Introduction The microbiota includes the collection of microorganisms that colonize our body, playing a pivotal role in maintaining homeostasis and modulating immune responses. An imbalance in the composition of these microbes is associated with various diseases, including oncological conditions [1]. From a methodological perspective, several aspects should be considered during microbiome analysis, such as the compositional nature of the data, its high dimensionality, overdispersion, and the prevalence of zero-inflated count data [2]. The institutional microbiome project currently active at the Fondazione IRCCS Istituto Nazionale dei Tumori was designed to assess the feasibility of investigating the microbiota in different tumors settings and biological matrices, with the final aim of identifying microbial communities able of distinguishing patients characterized by worse prognosis from those with less aggressive disease. The cancer settings included in the projects are lung, breast and prostate cancer, as well as pseudomyxoma peritonei. Objectives Given the unique characteristics of microbiome data, we propose a unified workflow designed for analysing data from various cancer settings to ensure consistency and comparability across the different cancer types. Methods Biological samples analysed in this study were disease-specific and include, tumor tissues and matched normal counterpart for lung cancer, tumor tissues for breast and prostate cancer, matched tumor tissue, feces and mucin for pseudomyxoma peritonei. Samples were processed using the same standardized analytical pipeline across all pathologies. This process includes bacterial DNA extraction, enrichment, library preparation and sequencing of the variable regions of the bacterial 16S rRNA gene. Microbial communities were firstly characterized in terms of alpha- and beta-diversity: the first one quantifies the diversity within a given sample in terms of richness or eveness [3], whereas second one assesses diversity differences between sample-groups. Specifically, for alpha-diversity we used a set of different indices: Chao1, Hill and Observed for richness, Gini-Simpson and Shannon for eveness [3]; for beta-diversity the Principal Coordinate Analysis (PCoA) analysis [4,5] was adopted together with the PERmutational Multivariate ANalysis of VAriance (PERMANOVA) [4] and PERmutational Multivariate analysis of DISPersion (PERMDISP) tests [6] by using the Bray-Curtis distance metrics [5]. Then, the workflow incorporates tests and statistical models for both continuous and categorical data to identify bacterial taxa that are differentially expressed or present in distinct biological matrices or associated with clinical-pathological characteristics investigated in each cancer context. Test for paired or unpaired groups comparison were included for both continuous and categorical data analysis. Results Using lung cancer as a model setting, matched tumor and normal counterpart of 155 lung cancer patients (stage I-III), were profiled using 16S rRNA gene sequencing for a total of 310 observation and 63 identified bacteria taxa (i.e. genus level). The analysis revealed distinct microbial compositions, in terms of beta-diversity, according to histology. Moreover, by modelling the count data and its presence/absence, a specific subset of bacteria was significantly associated with tumor progression and aggressiveness; specific bacteria were also found differentially expressed between tissue types (tumor or normal counterpart). We are now applying this workflow at the other settings, with the final aim of better understanding the bacteria that characterize tumor aggressiveness. Conclusion The developed workflow allows: (i) the use of a shared pre-analytical and analytical workflow of analysis among the different tumor settings under investigation, (ii) the characterization of the microbial community within/between samples and (iii) the evaluation of associations between specific taxa bacteria and tumor characteristics.
