tbuckley/cabot-search huggingface dataset:
Rectal adenocarcinoma: Outcomes of adjuvant chemotherapy after neoajuvant chemoradiotherapy in a retrospective cohort.
Authors: Vanessa Pachón Olmos, Pablo Reguera Puertas, Reyes Ferreiro Monteagudo, FEDERICO LONGO, Mercedes Rodríguez Garrote, María Ángeles Vaz Salgado, Carmen Guillen, Maria Gion Cortés, Javier Molina CerrilloMD, Olga Martinez Saez, Maria Villamayor Delgado, Javier Die Trill, Estela Tobaruela de Blas, Irene Moreno Montes, Juan Carlos García Pérez, Juan Diego Pina, María Alejandra Caminoa-Lizarralde Aiza, Cayetano Sempere Ortega, Fernando López-Campos, Alfredo Carrato
Journal: Journal of Clinical Oncology (2017)

790 Background: The role of adjuvant chemotherapy (AC) after chemoradiotherapy and surgery in stage II and III of rectal cancer is not well defined. Neither the regimen nor the duration is clear. Besides, guidelines from different expert groups are conflicting. Methods: 224 patients diagnosed from January 2003 to December 2013 with rectal adenocarcinoma T3/T4 and/or positive node staged by ultrasound or magnetic resonance imaging was collected retrospectively from the Pathology Department data base. Results: Of the 224 patients 61.6% were male, median of age at diagnosis 68.6 years (range 31.3-85.4). All of them received 50.4 Gy with different concomitant regimens (capecitabine, continuous infusion of fluoracil or bolus of fluoracil-leucovorin). 13.4% of patients achieved a pathological complete response. 76.8% of the cohort received adjuvant chemotherapy. The main reasons for not receiving chemotherapy were ECOG ≥ 2, surgery complications and a decision of the patient. 51.2% of patients received an oxaliplatin based regimen and the median time of chemotherapy duration was 4 months (range 1-6 months). Local relapse was diagnosed in 6.3% of patients while a systemic relapse was found in 22.3%. Patients without AC had a mean overall survival (OS) of 85.5 months (CI 95% 70.7-100.4) versus 119.8 monts (CI 95% 110.8-128.8) in the AC cohort (p 0.002) without reaching the median after 58 months (range 8-153.9) median follow-up. Disease free survival (DFS) was also better in the AC cohort with a mean DFS of 104 months (CI 95% 94.3-113.6) versus 71.4 months (CI 95% 55.4-87.4), p = 0.01. Conclusions: AC after chemoradiotherapy and surgery in stage II and III rectal cancer as a standard does not exist. In our cohort, AC showed a significant improve in OS and DFS, but the limitations of a retrospective study should be considered, as well as the impact of surgery on metastasis and salvage chemotherapies. Randomized studies are clearly needed.
Survival difference among patients with hepatocelluar carcinoma (HCC) based on stage of disease: The pre- and post-sorafenib era.
Authors: Chintan Shah, Hardik Satish Chhatrala, Kinjal Vora, Rohit Bishnoi, Harini Bejjanki, Sreenivas Chandana
Journal: Journal of Clinical Oncology (2017)

411 Background: Sorafenib was approved for unresectable and metastatic HCC in 2007. We conducted this retrospective study using U.S. Surveillance, Epidemiology and End results (SEER) database to evaluate the relative survival rates of HCC patients before and after the approval of sorafenib. Methods: We analyzed SEER database: Incidence - SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2015 Sub (1973-2013 varying). Relative survival at 12,24,36,48 and 60 months interval was measured for patients diagnosed with HCC between 2001 and 2013. Relative survival rates were compared between pre sorafenib (2001-2007) and post sorafenib (2008-2013) eras. Results: A total of 54,901 patients (23,963 in pre sorafenib era and 30,938 in post-sorafenib era) were reported with HCC in SEER database. Relative survival at 5-years significantly improved for HCC patients diagnosed after 2007 (16.00±0.30% vs 18.90±0.30% for pre and post sorafenib era respectively; P-value &lt; 0.001). Relative survival for HCC patients with the solitary tumor was significantly improved (33.10±0.80% vs 35.40±0.90% survival at 5 years for pre and post sorafenib era respectively; P-value &lt; 0.001). Similarly, survival was found to be significantly improved for patients with multiple tumors without vascular invasion (17.10±0.70% vs 19.40±0.80% survival at 5 years for pre and post sorafenib era respectively; p-value &lt; 0.001). Relative survival continued to be poor with no statistically significant difference at any intervals for patients with tumor with vascular invasion (P-value 0.748) or distant metastasis (P-value 0.055). Survival difference was not significant among different age groups and gender between pre and post sorafenib eras. Conclusions: While relative survival significantly improved in post sorafenib era, it is largely limited to patients with the localized disease with the solitary tumor or multiple tumors without any vascular invasion or metastasis. Survival in patients with advanced stage HCC remains poor and has not shown significant improvement since the approval of sorafenib. The study shows better alternatives are needed for advanced-stage unresectable HCC patients.
