tbuckley/cabot-search huggingface dataset:
Characteristics and treatment prognosis of 23 cases of male breast cancer.
Authors: Hongliang Wei
Journal: Journal of Clinical Oncology (2018)

e12595 Background: To investigate the characteristics, treatment and prognosis of male breast cancer(MBC). Methods: :A total of 23 cases of male breast cancer in our hospital from August 2006 to July 2015 were analyzed retrospectively, 113 cases of female breast cancer(FBC) treated in the same period were selected as control .We evaluated the patient's clinical data and treatment, and followed up the patient. The Kaplan-Meier methodwas employed to estimate the survival rate, the Log-rank test was adopted to compare the survivals between two groups. Results: In this study, for MBC, the median age is 60 years (36-84), the tumor size ranged 2-5cm accounted for 60.9%, patients with lymph node metastasis accounted for 34.7%, clinical stage was mainly in phase II, hormone receptor positive proportion 95.7%, Her-2 positive rate is 13%,most patients were type of luminal, the histological classification are mainly invasive ductal carcinoma which accounted for 78.3%, 52.2% of the patients had other systemic diseases,such as high blood pressure, heart disease, diabetes. These clinical features of MBC are different from that of FBC. In the treatment about MBC, 91.3%underwent modified radical mastectomy, 73.9% received adjuvant chemotherapy, 26.1% received radiotherapy, 54.5% received endocrine therapy. The 5 year survival rate and the 5 year disease-free survival rate in MBC were 86% and 75.3% respectively. These values were not significantly different from the FBC. Univariate analysis indicated that the axillary lymph nodestatus, clinical stage and endocrine therapy significantly affected the prognosis of the patients (P < 0.05).Age, comorbidities, chemotherapy and radiotherapy did not significantly affect prognosis. Conclusions: Compared with FBC,MBC were usually associated with advanced age,more complications and late stage.Histological classification are mainly invasive ductal carcinoma.Modified radical mastectomy is a widely accepted procedure. Chemotherapy and radiotherapy do not significantly improve the prognosis.Most of MBC patients are hormone receptor positive and benefit from adjuvant endocrine therapy.Tamoxifen is the first choice for endocrine therapy.
TOPACIO/Keynote-162 (NCT02657889): A phase 1/2 study of niraparib + pembrolizumab in patients (pts) with advanced triple-negative breast cancer or recurrent ovarian cancer (ROC)—Results from ROC cohort.
Authors: Panagiotis A. Konstantinopoulos, Steven E. Waggoner, Gregory A. Vidal, Monica M. Mita, Gini F. Fleming, Robert W. Holloway, Linda Van Le, Jasgit C. Sachdev, Eloise Chapman-Davis, Gerardo Colon-Otero, Richard T. Penson, Ursula A. Matulonis, Young B. Kim, Kathleen N. Moore, Elizabeth M. Swisher, Bruce Jeffrey Dezube, Jing Y. Wang, Nathan Buerstatte, Sujata Arora, Pamela N. Munster
Journal: Journal of Clinical Oncology (2018)

106 Background: Platinum-resistant OC (PROC) has few treatment options. Niraparib is an oral PARP inhibitor (PARPi) approved for maintenance treatment of ROC. Anti–programmed death (PD)–1 monotherapies (eg, pembrolizumab) have shown low level activity in ROC, and beyond BRCAmut, PARPi have shown minimal activity in PROC. Preclinical data demonstrate synergy with PARPi + anti-PD-1 combinations. Methods: Eligible pts must have experienced a response lasting ≥6 months to first-line platinum therapy and were considered to have PROC per investigator’s assessment (eg, pts not eligible for further platinum) and no more than 5 prior treatment lines. While primary platinum-refractory (PRef) disease was excluded, secondary PRef disease was not. A phase 1 study previously established RP2D of niraparib 200 mg orally once daily + pembrolizumab 200 mg IV every 21 days. Primary and secondary endpoints included objective response rate (ORR = CR+PR) and disease control rate (DCR = CR+PR+SD). Genetic biomarkers were assessed by Stand Up To Cancer (SU2C) Ovarian Cancer Dream Team. Results: As of Jan 2018, 60/62 pts were evaluable for response assessment (≥1 on-study scan). Median age was 60 years. Median prior lines of chemotherapy was 2 (range: 1-5). Based upon platinum-free interval (PFI) to last platinum treatment, 64% of pts had PROC (PFI < 6 months), 19% had PRef disease (PFI < 30 days), and 17% had platinum-sensitive (PSens; PFI ≥6 months) disease. Twenty pts remain on treatment and 11 have received treatment for ≥6 months. Among the 60 evaluable pts, ORR/DCR were 25%/68%; among the 11 tumor BRCA (tBRCA) mut evaluable pts, ORR/DCR were 45%/73%. Responses were observed in 11/38 PROC pts, 2/11 PRef pts, and 1/10 PSens pts (platinum status unknown in 1 responder). Durability of response data will be presented. Follow-up is ongoing. The most common grade ≥3 TEAEs were anemia (19%) and thrombocytopenia (9%). Conclusions: With ORR of 25% in all PROC and ORR of 45% in tBRCAmut pts, niraparib + pembrolizumab appears promising. Additional evaluation of this combination in ROC is warranted. No new safety signals were identified with the combination. Clinical trial information: NCT02657889.
Abstract 57: Effect of J Wave and QTc Prolongation on Mortality and Neurological Injury in Patients Undergoing Therapeutic Hypothermia Post Cardiac Arrest
Authors: Natasha Fonseka, Prachi U Thanawala, Martin Harari, Gregary Marhefka
Journal: Circulation (2014)