Increased Incidence of Melanoma, Prostate, Lung, Bladder, Renal and Thyroid Cancer after Diagnosis of Primary Cutaneous B-Cell Lymphoma: A SEER Database Analysis
Increased Incidence of Melanoma, Prostate, Lung, Bladder, Renal and Thyroid Cancer after Diagnosis of Primary Cutaneous B-Cell Lymphoma: A SEER Database Analysis
Read moreInforming Patient Surveillance for the Growing Number of Survivors of Lung Cancer
Informing Patient Surveillance for the Growing Number of Survivors of Lung Cancer
5Taxonomic variation, plastic degradation, and antibiotic resistance traits of plastisphere communities in the maturation pond of a wastewater treatment plant
Wastewater treatment facilities can filter out some plastics before they reach the open environment, yet microplastics often persist throughout these systems. As they age, microplastics in wastewater may both leach and sorb pollutants and fragment to provide an increased surface area for bacterial attachment and conjugation, possibly impacting antimicrobial resistance (AMR) traits. Despite this, little is known about the effects of persistent plastic pollution on microbial functioning. To address this knowledge gap, we deployed five different artificially weathered plastic types and a glass control into the final maturation pond of a municipal wastewater treatment plant in Ōtautahi-Christchurch, Aotearoa/New Zealand. We sampled the plastic-associated biofilms (plastisphere) at 2, 6, 26, and 52 weeks, along with the ambient pond water, at three different depths (20, 40, and 60 cm from the pond water surface). We investigated the changes in plastisphere microbial diversity and functional potential through metagenomic sequencing. Bacterial 16S ribosomal RNA genes composition did not vary among plastic types and glass controls (P = 0.997) but varied among sampling times [permutational multivariate analysis of variance (PERMANOVA), P = 0.001] and depths (PERMANOVA, P = 0.011). Overall, there was no polymer-substrate specificity evident in the total composition of genes (PERMANOVA, P = 0.67), but sampling time (PERMANOVA, P = 0.002) and depth were significant factors (PERMANOVA, P = 0.001). The plastisphere housed diverse AMR gene families, potentially influenced by biofilm-meditated conjugation. The plastisphere also harbored an increased abundance of genes associated with the biodegradation of nylon, or nylon-associated substances, including nylon oligomer-degrading enzymes and hydrolases.IMPORTANCEPlastic pollution is pervasive and ubiquitous. Occurrences of plastics causing entanglement or ingestion, the leaching of toxic additives and persistent organic pollutants from environmental plastics, and their consequences for marine macrofauna are widely reported. However, little is known about the effects of persistent plastic pollution on microbial functioning. Shotgun metagenomics sequencing provides us with the necessary tools to examine broad-scale community functioning to further investigate how plastics influence microbial communities. This study provides insight into the functional consequence of continued exposure to waste plastic by comparing the prokaryotic functional potential of biofilms on five types of plastic [linear low-density polyethylene (LLDPE), nylon-6, polyethylene terephthalate, polylactic acid, and oxygen-degradable LLDPE], glass, and ambient pond water over 12 months and at different depths (20, 40, and 60 cm) within a tertiary maturation pond of a municipal wastewater treatment plant.
Read moreTravel Distance and Its Impact on Wait Time for Positron Emission Tomography–Computed Tomography in Patients with Cancers
To examine travel distance and its impact on wait time for positron emission tomography–computed tomography (PET/CT) in patients with lung and prostate cancers and lymphoma in Alberta. We used the Alberta cancer registry and diagnostic imaging database to identify patients with lung and prostate cancers and lymphoma who had a PET/CT scan during April 2017 and March 2023. The Alberta Facilities Distance/Time Look Up Table was used to calculate travel distance from the patient’s residence to the PET/CT facility. Negative binomial regression was used to assess the association between travel distance and wait time for PET/CT. The study included 9503 patients. Lung cancer accounted for 43.4% of the patients, followed by lymphoma (37.1%) and prostate (19.5%) cancer. There were more female patients with lung cancer (55.5%) than lymphoma (42.9%; p < 0.001). The mean (SD) age was 66.8 (13.8) years and lymphoma patients were younger (59.6 years) than lung (70.3 years; p < 0.001) or prostate (72.7 years; p < 0.001) cancer patients. Diabetes (14.2%) was the most prevalent comorbidity. The median (IQR) travel distance was 21 (12–121) km and this was shorter for urban (16 km) than rural (148 km; p < 0.001) patients, but the wait time was similar (median = 20 vs. 21 days; p = 0.378). There were no significant associations between travel distance and wait time (IRR = 1.00; p = 0.108). The results were robust in subgroup analyses by type of cancer and scan priority. There were no associations between travel distance and wait time for PET/CT. Additional research is warranted to examine the potential impact of longer travel distances on overall access to care and patient outcomes.
