bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment outcomes and healthcare resource utilization (HRU) in patients (Pts) with newly diagnosed multiple myeloma (NDMM) with lenalidomide (LEN) only or no maintenance: Connect MM registry.
Authors: Rifkin Robert M. , Jagannath Sundar , Durie Brian G. , Shah Jatin J. , Narang Mohit , Terebelo Howard R. , Gasparetto Cristina , Toomey Kathleen , Hardin James W. , Wagner Lynne I. , Parikh Kejal , Abouzaid Safiya , Srinivasan Shankar , Kitali Amani , Zafar Faiza , Abonour Rafat 
Published: September 2018

e19527 Background: Maintenance therapy (MT) post autologous stem cell transplant (ASCT) improves clinical outcomes in MM, but the effect of continued treatment on HRU is largely unknown. In the Connect MM registry, 1493 NDMM pts are enrolled in cohort 1 (Sept 2009–Dec 2011) in a mostly community setting; of pts receiving MT, 70% received LEN-only MT. The effect of LEN-only vs no MT on progression-free survival (PFS), overall survival (OS) and HRU was evaluated. Methods: Adults with NDMM who completed induction and single ASCT without subsequent consolidation and received LEN-only or no MT were compared. HRU (hospitalization, surgery/procedures, concomitant medications [growth factor, bisphosphonate, neuropathic pain medication]) was assessed from 100 days post-ASCT to end of years 1 and 2. Data cutoff was Jan 7, 2016 (median follow-up of 39.3 mo). Results: 421 pts met the analysis criteria stipulated above. Of these, 180 received LEN-only MT, and 165 did not receive MT. Median age was 60 y (range, 24-78 y); 60% were men; 86%, white. Besides serum creatinine, calculated International Staging System stage, history of monoclonal gammopathy of unknown significance, del(17p), and induction regimen, characteristics were similar across groups. PFS and OS were significantly improved with LEN-only vs no MT (Table). Rate of hospitalization/100 person-years (PY) was similar across groups ( P= NS, all comparisons) at the end of years 1 and 2. Median duration of hospitalization was numerically longer with no MT. Procedures/surgeries and concomitant medication use were similar across both groups at the end of years 1 and 2. Conclusions: For pts with NDMM, LEN-only vs no MT significantly improved survival outcomes without affecting HRU. Clinical trial information: NCT01081028. [Table: see text]
Analysis of efficacy and safety of POM as a replacement therapy for lenalidomide for relapsed/refractory multiple myeloma pts refractory to a lenalidomide-containing combination regimen.
Authors: Berenson James R. , Cohen Alexa , Spektor Tanya M. , Lashkari Ashkan , Mackintosh Roy , Bessudo Alberto , Robinson Michael Oren , Jhangiani Haresh S. , Gabrail Nashat Y. , Nakhoul Ibrahim , Kubba Samir V. , Neidhart Jeffrey D. , Maluso Tina , Swift Regina A. , Vescio Robert A. , Eshaghian Shahrooz 
Published: September 2018

e19528 Background: Pomalidomide (POM) is a third –generation immunomodulatory drug shown to be safe and effective for the treatment of relapsed/refractory multiple myeloma (RRMM) for patients (pts) previously treated with bortezomib and lenalidomide (LEN) and in combination with dexamethasone it has been shown to overcome resistance in RRMM. In this phase 2 trial, we are evaluating the efficacy, safety and tolerability of POM as a replacement therapy for LEN for pts who have progressed receiving a LEN combination regimen. Methods: This is a phase 2, multicenter, open-label and non-randomized study. Pts who have failed a combination regimen containing LEN were treated with POM along with all of the other drugs previously used in the regimen. POM administered orally (dose is determined based on the previous regimen) on days 1-21 of a 28-day cycle, whereas other drugs are administered using the same schedule(s), dose(s) and drug combination as the last LEN-containing regimen that the patient received and failed. The planned enrollment on the study will be 45 pts. Results: To date, a total of 29 pts have been enrolled, 25 pts are evaluable and 12 pts have discontinued treatment. Of the evaluable pts, 9 (36%) and 16 (64%) received 3mg and 4mg of POM, respectively. The median age of all pts was 72 years (range, 52-81), and 17 (68%) were males. Pts have received a median of 3 prior treatments (range, 1-7). The median follow-up time for all pts is 3.1 months (range, 0.2-8.1). Amongst evaluable pts, 5 (23.8%) pts achieved at least a minimal response, 10 (47.6%) pts showed stable disease while 6 (28.6%) pts exhibited disease progression. At the time of data cutoff, only 17 pts have completed more than 1 full cycle of treatment; and, thus, the overall response and clinical benefit rates are fairly low (14.3% and 23.8%, respectively) but expected to improve with further follow up. The median PFS for the cohort was 7.6 months. Common ≥ Gr3 adverse events were neutropenia (8%), hypomania (4%) and leukopenia (4%). Conclusions: We show thatPOM appears to be promising replacement therapy for LEN in RRMM pts who have progressed within receiving a LEN combination regimen.
Efficacy and toxicities of gemcitabine and cisplatin combination chemotherapy in advanced thymoma and thymic carcinoma.
Authors: Fang Jian , Wang Yang 
Published: September 2018

