tbuckley/cabot-search huggingface dataset:
Prognostic effects of 25-hydroxyvitamin d levels in gastric cancer.
Authors: Chao Ren, Rui-hua Xu
Journal: Journal of Clinical Oncology (2012)

e14653 Background: Results from large epidemiologic studies on the association between vitamin D and gastric cancer are controversial. Vitamin D significantly promotes apoptosis in the undifferentiated gastric cancer cell, but the prognostic effects of its levels are unknown. Methods: 197 gastric carcinoma patients who received treatment in the cancer centre of Sun Yat-sen University from January 2002 to January 2006 were involved in the study. The stored blood drawn before any treatment was assayed for 25-hydroxyvitamin D levels. The clinicopathologic data were collected to examine the prognostic effects of vitamin D. Results: The mean vitamin D levels of the 197 gastric patients was 49.85±23.68nmol/L, among whom 114(57.9%) were deficient in Vitamin D(&lt;50nmol/L), 67(34%) were insufficient (50-75nmol/L) and 16(8.1%) were sufficient (&gt;75nmol/L). Clinical stage (p=0.004) and lymph node metastasis classification (p=0.009) were inversely associated with vitamin D levels. The patients with high vitamin D levels group (≥50nmol/L) had a higher overall survival compared with the low vitamin D levels group (&lt;50nmol/L)(p=0.018). Multivariate analysis indicated that vitamin D levels were an independent prognostic factor of gastric cancer (p=0.019). Conclusions: Vitamin D deficiency may be associated with poor prognosis in gastric cancer.
Screening for psychosocial distress: A transformative journey.
Authors: Terri Stuart-McEwan, Alyssa Macedo, Gary Rodin, Sabira Bagha, Yvonne Leung, Lindsay McColl, Alexis Twiddy, Kathy Davison, Madeline Li
Journal: Journal of Clinical Oncology (2016)

e18176 Background: Routine use of patient reported outcomes for psychosocial distress screening has been internationally advocated by cancer care organizations. In response, Princess Margaret (PM), Canada’s largest comprehensive cancer centre, established the Distress Assessment and Response Tool (DART) as a clinical standard of care. DART is an electronic distress screening tool that detects patients’ physical, emotional and practical needs, and is linked to inter-professional collaborative care pathways. With 100 tablet computers in clinic and over 300,000 screens completed to date, DART is one of the largest single institution psychosocial distress screening programs worldwide. This abstract outlines key quality improvement strategies to support successful integration of DART into standard care and its transformative impact on care delivery. Methods: DART implementation began with a pilot in 2010 with graded expansion to all 15 disease sites by 2012. Several quality improvement strategies were implemented including creation of standardized screening processes, and utilization of audit and feedback tools such as Monthly Performance Report Cards, and Symptom Prevalence Update Reports. Positive behaviour was reinforced with the establishment of a champion program. Results: Since 2013, PM has maintained screening rates above the provincial 70% target. The DART program is associated with high levels of clinician satisfaction and site based accountability. Patient satisfaction with clinician response to emotional and physical distress remains high, at 93% and 97%, respectively. Preliminary findings suggest that clinician response to threshold distress was associated with increased patient completion of planned chemotherapy cycles (p < 0.01, n = 66), and increased psychosocial service use independent of age and gender (p < 0.001, n = 349). Novel triage processes and programs have been developed. Conclusions: A quality improvement approach with integrated knowledge translation is critical to sustainable integration of DART into clinical practice. Psychosocial distress screening programs have the potential to improve the cancer patient experience and health outcomes.
Abstract 19716: A High Intensity Interval Training Protocol is Not Better Than Customary Continuous Exercise for a Rat Model of Chronic Thromboembolic Pulmonary Hypertension
Authors: Mary Beth Brown, Evandro Neves, Gary Long, Jeffrey Kline
Journal: Circulation (2016)

