bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adult participation in oncology clinical trials by indication, race, and age.
Authors: Combest Austin James , Reitsma Dirk J. , Moseley Angelena , Steele Savanna D. , Bonneterre Marie-Edith Anne 
Published: March 2020

e17586 Background: According to the National Cancer Institute (NCI), approximately 3 percent of adult cancer patients participate in clinical trials despite the NCCN guidelines frequently recommending clinical trials as standard of care in many circumstances (Mooney, 2010). In a large analysis of NCI Cancer Therapy Evaluation Program (CTEP) trials, 40 percent of trials failed to achieve minimum enrollment, including 3 of 5 phase III trials (Cheng, 2010). Additionally, concerns about unequal access to clinical trials led Congress to enact the National Institutes of Health (NIH) Revitalization Act 20 years ago (June 10, 1993). Using data from Ipsos’ Tandem Oncology Monitor, a robust, nationwide system that collects actual prescriptions and clinical trial participation by indication from 500 oncologists and hematologists from the United States, we evaluated current participation and ethnic diversity in clinical trials. Methods: We assessed adult clinical trial participation from October 2011 to September 2012. Age, ethnicity and practice type were also collected to identify descriptive trends. Results: With regards to indication, clinical trial participation ranged from 1 percent (prostate, renal cell and head and neck) to 12 percent (thyroid) averaging between 2 and 3 percent. We observed a decline in first-line metastatic melanoma participation between pre- and post- vemurafenib/ipilimumab approval (9%-pre versus 2%-post). Patient diversity results are included in the Table. Conclusions: Despite efforts to increase oncology clinical trial participation, we have observed overall low clinical trial participation. Additionally, we observed better trial participation in the youngest age groups and minor differences between ethnic categories. Continued focus on increasing trial participation and patient diversity is still needed. [Table: see text]
How breast cancer care is coordinated in hospitals serving predominantly minority women.
Authors: McAlearney Ann Scheck , Moss Alexandra , Franco Rebeca , Bickell Nina A. 
Published: March 2020

e17592 Background: Underuse of adjuvant breast cancer treatment results from system failures and occurs more commonly in minority women. We assessed organizational processes associated with care coordination prior to implementing an intervention. Methods: We interviewed 29 clinical and 20 administrative key informants from 6 hospitals with high volumes of minority breast cancer patients. We analyzed qualitative interview data using the constant comparative method. Results: Hospitals varied in approaches to coordinate adjuvant therapy delivery. All hospitals made a “basic” effort to follow up with patients who missed appointments (e.g., certified letters), but some sites included “extra” efforts such as clinician calls. Processes to coordinate handoffs among providers involved use of clerical staff to reach out across specialties in most sites; several sites also explicitly involved clinicians. Effective tracking and handoffs were hindered where electronic health record (EHR) systems were not fully integrated. A critical distinction was whether breast cancer care delivery was integrated within the hospital. Better integration appeared to facilitate communication among clinicians, as well as promote service coordination. Accountability was an important factor contributing to integration, particularly in sites that were less integrated. Conclusions: Appropriate delivery of adjuvant therapies to breast cancer patients appears to be facilitated by better integration of care and services within the hospitals we studied. A fully integrated EHR and enhanced processes for tracking no shows and supporting handoffs seemed to increase integration in these hospitals. Integration was further facilitated when there was accountability for results. Strong clinical leadership can promote integration, but its impact may be lessened if hospitals’ processes are integrated. [Table: see text]
Impact of the distance from a radiation oncology treatment facilty on initiation of therapy and its influence on survival in patients with stage III and IV NSCLC.
Authors: File Danielle M. , Arce-Lara Carlos Eduardo , Whittle Jeffrey C. , Gore Elizabeth , Santana-Davila Rafael 
Published: March 2020

