tbuckley/cabot-search huggingface dataset:
The protective effect of physical activity on risk of hepatocellular carcinoma in USA.
Authors: Ahmed S Shalaby, Gehan Botrus, Ahmed Omar Kaseb, Donghui Li, Reham Abdel-Wahab, Robert A. Wolff, Sahin Lacin, Milind M. Javle, Ernest Hawk, Manal Hassan
Journal: Journal of Clinical Oncology (2016)

e15642 Background: In the United States, the incidence of hepatocellular carcinoma (HCC) has been tripled over the last two decades. Despite the overwhelming effect of environmental risk factors of this cancer, the impact of physical activity on HCC is unclear. The current study aimed at addressing such association in USA. Methods: Under the IRB approval from University of Texas m D Anderson Cancer Center, we conducted hospital-based case-control where cases are pathological or radiological diagnosed with HCC. Controls are spouses of patients at M. D. Anderson who had cancers other than GI cancers. Between 2005 and 2014 total of 660 cases and 629 controls were enrolled. Cases and controls were interviewed for past history of moderate and vigorous physical activity. Subjects were also interviewed for lifetime activity of their jobs and how they describe their lifestyle at work and free time. We performed multivariate logistic regression analyses to estimate adjusted odds ratio (OR) and 95% confidence interval (CI). The estimated ORs were adjusted for age, race, diabetes, prior history of obesity, hepatitis C virus, hepatitis B virus, cigarette smoking, alcohol drinking, and family history of cancer. Results: Rare engagement in moderate and vigorous activity was frequently reported by HCC cases than by healthy controls (17% versus 9% for moderate activity, P= .0001; 46% versus 29% for vigorous activity, P= .001). Heavy engagement in physical activity was associated with 56% reduction in HCC risk where the estimated OR (95% CI) was 0.44 (.28-.68). Yet job activity was not associated with risk reduction. Moreover, moderate or vigorous lifestyle activity at work or free time was not associated with HCC prevention as compared to lifestyle with sedentary or light activity. The estimated ORs (95% CI) were .72 (.52-1.0) and 1.1 (.64-1.82) for moderate and vigorous lifestyle respectively. Conclusions: This study showed that physical activity not the job-or lifestyle-related activity is independently associated with HCC prevention. Our findings was supported by the protective effect of physical activity on fatty liver development and progression, the mechanism of protective effect of physical activity on HCC risk should be studied by future trials.
The safety profile of a selective EGFR TKI epitinib (HMPL-813) in patients with advanced solid tumors and preliminary clinical efficacy in EGFRm+ NSCLC patients with brain metastasis.
Authors: Qing Zhou, Bin Gan, Liwei Yuan, Ye Hua, Yi-Long Wu
Journal: Journal of Clinical Oncology (2016)

e20502 Background: Epitinib is a selective EGFR-TKI designed for optimal brain penetration. In preclinical species, epitinib demonstrated favorable drug exposures in the brain and is warranted clinical investigation for CNS tumors with EGFRm+ such as NSCLC brain metastases. Methods: This is a first-in-human study. Patients with advanced solid tumors were enrolled in dose escalation phase. In expansion phase, only EGFRm+ NSCLC patients with brain metastases were eligible. Epitinib was administered orally q.d. Dose escalation started at 20 mg and followed a classic 3+3 design. All patients were assessed for AEs/ DLTs, PK, and tumor response. Results: A total of 36 patients were enrolled in dose escalation phase at 7 dose levels up to 240 mg. No DLT was observed. Although MTD was not reached, 160 mg q.d. was selected as the RP2D. The most common AEs were skin rash (60.0%), diarrhea (34.3%), elevated AST (34.3%)/ALT (31.4%) and hyperbilirubinemia (28.6%). AEs of Elevated AST (2.9%)/ALT (2.9%) and hyperbilirubinemia(5.7%) were grade 3. Among 34 evaluable patients, one (2.9%) patient (80 mg cohort, EGFRm+ and TKI naïve) reached PR with a duration of response over 36 months. Epitinib drug exposure increased proportionally up to 160 mg and appeared to plateau above 160 mg. The average T 1/2 ranged between38 and54h. A dose expansion study in EGFRm+ NSCLC patients with brain metastases is ongoing. As of 30 Oct, 2015, 12 patients were treated with epitinib at 160 mg q.d. Among 12 evaluable patients, 5 reached PR (all treatment naïve) and showed dramatic shrinkage of brain lesions. The rest 5 prior -TKI treated patients had SD in the brain. 2 progression events observed with one in liver and the other in brain, respectively. Conclusions: Epitinib was well tolerated in patients with advanced solid tumors. Its safety profile is consistent to EGFR-TKIs. The RP2D of 160 mg q.d. was selected based on safety, PK and preliminary efficacy data. Clear clinical efficacy was observed in untreated EGFRm+ NSCLC patients with brain metastases. Taken together, these data support further development of epitinib for the treatment of EGFRm+ NSCLC patients with brain metastasis. Clinical trial information: NCT02590952.
Postoperative chemotherapy or no further treatment for patients with node-negative stage I-II intermediate or high risk endometrial cancer: The ENGOT-EN2/DGCG trial.
Authors: Mansoor Raza Mirza, Caroline Lundgren, Frederic Kridelka, Annamaria Ferrero, Stefano Greggi, Rene dePont Christensen, Ana Santaballa, Pamela T. Soliman, Tally Levy, Jalid Sehouli, David Cibula, Annika Auranen, Bente Lund, Eva Roennengart, Frederic Amant
Journal: Journal of Clinical Oncology (2017)