e20007 Background: Thymoma and thymic carcinoma are rare thymic epithelial tumours. This study investigated the efficacy of first-line gemcitabine and cisplatin combination chemotherapy in advanced thymoma and thymic carcinoma Methods: Retrospective review of patients with histologically-confirmed invasive, metastatic thymoma or thymic carcinoma treated with gemcitabine plus cisplatin as a first-line therapy between August 2008 and February 2016 at the Department of Respiratory Medicine II Peking University Cancer Hospital and Institute. The objective response rate was the primary end point. Results: Forty patients, 13 with thymoma and 27 with thymic carcinoma, were identified. Nine received gemcitabine and cisplatin combined with Endostar (injectable recombinant human Endostatin); 31 received gemcitabine and cisplatin only. Of the 13 patients with thymoma, four (30.8%) achieved a partial response (PR) and nine (69.2%) had stable disease (SD); no patients had a complete response (CR) or progressive disease (PD). Among the 27 patients with thymic carcinoma, 13 (48.1%) achieved a PR, 12 (44.4%) had SD and two (7.4%) had PD; no patients had a CR. In thymic carcinoma, progression free survival (PFS) was 25 months and median survival (OS) was 41 months; in thymoma, median PFS was 29 months and median OS was 77 months. As no patients achieved a complete response, objective response was defined as partial response in this study. Conclusions: This retrospective analysis indicates gemcitabine plus cisplatin has moderate efficacy and could represent a suitable first-line therapy for thymic carcinoma and thymoma, especially for patents who cannot tolerate anthracyclines. [Table: see text]
Prophylactic cranial irradiation (PCI) in limited-disease small-cell lung cancer (LD-SCLC) patients with brain imaging.
Authors: Mamesaya Nobuaki , Wakuda Kazushige , Kotake Mie , Fujiwara Takumi , Kobayashi Haruki , Kawamura Takahisa , Nakashima Kazuhisa , Omori Shota , Ono Akira , Kenmotsu Hirotsugu , Naito Tateaki , Murakami Haruyasu , Takahashi Toshiaki 
Published: September 2018

e20010 Background: PCI is recommended for patients with LD-SCLC who have a good response to initial therapy. But this recommendation has been made based on studies in which brain imaging was not a standard component of initial staging or follow-up. The aim of this study was to evaluate the efficacy of PCI for LD-SCLC patients with brain MRI immediately before PCI administration. Methods: This single-center, retrospective study included patients with LD-SCLC who achieve a good response to initial therapy without BM confirmed by MRI between 09/2002 and 06/2015. Responses were classified as CR and PR, according to RECIST. We categorized these patients into three groups: C: patients who achieved CR and received PCI; P: patients who achieved PR and received PCI; N: patients who did not receive PCI, regardless of responses. We compared OS, progression free survival (PFS), and the cumulative incidence of BM at 3 years (3yBM) among these groups. Results: A total of 79 patients were included in this study. At baseline, age and PS differed significantly between C and N. In P, patients were also younger than N. Although there were no statistical significances in OS and PFS between C and N, differences in 3 years OS rate and median PFS were numerically large. The 3yBM in C revealed marginal significance compared with N. However, No differences were observed with OS, PFS, and 3yBM between P and N. Conclusions: PCI may not add clinical benefit to LD-SCLC patients who did not achieve CR after initial therapy if absence of BM could be confirmed by MRI immediately before PCI administration. [Table: see text]
Bone marrow examination (BMex) in staging of SCLC after implementation of PET/CT scan.
Authors: Holmskov Hansen Karin , Eriksen Mette Boes , Schytte Tine , Hansen Olfred 
Published: September 2018