e17594 Background: Patients with stage III and IV lung cancer require multidisciplinary care. The Milwaukee VA is the only center within the Veterans Health Administration in the state that has a radiation oncology facility. Patients frequently travel from across the state to receive treatment here. We conducted a retrospective review of cases seen in our institution to determine if the distance from the patients’ home to our center influenced their outcome. Methods: Patients with NSCLC treated between 2000 and 2012 were identified from our internal registry. Type of treatment was identified from the registry and confirmed in a chart review.. SAS 9.2 was used for statistical analysis and to measure distance between the patients’ home address and our center. Results: We included 230 patients with stage III disease treated with radiation therapy and 139 patients with stage IV treated with chemotherapy. Of those with Stage III (53% with IIIA and 47% IIIB) 41.3% (n=95) received concurrent radiation therapy and chemotherapy, 14% received sequential therapy, 40% received radiation therapy alone and 5% were treated with chemotherapy followed by palliative radiation. In those with metastatic disease 61% received palliative radiation at some point during their treatment. Median distance between the patients’ home and the Milwaukee VA was 57miles (IQR 10-109) in patients with stage III disease and 22 (IQR 5-84) in those with metastatic disease. There was no correlation between the distance travelled and the time to first treatment in either stage (r=0.008 in stage III and r=0.05 in stage IV). In a univariate analysis living further than 50 miles did not appear to influence survival in stage III (median OS 14.6 vs. 16.4 months p=0.25) nor stage IV disease(9.7 vs 8 p=0.55). In a multivariate analysis when controlling for age, time to first treatment and distance as a continuous variable was not associated with survival in patients with stage III(HR 1.01, 95% CI 0.99-1.02 p=0.15) or stage IV disease (HR 1.01, 95%CI 0.98-1.04 p=0.35). Conclusions: Distance traveled to a radiation oncology treatment facility in this cohort did not influence survival in patients with stage III and IV NSCLC.
A prospective single center study from a developing country to evaluate the prevalence of vitamin-D deficiency in patients with de novo hematologic malignancies.
Authors: Shetty Nishitha , Sengar Manju , Menon Hari , Dangi Uma Bhaskar , Ghadge Meera , Inamdar Nitin , Shinde Bhoopal , Kumar Santhosh , Ghosh Joydeep , Rajamanickam K. Deepan , Sheth Vipul , Philip Deepa susan , MV Chandrakant 
Published: March 2020

e18004 Background: Vitamin-D deficiency is a global problem due to lack of sunlight exposure or dietary deficiency. Few studies have correlated vitamin-D deficiency with poor outcome in patients with diffuse large B-cell lymphomas and chronic lymphocytic leukemia. Expression of vitamin-D receptors on both normal and malignant hematopoietic cells suggests its possible role in pathogenesis, response to therapy and as a potential therapeutic target in haematological cancers. Given the high prevalence of malnutrition in our country and the potential impact of vitamin-D deficiency in haematological malignancies we conducted this prospective study to identify its prevalence in this subset of patients. Methods: Consecutive patients (15-50 years) with de novo haematological cancers who were registered at our centre over a three months period were evaluated. Patients who had received bisphosphonates or calcium and vitamin-D supplementation were excluded. Demographic variables, performance status, lifestyle (sedentary or non-sedentary), diet (vegetarian or mixed), consumption of milk products, serum 25 (OH) D, albumin and calcium levels were recorded. Levels <30ng/ml and <20ng/ml were considered as insufficient and deficient respectively. Results: A total of 126 patients (70% males) were enrolled. Median age was 35 years. Distribution as per histology was acute leukemia-59, lymphomas-53, chronic myeloid leukemia-14. 78% patients had non-sedentary life style and were consuming mixed diet and milk. 90% patients had performance status ≤2. Serum albumin>3.5 gm/dL and normal calcium levels were seen in 90%. Vitamin-D deficiency was seen in 12% patients whereas 73% patients were vitamin D insufficient. Keeping the cut-off <25 ng/mL, 82% patients were deficient. Deficiency did not correlate with age, underlying diagnosis, lifestyle or dietary habits. Conclusions: Our study identified a very high prevalence of vitamin-D deficiency in patients with haematological malignancies. This could be one of the factors responsible for the aggressive nature of disease and poor outcome in our patients.
BCL3 and NSCLC: Are they related?
Authors: Dimitrakopoulos Fotinos-Ioannis D , Kottorou Anastasia E , Antonacopoulou Anna G , Marousi Stella , Koukourikou Ioulia , Scopa Chrisoula D , Dougenis Dimitrios , Papadaki Helen , Kalofonos Haralabos 
Published: March 2020