Read more3Where Should the Cancer Control Interventions Target: A Geospatial Hotspot Analysis for Major Cancer Mortality 2018 to 2022 in the United States
Background:Identifying changes in geographic disparities of cancer mortality reveals locations where cancer prevention and control efforts should be focused/targeted. We use recent cancer surveillance data to demonstrate the geographic disparity of major cancer mortality rates in the United States and its shift compared with previous data.Methods:This cross-sectional study used the 2018 to 2022 county-level mortality rates of colorectal, lung, breast, and prostate cancers from the Centers for Disease Control mortality data. Counties with suppressed death counts were imputed by spatial regression models. Getis–Ord Gi* statistics were used to evaluate the spatial clustering of county mortality. Identified hotspot counties were visualized and compared with literature for hotspot pattern change.Results:A total of 3,108 US mainland counties were included. Cancer mortality rates were significantly higher in 244 counties for colorectal, 456 for lung, 147 for breast, and 180 for prostate cancers. Hotspot areas were central Appalachia (colorectal and lung cancers), Lower Mississippi Delta (colorectal, breast, and prostate cancers), Midwest (colorectal and lung cancers), north Michigan/Wisconsin (lung and prostate cancers), north Florida (lung cancer), and the West (prostate cancer).Conclusions:West central Appalachia and Lower Mississippi Delta continue to be hotspots for major cancer types, whereas previously identified eastern North Carolina/Virginia hotspots shrunk, east Oklahoma and North Florida emerged as new hotspots for lung cancer, and several hotspots emerged in the West for prostate cancer.Impact:This study updated the analyses for geospatial disparity in major cancer mortality since 2018, illustrating recent changes in the disparity pattern and pinpointing areas that cancer prevention and control efforts should target.
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164Neighborhood and Individual Socioeconomic Disadvantage and Survival Among Patients With Nonmetastatic Common Cancers
Disadvantaged neighborhood-level and individual-level socioeconomic status (SES) have each been associated with suboptimal cancer care and inferior outcomes. However, independent or synergistic associations between neighborhood and individual socioeconomic disadvantage have not been fully examined, and prior studies using simplistic neighborhood SES measures may not comprehensively assess multiple aspects of neighborhood SES. To investigate the associations of neighborhood SES (using a validated comprehensive composite measure) and individual SES with survival among patients with nonmetastatic common cancers. This prospective, population-based cohort study was derived from the Surveillance, Epidemiology, and End Results-Medicare database from January 1, 2008, through December 31, 2011, with follow-up ending on December 31, 2017. Participants included older patients (≥65 years) with breast, prostate, lung, or colorectal cancer. Neighborhood SES was measured using the area deprivation index (ADI; quintiles), a validated comprehensive composite measure of neighborhood SES. Individual SES was assessed by Medicare-Medicaid dual eligibility (yes vs no), a reliable indicator for patient-level low income. The primary outcome was overall mortality, and the secondary outcome was cancer-specific mortality. Hazard ratios (HRs) for the associations of ADI and dual eligibility with overall and cancer-specific mortality were estimated via Cox proportional hazards regression. Statistical analyses were conducted from January 23 to April 15, 2021. A total of 96 978 patients were analyzed, including 25 968 with breast, 35 150 with prostate, 16 684 with lung, and 19 176 with colorectal cancer. Median age at diagnosis was 76 years (IQR, 71-81 years) for breast cancer, 73 years (IQR, 70-77 years) for prostate cancer, 76 years (IQR, 71-81 years) for lung cancer, and 78 years (IQR, 72-84 years) for colorectal cancer. Among lung and colorectal cancer patients, 8412 (50.4%) and 10 486 (54.7%), respectively, were female. The proportion of non-Hispanic White individuals among breast cancer patients was 83.7% (n = 21 725); prostate cancer, 76.8% (n = 27 001); lung cancer, 83.5% (n = 13 926); and colorectal cancer, 81.1% (n = 15 557). Neighborhood-level and individual-level SES were independently associated with overall mortality, and no interactions were detected. Compared with the most affluent neighborhoods (ADI quintile 1), living in the most disadvantaged neighborhoods (ADI quintile 5) was associated with higher risk of overall mortality (breast: HR, 1.34; 95% CI, 1.26-1.43; prostate: HR, 1.51; 95% CI, 1.42-1.62; lung: HR, 1.21; 95% CI, 1.14-1.28; and colorectal: HR, 1.24; 95% CI, 1.17-1.32). Individual socioeconomic disadvantage (dual eligibility) was associated with higher risk of overall mortality (breast: HR, 1.22; 95% CI, 1.15-1.29; prostate: HR, 1.29; 95% CI, 1.21-1.38; lung: HR, 1.14; 95% CI, 1.09-1.20; and colorectal: HR, 1.23; 95% CI, 1.17-1.29). A similar pattern was observed for cancer-specific mortality. In this cohort study, neighborhood-level deprivation was associated with worse survival among patients with nonmetastatic breast, prostate, lung, and colorectal cancer, even after accounting for individual SES. These findings suggest that, in order to improve cancer outcomes and reduce health disparities, policies for ongoing investments in low-resource neighborhoods and low-income households are needed.
