tbuckley/cabot-search huggingface dataset:
Abstract 12591: STAT3 Activation Prevents Mesenchymal Stem Cell Apoptosis and Improves Infarct Repair
Authors: Yu-Ting Xuan, Yanqing Zhu, Ou-Li Wang, Guangming Cheng, Harold Elias, Arash Davani, Yanjuan Yang, Magdy Girgis, Robert J Vincent, Jeryl Hauptman, Buddhadeb Dawn
Journal: Circulation (2012)

The role of STAT3 in mesenchymal stem cell (MSC) biology remains unclear. We hypothesized that STAT3 activation would prevent MSC apoptosis, promote angiogenesis, and enhance infarct repair. Treatm...
Computerized histomorphometric features of glandular architecture predict risk of biochemical recurrence following radical prostatectomy: A multisite study.
Authors: Patrick Leo, Andrew Janowczyk, Robin Elliott, Nafiseh Janaki, Rakesh Shiradkar, Xavier Farrè, Kosj Yamoah, Timothy Rebbeck, Natalie Shih, Francesca Khani, Brian D. Robinson, Lauri Eklund, Otto Ettala, Pekka Taimen, Peter Bostrom, Michael D Feldman, Sanjay Gupta, Priti Lal, Anant Madabhushi
Journal: Journal of Clinical Oncology (2019)

5060 Background: Following a radical prostatectomy (RP) for prostate cancer, a patient may experience biochemical recurrence (BCR), defined as two consecutive prostate specific antigen (PSA) readings &gt; 0.2 ng/mL. BCR is correlated with metastasis and disease specific survival. Extant molecular based companion diagnostic tests for predicting risk of BCR and disease progression tend to be expensive and tissue destructive. We sought to evaluate whether computer extracted features of glandular architecture from routine digitized H&amp;E slides could predict post-RP BCR risk. Methods: RP specimens from 683 patients (184 with BCR, 499 without) with post-surgical PSA follow-up information were gathered from six sites. Median non-BCR follow-up was 3.2 years. A representative tumor area was annotated on the diagnostic H&amp;E slide of each patient. 324 (131 BCR) patients from two sites formed the training set. The other 359 (53 BCR) patients formed the validation set. Glands were segmented by a deep learning model. 216 features describing gland arrangement, shape, and disorder were then extracted. An elastic net Cox proportional hazards model was constructed from the training set using the top 10 stable features identified via feature selection. Risk score thresholds were chosen on the training set to stratify patients into low-, medium-, or high-risk. Validation set results were evaluated by the log-rank test and hazard ratio. For the 172 (37 BCR) patients for whom Gleason grade and preoperative PSA values were available, risk classifications were compared using Cox proportional hazards regression. Results: Nine of the top features were gland shape features and one was a gland arrangement feature. The hazard ratio between the low- and high-risk groups on the validation set was 3.04 (p &lt; 0.05). The histomorphometric classifier was predictive of BCR (p &lt; 0.05, hazard ratio = 1.63) independent of Gleason grade group and preoperative PSA in multivariate testing. Conclusions: Computer extracted features of gland morphology can stratify post-RP patients by BCR risk. Our computerized histomorphometric model could serve as a prognostic tool in the post-RP setting.[Table: see text]
Are patients with advanced colon cancer availing of palliative care services?: Findings from a high-volume urban center.
Authors: Daniel S Jamorabo, Benjamin D Renelus, Pragnan Kancharla, William M Briggs
Journal: Journal of Clinical Oncology (2019)