High intensity interval training (HIIT) is superior to continuous exercise training (CExT) for reversing cardiac remodeling and dysfunction and improving exercise capacity in heart failure. Our gro...
Next-generation sequencing of esophageal carcinosarcoma to reveal high frequency of actionable PIK3CA gene mutations.
Authors: Hongyang Lu, Shifeng Yang, Zhiming Jiang, Fajun Xie, Jing Qin, Lei Gong, Na Han, Yun Fan, Weimin Mao
Journal: Journal of Clinical Oncology (2017)

e15503 Background: Esophageal carcinosarcoma (ESC) is a rare malignant esophageal neoplasm consisting of both carcinomatous and sarcomatous components. Drive genes mutations may potentially serve as novel biomarkers to targeted therapy in ESC, and they also may explain the mechanisms of the unique dual-differentiation pattern. Actionable gene alterations with any significant frequency in ESC were unknown due to specimen numbers and limited studies. A comprehensive study of clinical characteristic and molecular alterations in ESC is needed to better understand biology and guide therapy. Methods: Fifteen cases of ESCs which received surgical resection were retrospectively collected from the Zhejiang Cancer Hospital in China between 2009 and 2016, next generation sequencing was performed to identify genotypic changes, and clinical characteristic of these patients was also collected and analyzed. Results: ESC patients are easily occurred in male, heavy smokers, and old patients. The mainly gross types were medullary and fungating type. Mutation of phosphatase and tensin homologue ( PTEN), MAP2K1(MEK1), anaplastic lymphoma kinase ( ALK), RET, and NF1 were detected in one patient respectively. Mutation of ERBB2(HER2), MET and single copy loss of Rb1 were detected in two patients respectively. Mutation of ROS1 and phosphoinositide-3-kinase catalytic alpha ( PIK3CA) were detected in three patients respectively. Conclusions:PIK/AKT pathway may be important in pathogenesis of ESCs, and it may be an ideal therapeutic target.
Association of CTC detection by AdnaTest with outcome on enzalutamide in chemotherapy-naïve castration-resistant prostate cancer: Exploratory results from PREMIERE—A SOGUG trial.
Authors: Albert Font Pous, Sergio Vazquez-Estevez, Aranzazu Gonzalez del Alba, Begoña Mellado, Ovidio Fernandez Calvo, Maria Jose Mendez, María José Juan Fita, Angel Rodriguez Sanchez, Begoña Pérez-Valderrama, Enrique Gallardo, Carmen Santander, M Isabel Sáez, Javier Puente, Teresa Alonso, Maria Piedad Fernandez Perez, Alberto Martínez, Maria Jose Lopez-Andreo, Enrique Grande, Enrique González-Billalabeitia, Daniel Castellano
Journal: Journal of Clinical Oncology (2017)

5052 Background: Circulating tumor cells (CTCs) enumeration using CellSearch correlates with clinical outcome in prostate cancer, but is limited for gene expression analysis. AdnaTest ProstateCancer is a commercially available CTC immune-enrichment and PCR-related detection method that allows gene expression studies (Antonarakis E, NEJM 2014). It has demonstrated incremental detection of CTCs in patients with no CTCs identified by CellSearch (Samoila A, ASCO 2013) but needs to be clinically qualified. There is a strong need for studies to assess the association with the clinical outcome in CRPC. Methods: Between February and November 2015, 98 asymptomatic or oligo-symptomatic chemotherapy-naïve mCRPC pts were recruited in 16 institutions. Although initially designed to study the predictive value of TMPRSS2-ETS, data emerging after the trial was initiated led the group to prioritize alternative predefined exploratory biomarkers, including plasma AR (Grande E, ASC0 2017 #) and CTC characterization (Grande E, ESMO 2016). Outcome measures included PSA-PFS (sPFS), radiographic PFS (rPFS) and OS. Cox regression was used for survival analyses and Fisher’s exact test for PSA response. Results: Ninety-eight patients had CTC blood samples available. CTCs were detected at baseline, 12 weeks and progression in 36% (35/98), 27% (26/95) and 78% (32/41), respectively. The CTC conversion rate (positive to negative after 12 w) was 43% (15/35). All CTC conversions had ≥50% decline in PSA (15/15) whereas only 35% (7/20) of pts with persistent CTCs. At first interim analysis, with a median follow-up of 10.6 months, detection of CTCs at baseline was associated with worse sPFS (median, 7.59 m versus NR, HR, 3.67; 95% CI 1.90-7.10; P &lt; 0.001), rPFS (median, 12.9 m versus NR; HR, 7.61; 95% CI, 2.80-20.64; P &lt; 0.001) and OS (medians NR, HR, 9.51; 95% CI, 1.11-81.52; P = 0.0398). CTC positive pts were less likely to have a ≥90% decline in PSA (OR, 2.88; 95% CI, 1.13-7.72; P = 0.02). Conclusions: CTC detection using AdnaTest is associated with an adverse outcome in chemotherapy-naïve asymptomatic or oligo-symptomatic mCRPC pts. Clinical trial information: NCT02288936.
5-fu continuous pump infusion via superficial temporal artery cannula for high T-staged nasopharyngeal cancinoma: A phase I clinical trial.
Authors: Li Xiang, Jing-Bo Wu, PeiRong Ren, Sheng Lin, Qinglian Wen
Journal: Journal of Clinical Oncology (2018)