Safety and feasibility of yttrium-90 (Y-90) treatment for primary and metastatic liver tumors at a community hospital.
Authors: Brandon Keith Martinez, Niraj K. Gupta, Vincent Flanders, Kannan Natarajan, Marc Underhill, Jeff Cooke
Journal: Journal of Clinical Oncology (2013)

e14698 Background: Y-90 microspheres administered via hepatic artery is being increasingly utilized in the management of pri/metastatic liver cancers. We report safety/efficacy data on Y-90 therapy performed at a community hospital treating high volume of cancer patients. Methods: Multi-disciplinary tumor conferences were used for appropriate patient selection and pts. were seen on referral in the I/R clinic. Liver/tumor volume calculations were performed on pre-treatment imaging. Prescribed activity was calculated by BSA methods. Fractional tumor, liver-flow characteristics and lung shunt fractions were determined using Tc-99m MAA scan. All pts. recieved Y-90 resin microspheres, SIR-Spheres (Sirtex Medical Inc, Lake Forest, IL). Response to therapy was assessed by imaging studies and/or tumor markers. Results: 27 pts. were treated between Apr 2012 and Jan 2013 with 46 doses delivered. Male 46%/ Female 54%;Median age:58 yrs (29-86). ECOG P.S. of 22 pts. was 0-2, 5 had P.S. of 3. Tumor types; 11 (40%) colon, 2 breast, 2 cholangioca, 3 NET, 2 HCC, 1 ovarian, cervical, gastric, GIST, urothelial, uveal melanoma and pancreatic adenoca. Percent tumor involvement was between 0-25% in 16 (59.25%) and 25-50% in 11 (40.75%). Average whole liver administered activity was 48.33 mCi (33.9-62.9 mCi). Early imaging on 18 patients revealed 84% response rate (PR+SD). 1 patient with cholangiocarcinoma was downstaged to surgical resection.One patient with Childs class-B cirrhosis and multifocal HCC developed liver failure following treatment and died. 5 deaths from progression of disease occurred in hevaily pre-treated pts. with extrahepatic disease. 2 patients had coil migration during mapping angiography, however, microsphere distribution was unaffected due to intrahepatic collaterals. Out of 46 delivered doses, 6 (13%) grade-3 toxicities including, severe fatigue, nausea and vomiting resulted in short term hospitalization. Conclusions: Y-90 can be safely and efficiently delivered in a community setting. Development of a community-based radioembolization program, although challenging, can be successfully accomplished with establishing a dedicated multi-disciplinary team.
Cerebellar granule cells acquire a widespread predictive feedback signal during motor learning
Authors: Andrea Giovannucci, Aleksandra Badura, Ben Deverett, Farzaneh Najafi, Talmo D Pereira, Zhenyu Gao, Ilker Ozden, Alexander D Kloth, Eftychios Pnevmatikakis, Liam Paninski, Chris I De Zeeuw, Javier F Medina, Samuel S-H Wang
Journal: Nature Neuroscience (2017)
Predictive factors for long-term survival after conversion surgery for unresectable gastric cancer: A retrospective analysis.