e23101 Background: Palliative care is integral to cancer treatment. Our goal was to investigate the factors associated with palliative care service involvement for hospitalized colon cancer patients. Methods: We carried out a retrospective study of all colon cancer patients diagnosed and hospitalized at our institution from 1/1/2010 through 12/31/2017. We identified 667 patients, including 370 women (55%). We used Fisher’s exact test to find statistically significant differences in proportions of patients seen by the palliative care service based on sex, race, cancer stage, surgical intervention, and chemotherapy administration. Results: We found that 561/667 (84%) colon cancer patients were not evaluated by the palliative care service (including 301 women; 54%) and that overall they were unlikely to have been evaluated regardless of sex, race, cancer stage, or chemotherapy (Table). Patients who underwent surgery were equally likely to be seen by the team as those who did not have surgery. We found that 53% (150/285) of patients with Stage III and IV disease received neither chemotherapy nor palliative care evaluation. Conclusions: The palliative care service is underutilized at our facility even when patients with advanced stage disease are hospitalized. Even when patients are not on chemotherapy, the palliative care service remains uninvolved. This may be due to inadequate staffing, misconceptions that providers and patients have about palliative care, or lack of coordination between inpatient and outpatient providers. We did not find that palliative care service utilization led to a statistically significant difference in survival, but their involvement is critical to helping address patients’ goals of care and symptoms. It is also instrumental to improving cancer patients’ quality of life both in the outpatient and inpatient setting, regardless of cancer stage or survival, as in our patient population. More effort is needed to include the palliative care service in the care of patients with advanced colon cancer. [Table: see text]
Self-reported health and survival in older patients diagnosed with multiple myeloma.
Authors: Nadia Azmi Nabulsi, Ali Alobaidi, Brian Talon, Alemseged Ayele Asfaw, Jifang Zhou, Lisa K. Sharp, Karen Sweiss, Pritesh Rajni Patel, Brian C-H Chiu, Naomi Ko, Gregory Sampang Calip
Journal: Journal of Clinical Oncology (2019)

6582 Background: The strength of associations between pre-diagnosis self-reported health (SRH) and mortality differ by medical condition, with a moderately strong association reported among cancer patients. Less is known about the impact of SRH on survival among patients diagnosed with multiple myeloma (MM). We aimed to evaluate pre-diagnosis SRH in relation to survival in a cohort of older MM patients. Methods: We analyzed a prospective cohort from the Surveillance, Epidemiology, and End Results (SEER)-Medicare Health Outcomes Survey (MHOS) database of patients 65 years and older diagnosed with first primary MM. Survey responses to a single general health question (asking patients to self-report their health as excellent, very good, good, fair, or poor) were used to determine pre-diagnosis SRH, grouped as high (excellent/very good/good) or low (fair/poor). We used multivariable Cox proportional hazards models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for associations between SRH and risks of all-cause and cancer-specific mortality. Results: Of 521 MM patients with pre-diagnosis SRH data, the mean (SD) age at diagnosis was 76.8 (6.1) years with 60% of patients identifying as white, 18% as black, and 32% reporting low SRH. Compared to patients reporting high SRH, patients reporting low SRH were older, had lower education levels, more comorbidities, and lower Veterans-RAND 12 physical health and mental health component summary scores. In multivariable analyses, MM patients with low SRH had a 28% increased risk of all-cause mortality (HR = 1.28, 95% CI = 1.00, 1.64) and a non-statistically significant 19% increased risk of cancer-specific mortality (HR = 1.19, 95% CI = 0.87, 1.61) compared to MM patients reporting high SRH. Conclusions: Our findings suggest that lower SRH is highly prevalent among MM patients prior to diagnosis and is associated with modestly increased all-cause mortality. At a minimum, low SRH deserves clinical attention to determine how older MM patients’ quality of life may be compromised. The mechanism by which SRH affects mortality in MM should be further assessed and efforts should be made to identify whether any of the underlying mechanisms linking SRH and mortality in MM are mutable.
Real-world effectiveness of ribociclib + aromatase inhibitor, or endocrine monotherapy, or chemotherapy as first-line treatment in postmenopausal women with HR-positive, HER2-negative locally advanced or metastatic breast cancer: Baseline data from the RIBANNA study.
Authors: Achim Wöckel, Thomas Decker, Peter A. Fasching, Christian Jackisch, Diana Luftner, Frederik Marme, Toralf Reimer, Christian Roos
Journal: Journal of Clinical Oncology (2019)