e18011 Background: To present the maximum tolerated dose(MTD) , safety, and efficacy of 5-Fu continuously pump infusion via superficial temporal artery cannula for high T staged nasopharyngeal cancinoma. Methods: 29 patients with histologically confirmed nasopharyngeal cancinoma were eligible in the phase I trial. They received induction chemotherapy which consisted of cisplatin (20 mg/m2/d ,days 1-5) and 5-FU(pump infused continuously for 120 hours in different dose gradient),while the regimen was administrated via superficial temporal artery. The MTD of 5-Fu was determined by detecting increasing doses in different groups until the highest dose with acceptable toxicities were obtained. Dose-limiting toxicity (DLT) was defined as any grade 4 or more serious toxicity,and the trial was closed when the rate of DLT exceeded 25%.The total length of the chemotherapy cycle was 21 days. Followed with 2 circles chemotherapy, the radical radiotherapy was conducted. We assessed efficacy, toxicity and life quality, especially on the oral mucositis and radiation brain damage. Results: There were six dose gradients of 5-Fu,including 200mg/m2(6 cases), 250mg/m2(6 cases), 300mg/m2(5 cases), 350mg/m2(5 cases), 400mg/m2(5 cases),450mg/m2 (5 cases)and 500mg/m2(2 cases). No toxicities of grade III or above was observed in the group with dose of not exceeding 350 mg/m2.In the group of 400mg/m2,there were 2 patients developed grade III oral mucositis.And 1 cases was found with grade IV toxicity in the 450mg/m2 group.The 2 patients enrolled in the group of 500mg/m2 all were observed the grade IV toxicity mainly included oral mucositis,so the test was terminated. The overall response rates for the primary mass and lymph nodes were 93% and 100%, respectively. The 5-year overall survival (OS) was 80%.The 5-years progression-free-survival(PFS) was 73.3%.The MTD of 5-Fu was 450mg/m2,we also determined the optimal dose was 400mg/m2 according to the response,toxicities and survival. Conclusions: 5-Fu continuously pump infusion via superficial temporal artery cannula results in promising efficacy and tolerability in patients with high T staged nasopharyngeal cancinoma,the MTD was 450mg/m2.
Outpatient induction therapy in newly diagnosed non M3 acute myeloid leukemia.
Authors: Ashish Manne, Harry M. Barnes, Keith Thompson, Stephen L. Davidson, Scott A. McDaniel, John Edward Reardon, Naresh Bellam
Journal: Journal of Clinical Oncology (2016)