e20014 Background: Correct staging of small cell lung cancer (SCLC) in limited disease (LD) or extensive disease (ED) is crucial as it has an impact on the therapeutic decision-making. The staging procedures in SCLC in the late 1990s included chest X-ray, blood samples, abdominal ultrasonography (UL), and iliac crest BMex. The aim of this study was to evaluate the continued eligibility of performing BMex in patients (ptt) with SCLC as a routine staging procedure, and to see how often therapeutic decisions were influenced by a positive BM before and after the PET/CT scan era. Methods: All diagnostic and staging procedures were registered in ptt with SCLC referred to our department from 1995 to 1999 in cohort 1 (C1). Cohort 2 (C2) included SCLC patients referred from 2009 to 2013. In C2 results of PET/CT in terms of bone metastases were related to results of BMex. Results: In C1 194 ptt was referred with 136 (70%) having ED. BMex was omitted in 32 (17%) fragile ptt having known ED while all LD ptt underwent BMex. BM involvement was seen in 37 (23%) of all 162 BMex and 36% of the 104 ED ptt examined. When BM was negative the staging of ED was due to other imaging. The BM had an impact on therapeutic decision-making in 5 (4%) of 136 having ED and 5 (3%) of 162 BMex. In C2 211 ptt of 292 (72%) had ED and 203 (70%) of all ptt underwent BMex. BM biopsy was done in 137 (65 %) ED and in 66 (69 %) LD. Of 137 ED ptt BM involvement was found in 31 (23 %) cases. A PET/CT scan was performed in 13 (42 %) of these ptt of which bone metastases was found in 12 (92 %). One patient (8%) had a PET/CT without bone lesions. Bone metastases were seen at PET/CT scan in 61 ptt in C2, of these 22 (36%) had negative BM, whereas 12 (20%) had BM involvement and in 3 ptt (5%) BMex were inconclusive. No BMex was performed in 24 ptt (39%). BMex had an impact on therapeutic decision-making in 3 (1.4%) of 211 having ED and 5 (2.5%) of 203 BMex. Conclusions: Due to staging by PET/CT and CT scan in SCLC ptt the impact of BMex in the therapeutic decision-making has decreased and fewer ptt are undergoing BMex. Though a negative PET/CT cannot exclude BM involvement BMex may be considered omitted.
Immunogenomic profiling of non-small cell lung cancer: The ICON project.
Authors: Sepesi Boris , Lacerda Lara , Zhang Jianjun , Bernatchez Chantale , Karpinets Tatiana , Vaporciyan Ara A. , Wistuba Ignacio Ivan , Roarty Emily , Heymach John , Gibbons Don Lynn ,   ICON Team
Published: September 2018

e20034 Background: Previous attempts to define tumor immune environment in non-small cell lung cancer (NSCLC) did not present comprehensive analyses. We established immunogenomic profiling project of NSCLC (ICON) to integrate immune, proteomic, genomic, transcriptomic, demographic, clinical, pathologic, and outcome data from surgically resected lung cancers. Methods: Tumor, normal lung tissue, and blood are collected at the time of surgery and blood after surgery up to 1 year. Samples are processed for tumor infiltrating lymphocyte (TILs) isolation and expansion; generation of patient derived xenografts (PDX), immunohistochemical (IHC) evaluation of immune cells and markers, genomic and proteomic analyses. Results: 73 (75%) out of 98 enrolled patients, median age 66 years, contributed samples to ICON; 33 (46%) males, 62 (85%) former smokers, 11 (15%) never smokers. 50 (68%) had adenocarcinoma, 17 (23%) squamous cell carcinoma, 3 (4%) small cell, and 3 (4%) pleomorphic carcinoma. 30 (41%) had stage I, 28 (38%) stage II, and 14 (19%) stage III disease, and one stage 4; 9 (12%) patients received neoadjuvant chemotherapy. Median tumor size was 4.0 cm and 67 (92%) underwent R0 resection. TIL expansion was successful in 47/67 (70%) cases. Phenotypic and functional analysis of freshly isolated and cultured TIL is ongoing. Preliminary results show suppression of intratumoral CD8+ cells as demonstrated by low perforin (p = 0.0002) and high CD8+ PD1 (p = 0.0007) levels as compared to normal tissue; however tumor CD8+CD28 co-stimulatory molecule expression was high p = 0.0003. PDX success rate has been 27%. IHC analyses show higher CD8+PD1, CD3, CD8+BTLA expression in SCC than in adenocarcinoma (p = 0.05). Exome sequencing and RNA sequencing from 19 patients show median mutation burden 466/tumor. Subclonal analysis, neoantigen prediction and expression status of predicted neoantigens are ongoing. Conclusions: ICON is an ambitious multi-team project designed to integrate wide range of tumor related data. Preliminary analysis demonstrates the project to be feasible with high rate of data acquisition. Tumors profiled from ICON will serve as a reference for the upcoming neoadjuvant single and dual checkpoint immunotherapy trial.
Multifocal adenocarcinoma of the lung: Factors predictive for local therapy.
Authors: Mooradian Meghan , Price Melissa C , Muzikansky Alona , Lennes Inga Tolin , Lanuti Michael , Willers Henning , Digumarthy Subba , Sequist Lecia V. 
Published: September 2018