TPS5613 Background: Patients with medium and high-risk stage I and II endometrial cancers (EC) have, despite radical surgery, a high risk for progression. Adjuvant brachytherapy or EBRT is the traditional therapy for many decades although without impacting on survival. Several studies have failed to demonstrate superiority of adjuvant chemotherapy in unselected population with a high number of low-risk patients. It is of utmost importance to demonstrate efficacy of adjuvant combination chemotherapy in a randomized trial comparing to no further treatment in the medium and high-risk node negative stage I and stage II patients. Methods: The primary objective of this trial is to evaluate the effect on overall survival of carboplatin-paclitaxel combination chemotherapy against no further systemic treatment. Key eligibility criteria include: histologically confirmed EC, stage I grade 3 endometrioid adenocarcinoma or stage II endometrioid adenocarcinoma or stage I and II type 2 histology (clear cell, serous, squamous cell carcinoma, carcinosarcoma or undifferentiated carcinoma); prior surgery with pelvic lymphadenectomy or sentinel lymph node biopsy. Patients may receive vaginal brachytherapy in both arms. 240 patients are randomized to receive six courses of adjuvant carboplatin (AUC5) and paclitaxel (175mg/m2) combination on day one every 21 days or no further treatment (1:1 randomization). Primary endpoint is overall survival of endometrioid subgroup. Secondary endpoints include overall survival of whole study population, disease specific survival, progression-free survival, toxicity, compliance, Quality of Life (assessed via EORTC QLQ-C30 and EORTC QLQ-EN24), rate of isolated pelvic or distant relapses, as well as mixed relapses. Trial is enrolling patients. The following cooperative groups are participating: DGCG (DK), NSGO (DK, FIN, SWE), BGOG (BEL), MaNGO (ITA), MITO (ITA), GEICO (SPA), NOGGO (GER), CEEGOG (Czech), ISGO (ISR) &amp; MDACC (USA). Clinical trial information: NCT01244789.
Favorable Outcome With Pemetrexed Treatment for Advanced BRAF-V600E-Positive Lung Adenocarcinoma in a Patient Followed up Over 8 Years
Authors: Yoko Nakanishi, Yoshiko Nakagawa, Ichiro Tsujino, Tetsuo Shimizu, Noriaki Takahashi, Shu Hashimoto, Shinobu Masuda
Journal: Journal of Thoracic Oncology (2018)
Association of biomarkers of insulin resistance and inflammation with skeletal muscle index (SMI) in stage IV non-small cell lung cancer (NSCLC).
Authors: Marta Batus, Samantha Kerns, Selina Sayidine, Cristina L. Fhied, Sanjib Basu, Philip Bonomi, Jeffrey Allen Borgia, Mary J. Fidler, Palmi Shah
Journal: Journal of Clinical Oncology (2016)