e18527 Background: Induction chemotherapy in non M3 Acute Myeloid Leukemia with cytarabine and an anthracycline is generally initiated as an inpatient fearing complications like neutropenic fever, risk of bleeding and need for regular blood and platelet transfusions due to aplasia. We report the feasibility of outpatient induction therapy for newly diagnosed non M3 acute myeloid leukemia. Methods: We identified 16 patients who received cytarabine and an antracycline between 2010 and 2015 at the Montgomery Cancer Center, Montgomery, Alabama. Six out of those sixteen patients received induction in an outpatient setting with intravenous chemotherapy with 7 days of cytarabine as a continuous infusion and 3 days of an anthracycline. We retrospectively reviewed the charts of these 6 patients. Results: The mean age of subjects was 57 (range 34-76). The mean blood counts prior to induction were: WBC - 25.57 cells/µL (range 2.3 - 84); hemoglobin level 8.97 g/dl (range 7.4 -11.2); platelet count 76.67 K/µL (range 20 -291). One patient had favorable risk cytogenetics, three had intermediate risk cytogenetics and two had poor risk cytogenetics . Half of the patients achieved complete remission (50%). The 3 patients who did not achieve complete remission were treated as an outpatient with a hypomethylating agent. All the subjects in the study developed at least one episode of neutropenic fever. Mean time of onset of fever was 6.15 days after initiation of therapy (range 2-13 days ). Five subjects were admitted to the hospital for neutropenic sepsis. Average length of hospitalization was 16 days ( range 0-27). Amongst the subjects, a total of 17 PRBCs and 5 platelets were transfused prior to admission. One patient was intubated and one had profuse nose bleeding. None of the patients died during induction therapy. Conclusions: Induction therapy for AML with cytarabine and anthracyline can be administered in an outpatient setting in a subset of carefully selected subjects with close monitoring and well equipped outpatient supportive care facilities. This strategy will cut down costs by decreasing length of stay in medically stable patients, as well as hospital related morbidity (like nosocomial infections) and can potentially improve quality of life.
Iconic: Peri-operative immuno-chemotherapy in operable oesophageal and gastric cancer.
Authors: Sonia Mansukhani, Michael Davidson, Angela Gillbanks, Clare Peckitt, Annette Musallam, Ruwaida Begum, Daniel Morganstein, Andrew Wotherspoon, Angela M. Riddell, James M Kinross, Julian Marchesi, Katharina von Loga, William H. Allum, Sheela Rao, David J. Watkins, Ian Chau, David Cunningham, Naureen Starling, Asif Chaudry, Marco Gerlinger
Journal: Journal of Clinical Oncology (2018)

TPS4139 Background: Peri-operative chemotherapy with 5FU, oxaliplatin and docetaxel (FLOT) is a new standard of care in resectable gastro-oesophageal adenocarcinoma (GOA), however with 3y survival rates of only 57% there is a need to further improve outcomes by developing innovative therapeutic combinations. PD1/PDL1 checkpoint inhibitors have shown activity in GOA and we are conducting a single-arm phase II trial to investigate the safety and efficacy of the anti-PDL1 antibody avelumab in combination with FLOT (FLOT-A) as peri-operative therapy in resectable GOA. The combination aims to generate synergy by enhancing progression through the cancer-immunity cycle via the pro-immunogenic effect of FLOT chemotherapy and simultaneous avelumab-induced release of the immune inhibitory effect of the PD1/PDL1 checkpoint. Methods: The 2-stage trial design will evaluate the safety and efficacy of avelumab (starting dose: 10mg/kg IV 2 weekly, pre-planned dose reduction to 7mg/kg IV 2 weekly if dose limiting toxicities occur) with standard dose FLOT chemotherapy (5FU 2600mg/m2/24hr, leucovorin 200mg/m2, oxaliplatin 85mg/m2 and docetaxel 50mg/m2) for pts with operable GOA treated on a peri-operative pathway. Stage 1 will establish the safe and maximum tolerated dose of FLOT-A using a 3+3 dose finding design. Stage 2 will assess the efficacy of FLOT-A based on pathological complete response (pCR) rate and peri-op safety. The primary endpoint is pCR. Using an A'hern single stage design to rule out a lower limit of 10% pCR rate and demonstrate an increase to 25% requires the inclusion of 40 pts, to achieve 80% power and a 1-sided 0.05 significance level. An interim analysis will assess safety and Mandard tumour regression grading (TRG) after 15 pts become evaluable. If ≥5 pts achieve TRG 1-3 the trial will expand to 40 pts. Secondary endpoints are ORR, PFS and OS. Exploratory objectives will investigate dynamic changes of immune infiltrates in baseline and on-treatment biopsies and correlate neoepitope load, blood lymphocyte activation and faecal microbiome with tumour response. Recruitment commenced in July 2017 and 40 pts will be recruited in 2 years. Clinical trial information: NCT03399071.
Abstract 21421: Identification of Nherf1 as a Regulator of Right Ventricle Cardiomyocyte Hypertrophic Remodeling With Implications for Pulmonary Hypertension
Authors: Neil Kelly, Mohammad Alhamaydeh, Alexander Hoyt, Stephanie Mutchler, Megan Yeung, Jeffrey Baust, Imad Al Ghouleh
Journal: Circulation (2017)