e12520 Background: Ribociclib, a selective CDK4/6 inhibitor, in combination with an aromatase inhibitor (AI) is approved for the treatment of HR+/HER2- advanced breast cancer (aBC) (locally advanced or metastatic). Real-world evidence for the effectiveness, safety and tolerability of ribociclib + AI in routine clinical practice is needed to support its use. Methods: RIBANNA (CLEE011ADE03) is a non-interventional study running in Germany since October 2017 involving up to 3020 postmenopausal patients receiving ribociclib + AI, endocrine monotherapy (ET), or chemotherapy (CT) as first-line treatment for HR+/HER2- aBC, prescribed in line with German guidelines. Data are collected from clinical practice in all three cohorts. Further lines of treatment are documented to examine outcomes of sequential therapy. Results: 461 patients enrolled to October 9, 2018 (Table). First-line mean daily ribociclib dose was 382 mg including and 540 mg excluding dose interruptions; mean duration of exposure to ribociclib: 128 days. Ribociclib was given in combination with anastrozole (8%), exemestane (7%), and letrozole (83%); ET comprised a selective estrogen receptor degrader (25%), nonsteroidal AI (64%), steroidal AI (5%), and a selective estrogen receptor modulator (7%); CT included taxane-based monotherapy (30%) or combination therapy (27%), anthracycline-based combination therapy (5%), other monotherapy (23%) or other combination therapy (13%). Conclusions: Population characteristics from the RIBANNA study show a diverse group of patients from a real-world setting of ribociclib treatment. Baseline demographics and characteristics. Clinical trial information: CLEE011ADE03. [Table: see text]
Pharmacy cost in cancer.
Authors: Surbhi Shah, Nathan Rubin
Journal: Journal of Clinical Oncology (2019)

e18358 Background: Health care spending in US is highest in the developed world and contributes to up to 1/5 of the GDP. The price escalation is steep and contribution from cancer care is soaring. The cost of medications is deemed to be the leading cause of increased health care spending. In this era of precision medicine, with more effective and better tolerated drugs, patients are using them for longer periods of time, adding to the ever mounting health care spending. Methods: We used a large claims based data set US database MarketScan to explore the economic burden of drug cost in cancer care. Between January 1, 2013 and September 30, 2015 we identified 195,290 enrollees with active cancer. We analyzed the economic burden of medications for overall cancer care by exploring the total cost of care and the pharmacy expenditure by various classes of drugs for these patients. The perspective was that of the health care system as the costs included payments by the insurer and the patient. Results: There were 195,290 active cancer patients in this analysis. Mean age was 61 years, 55% were females. Breast cancer was the most common diagnosis. Mean total cost of care and total drug cost per patient over the study period was $141,415 and $13,579, respectively. The total pharmacy expenditure across all study patients was ~2.5B. Antineoplastic drugs make up the largest portion of the total pharmacy expenditure at 39%. Cost contribution based on drug categories were anti-infective (6%), cardiovascular (6%), central nervous system (including opiates, anti-nausea medications and antidepressants) (7%), blood formulations (including anticoagulants) (8%), hormones (8%) and gastrointestinal drugs (4%) respectively. Conclusions: Based on the real world information from a large insurance claims database, this study quantifies the contribution of various drug classes to the cost of cancer care. Antineoplastic contribute to &gt; 1/3rd of the total pharmacy spending. With increasing trend for immunotherapy and combination therapy drug costs are bound to go up even more steeply. Unless drug prices are regulated, we are looking towards an unsustainable level of growth in the health care spending in cancer care.
The characterization of <i>ERBB</i> family mutations in Chinese biliary tract cancers.
Authors: Tianqiang Song, Wei Zhang, Huikai Li, Ping Chen, Xiaoqian Chen, Junping Shi, Shuirong Zhang, Ming Yao, Kai Wang
Journal: Journal of Clinical Oncology (2019)

