tbuckley/cabot-search huggingface dataset:
AB0856 RISK FACTORS OF CIRRHOSIS- RELATED OSTEOPOROSIS
Authors: Nouha Trad, Dhilel Issaoui, Hela Kchir, Sabrine Soua, Hatem Chaabouni, Nadia Maamouri
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Osteoporosis, that may lead to a high risk of fractures and compromises quality of life, is the main bone disturbance among cirrhotic patients. Despite that, it tends to be under-diagnosed. <h3>Objectives</h3> To determine frequency of osteoporosis and identify risk factors associated among cirrhotic patients. <h3>Methods</h3> We performed a retrospective analysis of data from consecutive cirrhotic patients recruited from <b>January 2010 to December 2017</b> and who had at least one bone mineral density measurement (BMD). By definition from the World Health Organization, osteoporosis is defined by bone densitometry as a T score &lt; -2.5 and osteopenia as a T score between -1 and -2.5. <h3>Results</h3> 227 patients with an average age of 65.5 years [24-90] were included. Thirty one had a BMD: ten patients with HCV-related cirrhosis (HCV), seven patients with HBV-related cirrhosis (HBV) and 14 patients with autoimmune liver disease (eight cases of primary biliary cholangitis (PBC), two cases of primary sclerosing cholangitis (PSC), two cases of autoimmune hepatitis (AIH) and two cases of overlap syndrome (PBC+AIH)).. Osteopenia was observed in seven patients (22.5%): three cases of HCV, two cases of PSC and two cases of overlap syndrome. 17 patients had an osteoporosis (54.8%): six cases of HCV, three cases of HBV, five cases of PBC, two cases of AIH and one case of PSC. Osteoporosis is most common in postmenopausal women with significant correlation (p&lt;0,001). Hyperbilirubinaemia and increased Gamma Glutamyl Transferase (GGT) were significantly correlated with osteoporosis (p&lt;0.05). However, there was no significant correlation between osteoporosis and body mass index or the Child-Pugh score. <h3>Conclusion</h3> In our study, 54.8% of cirrhotic patients who have had a BMD, had an osteoporosis. It was more frequent among postmenopausal women with hyperbilirubinaemia and increased GGT. The systematic realization of BMD in these patients could contribute to better management. <h3>Disclosure of Interests</h3> None declared
ABT-806 derived antibody drug conjugates (ADCs) inhibit growth of malignant mesothelioma in-vivo.
Authors: Puey Ling Chia, Diana Cao, Hui Kong Gan, Edward B. Reilly, Andrew Phillips, Thomas John, Andrew Mark Scott
Journal: Journal of Clinical Oncology (2019)

e14677 Background: Malignant mesothelioma (MM) is an aggressive malignancy of the pleura with limited therapeutic options, and is associated with a poor prognosis. EGFR is known to be highly over-expressed in mesothelioma with reported EGFR overexpression between 44 to 97%. We have investigated an anti-EGFR antibody (ABT-806), which is tumor specific and robustly inhibits EGFR-expressing tumors. We have previously shown that ABT-806 ADCs demonstrate potent anti-tumor activity in 806 immunohistochemistry (IHC) positive MSTO-211H MM cell line xenograft model. We present data in MM using ABT-806 novel ADCs [ABT-414 (ABT-806- monomethyl auristatin F), ABBV-221 (ABT-806- monomethyl auristatin E) and ABBV-321 (ABT-806- pyrrolobenzodiazepine)] in MM patient derived xenografts (PDX). Methods: We evaluated expression of EGFR and mAb 806 IHC in MM cell lines and PDXs. PDXs were implanted into 5 to 10 NOD-Scid mice per group and treated with control ADC, saline, cisplatin or ABT-806 ADCs and followed longitudinally with caliper measurements. Comparative statistics were performed in Graphpad prism. Results: Three PDX models were selected according to their 806 IHC statuses (2 epithelioid 806 IHC positive, 1 biphasic histology 806 IHC negative). In one epithelioid PDX model, ABBV-321 resulted in significantly reduced tumor growth on day 27 post therapy with median tumor volumes of 180 mm3 (ADC control) compared with 78mm3 (ABBV-321; p = 0.0159 two-sided). Moreover, the median survival was also significantly longer in ABBV-321 treated models (p = 0.018). In the other epithelioid PDX model, ABBV-321 also resulted in significant responses (median 428mm3 (ADC control) vs 167mm3 (ABBV-321, p = 0.0201). In the 806 IHC negative PDX model, the differences in tumor volumes between all groups were found to be non-statistically significant (ADC control vs ABT-414, ADC control vs ABBV-221, ADC-control vs ABBV-321 groups) with p = 0.0597 for one-way ANOVA. MSTO211H cell line xenograft model also demonstrated significant anti-tumor response to both ABT-414 and ABBV-221 (p &lt; 0.01). Conclusions: In a disease with limited therapies, ABT-806 targeting ADCs in MM demonstrated significant responses in 806+ PDX and cell lines. These data support clinical expansion of these compounds in 806+ MM patients.
Trends from NSQIP 2015 to 2017 in neoadjuvant therapy use before pancreatic adenocarcinoma resection.
Authors: Rebecca C Gologorsky, Sora Ely, Dana Dominguez, Michelle Huyser, CK Chang
Journal: Journal of Clinical Oncology (2019)