e18507 Background: NFkB pathways have become objects of detailed research in the last years, although, little is known of the possible role of BCL3 in lung carcinogenesis. The aim of this study was to define the relation of the BCL3 single nucleotide polymorphism rs8100239 with NSCLC and its association with BCL3 protein expression. Methods: Using Tagger and Sysnps programs, we chose the rs8100239 polymorphism of BCL3.We used 294 blood and FFPE normal tissue specimens from patients with NSCLC and 280 blood specimens from healthy donors. DNA isolation was performed using the Qiagen DNA blood and the QIAamp DNΑ FFPE Tissue kits. Samples were genotyped using real-time PCR. Immunohistochemical analysis for BCL3 was performed on 90 FFPE specimens (80 tumors and 10 tumor-adjacent normal tissues) from NSCLC patients. Results: Approximately half of the healthy donors (45.5%) were AT heterozygotes, 36.6% were TT and 17.9% were AA homozygotes. The respective frequencies in patients were 43.8%, 33.1% and 23.1%. There was no statistically significant difference in allele frequencies between healthy controls and patients (p=0.297). However, patients of stage II carrying a T allele displayed two and five-year survival benefit compared to patients with AA genotype (p<0.001). Immunohistochemical analysis for BCL3 protein revealed a statistically significant difference between malignant and normal lung tissue (p<0.001). More specifically, BCL3 was detected in both the cytoplasm and nucleus in neoplastic tissues with strong intensity, whereas in non neoplastic tissue no immunostaining was noticed. BCL3 protein levels were not associated with the polymorphism. However, cytoplasmic expression of BCL3 was correlated with age (p=0.009), histological subtype (p=0.031) and disease stage (0.038). Furthermore, tumors with smaller diameter had higher BCL3 nuclear expression levels than larger tumors (p=0.009). Conclusions: Patients of stage II carrying a T allele had improved two and five-year survival. BCL3 expression is not correlated with rs8100239 status. However, it is related to histological subtype, stage and maximum diameter while it differs between malignant and normal lung tissue. This research has been co-financed by the EU and Greek national funds (Heracleitus II Program).
Treatment-free interval (TFI) after first-line therapy (FLT) and disease control rate (DCR) on second-line therapy (SLT): Impact on overall survival (OS) in relapsed malignant pleural mesothelioma (MPM).
Authors: Viganò Maria G , Gregorc Vanesa , Ghio Domenico , Bulotta Alessandra , Rossoni Gilda , Sallemi Claudio , Colombi Scialini , Rossoni Gloria , Lambiase Antonio , Bordignon Claudio 
Published: March 2020

e18528 Background: Both TFI (the time elapsing from FLT completion to SLT initiation) and DCR (the rate of nonprogression at first tumor evaluation) have been found to predict OS in other tumor types. Methods: The impact on outcome of TFI after FLT and DCR on SLT was tested in an individual patient pooled analysis of 261 MPM patients (pts) who had radiologic progressive disease (PD) after a pemetrexed-based FLT before entering a ph 2 trial with single-agent NGR-hTNF (n=50) and a ph 3 trial with single-agent gemcitabine, vinorelbine or doxorubicin plus NGR-hTNF/placebo (n=211). In both trials, response to SLT was assessed every 6 weeks by MPM-modified RECIST. Progression-free survival (PFS) and OS were computed from SLT start. By ROC analysis, the cutpoint for estimating TFI in relation to OS was set at 6 months (AUC=0.59; p=.009). Results: After FLT, 60 pts (23%) had partial response (PR), 135 (52%) stable disease (SD), for a DCR of 75%, and 66 (25%) early PD. Median time to PD was 7.0 months (95% CI, 6.2-7.4) and median TFI was 4.4 months (3.8-5.0), with 97 pts (37%) having a TFI > 6 months. Among baseline factors (age, sex, PS and histology) used in logistic regression, only younger age was related to higher odds to attain a TFI > 6 months (OR=1.9; 95% CI, 1.2-3.3). A TFI > 6 months (vs ≤ 6) was weakly related to DCR (Spearman's r=0.16; p=.01) and strongly associated with longer PFS and OS, with HR of 0.48 (0.36-0.65) and 0.59 (0.42-0.83), respectively. After SLT, 9 pts (3%) had PR, 130 (50%) SD, for a DCR of 53%, and 122 (47%) early PD. Of 60 pts responding to FLT, 23 (38%) progressed early on SLT, while of 66 pts progressing early during FLT, 32 (48%) experienced disease control on SLT. Baseline factors did not relate with DCR at week 6. On landmark analysis set at the 6-week time point, DCR (vs PD) was associated with OS benefit (HR=0.46; 0.32-0.65), which persisted after adjusting for baseline factors (HR=0.40; 0.27-0.57). Conclusions: With a smaller HR, an early-look measure such as 6-week DCR on SLT shows some advantage over TFI after FLT in predicting subsequent OS. In relapsed MPM, TFI as stratification factor and DCR as surrogate endpoint may be considered. Clinical trial information: NCT00484276-NCT01098266.
Sensitivity of malignant mesothelioma lacking Merlin to the FAK inhibitor VS-6063: Evaluation of merlin/NF2 status in clinical samples.
Authors: Pachter Jonathan A. , Shapiro Irina M , Weaver David T. , Vidal Christian M. , Ring Jennifer E. , Keegan Mitchell , Xu Qunli , Menges Craig , Testa Joseph R. , Paterson Daniel 
Published: March 2020