Introduction &amp; Hypothesis: The molecular mechanisms underlying right ventricle (RV) hypertrophic remodeling (both adaptive and maladaptive) in response to sustained pressure overload, such as that experienced during pulmonary hypertension (PH), are inadequately understood. Our previous work demonstrating a role for the cytosolic organizer protein p47 phox in pressure overload-induced RV hypertrophy and our recent publication on a direct interaction between p47 phox and ERM-binding cytoskeletal protein Nherf1 lead us to hypothesize that Nherf1 is a regulator of RV cardiomyocyte hypertrophy. Methods &amp; Results: Cardiomyocyte-derived H9C2 cells and RV rat neonatal cardiomyocytes isolated from 1-day-old pup hearts (RV-RNCM) were subjected to neurohormonal hypertrophic stimulation using angiotensin II (AngII, 1 &amp; 10 μM). RV pressure overload was induced in mice by pulmonary artery banding (PAB; 3wk). AngII treatment resulted in H9C2 and RV-RNCM hypertrophy and induced Nherf1 protein expression. The AngII-induced hypertrophy was attenuated by Nherf1 gene knockdown using siRNA. Moreover, Co-IP studies revealed an Nherf1-p47 phox association in H9C2 cells that is enhanced by pro-hypertrophic AngII-treatment. Sequential loss of function strategies educated by novel in silico gene network analyses of PH gene intersected with cardiomyopathy gene networks, combined with a careful consideration of our previous findings and the literature, identified potential involvement of Hippo pathway transcriptional co-activators Yap/Taz, water channel aquaporin1 (Aqp1), and apoptosis signal-regulating kinase 1 (Ask1) in this pathway. In vitro , co-IP studies revealed a Nherf1-Yap association and interruption of Ask1 or Aqp1 reduced AngII-induced cardiomyocyte cellular hypertrophy. In vivo , PAB induced an increase in Nherf1 expression and association with p47 phox . Conclusion: The present study supports a new role for Nherf1 in mediating pro-hypertrophic cardiomyocyte cellular responses and implicates a molecular network previously not connected to either the RV or Nherf1. These data identify potential therapeutic targets for RV dysfunction in PH and shed light on novel molecular mechanisms so far untested in the pressure overloaded right heart.
DNA damage repair (DDR) germline mutations in patients (Pts) with urothelial carcinoma (UC).
Authors: Maria Isabel Carlo, Joseph Vijai, Diana Mandelker, Yelena Kemel, Ashley Marie Regazzi, Liying Zhang, Zsofia Kinga Stadler, Michael Francis Walsh, Karen Anne Cadoo, David B. Solit, Jonathan Coleman, A. Ari Hakimi, Samuel Funt, Gopa Iyer, Jonathan E. Rosenberg, Mark E. Robson, Kenneth Offit, Dean F. Bajorin
Journal: Journal of Clinical Oncology (2018)