e20041 Background: Multifocal Adenocarinoma (MAC) of the lung is a clinical entity of multiple synchronous or metachronous, often ground-glass opacities (GGO) on CT scan, typically indolent-behaving cancers. There is a paucity of clinical data to guide treatment decisions. MACs are often monitored via serial imaging with local therapy (radiation, surgery) employed at the discretion of the clinician. We sought to examine factors predictive of local therapy (Tx) at our institution, to develop standardized objective radiolographic parameters to guide treatment. Methods: We retrospectively reviewed pts seen in the MGH Thoracic Oncology Clinic from 2009-15. 39 pts with MAC were identified and serial CT scans were reviewed, assessing up to 5 nodules per pt. We excluded pts presumed to have MAC by imaging but without confirmatory pathology, those with calcified nodules and < 3 yrs of imaging. Demographics and clinical information were collected and univariant and multivariable logistic regression models were fit to assess correlation with Tx. Results: Among the 39 pts, 84% were female and 92% were smokers (18% active, 51% former > 10pkyr, 23% former < 10pkyr). 149 nodules were identified with median size 11mm (range 5-55mm); the majority of pts had ≥3 nodules (36/39). 66 (44%) nodules received Tx (10 RT, 56 surgery). Radiographic variables significantly associated with Tx were baseline nodule size (p = 0.02) and solid density (p < 0.001). Nodules > 2.5cm at baseline had Tx 77% of the time, while those ≤ 0.7cm had Tx 41%. Median length of monitoring before Tx was 2.1yrs for solid nodules, 3.5yrs for subsolid nodules, and > 11yrs for pure GGOs. Other observations included discordant genotypes between nodules within 1 pt and an overall pattern of nodule contraction just prior to growth acceleration. Conclusions: Lung MAC cases can be successfully managed with serial observation and intervention on growing solid or subsolid nodules. Those with GGO components can often be surveilled for yrs, or if pure GGO, for a decade or more. Larger size at baseline and solid density significantly correlate with the use of Tx. Examples of nodule contraction with concurrent enlargement of the solid component will be presented at ASCO, as this may be an important clinical warning sign.
Computer extracted measurements of intra-tumoral heterogeneity on H&E stained tissue images to distinguish short term and long term survivors in patients with non-small cell lung carcinoma.
Authors: Lu Cheng , Khunger Monica , Thawani Rajat , Velcheti Vamsidhar , Madabhushi Anant 
Published: September 2018

e20052 Background: Molecular and morphologic heterogeneity is an important characteristic of cancer. This spatial and temporal tumor heterogeneity has important implications on tumor behavior and response to therapies. This study aims to evaluate the role of computer extracted features of intra-tumoral heterogeneity (ITH) from digitized whole slide H&E stained images of early stage NSCLC patients treated with surgery as a prognostic marker for survival. Methods: A cohort of 89 early stage NSCLC patients treated with surgery with long term survival data were identified. 28 patients had OS> 3 years from the date of definitive surgery and were defined as long term survivors and 61 patients had OS < 3 years, and were defined as short term survivors. Corresponding H&E stained whole mounted lung tissue images was digitally scanned and a thoracic pathologist marked the primary tumor margins on these images. Our computational approach involved determining the variance in measurements relating to nuclear size, shape, and texture across the tissue section; Each feature was then assigned a morphologic diversity score (MDS) based off the variance; the top predictive MDS features were identified via Wilcoxon Rank Sum Test and then evaluated via a quadratic classifier using 3-fold cross validation. Kaplan-Meier (KM) survival analysis was performed for the ITH features, as well as T- and N-stage. Results: The top ranked MDS features yielded a mean area under the receiver operating characteristic curve (AUC) of 0.66 in discriminating short term from long term survivors. A p=0.00657 (see Table) was obtained for KM-analysis of the ITH features. Conclusions: Computer extracted image features of ITH enabled differentiation of NSCLC patients with short and longer term survival. Large scale multi-site validation will need to be done to establish ITH measurements as a prognostic biomarker for NSCLC patients. [Table: see text]
Co-occurrence of targetable aberrations in non-small cell lung cancer patients harboring MAP2K1 mutations.
Authors: Holzem Alessandra , Nogova Lucia , Ihle Michaela A. , Wompner Claudia , Bitter Elisabeth , Michels Sebastian Yves Friedrich , Fischer Rieke Nila , Kron Anna , Gerigk Ulrich , Kern Jens , Kaminsky Britta , Randerath Winfried , Lorenz Joachim , Kambartel Karl-Otto , Merkelbach-Bruse Sabine , Büttner Reinhard , Scheffler Matthias , Wolf Juergen 
Published: September 2018