10013 Background: The aim of this project was to correlate pretreatment levels of circulating biomarkers of insulin resistance and inflammation with sarcopenia in stage IV NSCLC patients receiving platinum doublet chemotherapy. For this, a skeletal muscle index was evaluated at L1 in baseline CT images to serve as a surrogate for sarcopenia. Methods: Pretreatment serum from 93 patients with frontline stage IV NSCLC was evaluated for 13 metabolism biomarkers with the Bio-Plex Pro Human Diabetes Assay Panel and 20 inflammation-related biomarkers using the Milliplex Human High Sensitivity T Cell Panel. All patients were treated with standard platinum doublet based chemotherapy. All patients had SMI calculated from baseline CT images using the Slice-O-Matic software package (Tomovision); where SMI = (muscle cross sectional area in cm2) / height in m2. Associations of biomarkers with SMI were assessed using a Spearman’s Rank Correlation Coefficient. The Log-Rank test was performed to evaluate the association of individual biomarkers with overall survival (OS). Results: High levels of C-peptide and adipsin were associated with favorable OS and increase in baseline SMI (see Table). Low levels of ghrelin were inversely associated with SMI values and associated with favorable OS. High levels of adiponectin (with low levels of adiponectin being correlating with obesity in the literature) were associated with good OS and diminished SMI. Conclusions: High values of several biomarkers of insulin resistance and inflammation were associated with both a shortened survival and sarcopenia in frontline NSCLC patients receiving platinum double therapy. These findings suggest a certain subset of patients that may have improvements in cancer cachexia by targeting insulin resistance and inflammation. Biomarkers SMI Log-Rank test Spearman Correlation p-value p-value Adiponectin -0.413 3.88E-05 0.362 Ghrelin -0.238 0.021 0.0053 C-Peptide 0.198 0.056 0.0149 Adipisin 0.389 0.0001 0.0148
TCT-239 Impact of Post-stenting Balloon Dilatation on 5-year Clinical Outcomes in Patients with Acute Coronary Syndrome underwent Percutaneous Coronary Intervention
Authors: Kareem Abdelshafi, Seung-Woon Rha, Ji Young Park, Byoung Geol Choi, Se Yeon Choi, Jae Kyeong Byun, None Ahmed Mashaly, Yoonjee Park, Won Young Jang, Woo Hyeun Kim, Eun Jin Park, Ja Yeon Choi, Jin Oh Na, Cheol Ung Choi, Eung Ju Kim, Chang Gyu Park, Hong-Seog Seo
Journal: Journal of the American College of Cardiology (2018)
Effect of cabazitaxel regimens on the growth of prostate cancer cells and the antitumor properties of PEDF.
Authors: Stephanie Filleur, Courtney Jarvis, Dalia Martinez-Marin, Thomas Nelius
Journal: Journal of Clinical Oncology (2018)

e24002 Background: Taxanes-based chemotherapies represent the major therapeutic alternative for symptomatic mCRPC. While docetaxel is the most commonly prescribed Taxane for mCRPC; cabazitaxel has been approved for patients unresponsive to docetaxel. Still mCRPC remains incurable and patients often experience severe side effects. Recently, the FIRSTANA trial showed no superiority in overall survival between cabazitaxel and docetaxel in mCRPC patients. Inversely, different toxicity profiles were reported suggesting that cabazitaxel may be used as first line treatment option for certain patients. Thus, a deeper characterization of cabazitaxel’ modes of action as well as a reevaluation of its conventional dose and schedule are necessary. In this study, our goal was therefore to evaluate the anti-tumor efficacy of various cabazitaxel regimens delivered as monotherapy or in combination with PEDF, a known anti-angiogenic and anti-neoplastic agent. Methods: CRPC cells undergoing Taxane were evaluated for cell proliferation, migration, death, and apoptosis using crystal violet staining, chemotaxis, cell cycle and TUNEL assays. In vitro data were validated in CL1 CRPC xenografts where mice received intermittent (5mg/kg; ev. 4d) or metronomic low-doses (1mg/kg, d1-10; 0.5mg/kg, ev. other day; 0.1mg/kg, ev. day) cabazitaxel +/-PEDF. Results: We found that cabazitaxel inhibits the proliferation of CRPC cells with a higher efficacy than docetaxel in vitro. As expected, high-doses of Taxanes blocked the cells in mitosis. Surprisingly, low-doses of cabazitaxel induced more cell death than docetaxel mainly through apoptosis. In vivo, intermittent cabazitaxel lead to disease stabilization when combined with PEDF. Unexpectedly, low-doses of cabazitaxel delayed tumor growth with severe toxicity for some of the doses tested. Other results showed that PEDF and low-doses of cabazitaxel combination inhibited the migration of tumor cell and increased the tumoricidal activity of macrophages toward CRPC cells. Conclusions: Our findings highlight the great promise of cabazitaxel and predict a possible move of cabazitaxel forward within the therapeutic sequence of mCRPC.
Prediction model for cervical lymph node metastasis using CT characteristics in patients with head and neck squamous cell carcinoma.
Authors: Young Jun Choi, Mi Sun Chung, Jeong Hyun Lee
Journal: Journal of Clinical Oncology (2017)

