 patients, RR 10.5%, ODC 26.1%. Bevacizumab/carboplatin-paclitaxel to 8 patients, RR 12.5%, ODC 25%. Outcomes in nonsmokers are better compared to smoker patients: RR 16.6% vs 12.1%. ODC 22.5% vs 18.2%. Longer survival (2.3 months more) and higher survival rate noted for women than that for men at all stages of the disease. RR is 16.3% in adenocarcinoma cases, 12.5% in squamous cell. For all groups: One year survival 16.5%, 2 years 5.5%, and 5 years 1%. Conclusions: Patients with NSCLC present with advanced stages. The management of NSCLC at our Center mirrored the evolution of management using conventional chemotherapy.