e15595 Background: Next generation sequencing has been applied to identify actionable mutations in biliary tract cancers (BTCs). ERBB family genes, especially ERBB2 and ERBB3, serve as effective biomarkers for BTCs targeted therapy as shown in MyPathway and SUMMIT clinical trials. However, the distribution and major mutation types of ERBB family genes were not clear in Chinese BTC patients. Methods: Deep sequencing targeting 450 cancer genes was performed on FFPE and matching blood samples collected from a cohort of 716 Chinese BTC patients. Genomic alterations including single nucleotide variations (SNV), short and long insertions/deletions (Indels), copy number variations, gene rearrangements and fusions were analyzed. Results: A total of 14% (101/716) of patients with a median age of 62 years old, including 45 males and 56 females, were identified harboring ERBB family mutations. Somatic ERBB family mutations occurred with a rate of 29% in gallbladder carcinoma (GBCA), 13% in extrahepatic cholangiocarcinoma (EHCCA), 12% in hilar cholangiocarcinoma (HCCA) and 8% in intrahepatic cholangiocarcinoma (IHCCA). No germline mutation was detected. A high rate of ERBB2 gene amplification was observed in GBCA (17%). In IHCCA and EHCCA, SNV/Indel accounted for 3% and 5%, respectively, and was the major variation in ERBB2. In HCCA, SNV/Indel was the most common mutation in ERBB3 (8%). In BTC patients, TP53 (81%) and CDK12 (36%) were the top-ranked co-mutant genes with ERBB2. The mutant frequency of CDK12 was significantly different between patients with or without an ERBB2 mutation ( p&lt; 0.001). ERBB2 S310F/Y, ERBB3 V104L/M were hotspot mutations within the ERBB family in BTCs. Conclusions: ERBB family mutations were detected in 14% of Chinese BTC patients. Similar to Western populations (PMID: 27622582), ERBB2 gene amplification was the most common mutation in GBCA in Chinese patients. Unlike ERBB2/ ERBB3 amplification which has been reported as the major mutation in previous studies, our study of other BTC types revealed ERBB2/ ERBB3 SNV/Indel as the major mutation. BTC patients harboring ERBB family mutations have the potential to benefit from pan-HER inhibitors.
<i>​</i>obesity and metastatic melanoma: A national perspective from the pre-immune checkpoint inhibitor era.
Authors: Aakash Desai, Harsh V Parmar, Upendra P. Hegde
Journal: Journal of Clinical Oncology (2019)

e21032 Background: There is an ongoing debate about correlation of obesity with favorable outcomes in patients with metastatic melanoma receiving treatment. Our study measured the differences in in-hospital outcome parameters such as length of stay (LOS), cost and mortality in patients with metastatic melanoma with respect to obesity. Methods: We used National Inpatient Sample (NIS) dataset from 2008 to 2014 to identify the diagnosis of Metastatic melanoma (ICD-9 code:172.9) among hospitalized patients. Data was matched and weighted to obtain a nationally representative sample for analysis. The AHRQ comorbidity measure of obesity was utilized to identify obesity as a coexisting medical condition that is not directly related to the principal diagnosis. Categorical and continuous variables were tested using Chi-square test and Student t-test respectively. Multivariate hierarchical regression was used for the analysis of primary outcomes of interest. Results: We identified a total of 1,809 cases of metastatic melanoma from 2008 to 2014. Among them, 908 (50.19%) were obese and 901 (49.80%) non-obese. 195 out of the 1,809 (10.77%) patients were treated with high dose infusion of IL-2. Overall, the mean LOS (≈6.03 days [non-obese] vs ≈5.72 days [obese], p = 0.949) and mean cost of hospitalization (16720.28$ vs 17639.95$, p = 0.428; mean difference of 919.67$) was not significantly different based on obesity as a comorbid condition. The mortality rate was found to be significantly lower in obese patients (41% vs. 59%, p = 0.017), but did not reach statistical significance on logistic regression analysis (OR:0.95, p = 0.130). Further subgroup analysis of patients with metastatic melanoma who received high dose IL-2, we found no significant differences in mean LOS (5.03 vs 7.03, p = 0.14) as well as mean cost of hospitalization (27432.72$ vs 41881.13$, p = 0.485) between non-obese and obese patients. However, the in-hospital mortality for patients undergoing high dose IL-2 therapy could not be studied given no cases of in-hospital mortality occurred in this subgroup. Conclusions: Our study demonstrates that there are no significant differences in in-hospital outcomes for patients with metastatic melanoma with respect to obesity, even in the subgroup of patients treated with IL-2 immunotherapy. Thus, there is a need for further studies to adequately understand the exact biological mechanism of obesity in metastatic melanoma, the influence of obesity on immunotherapy outcomes and its translation into patient care outcomes.
Paired whole exome and transcriptome analyses for the Immunogenomic changes during concurrent chemoradiotherapy in esophageal squamous cell carcinoma
Authors: Sehhoon Park, Je-Gun Joung, Yang Won Min, Jae-Yong Nam, Daeun Ryu, Dongryul Oh, Woong-Yang Park, Se-Hoon Lee, Yoon La Choi, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park, Jong-Mu Sun
Journal: Journal for ImmunoTherapy of Cancer (2019)