e17547 Background: Lymph node metastasis is a major prognostic determinant for patients with head and neck squamous cell cancer (HNSCC). This study aimed to construct a predictive model using CT characteristics of lymph node and tumor for patients with HNSCC to stratify the risk of lymph node metastasis. Methods: The study population was obtained from historical cohort of 472 cervical lymph nodes from 191 patients with HNSCC in a tertiary referral hospital. We analyzed preoperative CT images of lymph nodes according to diameter, ratio of long-to-short axis diameter, necrosis or cystic change, conglomeration, infiltration to adjacent soft tissue, and laterality (ipsilateral vs contralateral) and analyzed T stage. Reference standard was surgical pathologic results. Multivariate logistic regression analysis was performed to predict whether nodules were diagnosed as metastasis or benign. Results: CT features of lymph nodes, including minimal axial diameter, ratio of long-to-short axis diameter, necrosis or cystic change, and T stage were selected as predictors for lymph nodes metastasis. A 10-point risk scoring system was developed, and the risk of malignancy ranged from 7.3% to 99.8%, which was positively associated with increases in risk scores. The areas under the receiver operating characteristic curve of the development and validation sets were 0.886 and 0.879, respectively. Conclusions: We have devised a simple predictive model using the CT characteristics of lymph nodes and tumor for HNSCC to stratify the risk of cervical lymph node metastasis. [Table: see text]
Abstract P109: Racial/Ethnic Disparities in Post-Stroke Disability: A Focus on Outcome Measures
Authors: Suzanne Burns, Brandi White, Gayenell Magwood, Charles Ellis, Ayaba Logan, Joy Buie, Daniel Lackland, Robert Adams
Journal: Circulation (2018)

Background and Purpose: Several studies suggest that racial/ethnic minority groups experience worse disability across the course of stroke recovery. However, there is little consistency in the measurement of stroke outcomes, which may contribute to some inconclusive evidence of racial/ethnic disparities in post-stroke disability. The objective of the current review is to examine how stroke outcomes are measured to identify racial/ethnic disparities in disability and functioning among stroke survivors in the US. Methods: A review of the literature was conducted to identify outcome measures used in racial/ethnic disparities in post-stroke disability literature, use the International Classification of Functioning, Disability, and Health (ICF) model as a frame of reference for mapping the contents of the identified measures, and evaluate the time points of measured outcomes and racial/ethnic representation. Articles published between January 2001 and July 2017 were identified with our search criteria through Scopus, PubMed, CINAHL, and PsycINFO according to predefined inclusion criteria. Results: One hundred and ninety-four articles met inclusion criteria for full-text review and 41 articles were included in the final review. Although we found evidence of outcome measure content aligning with all ICF domains, little research has examined contextual factors in post-stroke disability disparities research. Additionally, we discovered the outcome measures are conducted across stroke recovery trajectories including pre-stroke, acute stroke, early recovery (≤90 days), and long-term (&gt;90 days) but little consistency in outcome measure use was discovered. African American and Hispanic populations were assessed most frequently and minimal studies examined disparities among other minority populations comprising the US (i.e., Asian, Native Hawaiian or Other Pacific Islander, American Indian or Alaska Native). Conclusions: A variety of outcome measures have been used to assess disparities in disability across the course of stroke recovery. Yet, the lack of consistency in what outcomes are measured and when specific outcomes are assessed may contribute to mixed findings in the racial/ethnic disparities literature. Additional concerns include the lack of evidence on validity of outcome measures among racial/ethnic minority populations, the lack of representation among all racial/ethnic populations comprising the US, and minimal emphasis placed on the disparities in personal and environmental factors that contribute to disability. This review sheds light on the need for additional disparities in post-stroke disability research focusing on contextual factors and greater representation among less studied populations in the US.
Ovarian preservation among women with early stage cervical cancer. A retrospective evaluation of the incidence of ovarian metastasis.
Authors: Jimmy A Billod, Efren Javier Domingo
Journal: Journal of Clinical Oncology (2018)