e15685 Background: Morbidity and mortality associated with surgical resection of pancreatic adenocarcinoma remains high, and prognosis is poor even after R0 resection. Preoperative chemoradiation, previously only indicated to downstage borderline-resectable disease, has been increasingly used even in cases that appear resectable at time of diagnosis. Response to therapy can be prognostic and guide clinical decision-making. We investigated significant trends over time in neoadjuvant treatment of patients within the National Surgical Quality Improvement Project (NSQIP) database treated surgically for pancreatic adenocarcinoma. Methods: We queried NSQIP data for patients who underwent pancreaticoduodenectomy or subtotal pancreatectomy for pancreatic adenocarcinoma in 2015-2017. We examined differences by year in neoadjuvant treatment use with Chi-square test. Results: There were 8626 patients included. Use of neoadjuvant treatment (chemotherapy or chemoradiotherapy) increased over the study period, and complication by pancreatic fistula and delayed gastric emptying decreased qualitatively over the same time (12% to 9%; 14% to 12%). This increase in use of neoadjuvant chemotherapy was significant among patients with T1, T2, and T3 tumors (Table 1). However, despite NCCN/ASCO guidelines recommending neoadjuvant for all patients with T4 tumors, only about a quarter of these patients received it, and this proportion did not change over time. Conclusions: Preoperative chemotherapy is particularly important in ≥T3 disease because of low rates (50%) of adjuvant therapy, likely secondary to postoperative morbidity. The NSQIP data reflects the trend toward increasing neoadjuvant therapy in lower-T stage disease, but not among patients with T4 disease. This may be because NSQIP data largely reflects community hospital populations, and this practice was first adopted by academic institutions. Based on our findings, it is important that medical oncology be involved early in the multidisciplinary care of patients with pancreatic adenocarcinoma.[Table: see text]
Case 18-1986
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Thomas J. Ryan, John T. Fallon
Journal: New England Journal of Medicine (1986)

Presentation of CaseA 44-year-old woman was admitted to the hospital because of chest pain.She was well until the afternoon before admission, when she was informed that her 17-year-old son had committed suicide by hanging earlier in the day. Half an hour later severe "crushing" substernal pain developed, with radiation to the left shoulder. The pain persisted and worsened, and after six hours she was taken to another hospital, where sublingual nitroglycerin was administered on three occasions, without relief. An electrocardiogram was reported to be unchanged from a routine tracing obtained several months earlier; Q waves were present in . . .
Effectiveness and tolerability of depot formulations of leuprorelin acetate in real life: Analysis of 932 patients with prostate cancer from Brazil.
Authors: Carla Simone Moreira Freitas, Aleida Nazareth Soares
Journal: Journal of Clinical Oncology (2019)

e16552 Background: Clinical trials have shown that androgen deprivation therapy (ADT) is a mainstay of treatment for locally advanced and metastatic prostate cancer. Real-life studies with broader selection criteria may help inform clinical practice. Methods: We reviewed the medical records of 1890 patients with prostate cancer seen at our institution between 01/07 and 07/18. We analyzed patients treated with long-acting leuprorelin acetate, grouping these patients into three strata according to the administration of ADT every 1, 3 or 6 months. The primary outcome was the prostate specific antigen (PSA) levels at 6 and 12 months after treatment initiation. We used Friedman test to compare the distribution of PSA levels over time within each treatment stratum, considering two-sided P values &lt; 0.05 as statistically significant. Results: We analyzed a total of 932 eligible patients, with a median age of 72 years and a median time since diagnosis of prostate cancer of 8.5 months. ADT was administered every 1, 3 and 6 months in 115, 637, and 180 patients, respectively. Nearly half of the patients had locally advanced disease. The table presents PSA levels in each stratum at the three time points. Sexual impotence and hot flashes were the most frequently reported toxicities. Conclusions: Our study confirms that serum PSA levels can be effectively reduced, with a favorable toxicity profile, in most patients treated with long-acting leuprorelin acetate. Administration every 6 months may bring the added benefit of convenience and cost savings in clinical practice.[Table: see text]
Incidence and outcome of interval breast cancer among women participating in the provincial population based screening program in Manitoba, Canada.
Authors: Saroj Niraula, Natalie Biswanger, Kathleen Decker
Journal: Journal of Clinical Oncology (2019)