e18541 Background: Malignant pleural mesothelioma (MPM) is an aggressive tumor in the pleural lining of the lung often resulting from prior exposure to asbestos. MPM patients are usually diagnosed at an advanced stage of disease and the prognosis is poor. Median survival after diagnosis is 9 to 12 months and standard-of-care agents such as cisplatin and pemetrexed have only a modest impact on median survival time for MPM patients. New therapeutic modalities are urgently needed to improve the prognosis of MPM patients. 40-50% of MPM patients exhibit homozygous disruption of the NF2 tumor suppressor gene by mutation and/or deletion resulting in lack of expression of functional merlin protein. Methods: Proliferation of drug-treated mesothelioma cell lines in 3-dimensional (3D) Matrigel culture was assessed by MTS, and MPM xenograft growth was measured in vehicle- vs. FAK inhibitor-treated SCID mice. Since absence of merlin expression can theoretically result from several mechanisms including NF2 mutation and chromosome 22 abnormalities, we assessed NF2 gene deletion by FISH and merlin protein levels by IHC in the same human mesothelioma tumor samples. Results: Among a panel of mesothelioma cell lines in 3D culture, MPM lines lacking expression of merlin protein were found to be especially sensitive to the selective FAK inhibitor VS-6063. In contrast, MPM cell lines with wildtype merlin were less sensitive with EC50 values greater than 1 μM. Accordingly, oral dosing with a FAK inhibitor induced significant tumor growth inhibition in a merlin-negative mesothelioma model in mice. To enable the planned stratification of MPM patients by merlin status, an immunohistochemistry (IHC) assay has been optimized to quantify merlin protein levels. A merlin IHC H-score below the defined cutoff was associated with loss of at least one copy of chromosome 22, indicating that chromosomal deletion is an important mechanism of merlin loss in mesothelioma patients. Conclusions: These data support the clinical development of VS-6063 for treatment of malignant pleural mesothelioma patients stratified by merlin/NF2 status. A potentially pivotal mesothelioma trial is set to initiate in 2013.
Comparison of toxicity and outcomes of concurrent radiotherapy with carboplatin/paclitaxel (PC) or cisplatin/etoposide (PE) in stage III non-small cell lung cancer (NSCLC).
Authors: Liew Mun Sem , Sia Joseph , Harris Samuel John , Tafreshi Alireza , Starmans Maud HW , Feigen Malcolm , Boutros Paul C , White Shane , Zimet Allan Solomon , Lambin P. , Mitchell Paul , John Tom 
Published: March 2020

e18559 Background: Concurrent chemoradiotherapy (CCRT) has become the standard of care for patients (pts) with unresectable stage III NSCLC. Although 60Gy of radiotherapy is accepted as the standard radiation dose, the concurrent chemotherapy regimen is idiosyncratic to the institution with PC generally reserved for older and less fit pts. We retrospectively reviewed outcomes and toxicity of two widely used regimens at our institution (Austin Health, Melbourne): weekly PC (Belani et al, 2005) versus (vs) PE given weeks 1 and 5 (SWOG 9019) each with concurrent chest radiotherapy. Methods: Charts from stage III NSCLC pts treated with radical dose CCRT between 2000-2011 were reviewed. Clinical data including demographics, toxicity, and response were reviewed. Results: A total of 83 (PC: 50, PE: 33) pts were treated. PC pts were older [median age (range) 70 year (44-83) vs 63 year (32-76); p=0.001]. Other characteristics were comparable in PC and PE groups (Table). Increased grade (gr) ≥3 neutropenia was seen with PE (39% vs 12%, p=0.008). Other gr ≥3 toxicities were similar including febrile neutropenia, esophagitis and pneumonitis. With a median follow up of 17.2 months (mo), no statistical difference in overall survival (OS) (median PC 21.3 mo vs PE 13.7 mo; p=0.690) and relapse free survival (median PC 12.0 mo vs PE 11.1 mo; p=0.934) were observed. In multivariate analysis, where treatment type and age were included in the model, only more advanced stage predicted poorer OS (p=0.045). Conclusions: PC was more likely to be used in elderly pts. Despite this, PC resulted in significantly less hematological toxicity but achieved similar survival outcomes compared to PE. PC is an acceptable CCRT regimen especially in older pts. [Table: see text]
Predicting factors for early and long-term mortality after thoracotomy in patients with primary lung cancer.
Authors: van Arkel Cynthia , Dumoulin Daphne , van Straten Bart , ter Woorst Joost , Houterman Saskia , van den Borne Ben 
Published: March 2020

