bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective clinical experience with research biopsies in breast cancer patients.
Authors: Zeghibe Catherine A. , Luis Ines Maria Vaz Duarte , Frank Elizabeth S. , Sohl Jessica , Washington Kimberly E. , Silverman Stuart G. , Fonte Joseph M. , Mayer Erica L. , Overmoyer Beth , Richardson Andrea L. , Krop Ian E. , Winer Eric P. , Lin Nancy U. 
Published: March 2020

e17574 Background: There is active debate concerning the ethics and risks of non-clinically indicated biopsies (bxs) in patients (pts) with cancer. In this analysis we examined our single institution experience regarding acceptance, safety, and success rate with research biopsies in pts with breast cancer (BC). Methods: An IRB-approved ongoing prospective study at the Dana-Farber Cancer Institute collects research bxs from pts with BC. Research bxs are performed as additional passes at the time of a clinical bx (cohort 1) or as a separate procedure for banking purposes only (cohort 2) on known tumor or suspicious lesions. Bxs are not linked to a specific therapeutic or correlative trial. Bx-site related risks are pre-specified in consent forms. Grade 2-5 adverse events (AEs) associated with the procedure are prospectively collected. Chart review for bxs between 2005-2013 was performed in this analysis. Results: As of January 2013, 158 pts had consented to the study; 3 pts withdrew consent and 4 pts did not have bxs. 151 pts are in the analytic cohort (total bxs performed= 161); 82% in cohort 1, 18% in cohort 2. Most pts were white (89%) with a performance status of 0-1 (98%). A majority of pts (96%) underwent a bx in the setting of known or suspected metastatic disease. 39% of bxs were performed at time of diagnosis or first recurrence. The most common sites for bx were liver (38%, n=61), skin (24%, n=39) and breast (18%, n=29). Lung was uncommon (3%, n=4). Research biopsies were successfully performed in 114 (92%) pts in cohort 1 and 27 (100%) pts in cohort 2. In cohort 1, research biopsies were not successful in 10 pts. In 9 pts the clinical samples had insufficient material, leading to the forfeit of the banked research sample for clinical purposes; in 1 pt the bx was suspended for severe pain. Only 3 (1.9%) pts had AEs ≥ grade 2: 1 with grade 2 pain; 1 with grade 2 pneumothorax; and 1 with grade 3 pain. Conclusions: Our experience in an academic medical center suggests that pts with BC are willing to undergo research bxs outside the context of a therapeutic or translational trial. These procedures can be performed safely with a high rate of successful tissue collection. Additional data are needed to fully quantify the risks and to demonstrate the value of these procedures.
Analysis of survival in patients with chronic myelogenous leukemia in pre- and post-imatinib era involving comparison of large academic medical center versus national data: The Beaumont experience.
Authors: Aller Cynthia Barbara , Rigo Paul , Jaiyesimi Ishmael A. 
Published: March 2020

e18007 Background: Imatinib mesylate is first-line therapy for chronic myeloid leukemia (CML) since its introduction in May, 2001. Once deadly, CML is now a chronic disorder due to this medication.We sought to analyze the impact on survival in our patient population at Beaumont Health System, a tertiary care facility, versus all hospitals in the United States. Methods: Patients with CML were identified and categorized as pre- or post-2001 when first seen. Analysis of survival in intervals of 12 months in the two groups was done with the Elekta’s National Oncology Data Alliance Database (NODA): 1990-2000 and 2001-2010. Overall 5-year survival results are reported. Results: Analysis of survival was performed on pre- and post-2001 populations in Beaumont patients versus their national counterparts. In the pre-2001 population, 580 patients nationwide and 34 patients from Beaumont were analyzed for a total of 614 patients. In the post-2001 population 1,602 patients nationwide and 122 patients from the Beaumont were analyzed for a total of 1,724 patients. The pre-2001 group nationally showed a survival probability of 28% ± 1.8%, patients in the Beaumont group showed a survival probability of 26% ± 8%. Patients in the post-2001 nationwide group showed a survival probability of 56% ±1.4%, the Beaumont group showed a survival probability of 48% ±5.0%. Both groups showed a significant survival advantage after 2001 in the era of imatinib as first-line therapy for CML. Patients in the national analysis showed a survival advantage of 28% and patients in the Beaumont analysis showed a survival advantage of 22%. Conclusions: This analysis provides evidence for a survival advantage in the post-2001 era of imatinib mesylate therapy a first-line therapy for CML on both a national and our institution level. Differences in numbers of patients analyzed, drug availability, and implementation of molecular monitoring could account for variability of the results. This data supports the revolutionary nature of this medication in the treatment of CML in the United States since 2001.
Myelodysplastic syndrome (MDS) and autoimmune diseases (AD): Hypomethylating agents to treat both.
Authors: Al Ustwani Omar , Ford Laurie Ann , Sait Sheila N. J. , Block Anne Marie W. , Barcos Maurice P. , Griffiths Elizabeth A. , Thompson James E. , Wang Eunice S. , Ambrus Julian L. , Wetzler Meir 
Published: March 2020