The immunogenomic changes triggered by concurrent chemoradiation therapy (CCRT), a standard neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma (ESCC), are unknown. We aimed to analyze the early immunogenomic changes in ESCC induced by CCRT and to correlate them with clinical outcomes.We collected biopsy samples from 40 patients with ESCC and the surgical candidates were treated with 5-fluorouracil (5-FU)/Cisplatin and concurrent radiation therapy. Endoscopic biopsy was performed before and after one treatment cycle of 5-FU/Cisplatin and 5 to 18 fractions of radiation. We analyzed immunogenomic changes using paired whole-exome sequencing (n = 29) and paired whole-transcriptome sequencing (WTS, n = 23). Multiplex immunohistochemistry (IHC) was conducted in four representative pair samples.Fourteen out of 23 WTS samples (60.8%) showed increased immune scores after CCRT, as calculated by ESTIMATE. The rate of progression-free survival was higher in patients with increased immune scores compared with the remaining patients (83.1% vs. 57.1%, p = 0.25). Tumor mutation burden and neoantigen load were significantly reduced after CCRT (p < 0.001). We observed no specific correlation with non-synonymous mutations and no changes in the single-nucleotide variant spectrum after CCRT. Post-CCRT samples were enriched in gene sets related to immune signaling pathways, such as interferon gamma signaling and CD28 co-stimulation. Multiplex IHC showed an incremental trend in the proportion of CD4 positive cells in cytokeratin positive region after CCRT. However, CD8, CD20, FOXP1, PD-L1 showed no definitive trend. Proportion of immune cells calculated by CIBERSORT, showed that significant increase in neutrophils after CCRT.We have comprehensively analyzed the early immunogenomic changes induced in ESCC by CCRT and correlated them with clinical outcomes. Our results provide a potential basis for combining immunotherapy with CCRT for the treatment of ESCC.
Pathogenic germline mutation profile in Chinese lung cancers and related-driver mutation pattern.
Authors: Wenying Peng, Lin Wu, Lianpeng Chang, Jin Li, Jing Bai, Yanyan Zhang, Yanfang Guan, Meilin Jiang, Xingxiang Pu, Li Xu, Qianzhi Wang, Fang Xu, Bolin Chen, Jun Cao, Xin Yi, Ling Yang, Xuefeng Xia, Jianjun Zhang
Journal: Journal of Clinical Oncology (2019)

e13003 Background: Many cancers could be driven by germline mutation exampled as BRCA1/2 in breast or ovarian cancer. However, the candidate predisposition variants for Chinese lung cancer are largely unknown. Methods: We reviewed 1797 Chinese lung cancer patients with paired tumor-normal samples sequenced by a 1021 gene panel. The annotation of germline variants within 95 selected susceptible genes was based on ACMG 2015 version guideline. Results: The frequency of patients identified with pathogenic or likely pathogenic (P/LP) germline variants were 5.95% (107 in 1797), which elevated to 10.1% (9 in 89) in patients younger than 40. Totally, 112 mutations from 35 genes were screened out. Recurrent pathogenic germline genes were BRCA2 (n = 14), FANCA (n = 9), RAD51D (n = 7), MUTYH (n = 7), ATM (n = 7) and TP53 (n = 5). The average age at diagnosis was numerically 2 years earlier in patients with P/LP (mean, 58.2 vs. 60.0, p = 0.22) than other patients without significance, but different genes contribute to discordant effects. Significantly early onset age was found in germline BRCA1/ 2 mutation (median, 52.5 versus 60.0 yrs in patients without P/LP, p = 0.0080) while later onset age was associated with germline PMS2 mutation (median, 74 versus 60.0 yrs, p = 0.0214 ). In terms of clinical actionable somatic mutation, the frequency of KRAS (15/89, 16.85% versus 121/1429, 8.47%, p = 0.012) and c-MET (6/89, 6.74% versus 31/1429, 2.17%, p = 0.018) in germline mutant patients were significantly higher, while TP53 (41/89, 46.07% versus 847/1429, 59.27%, p = 0.019) was apparently less mutated in P/LP lung cancer. As for frequency of EGFR, ALK, ROS-1, RET and BRAF, mutation frequency were not significantly different in lung cancer with germline mutation. Conclusions: Our study delineated the pathogenic germline mutation landscape in Chinese lung cancers for the first time. Predisposition genes demonstrated clinical actionable roles in onset age and therapeutic interventions. Further follow up may clarify the contribution of germline mutation to somatic mutation driven targeted therapy response and prognosis.