e18562 Background: To determine factors predicting early and long term mortality in patients who underwent a thoracotomy because of primary lung cancer. Methods: Data of patients who underwent a thoracotomy in the Catharina Hospital Eindhoven between 1 January 1995 and 1 January 2011 have been collected retrospectively from the medical files. Early mortality was defined as mortality <30 days after surgery. Last date of follow up was 1 January 2013. Patients were divided in three periods according to date of surgery (1: 1995-1999, 2: 2000-2004 and 3: 2005-2010). Predicting factors for early mortality were assessed with uni- and multivariate logistic regression analysis. For long term mortality and survival predicting factors were assessed using the Cox proportional hazards model and Kaplan-Meier survival curves. Results: In total 501 patients underwent a thoracotomy due to primary lung cancer. Overall 30 day mortality was 5.8% (n=29). Early mortality was 3.0% for lobectomy (n=289), 0.2% for bilobectomy (n=29) and 11% for pneumonectomy (n=109). Multivariate analysis showed that age over 70 (p=0.002), pneumonectomy (p=0.008) and a pre-operative VO2max of <15 ml/kg/min (p=0.02) were significant predictors of early mortality. With respect to long term survival, 308 (62%) patients had died at the end of the follow-up period. Median survival time was 44 months, with an overall 5- and 10- year survival of 45% and 27% respectively. The 5- and 10-year survival for stage I, II and III-IV was 61% and 37%; 46% and 30%;16% and 6.6%, respectively (p<0.0001, log rank test). Finally Cox regression analysis showed that stage (stage I (HR 0.30; 95% CI 0.22-0.42), stage II (HR 0.38; 95% CI 0.26-0.57) compared to stage III-IV, FEV1% ≤70% (HR 1.57; 95% CI 1.61-2.11), a history of cerebrovascular disease (CVD) (HR 1.97; 95% CI 1.20-3.23) and surgery in an earlier time period (1 (HR 1.50; 95% CI 1.04-2.17); 2 (HR 1.46; 95% CI 1.05-2.02) compared to 3) were significant predictors of long term mortality. Conclusions: In this cohort age, pneumonectomy and pre-operative VO2max are significant predictors of early mortality. Significant predictors of long term mortality are disease stage, FEV1%, a history of CVD and surgery in an earlier time period.
Post-progression survival after treatment with epidermal growth factor receptor-tyrosine kinase inhibitor for advanced non-small cell lung cancer patients harboring epidermal growth factor receptor mutations.
Authors: Kogure Yoshihito , Kitagawa Chiyoe , Oki Masahide , Saka Hideo 
Published: March 2020

e19005 Background: Non-small cell lung cancer (NSCLC) patients harboring the epidermal growth factor receptor (EGFR) mutation show a survival benefit on treatment with EGFR-tyrosine kinase inhibitor (EGFR-TKI); however, few studies report on post-progression tumor behavior after treatment with EGFR-TKI. Methods: We retrospectively reviewed clinical data of stage IV or recurrent NSCLC patients harboring the EGFR mutation, who received EGFR-TKI as first-line treatment in our institute from 2009 to 2011. Results: Thirty-six patients received EGFR-TKI as first-line therapy. Thirty of these patients with recurrent NSCLC were enrolled in this study. The median age of the patients was76 years (range, 38–97), and the male/female ratio was 4/26. The median progression-free survival (PFS) after EGFR-TKI treatment was 8.2 months. Sites of relapse in patients with progressive disease (PD) were the brain, pleural effusion, bone, and lung (n=5, 13, 6, and 8, respectively). Twenty-one patients received sequential therapy: 11 patients received continued EGFR-TKI treatment beyond PD and 10 patients received second-line therapy. Second-line therapies were platinum-based doublet therapy, monotherapy, and another cycle of EGFR-TKI (n = 6, 2, and 2 patients, respectively). Post-progression survival (PPS) of all the patients after treatment with EGFR-TKI was 9.2 months, whereas that of patients who received EGFR-TKI as second-line chemotherapy was 14 months. Subgroup analysis according to the site of relapse showed that after first-line EGFR-TKI treatment, PFS tended to be higher for patients with a relapse in the brain (11.6 months) than for patients with sites of relapse other than the brain (8.2 months). Conclusions: PPS after EGFR-TKI therapy in patients treated with second-line chemotherapy was similar to the OS of NSCLC patients without an EGFR mutation. Subgroup analysis showed that patients with a relapse in the brain might survive longer.