e17504 Background: Cervical is the second most common cancer affecting Filipino women with the incidence rising among young women. This review looked into the incidence of ovarian metastasis among patients with early stage cervical cancer managed with radical hysterectomy. It also evaluated how many of these women needed to receive adjuvant radiation post-surgery. Methods: This was a 10 –year review of all histopathologic reports of patients with cervical cancer who were primarily managed with radical hysterectomy. Results: A total of 224 patients underwent radical hysterectomy, 12 patients had previous neoadjuvant chemotherapy hence excluded from the study. A total of 212 patients were included in the analysis. Majority had a final histopathologic diagnosis of squamous cell carcinoma and adenocarcinoma at 68% and 29%, respectively. About 3 % comprised the poor histologic types. The reported rates of metastasis to the parametria, corpus, fallopian tubes and nodes were 1.4%, 7.1%, 0.5%, and 10%, respectively. This study showed zero ovarian metastasis in all histologic types. Despite no reported ovarian metastasis in these group of patients, 75% of them required adjuvant therapy after primary surgery. Conclusions: This review revealed that the incidence of local metastasis in early stage cervical cancer is relatively low. However, if present, tumor size is consistently associated with local metastasis. Ovarian metastasis is nil among these group of patients. Ovarian preservation may be a practical option for young patients with early stage cervical cancer to prevent surgical menopause, with a consideration of transposition of the ovaries for patients who will receive adjuvant radiation. Premature ovarian failure associated with adjuvant radiation needs to be considered. Proper counseling and informed consent should be obtained in the treatment planning. The limitation of this report is of its retrospective design; henceforth a more extensive sectioning of the ovary is recommended so as not to miss occult metastasis. A prospective study would be necessary to validate the results of these retrospective reports.
Allogeneic transplant leads to markedly improved survival in older patients with AML.
Authors: Curtis Andrew Lachowiez, Rachel J. Cook, Gabrielle Meyers
Journal: Journal of Clinical Oncology (2017)

7048 Background: AML is a disease of the elderly, and outcomes with standard treatment are dismal. Allogeneic transplant is the only curative therapy for most patients with AML. Recent work has shown age is not a factor in transplant outcomes, and should not be a limiting factor for transplant. The treatment pathway for older patients with AML should take into account their disease risk, comorbidities, and treatments with a proven survival advantage. We investigated our institutional experience to help guide the establishment of optimal pathways for patients. Methods: We conducted a retrospective analysis of 118 patients over age 65 with AML treated at our institution between 2010-2015. Patients receiving therapy (n = 90) were categorized into two groups: intensive induction therapy (7+3 based) or induction therapy with a hypomethylating agent. The groups were well matched in regard to comorbidities. Results: In poor risk patients, complete remission (CR) was achieved in 42% (n = 30/71). Select patients up to age 75 proceeded to allogeneic transplant if they achieved CR. Survival in CR1 was higher in the transplant (n = 22, median 719 days, 95% CI: 366-1071 days), than in the non-transplant group (n = 8, median 257 days, 95% CI: 92-421 days, p-value &lt; .001). In analyzing all risk groups, overall survival was superior in transplant (median 1188 days) versus non-transplant recipients (median 185 days) (see 1, 2, and 3 year survival in table). No difference in median survival occurred based on age at induction (older than 70: n = 9, younger than 70: n = 16, p-value = 0.316). There was no difference in median survival based on chemotherapy regimen without transplant: intensive induction (n = 24, survival 250 days, p-value 0.179) compared to hypomethylating agents (n = 22, survival 139 days). Conclusions: We confirm that transplant can be safely performed in patients over 70 years of age, and highlight the survival advantage of transplant to chemotherapy alone. Additionally, our data found no survival benefit of hypomethylating agents in elderly patients with poor risk AML.[Table: see text]