Read more23Time after time: detecting annual patterns in stream bacterial biofilm communities.
SummaryTo quantify the major environmental drivers of stream bacterial population dynamics, we modelled temporal differences in stream bacterial communities to quantify community shifts, including those relating to cyclical seasonal variation and more sporadic bloom events. We applied Illumina MiSeq 16S rRNA bacterial gene sequencing of 892 stream biofilm samples, collected monthly for 36‐months from six streams. The streams were located a maximum of 118 km apart and drained three different catchment types (forest, urban and rural land uses). We identified repeatable seasonal patterns among bacterial taxa, allowing their separation into three ecological groupings, those following linear, bloom/trough and repeated, seasonal trends. Various physicochemical parameters (light, water and air temperature, pH, dissolved oxygen, nutrients) were linked to temporal community changes. Our models indicate that bloom events and seasonal episodes modify biofilm bacterial populations, suggesting that distinct microbial taxa thrive during these events including non‐cyanobacterial community members. These models could aid in determining how temporal environmental changes affect community assembly and guide the selection of appropriate statistical models to capture future community responses to environmental change.
Read more374Down-regulation of Micro-RNA-1 (miR-1) in Lung Cancer: Suppression of Tumorigenic Property of Lung Cancer Cells and Their Sensitization to Doxorubicin-Induced Apoptosis by miR-1
Micro-RNAs are approximately 21-25-nucleotide-long noncoding RNAs that regulate gene expression primarily at the post-transcriptional level in animals. Here, we report that micro-RNA-1 (miR-1), abundant in the cardiac and smooth muscles, is expressed in the lung and is down-regulated in human primary lung cancer tissues and cell lines. In situ hybridization demonstrated localization of miR-1 in bronchial epithelial cells. The tumor suppressor C/EBPalpha, frequently suppressed in lung cancer, reactivated miR-1 expression in the lung cancer cells. Repressed miR-1 was also activated in lung cancer cells upon treatment with a histone deacetylase inhibitor. These observations led us to examine the antitumorigenic potential of miR-1 in lung cancer cells. Expression of miR-1 in nonexpressing A549 and H1299 cells reversed their tumorigenic properties, such as growth, replication potential, motility/migration, clonogenic survival, and tumor formation in nude mice. Exogenous miR-1 significantly reduced expression of oncogenic targets, such as MET, a receptor tyrosine kinase, and Pim-1, a Ser/Thr kinase, frequently up-regulated in lung cancer. Similarly, the levels of two additional targets, FoxP1, a transcription factor with oncogeneic property, and HDAC4 that represses differentiation-promoting genes, were reduced in miR-1-expressing cells. Conversely, depletion of miR-1 facilitated N417 cell growth with concomitant elevation of these targets. Further, ectopic miR-1 induced apoptosis in A549 cells in response to the potent anticancer drug doxorubicin. Enhanced activation of caspases 3 and 7, cleavage of their substrate PARP-1, and depletion of anti-apoptotic Mcl-1 contributed to the sensitivity of miR-1-expressing cells to doxorubicin. Thus, miR-1 has potential therapeutic application against lung cancers.