Introduction:  Early therapeutic hypothermia (TH) is standard of care to improve survival and neurological recovery in comatose cardiac arrest survivors. Electrocardiogram (ECG) changes during TH include prolongation of QT interval and development of J waves (Osborne waves). We reviewed patients who received TH to assess whether the development of QT prolongation or J waves was associated with neurologic injury and/or death.   Methods:  This is a retrospective study of 45 patients who underwent TH after cardiac arrest between 2008 and 2013. QTc intervals and the presence of J waves were confirmed and extracted from ECGs proceeding, during and after completion of TH. In hospital mortality and sustained neurologic injury were collected from medical records. Neurological injury was quantified by using cerebral performance categories scale (CPC score). Favorable neurologic outcome was defined as CPC scores of 1-2 as they reflect good cerebral performance and moderate cerebral disability, respectively. Poor neurologic outcome was defined as CPC scores of 3-5 as they reflect severe cerebral disability, vegetative state, and brain death, respectively. Impact of J waves and QTc on in hospital mortality and neurologic injury was analyzed using logistic regression model.   Results:  In this cohort, there were 24 deaths and 21 survivors. The presence of a J wave (n=14) did not have any impact on mortality at discharge [odds ratio (OR) 0.65 95% confidence interval (CI) 0.15 to 2.76 p=0.56]. QT prolongation occurred in 41 of 45 patients. QTc prolongation did not have any impact on outcome [OR 0.99 95% CI 0.97 to 1.01 p=0.24]. Over 62% of our patient cohort had poor neurologic outcome at discharge with a CPC score of 3, 4 or 5. Presence of a J wave or QTc prolongation did not have any impact on neurologic injury (OR 0.45 95% CI 0.11 to 1.88 p=0.27) and (OR 0.99 95% CI 0.98 to 1.02 p=0.67), respectively.   Conclusions:  Therapeutic hypothermia induced ECG changes of QT prolongation and J waves were not associated with neurologic injury or death in this small sample population of cardiac arrest survivors. These findings warrant further investigation in a larger population.
Acceptance and Commitment Therapy for the Management of Suicidal Patients: A Randomized Controlled Trial
Authors: Déborah Ducasse, Isabelle Jaussent, Véronique Arpon-Brand, Marina Vienot, Camelia Laglaoui, Séverine Béziat, Raffaella Calati, Isabelle Carrière, Sébastien Guillaume, Philippe Courtet, Emilie Olié
Journal: Psychotherapy and Psychosomatics (2018)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; The management of suicidal crisis remains a major issue for clinicians, driving the development of new strategies to improve suicide prevention. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We conducted a randomized controlled trial comparing a 7-week acceptance and commitment therapy (ACT) versus relaxation group, as adjunct to treatment as usual for adult outpatients suffering from a current suicidal behavior disorder. The primary outcome was the rate of change in the Columbia Suicide Severity Rating Scale suicidal ideation subscore (adding severity and intensity subscores). Secondary outcomes were the rates of change for depressive symptomatology, psychological pain, anxiety, hopelessness, anger, quality of life, and therapeutic processes. Assessments were performed in the 2 weeks preceding the beginning of the treatment (pretreatment assessment), and within 1 week (posttherapy assessment) and 3 months (follow-up assessment) after therapy completion. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Forty adults were included and randomized. The rate of change in ACT for suicidal ideation at the posttherapy assessment was higher than in the relaxation group (β [SE] = –1.88 [0.34] vs. –0.79 [0.37], respectively; &lt;i&gt;p&lt;/i&gt; = 0.03). ACT effectiveness remained stable at the 3-month follow-up. We found a similar pattern of change for depressive symptomatology and anxiety, psychological pain, hopelessness, anger, and quality of life. Therapeutic processes improved more in the ACT group than in the relaxation group. Treatment adherence was high in the ACT group, all participants reported satisfaction with the program. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Through its effectiveness in reducing suicidal ideation and improving the clinical dimensions associated with suicidal risk in patients suffering from a suicidal behavior disorder, ACT could be developed as an adjunctive strategy in programs for suicide prevention.
Hijacking a key chromatin modulator creates epigenetic vulnerability for MYC-driven cancer
Authors: Zhenhua Yang, Kushani Shah, Theodore Busby, Keith Giles, Alireza Khodadadi-Jamayran, Wei Li, Hao Jiang
Journal: Journal of Clinical Investigation (2018)