e18018 Background: AD occurring in the setting of MDS is challenging to recognize and incorporate into the treatment plan. We assessed the clinical presentations, laboratory abnormalities and outcome of patients with MDS and AD. Methods: Records of MDS patients treated at Roswell Park Cancer Institute between 2007 and 2010 were reviewed (n=123). Results: AD was identified in 10 MDS patients (8.1%): 70% were males, median age was 60.6 years (41-75). AD manifested as seronegative polyarthritis in 2, bronchiolitis obliterans in 2, Hashimoto’s thyroiditis in 2, and 1 (10%) for each of rheumatoid arthritis, systemic lupus, polymyalgia rheumatica, Sjogren syndrome and relapsing polychondritis. Laboratory autoimmune markers were: anti nuclear antibodies in 2, rheumatoid factor in 2, anti-double stranded DNA in 1 and anti phospholipid syndrome with thrombosis in 1. Corticosteroids were the most common used treatment for AD (60%). Regarding the MDS diagnosis; 50% had refractory anemia with excess of blasts-1 and -2, 20% refractory anemia with ring sideroblasts, 10% for each of chronic myelomonocytic leukemia, refractory anemia and MDS/myeloproliferative neoplasm. Normal cytogenetics were noted in 70% of patients, 20% with complex karyotype and 10% had monosomy 7. Hypomethylating agents were used to treat MDS in 80% of patients and in one case were associated with concomitant improvement of AD. Overall survival from diagnosis with MDS was 54 months (6-127). Conclusions: Our experience with one patient and review of the literature suggest that both AD and MDS could benefit from treatment with hypomethylating agents. This warrants a prospective clinical trial.
A National Cancer Data Base report on mesothelioma.
Authors: Brin Lauren , Warlaumont Mary , Fuller Timothy , Silberstein Peter T. 
Published: March 2020

e18501 Background: This is the first report on mesothelioma using Commission on Cancer National Cancer Database information and this is the largest study on mesothelioma to date. Methods: Using the National Cancer Database (NCDB) 26,605 patients diagnosed with mesothelioma between 2000 and 2010 were identified and analyzed. The NCDB contains data from more than 70% of all new cancers diagnosed in the U.S. each year. Results: The majority of mesothelioma patients are Caucasian (89%), males (78%), over the age of 70 (60%), and are diagnosed with stage IV disease (41%). The majority of patients (41%) received no first course treatment. The patients that were most likely to have surgery include patients <70 years old, at academic centers, with stage I-III disease, and of these only 37% received surgery and 15% received no first course treatment. The youngest patients <50 years received the most surgical therapy (36%) and the oldest patients >80 received the least (12%). Patients with private insurance received more surgical treatment (28%) than patients with Medicaid (22%), Medicare (18%), and VHA (12%)(p<0.009). Private insurance holders also received no first course treatment less often (29.6%) than Medicaid (37%), Medicare (46%), VHA (52%), and uninsured patients (37%)(p<0.002). Conclusions: The majority of patients with mesothelioma are elderly, Caucasian males and many of which do not receive treatment. The standard of care for resectable stage I-III mesothelioma includes surgery and chemotherapy. The results from this study indicate that 41% of all patients received no first course treatment and only 21% of patients received surgical treatment. Of patients most likely to receive surgery, only 37% of patients received surgical treatment and 15% of these patients did not receive any first course treatment. Age and insurance status also affect treatment as the youngest patients and private insurance holders received the most surgical treatment. [Table: see text]
En bloc resection of pulmonary sulcus non-small cell lung cancer invading the spine: A systematic review and pooled analysis.
Authors: Collaud Stephane , Fadel Elie , Schirren Joachim , Yokomise Hiroyasu , Bolukbas Servet , Dartevelle Philippe , Keshavjee Shaf , Waddell Thomas K. , de Perrot Marc 
Published: March 2020