Authors: Tamotsu Sagawa, Kyoko Hamaguchi, Akira Sakurada, Fumito Tamura, Tsuyoshi Hayashi, Koshi Fujikawa, Yasuo Takahashi, Yasushi Sato
Journal: Journal of Clinical Oncology (2017)

205 Background: Chemotherapy occasionally converts an initially unresectable gastric cancer to a resectable cancer. However, the association between clinical factors and long-term prognosis after conversion surgery for unresectable gastric cancer has not been investigated. Methods: We retrospective reviewed 36 gastric cancer patients who underwent conversion surgery at our institute between 2005 and 2015. Clinicopathologic characteristics and patient outcomes were analyzed, with particular focus on the potential to predict long-term survival. Results: The number of incurable factors was one in 31 patients and two in 5, including metastases to non-regional lymph node in 22, peritoneum in 10, liver in 6, and lung in 3. The regimen of chemotherapy was Docetaxel/CDDP/S-1 in 23 patients, Docetaxel/CDDP/S-1+Trastuzmab in 7, S-1/CDDP in 2, Docetaxel/S-1 in 1, CPT/CDDP in 1, and S-1 monotherapy in 1. Complete resection with no residual tumor (R0) was achieved in 25 of 36 patients, microscopic residual tumor status (R1) in 10, and macroscopic residual tumor (R2) in 1. The 3-year overall survival (OS) rate among the 36 patients who underwent conversion surgery was 60.3 % (median survival time, 1200 days). The 3-year OS rate among patients who underwent R0 resection was 70.8 % (median survival time, 1503 days). Patients who underwent R0 resection had significantly longer OS times than those who underwent R1 and R2 resection ( p=0.0124). We selected 16 variables in addition to residual tumor for Kaplan–Meier analysis. According to the log rank test, the following four variables were significantly associated with a better OS: clinical response to 1 st line therapy (CR or PR vs. SD or PD)( p=0.0283), pathological response grade (1b-3 vs. 0-1a) ( p=0.0304), pathological tumor depth (CR or T1~T3 vs. T4) ( p=0.0261), and pathological nodal stage (N0〜2 vs. N3) ( p=0.0086). Conclusions: Our data indicates that clinical response to 1 st line therapy in preoperative characteristics, R0 resection, pathological response grade, pathological tumor depth, pathological nodal stage in postoperative characteristics are predictive factors that can be expected to long-term survival.
The association of PET response with complete pathological response (CPR) and residual nodal disease (RND) after induction chemoradiotherapy (CRT) and resection of esophageal cancer: A review of 493 cases
Authors: S. A. Barnett, N. P. Rizk, P. S. Adusumilli, B. J. Park, M. S. Bains, R. M. Flores, K. A. Goodman, D. H. Ilson, T. J. Akhurst, V. W. Rusch
Journal: Journal of Clinical Oncology (2009)

4552 Background: RND and lack of CPR of the primary tumor correlate with poor survival after induction CRT and resection of esophageal cancer. PET response to CRT (SUV max change and post-induction SUV max ) is used by some clinicians as an indicator of CPR and RND in order to stratify patients after CRT to observation alone vs completion resection. We aimed to investigate the association of PET response with CPR and RND after induction CRT and resection of esophageal cancer. Methods: An IRB-approved retrospective review of an institutional surgical database identified patients who underwent resection of esophageal squamous cell (SCC) and adeno carcinoma (AC) following CRT. The database was locked on Sept 30, 2008. Categorical variables were analyzed by chi square, continuous variables by t-test, and survival by the Kaplan-Meier method. Results: From 1/96 to 3/08, 493 patients were identified, 82% were male. Median age was 62, chemotherapy cisplatin-based in 87%, mean radiation 50 Gy, in-hospital mortality 4.1% and R0 resection rate 88%. Pathology revealed AC in 80%, lack of CPR in 73% and RND in 35%. While in AC patients CPR and lack of RND were both associated with prolonged survival, PET response was not associated with either. In SCC patients, prolonged survival was associated with CPR but not with lack of RND. In SCC, PET response was associated with CPR but not RND. In these patients, reduction in SUV max &lt;50, 50–75 and &gt;75% was associated with CPR rates of 29, 44 and 85% respectively (p=0.02). Conclusions: These results do not support the use of PET response to justify observation alone after CRT in esophageal AC. With respect to SCC, though exploratory, these provocative results support further study of the use of PET response to predict CPR. [Table: see text] No significant financial relationships to disclose.