While the genomic binding of MYC protein correlates with active epigenetic marks on chromatin, it remains largely unclear how major epigenetic mechanisms functionally impact the tumorigenic potential of MYC. Here, we show that, compared with the catalytic subunits, the core subunits, including DPY30, of the major H3K4 methyltransferase complexes were frequently amplified in human cancers and selectively upregulated in Burkitt lymphoma. We show that DPY30 promoted the expression of endogenous MYC and was also functionally important for efficient binding of MYC to its genomic targets by regulating chromatin accessibility. Dpy30 heterozygosity did not affect normal animal physiology including lifespan, but significantly suppressed Myc-driven lymphomagenesis, as cells failed to combat oncogene-triggered apoptosis as a result of insufficient epigenetic modulation and expression of a subset of antiapoptotic genes. Dpy30 reduction also greatly impeded MYC-dependent cellular transformation, without affecting normal cell growth. These results suggest that MYC hijacks a major epigenetic pathway - H3K4 methylation - to facilitate its molecular activity in target binding and to coordinate its oncogenic program for efficient tumorigenesis, meanwhile creating "epigenetic vulnerability." DPY30 and the H3K4 methylation pathway are thus potential epigenetic targets for treating certain MYC-driven cancers.
Effect of induction chemotherapy with cisplatin, fluorouracil, with or without taxane on locoregionally advanced nasopharyngeal carcinoma: a retrospective, propensity score‐matched analysis
Authors: Guo‐Ying Liu, Xing Lv, Yi‐Shan Wu, Min‐Jie Mao, Yan‐Fang Ye, Ya‐Hui Yu, Hu Liang, Jing Yang, Liang‐Ru Ke, Wen‐Ze Qiu, Xin‐Jun Huang, Wang‐Zhong Li, Xiang Guo, Yan‐Qun Xiang, Wei‐Xiong Xia
Journal: Cancer Communications (2018)

Abstract Background Available data in the literature comparing different induction chemotherapy (IC) regimens on locoregionally advanced nasopharyngeal carcinoma (NPC) are scarce. The purpose of the present study was to evaluate the outcomes of locoregionally advanced NPC patients who were treated with taxane, cisplatin and 5‐fluorouracil (TPF) or cisplatin and 5‐fluorouracil (PF) as IC followed by concurrent chemoradiotherapy (CCRT). Methods In total, 1879 patients with locoregionally advanced NPC treated with IC and CCRT from a prospectively maintained database were included in the present observational study. We compared overall survival (OS), disease‐specific survival (DSS), distant metastasis‐free survival (DMFS), and locoregional relapse‐free survival, using the propensity score method. Results In total, 1256 patients received TPF or PF as IC backbone. The TPF group showed significantly better OS (hazard ratio [HR], 0.660; 95% confidence interval [CI] 0.442–0.986; P = 0.042), DSS (HR, 0.624; 95% CI 0.411–0.947; P = 0.027) and DMFS (HR, 0.589; 95% CI 0.406–0.855; P = 0.005) compared with the PF group in multivariable analyses. Propensity score matching identified 294 patients in each cohort and confirmed that TPF was associated with significantly improved 5‐year OS (88.1% vs. 80.7%; P = 0.042), DSS (88.5% vs. 80.7%; P = 0.021) and DMFS (87.9% vs. 78.6%; P = 0.012) rates compared with the PF group. There were no significant differences in locoregional relapse‐free survival before or after matching. Conclusions In our study, IC with the TPF regimen combined with CCRT showed improved long‐term survival for the patients with locoregionally advanced NPC compared with the PF regimen. However, a prospective randomized clinical trial to validate these findings is necessary.
Implications of the 21-gene recurrence score assay (Oncotype DX) on adjuvant treatment decisions in ER-positive early-stage breast cancer patients: Experience of Kuwait Cancer Control Center.
Authors: Mohamed Salah Fayaz, Heba Eissa, Gerges Attia Demian
Journal: Journal of Clinical Oncology (2018)