1516 Background: We previously reported on germline mutations in cancer predisposition genes in 113 pts with UC, with a 19% rate of pathogenic or likely pathogenic (P-LP) variants in DDR genes. Here we report on an expanded cohort of 176 pts and on a separate cohort of 327 anonymized specimens devoid of clinical annotation. Methods: Pts with UC malignancies were prospectively enrolled to a matched tumor-germline DNA sequencing protocol from 3/2013 to 9/2017; starting in 2014, patients could opt in to receive germline results. Germline analysis was done with an institutional, CLIA-certified next generation sequencing (NGS) platform (IMPACT) and analyzed for germline mutations. This analysis includes pts seen in medical oncology clinics who consented to receive germline results (Cohort 1), and additional pts seen in urology and medical oncology clinics who had anonymized germline testing (Cohort 2) with an extended DDR panel. Results: Cohort 1 consisted of 176 pts, 90% with muscle invasive or metastatic disease, median age 63 (31-87), 76% male. Primary sites were bladder (B) (70%), upper tract (UT) (28%), or unknown (2%). 8% had early onset (≤45 yrs at diagnosis), 9% had a family history of UC, 19% had documented non-UC cancers. 30 P-LP DDR gene mutations were identified in 28 patients. The most frequent mutations are shown in the Table. P-LP mutations were present in 29% of pts with UT and 13% of pts with B primaries. Of pts with DDR germline mutations, 29% did not have additional somatic DDR mutations. Cohort 2 consisted of 327 anonymized pts. 32 P-LP DDR germline mutations, including in ERCC2 and ERCC3, were identified in 30 pts. Including both cohorts, 77% of mutations were of high or moderate penetrance. Conclusions: Germline predisposition genes are common in UC pts and may be greater in higher stage disease, further investigation into mutation frequency by stage is warranted. Most mutations are highly penetrant and have profound implications for both pts and family members. Clinical trial information: NCT01775072.Gene Mutations Cohort 1 (%) Total n = 176 Mutations Cohort 2 (%) Total n = 327 Total DDR 30 (17) 32 (9.8) MSH2 5 (2.8) 4 (1.2) BRCA1 5 (2.8) 3 (0.9) CHEK2 4 (2.2) 3 (0.9) BRCA2 3 (1.7) 5 (1.5) MSH6 2 (1.1) 0 MLH1 2 (1.1) 0 MUTYH 2 (1.1) 3 (0.9) ERCC2 * 4 (1.2) ERCC3 * 4 (1.2) *Not analyzed
Comparative efficacy and safety of pemetrexed or paclitaxel plus thoracic radiation therapy (TRT) in elderly patients with nonsquamous locally advanced NSCLC.
Authors: Ge Bai, Yong Xing Bao, Rui Mao, Chao Zheng, Lei Xiao, Mayinur Eli, Hua Zhang, Hua Rong Zhao
Journal: Journal of Clinical Oncology (2018)

8509 Background: Concurrent chemoradiotherapy is the standard treatment of locally advanced NSCLC, which can significantly reduce the risk of death and prolong the survival of patients.As we focus on the tolerance and side effects of elderly patients with concurrent chemoradiotherapy.The purpose of this study is to compare the efficacy and safety of Pemetrexed versus Paclitaxel plus thoracic radiation therapy (TRT) in elderly patients with locally advanced nonsquamous NSCLC,to provide the basis for the choice of the best chemotherapy for elderly patients. Methods: Patients (66years-75years) with stage IIIA/B unresectable nonsquamous NSCLC in our single center, randomly received (1:1) pemetrexed 500 mg/m2 d1 every 3 weeks plus concurrent TRT (arm PEM), or paclitaxel 45 mg/m2 d1 every weeks plus concurrent TRT (arm PAC). TRT: 60~66 Gy/2 Gy/30~33f IMRT radiotherapy. Results: Eighty-two patients were eligible to enter the group and completed treatment (41 in arm PEM,41 in arm PAC ).The objective remission rate (CR+PR) of PEM group was significantly higher than PAC group (72. 0% v 56. 0%;P = 0. 021);The 2 year overall survival rate of the PEM group was significantly higher than PAC group (49.6% v 30.7%;P = 0.037).The incidence of radioactive pneumonia PEM group was lower than PAC group (20.1% to 33.1%;P = 0.032);While, no statistically significant difference between bone marrow suppression and digestive tract reaction. Conclusions: Pemetrexed combined with TRT was superior to paclitaxel concurrent chemoradiotherapy for elderly nonsquamous LA-NSCLC.