e18503 Background: Treatment of locally advanced NSCLC is debated. While survival for inoperable disease ranges between 3-17%, carefully selected patients can be cured when treated surgically in a multimodality concept. Here, we conducted a systematic literature review and pooled data analysis of patients after en bloc resection for pulmonary sulcus NSCLC invading the spine. Outcome and prognostic factors were described. Methods: The MEDLINE database was searched using the PubMed engine to retrieve all relevant articles related to en bloc resection for pulmonary sulcus NSCLC invading the spine. All articles’ corresponding authors were contacted to share their most updated anonymized patient’s data. Data were pooled and analyzed, focusing on outcome and prognostic factors. Results: Search strategy yielded a total of 134 articles. Out of these, only 6 were relevant and non-duplicative. Four out of 6 authors were able to share updated data for a total of 135 patients. All tumors were resected en bloc with the lung, chest wall and spine. Induction treatment was administered in 87 (64%) patients and consisted of chemotherapy (n=32), radiation (n=1) or concurrent chemoradiation (n=54). Spine resections included total (n=23), hemi- (n=94) and partial (n=18) vertebrectomies. Complete resection was achieved in 120 (89%) patients. Five patients died in the postoperative period (4%). Adjuvant treatment was administered in 70 (52%) patients and included chemotherapy (n=16), radiotherapy (n=22) or chemoradiation (n=32). Median follow-up was 26 months. Overall 3-, 5- and 10-year survivals were 57%, 43% and 27%, respectively. Results of the univariate analysis (Cox, Breslow tests) identified incomplete surgical resection (R0 vs R1/2, p<0.001) as the only significant prognostic factors among the variables tested (age, histology, pN stage, type of induction/adjuvant treatment, type of lung resection). Conclusions: Multimodality therapy including en bloc resection for pulmonary sulcus NSCLC invading the spine provides excellent long-term survival. Complete surgical resection is the only determinant for survival. No difference was shown for patients treated with induction vs adjuvant therapy.
Irinotecan in combination with platinum in refractory or relapsed small cell lung cancer.
Authors: Yu Shufei , Wang Yan 
Published: March 2020

e18504 Background: To evaluate the efficacy and safety of irinotecan in combination with platinum against refractory or relapsed small cell lung cancer. Methods: In this retrospective study, we analyzed the data of 1,140 patients who diagnosed small cell lung cancer at our hospital between 2009 and 2012. Of all the patients, 34 were treated with irinotecan and nedaplatin (irinotecan 60mg/m2 on days 1,8 nedaplatin 85mg/m2 day 1,every 3 weeks), and 20 patients were treated with irinotecan and cisplatin (irinotecan 60mg/m2 on days 1,8 cisplatin 75mg/m2day 1,every 3 weeks ) as the second line treatment. Prognostic factors of overall survival (OS) were estimated by Kaplan-Meier and Cox's Regression-proportional hazards model. Results: Of 54 eligible patients, median progression free survival (PFS) was 21weeks, and median OS was 58 weeks. Median PFS was 23 weeks for irinotecan plus nedaplatin and 19 weeks for irinotecan plus cisplatin (P=0.410). Median OS was 62 weeks and 58 weeks, respectively (P=0.714).The response rate (RR) was 29% and 33.3%, respectively (HR 0.818,95%CI 0.234to2.855; P=0.753). In multivariate analysis, younger age, extensive stage while diagnosed, brain metastasis, treated with 3 cycles of irinotecan in combination with platinum or less, and PS≥1 were all associated with a statistically significant increase in the mortality harzard. Toxicity profile was slightly different for each of the arms: hematologic toxicity was higher with nedaplatin, and diarrhea was higher with cisplatin. Conclusions: Irinotecan plus platinum is effective and tolerable for refractory and relapsed small cell lung cancer. [Table: see text]
Analysis of the p38MAPK pathway in the prognosis of patients with surgically resected stage I-II NSCLC.
Authors: Pardo-Coto Pablo , Esteban Emilio , Astudillo Aurora , Gracia Jose Manuel , Corral Norberto , Izquierdo Manuel Marta , Lopez Carolina Muriel , Sanmamed Miguel F. , Gutierrez Restrepo Eduardo , Valle Pereda Miguel , Alvarez Fernandez Carlos , Pérez Arnillas Quionia , Berros Fombella Jose Pablo , Jiménez Paula , Vieitez de Prado Jose Maria , Fra Joaquin 
Published: March 2020