e12582 Background: To evaluate the impact of Oncotype DX as a tool for adjuvant treatment decision of ER-positive, early stage breast cancer patients diagnosed in Kuwait and to determine which clinicopathological criteria derived the greatest advantage Methods: This retrospective study was designed to review patients with ER-positive, HER2−negative, stage I–IIIA, N0/N1 breast cancer who were tested for Oncotype Dx and treated in Kuwait Cancer Control Center. We used McNemar test to assess the association of Recurrence Score results with the changes in the treatment decisions. Results: Between January 2011 and October 2017, 100 patients at a median age of 50 years (range 38-74 years) were included. The TNM stage distribution was 34, 63 and 3 patients for stage I, II and IIIA respectively. Ki67 was available in 89 patients, 51 had Ki67 ≤ 15% and 38 patients had Ki67 > 15%. Fifty-four patients had Luminal A and 46 had luminal B tumors. The Recurrence Score results were low, intermediate and high risk in 54, 34 and 12 patients respectively. Before the test results, adjuvant chemoendocrine therapy was recommended for 46 patients while 54 were advised for endocrine therapy, according to the multidisciplinary team consensus. After getting the test results, 25 patients received chemoendocrine therapy (1,12 and 12 patients in the low, intermediate and high risk groups respectively) and 75 received endocrine treatment. Treatment change was documented in 37 patients (8 patients from endocrine to chemoendocrine therapy and 29 from chemoendocrine to endocrine treatment; p = 0.001, McNemar test). Treatment change was significant among patients ≤ 50 years (p = 0.002), luminal B tumors (p < 0.0001), stage II&IIIA disease (p < 0.0001) and node positive disease (p = 0.002). At a median follow-up of 12 months (3-75 months), one patient in the low risk group developed systemic relapse. Conclusions: Oncotype DX testing resulted in significant changes in the adjuvant treatment decisions in ER-positive, HER2-negative early breast cancer particularly in the case of young patients, Luminal B tumors, N1 disease and stage II-IIIA disease.
Robotic surgery for rectal cancer: Short-term and oncological outcomes for 607 consecutive patients.
Authors: Akio Shiomi, Tomohiro Yamaguchi, Hiroyasu Kagawa, Yushi Yamakawa, Akinobu Furutani, Yusuke Yamaoka, Shoichi Manabe, Yusuke Ogi, Hitoshi Hino, Yoshinobu Nagasawa
Journal: Journal of Clinical Oncology (2018)

756 Background: Conventional laparoscopic surgery (CLS) for rectal cancer has several inherent technical difficulties, including a limited range of motion of the instruments.Robot-assisted laparoscopic surgery (RALS) has some technical advantages over CLS because it improves dexterity with an increased range of movements at the tips of the instruments. The purpose of this study was to evaluate the short-term and oncological outcomes of RALS for rectal cancer, including robotic, autonomic nerve-preserving, lateral lymph node dissection (RALLD), a new, technically challenging procedure. Methods: Between December 2011 and August 2017, 607 consecutive patients underwent RALS for rectal cancer. Surgical outcomes, pathological results, and oncological results were investigated retrospectively. Results: There were 403 males and 204 females; 577 patients had adenocarcinoma, 19 had carcinoid tumor, 8 had GIST, and 2 had other malignant tumor. The types of procedures performed were: 453 anterior resections, 93 intersphincteric resections, and 61 abdominoperineal resections. RALLD was performed in 202 patients (33.3%). Preoperative chemoradiotherapy was performed in 34 patients. The overall median operative time was 257(109-683) min. In cases without RALLD, the median operative time was 217 (109-545) min, while median operative time was 420 (162-683) min with RALLD. None of the cases was converted to an open or laparoscopic procedure.There was no surgical mortality. The overall complication rate for Clavien-Dindo classification grade III-IV was 3.0%. The oncological results for 279 patients with primary rectal adenocarcinoma, operated before December 2014 was also investigated (Stage I/II/III 115/48/116). The 5-year overall survival was 96.6%, the 3-year relapse free survival was 88.3%, and 3-year local relapse free survival was 98.5%. The 3-year RFS of pStage I/II/III was 96.2/89.6/79.6% respectively. Conclusions: RALS for rectal cancer is a feasible procedure with low morbidity and a low conversion rate, and acceptable oncological results.
Circular RNA-ZNF609 regulates retinal neurodegeneration by acting as miR-615 sponge
Authors: Jia-Jian Wang, Chang Liu, Kun Shan, Bai-Hui Liu, Xiu-Miao Li, Shu-Jie Zhang, Rong-Mei Zhou, Rui Dong, Biao Yan, Xing-Huai Sun
Journal: Theranostics (2018)