6595 Background: The province of Manitoba, Canada has an organized population based biennial mammographic screening program. Here we report outcomes of women diagnosed with Interval Cancers (IC), defined as cancer diagnosed within 24 months of a normal screening mammogram and before the next screening mammogram, compared to Screen Detected (SD) cancers. Methods: The Manitoba Cancer Registry was used to obtain data about tumor and host characteristics and cause-specific mortality for women 52 to 64 years of age diagnosed with invasive breast cancer from January 2004 to December 2010. Lead time bias in SD cancers was adjusted based on Duffy's correction factor. Competing risk analysis was used to examine the risk of death by cancer detection method. To examine the relationship between breast cancer detection type and personal and tumour characteristics, we performed multinomial logistic regression analysis with age, area-level income quintile, tumour grade, hormone receptor, and HER2 receptor as independent variables. Results: There were 5,884 women diagnosed with invasive breast cancer during the study period of which 1,338 were SD, 362 were IC, and the remainder were diagnosed outside the screening program or were non-compliant to screening. IC were more likely than SD cancers to be high grade [Odds Ratio (OR) 3.8, 95% Confidence Interval (CI): 2.1-6.8], and ER negative [OR 1.7, 95% CI: 1.02-3.12]. At data cut-off date of June 30, 2012, risk of death from breast cancer was significantly higher for IC compared to SD cancers [Hazard Ratio (HR) 4.18, 95% CI: 1.97-8.87)], for sojorn time (period when tumour is asymptomatic but screen detectable) of 2 years adjusting for area-level average income quintile and age. Sensitivity analyses with sojourn times of 1, 3, and 4 years showed similar results. Risk of non-breast cancer death was not increased with IC compared to SD cancers (HR 1.33, 95% CI: 0.43-4.15). Conclusions: Among women who participated in a systematic population-based screening program, IC occurred frequently; breast cancer-related death for IC was 4-times that of SD cancers. These results highlight the discordance between the principles underpinning population based breast cancer screening and natural history of these more lethal breast cancers.
A phase I study of a novel MDM2 antagonist APG-115 in patients with advanced solid tumors.
Authors: Drew W. Rasco, Nehal J. Lakhani, Yufeng Li, Lichuang Men, Hengbang Wang, Jiao Ji, Yuefen Tang, Zhiyan Liang, Alex Amaya, Kathy Estkowski, Joan Sun, Yingjie Huang, Dajun Yang, Yifan Zhai
Journal: Journal of Clinical Oncology (2019)

3126 Background: APG-115 is a potent and orally active small-molecule MDM2 protein inhibitor. Binding to MDM2 protein, APG-115 restores p53 tumor suppressive function via induction of apoptosis in tumor cells retaining wild-type p53. In addition, enhanced antitumor activity was demonstrated in the syngeneic tumor models after APG-115 combined with PD-1 blockade. Methods: This Phase I study (APG-115-US-001) was designed to enroll the patients with advanced solid tumors in US (NCT02935907). Study objectives included to assess safety, dose limited toxicity (DLT), pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity (assessed every 8 weeks per RECIST v1.1). The patients received APG-115 orally every other day (QOD) at the designated dose (ranging from 10 to 300 mg) for first 21 days of a 28-day cycle, until disease progression. Results: Up until Jan 4 2019, total 28 patients were treated with APG-115 at various doses (one patient at 10mg, 20mg and 50mg, respectively; 14 patients at 100mg, 6 patients at 200mg, and 5 patients at 300mg). The median number of prior systemic anticancer therapies was 4 (range 0-15). The DLTs were observed during cycle 1, including one grade 2 thrombocytopenia at 200mg, one grade 3 thrombocytopenia at 300mg, and one grade 3 fatigue at 100mg and 300mg respectively. The most common AEs (reported in ≥10% of pts) included: fatigue, nausea, vomiting, diarrhea, decreased appetite, dehydration, neutrophil count decreased, white blood cell count decreased, pain in extremity, thrombocytopenia. The most common Grade 3 or 4 treatment related AEs were fatigue (10.7%), and thrombocytopenia (10.7%). Six patients had stable disease (SD) after two cycle treatments, two of them are continuing in this study. PK analyses indicated that exposure (Cmax and AUC) generally increases with the increase of dose level from 20 mg to 300 mg. Conclusions: APG-115 was well tolerated and had manageable adverse events. The MTD/RP2D of APG-115 monotherapy with oral administration, QOD for 21 days of a 28-day cycle for treatment of patients with advanced solid tumors was determined as 100 mg. Further evaluation of APG-115 in combination with pembrolizumab in patients with advanced solid tumors is ongoing. Clinical trial information: NCT02935907.
Lower survival outcomes in patients receiving an initial cancer diagnosis after presenting to the emergency department.
Authors: Hannah L. Conley, Raven V. Delgado, Justin D. McCallen, Eleanor Elizabeth Harris, Andrew Wenhua Ju, Kimberly Rathbun
Journal: Journal of Clinical Oncology (2019)