e20059 Background: MAP2K1 mutations are rare in non-small cell lung cancer (NSCLC) and considered to be mutually exclusive with known driver mutations. Activation of the MEK1-cascade might play a pivotal role in resistance to targeted inhibition of BRAF V600E, EML4-ALK and EGFR T790M. So far, however, only MAP2K1 K57N could be identified and linked functionally to resistance in preclinical models. Clinical trials combining specific inhibitors for predefined NSCLC subgroups with MEK inhibitors are ongoing. We sought to characterize frequency and type of MAP2K1-mutated NSCLC regarding curated targetable aberrations. Methods: Tumor tissue collected consecutively from 4590 NSCLC patients within the German Network Genomic Medicine (NGM) between 07/2014 and 07/2015 was analyzed for MAP2K1 mutations using next-generation sequencing (NGS) with a set of 102 amplicons in 14 genes. Clinical and molecular characteristics of these patients were determined and compared with an internal control group of NSCLC patients and an independent control group of The Cancer Genome Atlas (TCGA). Results: We identified 21 (0.5%) patients with MAP2K1 mutations. They were frequently found in adenocarcinomas (n = 20) and were significantly associated with smoking. The most common MAP2K1 mutation was K57N. Most of the patients (n = 16) had additional oncogenic driver aberrations, including mutations in ALK, EGFR or BRAF, ROS1 rearrangements and MET amplification. TP53 mutations were found in 11 patients. In only five patients (23.8%) MAP2K1 occurred exclusively. TCGA analysis revealed additional 10 patients with MAP2K1 mutations, whereof 9 had additional TP53 mutations and one had BRAF mutation. Whereof most patients in our cohort had stage IV NSCLC, all patients in TCGA were systemic treatment naive. Compared with local stages in TCGA, our findings strongly suggest that targetable co-occurring mutations might occur more frequently in advanced stage NSCLC patients. Conclusions: MAP2K1 mutations co-occur frequently with targetable aberrations in smoking stage IV patients. Combination of targeted therapy against known driver aberrations with MEK inhibitors might be a promising therapeutic approach for such patients.
Endobronchial ultrasound-guided transbronchial needle aspiration versus cervical mediastinoscopy in lung cancer diagnosis and mediastinal staging: A retrospective comparison study.
Authors: Zhang Rong , Ma Yuxiang , Xu Guoliang , Gao Xiaoyan , Luo Guangyu , Lin Qingguang , Yang Yunpeng , Wang Xin , Zhang Li 
Published: September 2018

e20066 Background: Invasive mediastinal lymph node staging is essential for resectable lung cancers. This retrospective study compares the diagnosis yield of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and cervical mediastinoscopy (CMS). Methods: Consecutive patients were analyzed from Jan 2009 to March 2016. Only pathologically confirmed results were accepted, and systematic mediastinal lymphadenectomy (SML) were used as the standard. The disease diagnosis and N stagingaccuracywere compared in this study. Results: 103 EBUS-TBNA patients and 232 CMS patients were included, 1014 mediastinal lymph nodes were biopsied in lung cancer patients. In per case analysis, there was no significant differences between EBUS-TBNA and CMS in disease diagnosis accuracy (89.4% vs. 81.2%, P = 0.097), and no significant difference in N staging accuracy (75.0% vs. 78.3%, P = 0.629). However, EBUS-TBNA had significantly higher disease diagnosis sensitivity than CMS (82.4% vs. 47.6%, P < 0.001). In lymph nodes diagnosis comparison (station #2, #4 and #7), both EBUS-TBNA and CMS showed very high accuracy, sensitivity, and specificity (94.7% vs. 99.6%, 88.6% vs. 94.8%, 97.2% vs. 100%), however CMS were slightly better. Positive lymph nodes had longer major and minor axes than negative nodes, and the positive rateswere as high as 59.2% in lymph nodes with a minor axis measuring ≥21mm. More complications and injuries were found in patients receiving CMS. Conclusions: For clinically suspected lung cancers, both EBUS-TBNA and CMS are favorable options for invasive mediastinal staging. EBUS-TBNA may be preferred for its higher disease diagnosis sensitivity and fewer complications.