Glaucoma is a major cause of visual impairment characterized by progressive retinal neurodegeneration.Circular RNAs are a class of endogenous noncoding RNAs that regulate gene expression in eukaryotes.In this study, we investigated the role of cZNF609 in retinal neurodegeneration induced by glaucoma.Methods: qRT-PCR and Sanger sequencing were conducted to detect cZNF609 expression pattern during retinal neurodegeneration.Immunofluorescence staining was conducted to detect the effect of cZNF609 silencing on retinal neurodegeneration in vivo.MTT assay, Ki67 staining, and PI staining were conducted to detect the effect of cZNF609 silencing on retinal glial cells and RGC function in vitro.Bioinformatics analysis, RNA pull-down assays, and in vitro studies were conducted to reveal the mechanism of cZNF609-mediated retinal neurodegeneration.Results: cZNF609 expression was significantly up-regulated during retinal neurodegeneration.cZNF609 silencing reduced retinal reactive gliosis and glial cell activation, and facilitated RGC survival in vivo.cZNF609 silencing directly regulated Müller cell function but indirectly regulated RGC function in vitro.cZNF609 acted as an endogenous miR-615 sponge to sequester and inhibit miR-615 activity, which led to increased METRN.METRN overexpression could partially rescue cZNF609 silencing-mediated inhibitory effects on retinal glial cell proliferation.Conclusion: Intervention of cZNF609 expression is a promising therapeutic strategy for retinal neurodegeneration.
Risk prediction model for heart disease among endometrial cancer survivors.
Authors: Mia Hashibe, Brenna Blackburn, Jihye Park, Kerry G. Rowe, John Snyder, Yuan Wan, Vikrant Deshmukh, Michael Newman, Alison M Fraser, Ken R Smith, Kim Herget, Theresa Louise Werner, Veronica Wendy Setiawan, Nan Hu, Patricia A. Ganz, David K. Gaffney, Yuan-Chin Amy Lee
Journal: Journal of Clinical Oncology (2018)

120 Background: There are an estimated 760,000 endometrial cancer survivors alive in the US today. We previously reported on increased heart disease (HD) risk among endometrial cancer survivors from our population-based cohort study. Although there are many risk prediction models for the risk of endometrial cancer, there are none to our knowledge for endometrial cancer survivors. Methods: We identified 2,994 endometrial cancer patients in the Utah Population Database, which links data from multiple statewide sources. We estimated hazard ratios with the Cox proportional hazards model for predictors of five-, ten- and fifteen-year risks. The Harrell’s C statistic was used to evaluate the model performance. We used 70% of the data randomly selected to develop the model and the rest of the data to validate the model. Results: A total of 1,591 patients were diagnosed with HD. Increased risks of HD among endometrial cancer patients were observed for older age, obesity at baseline, family history of HD, previous disease diagnosis (hypertension, diabetes, high cholesterol, COPD), distant stage, grade, histology, chemotherapy, and radiation therapy. The C-statistics for the risk prediction model were 0.69 for the hypothesized risk factors for HD, 0.56 for clinical factors, and 0.71 when statistically significant risk factors were included. With the final model selected, as one example, the absolute risks of HD were 17.6% at 5-years, 24.0% at 10-years and 32.0% at 15 years for a woman diagnosed with regional stage, grade I endometrial cancer in her fifties, was white, was obese at cancer diagnosis, had a family history of HD but no previous history of HD herself, had hypertension, but no history of diabetes or high cholesterol or COPD, and had radiation therapy treatment but no chemotherapy. The AUCs were 0.79 for the 5-year, 0.78 for the 10-year and 0.78 for the 15-year predictions. Conclusions: We developed the first risk prediction model for HD among endometrial cancer survivors within a population-based cohort study. Risk prediction models for cancer survivors are important in understanding long-term disease risks after cancer treatment is complete. Such models may contribute to management plans for treatment and individualized prevention efforts.