A phase IB/randomized phase II study of gemcitabine (G) plus placebo (P) or vismodegib (V), a hedgehog (Hh) pathway inhibitor, in patients (pts) with metastatic pancreatic cancer (PC): Interim analysis of a University of Chicago phase II consortium study.
Authors: Daniel Virgil Thomas Catenacci, Nathan Bahary, Martin J. Edelman, Sreenivasa R. Nattam, Robert de Wilton Marsh, Andreas Kaubisch, James Alfred Wallace, Deirdre Jill Cohen, Patrick J. Stiff, Bethany G. Sleckman, Sachdev P. Thomas, Heinz-Josef Lenz, Les Henderson, Ciara Zagaya, Michael Vannier, Theodore Karrison, Walter Michael Stadler, Hedy Lee Kindler
Journal: Journal of Clinical Oncology (2012)

4022 Background: Sonic Hh (SHh), the ligand for the Hh pathway, is over-expressed in &gt;80% of PC. V, a small molecule antagonist of the Hh signaling pathway, has activity in preclinical PC models. Methods: We conducted a multi-center, placebo-controlled, phase IB/randomized phase II trial of GV or GP. Eligible pts, KPS 80-100, had previously untreated metastatic PC, or had completed adjuvant therapy &gt; 6 months (mo) prior. Primary endpoint: progression-free survival (PFS). Correlatives: serial SHh serum levels; serial contrast perfusion CT imaging. To allow for early stopping due to lack of efficacy, a planned interim analysis was performed after approximately 50% of the expected number of PFS events occurred. The protocol stipulated that the trial would be terminated if the probability of rejecting the null hypothesis were the trial to continue (conditional power) was &lt;10%. All pts received G 1000mg/m 2 over 30 minutes, days (D) 1, 8, 15, Q28D. Pts, stratified by KPS (80 v 90/100), and disease status (newly-diagnosed/recurrent), were randomized to V (150 mg PO daily) or P. For pts on P, cross-over was allowed at progression. Results: 70 evaluable pts (V/P 35/35) enrolled at 12 sites 2/10-6/11. Pt characteristics: median age 63/63 (range 49-79/48-82); KPS 80: 8/8; 90: 12/14; 100: 15/13. Grade 3/4 toxicity (%pts): neutropenia 20/26; hyponatremia 3/11; fatigue 9/6; hyperglycemia 14/6; elevated alkaline phosphatase 9/11. Response (%): complete 0/3, partial 0/11, stable disease 49/31. Median PFS: 3.7/2.4 mo (95% CI: 2.4-4.6/1.9-3.7; adjusted HR 0.92 [0.52-1.64]). Upon progression/unblinding, 23 GP pts crossed over to GV. Median overall survival (OS): 6.3/5.4 mo (95% CI:4.9-7.8/4.2-8.0, adjusted HR 0.97, [0.47-2.01]). 1-year survival (%): 24/24. Laboratory and radiological correlatives will be presented. Conclusions: GV has an acceptable toxicity profile. This trial did not meet criteria for futility at this interim analysis. The study is expected to complete accrual of 112 pts in February 2012. The final analysis will be reported after 90 events. Funded by NCI N01-CM-62201.
Suppression of interferon-mediated anti-HBV response by single CpG methylation in the 5′-UTR of <i>TRIM22</i>
Authors: Keo-Heun Lim, Eun-Sook Park, Doo Hyun Kim, Kyung Cho Cho, Kwang Pyo Kim, Yong Kwang Park, Sung Hyun Ahn, Seung Hwa Park, Kee-Hwan Kim, Chang Wook Kim, Hong Seok Kang, Ah Ram Lee, Soree Park, Heewoo Sim, Juhee Won, Kieun Seok, Jueng Soo You, Jeong-Hoon Lee, Nam-Joon Yi, Kwang-Woong Lee, Kyung-Suk Suh, Baik L Seong, Kyun-Hwan Kim
Journal: Gut (2017)

Objective Interferons (IFNs) mediate direct antiviral activity. They play a crucial role in the early host immune response against viral infections. However, IFN therapy for HBV infection is less effective than for other viral infections. Design We explored the cellular targets of HBV in response to IFNs using proteome-wide screening. Results Using LC-MS/MS, we identified proteins downregulated and upregulated by IFN treatment in HBV X protein (HBx)-stable and control cells. We found several IFN-stimulated genes downregulated by HBx, including TRIM22 , which is known as an antiretroviral protein. We demonstrated that HBx suppresses the transcription of TRIM22 through a single CpG methylation in its 5′-UTR, which further reduces the IFN regulatory factor-1 binding affinity, thereby suppressing the IFN-stimulated induction of TRIM22 . Conclusions We verified our findings using a mouse model, primary human hepatocytes and human liver tissues. Our data elucidate a mechanism by which HBV evades the host innate immune system.