e18513 Background: TNM staging is the most important prognostic factor in Non-Small Cell Lung Cancer (NSCLC). The MAPK pathway, including p38, JNK and ERK, has been slightly studied in NSCLC, with controversial prognostic significance. Methods: The records of 211 patients with stage I-II NSCLC, surgically resected at Asturias University Hospital between 2000 and 2004 were retrospectively reviewed. Formalin-fixed, paraffin-embedded histological tumour specimens were used to construct tissue microarrays. The nuclear level of phosphorilated p38alpha (nP-p38), JNK (nP-JNK) and ERK (nP-ERK) was assessed using inmunohistochemistry (IHC). Phosphorilated protein expression was considered positive if the staining was present in at least 100% of the nucleus studied. EGFR was also analyzed with IHC following previous studies and was considered positive (EGFR+) if staining was observed in >10% of the cells. Clinicopahological data and outcome differences in terms of overall survival (OS) were compared between positive and negative patients. Results: Patients with nP+ for p38, JNK or ERK had a trend to better OS than those respectively negative for each protein (HR=0.68, p=0.14; HR= 0.75, p=0.16; HR=0.64, p=0.14), and the difference was significative for nP-p38+ in adenocarcinoma histology (p=0.012). EGFR+ patients had worse OS than EGFR- (HR=1.59, p=0.02), but in nP-p38+ patients, those with EGFR+ tumors had similar survival than EGFR- (p=0.9). Fifteen patients were positive for the three MAPK (MAPK “Triple Positive”, MTP), and had better OS than the rest not MTP (HR=0.20, p=0.01). In the univariant analysis, stage, histologic grade, surgery (pneumonectomy vs lobectomy), EGFR status and MTP had significant influence on OS. Multivariant analysis only confirmed the stage as an independent factor (p=0.01). Conclusions: TNM staging remains the most important factor in the prognosis of NSCLC. The activation of the MAPK pathway, its interaction with EGFR, and the MTP feature might have prognostic influence in this tumor and warrant confirmation in a large prospective trial. The potential therapeutic implications of pharmacological manipulation of the MAPK pathway highlight the importance of this study.
Ultrasound Elastography Pattern of lung squamous cell carcinoma: Preliminary report on a possible adjunctive tool for noninvasive imaging.
Authors: Sperandeo Marco , Trovato Guglielmo M. , Dimitri Lucia , Martines Giuseppe Fabio , Simeone Anna , Trovato Francesca M. , Piscitelli Angela Pamela , Catalano Daniela 
Published: March 2020

e18518 Background: Trans-Thoracic Ultrasound (TUS) guided Fine Needle Aspiration Biopsy (FNAB) provides a rapid and affordable method of diagnosing and staging lung cancer. It allows safe and easy access to sub-pleural masses. A total of 70% of pleural surface is accessible by TUS, and pulmonary processes, including masses, are visualized when they come up to pleura or are accessible via a sound window (e.g. pleural effusion or atelectasis), provided that no subcutaneous emphysema or pneumothorax is present. US Elastography is a novel approach useful to estimate the stiffness/elasticity of tissues. It is already a valuable tool for the definition of nodules (thyroid, breast, prostate cancer). The aim of our study was to assess if TUS Elastography of concurrent FNAB-proven lung cancer could be of help for a preliminary histological diagnosis. Methods: TUS with Elastography and FNAB after chest x-ray and CT-scan were performed in 57 patients (m 44, f 13; years 64,63±5,96). Tissue stiffness of the subpleural masses was scored from 1 (greatest elasticity) to 5 (no elasticity) using a convex 2-8 mHz probe and a MyLab-ElaXto Esaote-Biomedica equipment. Results: By TUS, subpleural solid masses (cm. 2-5) were detected and assessed by FNAB. Histological diagnosis were: small cell lung cancer (4/57), Adenocarcinoma (29/57), Squamous Cell Carcinoma (12/57, SCC) and poorly differentiated lung carcinoma (12/57). Patients' age and mass dimension are not significantly associated with any histotype. A significant lower elasticity of SCC (4,67±0,492) is observed vs. any of the other three histotypes of cancer (P<0.005). A score of 5 at Elastography is observed in 8/12 SCC and only in 7/45 of the other histotypes (χ2 p<0.0004 vs. any of the other histotypes; OR 10.857; 95% CI 2,557-46,093). By a MLR model, age, TNM and tumor dimension were not significant predictors of the Elastography score. Conclusions: TUS Elastography seems a novel imaging adjunctive tool reasonably suitable to help in the non-invasive diagnosis of Lung Squamous Cell Carcinoma.
The prognostic role of XRCC1, ERCC1, ERCC2, and TP53 single nucleotide polymorphisms (SNPs) in resected non-small cell lung cancer (NSCLC).
Authors: Geredeli Caglayan , Artac Mehmet , Yildirim Selman , Dede Isa , Inal Ali , Guler Tunc , Boruban Melih Cem , Zamani Ayse Gul , Bozcuk Hakan , Demirkazik Ahmet 
Published: March 2020