e18122 Background: Survival outcomes in cancer are better in patients who are diagnosed at an early stage, which can potentially be detected through screening and routine visits to a primary care physician. Patients who receive their initial cancer diagnoses following a visit to the Emergency Department (ED) may present at a later Stage when survival outcomes are worse. The characteristics of patients who receive their diagnosis following an ED visit versus those who do not are not well reported in the literature. Methods: A retrospective review was conducted in which a cohort was identified of all patients who presented to the ED in a hospital system in eastern North Carolina from 10/1/2014 to 9/30/2015 with a visit associated with an oncologic ICD-9 code. The chart was reviewed to determine if the initial results that directly led to the cancer diagnosis were obtained through the ED visit. Patient characteristics, cancer characteristics, and survival outcomes were collected. Factors significant on univariate analysis were included in a multivariate analysis. Chi-square tests, Kaplan-Meier log rank tests, and Cox regression analysis were used. Results: Initial diagnosis through the ED was recorded in 38.5% of patients (n = 400/1039). Median overall survival following diagnosis was lower in individuals diagnosed through the ED (13 vs. 41 months, p &lt; 0.001), in men (21 vs. 35 months, p &lt; 0.001), and in patients with a Charlson Comorbidity Index (CCI) of ≥9 (18 vs. 37 months, p &lt; 0.001) on univariate analysis. Patients diagnosed through the ED were more likely to be Stage IV (p &lt; 0.001). There was no association on multivariate analysis between the rate of diagnosis through the ED or overall survival with insurance status or race; however, it was difficult to determine the insurance status of a patient at the time of the initial ED visit, possibly due to retroactive coverage and other issues. Conclusions: Patients who received a cancer diagnosis through the ED have significantly shorter overall survival times from diagnosis. This remained significant when controlling for CCI, gender, age, and Stage. Further investigation into the public health factors that may contribute to patients receiving their cancer diagnosis in the ED is needed. A prospective study may be needed to record the insurance status at the initial ED visit.
Molecular correlates of PD-L1 expression in patients with non-small cell lung cancer.
Authors: Hira Rizvi, Chaitanya Bandlamudi, Adam Jacob Schoenfeld, Jennifer L. Sauter, Kathryn Cecilia Arbour, Amanda Beras, Jacklynn V. Egger, Marc Ladanyi, Mark Donoghue, Charles M. Rudin, Barry S. Taylor, Matthew David Hellmann
Journal: Journal of Clinical Oncology (2019)