Rab7b Promotes Megakaryocytic Differentiation of K562 Cells by Activating the Protein Kinase C/Extracellular Signal-Regulated Kinase Dependent Pathway.
Authors: Donghua He, Taoyong Chen, Mingjin Yang, Chaofeng Han, Yang Yang, Xuetao Cao, Zhen Cai
Journal: Blood (2009)
Everolimus as second-line treatment in metastatic renal cell carcinoma (mRCC) after first-line pazopanib (The RESCUE study): A retrospective analysis by the Hellenic GU Cancer Group (HGUCG) with international collaboration.
Authors: Konstantinos Koutsoukos, Marta Espinosa Montano, Loukas Kontovinis, Kimon Tzannis, Angelos Koutras, Christos Christodoulou, Vasiliki Bozionelou, Dimitra Stefanou, Marios Bakogeorgos, Nikolaos K. Kentepozidis, Alexandros Ardavanis, Haralabos Kalofonos, Ignacio Duran, Aristotelis Bamias, Konstantinos Papazisis
Journal: Journal of Clinical Oncology (2015)

e15601 Background: Pazopanib and everolimus are approved first and second line therapies in mRCC, respectively. However, real-world data on the efficacy and safety of everolimus as second-line treatment after pazopanib are lacking. Methods: Medical charts of mRCC patients from 8 centers from Greece and Spain were reviewed. Major inclusion criterion for this retrospective analysis was: first-line therapy with pazopanib AND 2nd-line therapy with everolimus. No other first- or second-line therapies were allowed. Results: Data from 30 patients (Table 1) treated with second-line everolimus between 19 Sep 2011 and 16 Jan 2014 are reported. Median treatment duration with pazopanib and everolimus was 5.7 and 3.5 months, respectively. Median PFS from everolimus initiation was 3.5 months (95% CI 2.4-6.3) and median OS 8.9 months (95% CI 6-15.9). After a median fup of 27 months, combined OS since pazopanib initiation was 14.8 months (95% CI 10.5-22.3). Best responses on everolimus were 15% PR, 27% SD and 58% PD. Most common toxicities were anemia (30%), stomatitis (20%), pneumonitis (14%), and fatigue (10%). Most toxicities were of grade 1/2. Grade 3/4 treatment-related toxicities were reported in only 9 patients: anemia (3), stomatitis (2), pneumonitis (1), proteinuria (1), pulmonary embolism (1), stomatitis+pneumonitis (1). Conclusions: This is the first study providing data exclusively on the sequence pazopanib-everolimus in mRCC. It demonstrated a favorable safety profile of everolimus after pazopanib. Despite the high response rate, median PFS and OS on everolimus were numerically shorter than previously reported. This could be attributed to the fact that the pazopanib-everolimus sequence was offered to patients with unfavorable prognosis, as suggested by the modest combined OS of our population. Table 1. Baseline characteristics (at the time of everolimus initiation) median Age 58 Sex M 19 (63%), F 11 (37%) ECOG PS 0 7 (24%) 1 15 (50%) 2 4 (13%) NR 4 (13%) Prior nephrectomy (radical & partial) 19 (63%) Histology Clear cell 28 (93%) Metastatic sites lung 77% lymph nodes 47% liver 37% other 33% bone 27% renal bed 20% brain 7%
Investigations of an improved esophageal cancer diagnostics approach.