Read more36Urinary 8-isoprostane levels and occurrence of lung, colorectal, prostate, breast and overall cancer: Results from a large, population-based cohort study with 14 years of follow-up
Urinary 8-isoprostane levels and occurrence of lung, colorectal, prostate, breast and overall cancer: Results from a large, population-based cohort study with 14 years of follow-up
Read more123Baseline Chest Radiograph for Lung Cancer Detection in the Randomized Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial
The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was initiated in 1992 to examine cause-specific mortality reduction from screening for these four cancers in men and women. We report lung cancer detection results of the baseline screening round. Of the 154,942 participants enrolled, who were aged 55-74 years with no history of PLCO cancers, 77,465 were randomly assigned to the intervention arm. Current or former smokers and never smokers in this arm received an initial single-view posterior-anterior chest radiograph. In the initial screen, 5991 (8.9%, 95% confidence interval [CI] = 8.7% to 9.2%) of radiographs were suspicious for lung cancer: 8.2% (95% CI = 7.9% to 8.5%) for women and 9.6% (95% CI = 9.3% to 10.0%) for men. Rates were highest for older age groups and for smokers. Among those 5991 participants with a positive screen, 206 (3.4%, 95% CI = 3.0% to 3.9%) underwent biopsy examination, 126 (61.2%, 95% CI = 54.5% to 67.8%) of whom were diagnosed with lung cancer within 12 months of the screen (59 in women and 67 in men). The positive predictive value was 2.1% (95% CI = 1.7% to 2.5%), and 1.9 lung cancers were detected per 1000 screens. Among these cancers, 44% (95% CI = 35% to 52%) were stage I non-small-cell lung cancer. High rates of lung cancer were found in current smokers (6.3 per 1000 screens) and in former smokers who had smoked within the past 15 years (4.9 per 1000 screens). The lung cancer detection rate among never smokers was 0.4 per 1000 screens; this group accounted for 11% (95% CI = 5.6% to 16.6%) of the cancers identified. In the baseline screen, nearly half the cancers were stage I. Whether this experience results in a reduction in lung cancer mortality is yet to be seen.
Read more60Heterogeneous mutation pattern in tumor tissue and circulating tumor DNA warrants parallel NGS panel testing
Liquid biopsy by genotyping circulating tumor DNA (ctDNA) has provided a non-invasive approach in assessing tumor genomic alterations in clinical oncology. However, emerging evidence in clinical settings has shown significant discordance in the genomic alterations between matched tumor tissue and blood ctDNA samples, and even between the same set of blood samples analyzed on different testing platforms. Thus, it is necessary to study underlying causes of discrepancies in these studies by genotyping tumor tissue and ctDNA in parallel using next generation sequencing (NGS) panels based on the same technology. Here we enrolled 56 non-small-cell lung cancer (NSCLC) patients and evaluated tumor tissue genotyping and ctDNA based liquid biopsy by parallel NGS panel testing and compared different sample preparation conditions. Somatic mutations in plasma cell-free DNA (cfDNA) were detected in 63.6% patients with early-stage NSCLC and 60% patients with advanced-stage NSCLC. The overall concordance between matched formalin-fixed paraffin-embedded sample and cfDNA was 54.6% in early-stage NSCLC patients and 80% in advanced-stage NSCLC patients. The positive concordance rate was 44.4% and 71.4% in early-stage and advanced-stage patients, respectively. Using fresh frozen tumor samples did not improve the overall concordance rate between matched tumor tissue and cfDNA. Processing blood samples beyond 4 h after blood draw significantly decreased the detection rate of somatic mutations in cfDNA. Thus, the concordance rate between tumor tissue-based and ctDNA-based genotyping in clinical samples can be affected by multiple pre-analytical, analytical and biologic factors. Parallel NGS panel testing on both sample types for each patient may be warranted for effective guidance of cancer targeted therapies and possible early detection of cancer.