e18521 Background: Identification of biomarkers that can be used for the prognostic evaluation of NSCLC patients is important. The aim of this study was to evaluate the potential prognostic value of XRCC1, ERCC1, ERCC2 and, TP53 SNPs in completely resected NSCLC patients. Methods: In total 130 patients, who had been surgically treated for NSCLC between 2000 and 2012, were included in this study. Analysis of SNPs from peripheral blood cells was performed by polymerase chain reaction. XRCC1 Arg399Gln, ERCC1 Asn118Asn, ERCC2 Lys751Gln and, TP53 Arg72Pro polymorphisms were evaluated in conjunction with clinical and pathological parameters and survival. Kaplan-Meier method and Cox regression analysis were used. Results: In the univariate analysis for disease free survival (DFS) post operative stage (HR,0.50; 95%CI, 0.26-0.96; P=0.03), ERCC2 genotype (HR, 2.47; 95%CI, 1.28-4.78; P=0.007) and PET-CT staging (HR, 0.27;95%CI, 0.14-0.52; P<0.001) were significant parameters. Adjuvant chemotherapy, age and the other SNPs were not significant. In the multivariate analysis post operative stage (HR, 0.40;95%CI, 0.20-0.81; P=0.01), ERCC2 genotype (HR, 2.66;95%CI, 1.35-5.27; P=0.005), PET-CT staging (HR, 0.24;95%CI, 0.12-0.47; P<0.001) retained their significance. The median DFS was 56.5 months (95%CI, 24.6-88.4 months) for the ERCC2 mutant (TT) and heterozygote (GT) genotypes, and 28.3 months (95%CI, 20.8-35.8 months) for the ERCC2 normal (GG) genotype (P=0.005). Conclusions: In addition to stage and PET-CT staging, ERCC2 genotype independently predicted DFS in resected NSCLC patients. Future prospective studies are needed for the further evaluation of potential prognostic SNPs in resected NSCLC.
Optimisation of EGFR TKI efficiency in the therapeutic scheme of EGFR wild-type lung cancer.
Authors: Cabart Mathilde , Raimbourg Judith , Lalier Lisenn , Bennouna Jaafar , Vallette Francois 
Published: March 2020

e18532 Background: EGFR tyrosine kinase inhibitors (EGFR TKI) have improved the therapeutic care of lung cancer patients but only a small sub-population of patients, namely those harboring EGFR-mutated tumors, benefit from this therapy. The observation that EGFR TKI enhance prognosis and quality of life in all patients when used as second line or maintenance treatment impelled us into the search of potential markers of the optimal introduction kinetics of EGFR TKI in the therapeutic scheme. Methods: We used lung cancer cell lines harboring either wild-type or mutated EGFR (NCI-H1650, NCI-H1975) to study the consequences of cisplatin treatment in vitro on the consecutive sensitivity to erlotinib. Results: Sub-lethal cisplatin pretreatment (3µM) enhances erlotinib toxicity in EGFR wild-type, but not EGFR mutated cells (A549 IC50 drops from 28 to 15µM for short-term or 12µM for long-term exposure). This correlates with EGFR activation following short-term or prolonged cisplatin treatment through the secretion of EGFR ligands. This activation of EGFR is concomitant to the decrease in other receptor tyrosine kinases phosphorylation including Met. Conclusions: The sensitivity of EGFR wild-type lung cancer cells to erlotinib in vitro is enhanced by cisplatin pretreatment. We identified potential markers of this sensitization, namely EGFR ligands, which serum level might be predicitive of the optimal efficiency of EGFR TKI. In vivo validation of these markers is under investigation. The concomitant decrease in other receptor tyrosine kinases phosphorylation suggests that the targeting of other receptor tyrosine kinases might potentiate EGFR TKI efficiency.