Authors: Geng Xi Jiang, Junjie Wu, Hua Xiao, Xiao Gang Zhang, Bao Xia Wang, Li Xin Yang, Qiang Li, Xing Tang, Da Lou, Xuedong Du, Chris Chang Yu
Journal: Journal of Clinical Oncology (2015)

e15059 Background: For esophageal cancer, no viable non-invasive detection technologies are available today. In this investigation, a newly developed IVD cancer diagnostic technology named Cancer Differentiation Analysis Technology (CDA) was investigated for esophageal cancer detection. In a CDA technology, multi-level and multi-parameter information is collected using a medical device fabricated by Anpac Bio-Medical Science Co., Ltd. which measures information relating to both protein fragments and cellular signals in blood samples in a single test. Methods: Blood samples were collected in EDTA vacutainer tubes, with 49 esophageal cancer patients and 303 healthy individuals (control group). CDA data was then collected, and analysis was carried out. Results: The results showed significant statistical difference between esophageal cancer and control groups with P value < 0.05 (Table 1). Also, CDA values at different stages of esophageal cancer samples showed possible effectiveness using CDA technology for early stage esophageal cancer detection (P value < 0.05 between stage I esophageal cancer and control groups). In addition, using a reasonable cut-off value, its sensitivity and specificity are about 70% and 90%, respectively. Conclusions: CDA technology is a promising approach for esophageal cancer diagnostics including early stage diagnostics. Keywords: Esophageal Cancer; CDA Table 1 CDA Test Results. Group Sample Size CDA Mean (rel. units) CDA STDEV (rel. units) Control Group 303 33.7 9.1 Esophageal Cancer Group 49 52.4 11.0
Pelvic SABR with HDR boost in intermediate- and high-risk prostate cancer (SPARE): Favorable early toxicity and quality-of-life outcomes.
Authors: Hima Bindu Musunuru, Andrea Deabreu, Melanie Davidson, Ananth Ravi, Joelle Antoine Helou, Ling Ho, Patrick Cheung, Danny Vesprini, Stanley K. Liu, William Chu, Renee Korol, Hans T. Chung, Alexandre Mamedov, Liying Zhang, Andrew Loblaw
Journal: Journal of Clinical Oncology (2017)

60 Background: ASCENDE-RT has provided level 1 evidence supporting the use of androgen deprivation therapy (ADT), external beam radiotherapy and brachytherapy boost in intermediate- and high-risk prostate cancer. The objectives of this study are to report early toxicity and quality of life (QOL) outcomes in patients treated on a hybrid protocol using five-fraction pelvic stereotactic ablative radiotherapy (SABR) with a MRI dose painted HDR brachytherapy boost (HDR-BT). Methods: A phase I/II study was performed where intermediate (IR) and high-risk (HR) prostate cancer patients received HDR-BT 15Gy in single fraction to the prostate and up to 22.5Gy to the MRI nodule. Gantry-based 25Gy SABR was delivered to pelvis, seminal vesicles and prostate in 5 weekly fractions. ADT was used for 6-18 months. Common Terminology Criteria for Adverse Events version 3.0 was used to assess toxicities. QOL was captured using EPIC at every follow-up. A minimally clinically important change (MCIC) definition was triggered if the EPIC QOL score at each time point decreases &gt; 0.5 SD, where SD is the standard deviation of baseline scores. Results: Thirty-three patients (NCCN 6.0% low IR, 45.5% high IR and 48.5% HR) completed this treatment with a median follow-up of 13.8 months (IQR 12.1, 18.8). The incidence of worst toxicities is shown in Table 1.The 3 grade 3 GU patients were due to temporary urinary catheterization in the acute period following HDR-BT. Mean (95% SD) EPIC urinary QOL scores were 82.5 (16.5), 83.2 (12.9) and 83.7 (16.3) at baseline, 3 months and 12 months and the bowel scores were 95.9 (3.8), 92.6 (8.2) and 90.5 (8.3), respectively. Proportion of patients experiencing MCIC at 3 months and 12 months were 20.8% and 14.3% for urinary domain, 47.8% and 53.9% for bowel domain; respectively (see Table). Conclusions: This novel treatment protocol incorporating MRI dose painted HDR brachytherapy boost and SABR pelvic radiation for intermediate- and high-risk prostate cancer in combination with ADT is feasible and well tolerated in the acute setting. Clinical trial information: REB 269-2014. [Table: see text]