Read moreMo1808 Post-Partum Antibiotic Treatment Disturbs Development of the Intestinal Microbiota
Mo1808 Post-Partum Antibiotic Treatment Disturbs Development of the Intestinal Microbiota
Negative associations between macronutrient quality index and lung cancer incidence and mortality: results from the prostate, lung, colorectal, and ovarian cancer screening trial
BackgroundPrior research has not examined the connection between the quality of macronutrients and the occurrence as well as fatality rates of lung cancer (LC). Consequently, to delve deeper into the correlations between macronutrient quality and the likelihood of developing LC, we carried out an extensive, long-term prospective cohort study of 101,755 American adults from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.MethodsOur research cohort comprised 154,887 adults, aged between 55 and 74, who were enrolled from 10 screening facilities across the United States. The macronutrient quality index (MQI) was derived from participants’ responses to a dietary history questionnaire (DHQ). To quantify the strength and precision of the relationships between MQI and the incidence as well as mortality of LC, we employed Cox proportional hazards regression modeling to estimate hazard ratios (HRs) alongside their corresponding 95% confidence intervals (CIs). Additionally, we conducted subgroup analyses to scrutinize whether the observed link between MQI and LC risk was subject to modification by potential confounding variables. To reinforce the reliability of our results, sensitivity analyses were also carried out.ResultsOver an average follow-up period spanning 8.82 ± 1.95 years (accumulating to 897,809 person-years of observation), we recorded 1,706 LC diagnoses, encompassing 1,464 cases of non-small cell lung cancer (NSCLC) and 242 cases of small cell lung cancer (SCLC). Additionally, there were 1,217 deaths attributed to LC, with 1,005 NSCLC-related and 212 SCLC-related fatalities. Our results demonstrate a distinct, statistically significant inverse association between a higher MQI and both a reduced incidence (HR Q4 vs. Q1: 0.65; 95% CI: 0.56–0.76; p < 0.001 for trend) and decreased mortality (HR Q4 vs. Q1: 0.71; 95% CI: 0.60–0.84; p < 0.001 for trend) of LC. This inverse relationship held true for both NSCLC and SCLC subtypes. The robustness of the associations between MQI and the incidence as well as mortality of LC was solidly affirmed through sensitivity analyses.ConclusionOur research outcomes imply that prioritizing the intake of higher-quality macronutrients could serve as a viable strategy to mitigate LC risk within the American population.
Read more13Inhomogeneity detection in phytoplankton time series using multivariate analyses
Inhomogeneity detection in phytoplankton time series using multivariate analyses
2Abstract 1884: Dietary intake of phytoestrogens and the risk of prostate cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Prostate cancer is the most common non-cutaneous cancer and second leading cause of cancer death among men in the U.S. Although ecologic and migrant studies suggest that diet plays a role in the etiology of prostate cancer, few specific nutrients that alter its occurrence have been identified in case-control and cohort studies. Phytoestrogens are a family of bioactive compounds that are abundant in soy products and some other food groups (e.g. legumes and chick peas). Experimental studies revealed that phytoestrogen intake may modulate the risk of prostate cancer due to their structural similarity to 17β-estradiol and the resulting competitive binding to estrogen receptors. Despite biological plausibility, it still remains elusive whether phytoestrogen intake influences prostate cancer risk in human populations. Therefore, the objective of the present study was to investigate the associations between dietary intake of phytoestrogens and the risk of total and advanced prostate cancer among 30,097 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). A total of 3628 cases of prostate cancer (including 396 advanced cases) have been documented during a median follow up of 11.5 years. Advanced prostate cancer were defined as stage II cancer with a Gleason score of ≥8, or stage III or stage IV cancer. Dietary intake of phytoestrogens was assessed with a validated food frequency questionnaire. Cox proportional hazards regression was performed to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for dietary intake of phytoestrogens in relation to prostate cancer risk. After adjustment for confounders, an increased risk of advanced prostate cancer was found for the higher dietary intake of isoflavones (HR: 1.58; 95% CI: 1.11, 2.24), genistein (HR: 1.42; 95% CI: 1.02, 1.98), daidzein (HR: 1.62; 95% CI: 1.13, 2.32), and glycitein (HR: 1.53; 95% CI: 1.09, 2.15). Conversely, it appears that the higher dietary intake of genistein was associated with a reduced risk of non-advanced prostate cancer (HR: 0.88; 95% CI: 0.78, 0.99) and total prostate cancer (HR: 0.90; 95% CI: 0.81, 1.00). The risk estimates presented above were obtained for comparisons between the quintile 5 and quintile 1 of respective phytoestrogen intake. In summary, our analysis of this national prospective cohort study suggests that dietary intake of phytoestrogens modulated the risk of prostate cancer and that some of these effects may differ by the aggressiveness of the disease. Citation Format: Michael Reger, Terrell Zollinger, Ziyue Liu, Josette Jones, Jianjun Zhang. Dietary intake of phytoestrogens and the risk of prostate cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1884. doi:10.1158/1538-7445.AM2015-1884
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