9018 Background: PD-L1 expression is the only FDA-approved predictive biomarker for patients with NSCLC treated with immune checkpoint inhibitors. The impact of tumor molecular profiling on tumor PD-L1 expression is not known. We hypothesized that somatic mutations and copy number alterations may be associated with distinct patterns of PD-L1 expression in patients with NSCLC. Methods: We examined patients with NSCLC in whom PD-L1 testing and targeted next-generation sequencing (MSK-IMPACT) were performed on the same tissue sample. PD-L1 expression was determined by IHC using the E1L3N antibody clone and categorized as PD-L1 high (≥ 50%), intermediate (1-49%), or negative ( &lt; 1%) expression. The association of PD-L1 with individual genes, pathways, tumor mutation burden, whole genome duplication (WGD), and aneuploidy (fraction of genome altered (FGA)) were evaluated. P-values &lt; 0.05 and q-values &lt; 0.15 were considered significant for individual genes. Results: 1023 patients with NSCLC had PD-L1 testing and MSK-IMPACT performed on the same tissue sample, 18% (n = 180) had high, 21% (n = 218) had intermediate, and 61% (n = 625) had negative PD-L1 expression. High PD-L1 expression was significantly enriched in metastatic vs primary lesions (p &lt; 0.001). There was a minor correlation between PD-L1 and TMB (spearman rho = 0.195) and PD-L1 and FGA (spearman rho = 0.11). Similar rates of WGD were found among patients with high, intermediate, and negative PD-L1 expression (p = 0.38). Mutations in KRAS and TERT were significantly enriched in PD-L1 high compared to other groups (p = 0.001, q = 0.14; p &lt; 0.001, q = 0.003). By contrast, mutations in EGFR and STK11 were associated with PD-L1 negativity (p &lt; 0.001, q = 0.001; p = 0.001, q = 0.14). Pathway analysis showed DNA repair (p &lt; 0.001), TP53 (p &lt; 0.001), and SWI/SNF (p = 0.04) pathways significantly associated with PD-L1 high compared to PD-L1 negative expression. Conclusions: The genetic features of NSCLC are associated with distinct patterns of PD-L1 expression. This data may provide insight to how the molecular phenotype can interact with the immunologic phenotype of tumors.
Host-Guest Chemistry in Supramolecular Theranostics
Authors: Guocan Yu, Xiaoyuan Chen
Journal: Theranostics (2019)

Macrocyclic hosts, such as cyclodextrins, calixarenes, cucurbiturils, and pillararenes, exhibit unparalleled advantages in disease diagnosis and therapy over the past years by fully taking advantage of their host-guest molecular recognitions. The dynamic nature of the non-covalent interactions and selective host-guest complexation endow the resultant nanomaterials with intriguing properties, holding promising potentials in theranostic fields. Interestingly, the differences in microenvironment between the abnormal and normal cells/tissues can be employed as the stimuli to modulate the host-guest interactions, realizing the purpose of precise diagnosis and specific delivery of drugs to lesion sites. In this review, we summarize the progress of supramolecular theranostics on the basis of host-guest chemistry benefiting from their fantastic topological structures and outstanding supramolecular chemistry. These state-of-the-art examples provide new methodologies to overcome the obstacles faced by the traditional theranostic systems, promoting their clinical translations.
Utilization and outcomes of high-dose chemotherapy and stem-cell rescue in patient with testicular cancer from 2005 to 2014 in United States.
Authors: Aakash Desai, Devashish Desai, Pushti Khandwala, Smith Giri, Leonard Joseph Appleman, Rahul Atul Parikh, Kathan Mehta
Journal: Journal of Clinical Oncology (2019)

e18246 Background: Testicular tumors are potentially curable by means of high-dose chemotherapy plus hematopoietic stem-cell rescue. This regimen is commonly used as salvage therapy, third-line or later therapy in patients with platinum-refractory disease. The utilization and real-world outcomes and complications of patients with testicular cancer undergoing autologous hematopoietic stem cell transplant (aHSCT) in United States are unknown. Methods: We queried National Inpatient Sample, a large inpatient data set in the United States, from 2005 to 2014 for male patients with testicular cancer or multiple myeloma (control group) receiving aHSCT and compared outcomes between these groups. The primary outcome was in-hospital mortality rate, and the secondary outcomes included in-hospital complications of aHSCT, length of stay and total charges. Outcomes were assessed by means of univariate analysis, multivariate regression and propensity score matched-pair analysis. Results: A total of 391 patients (weighted N = 1,909) with testicular cancer and 4,809 male patients (weighted N = 23,501) with multiple myeloma who underwent aHSCT from 2005 to 2014 were identified. Mean age of patients with testicular cancer was 32.3 years vs 59 years for multiple myeloma patients (p &lt; 0.001) There were no differences in in-hospital mortality rates (1.5% vs 1.4%, p = 0.85) or rates of intubation (2.3% vs 1.6%, p = 0.36), sepsis (7.7% vs 7.5%, p = 0.94), bacteremia (13.5% vs 15.6%, p = 0.42), or stomatitis (43.8% vs 38.8%, p = 0.87) between patients with testicular cancer and multiple myeloma receiving autologous HSCT. However, utilization of total parenteral nutrition was higher in patients with testicular cancer (12.9% vs 4.7%, p &lt; 0.001). There was no difference in length of stay (17.5 vs 17.5 days, p = 0.77) and total charges (121,120$ vs 123,729$, p = 0.74) between two groups. The results were consistent in multivariate and propensity score matched-pair analysis. Conclusions: The in-hospital outcomes of patients with testicular cancer receiving aHSCT appears to be similar to patients with multiple myeloma. However, overall utilization of aHSCT for testicular cancer appears to be low in United States.