tbuckley/cabot-search huggingface dataset:
Comparison of clinical characteristics and prognosis for hepatocellular carcinoma in Uyghur patients in Xinjiang of China.
Authors: Shasha Zhou, Lei Xiao, Hua Zhang, Ruili Zhang, Huarong Zhao, Hao Wen, Yongxing Bao
Journal: Journal of Clinical Oncology (2014)

e15177 Background: About 80%-90% of primary hepatic malignancy is hepatocellular carcinoma (HCC). Patients with HCC can be identified as negative for both hepatitis B surface antigen and anti-hepatitis C virus antibody, such HCC is known as non-B/non-C HCC (NBC-HCC). However, few investigations into NBC-HCC are currently reported. Hepatitis virus infection in Xinjiang region is significantly less prevalent than in other regions, which implies ethnic differences in HCC cases in Xinjiang. This report summarized the clinical features of Uyghur patients with HCC, and investigated the possible risk factors for NBC-HCC in Uyghur patients and compared the differences in clinical features of NBC-HCC and viral HCC. Methods: We retrospectively analyzed clinical data of 301 Uyghur patients with HCC, categorized as either non-B/non-C hepatocellular carcinoma (NBC-HCC) or viral HCC. Patients’ overall survival was analyzed by the Kaplan–Meier method; factors that might influence their prognosis and survival were analyzed using univariate (log-rank test) and multivariate Cox proportional hazard models. Results: Percentages of NBC-HCC patients without liver cirrhosis, having diabetes mellitus or living in rural areas were significantly higher than in the viral-HCC group. NBC-HCC patients tended to be diagnosed at advanced stage but had better Child-Pugh class than viral HCC patients. For all 301 patients, 0.5-, 1-, 3- and 5-year survival rates were 35.6 %, 20.3%, 13.7%, 4.5%, respectively; the two groups did not significantly differ in overall survival. Multivariate analysis by Cox model showed that age (RR=1.539, p=0.001), TNM stage (RR=12.708, p=0.000), portal vein tumor thrombus (PVTT; RR=2.003, p=0.000), Child-Pugh class (RR=1.715, p=0.000), and TACE+ radiotherapy (RT)/radiofrequency ablation (RFA) (RR=0.567, p=0.000) were significant independent prognostic factors for HCC patients. Conclusions: In Uyghur patients, clinical characteristics differ between NBC-HCC and viral HCC; HCC in the Xinjiang region also has certain regional features. Age, TNM stage, PVTT, Child-Pugh class and TACE+ RT/RFA significantly affect the patients’ survival.
Key biological processes driving metastatic spread of pancreatic cancer as identified by multi-omics studies
Authors: T.Y.S. Le Large, M.F. Bijlsma, G. Kazemier, H.W.M. van Laarhoven, E. Giovannetti, C.R. Jimenez
Journal: Seminars in Cancer Biology (2017)

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by a high metastatic burden, already at the time of diagnosis. The metastatic potential of PDAC is one of the main reasons for the poor outcome next to lack of significant improvement in effective treatments in the last decade. Key mutated driver genes, such as activating KRAS mutations, are concordantly expressed in primary and metastatic tumors. However, the biology behind the metastatic potential of PDAC is not fully understood. Recently, large-scale omic approaches have revealed new mechanisms by which PDAC cells gain their metastatic potency. In particular, genomic studies have shown that multiple heterogeneous subclones reside in the primary tumor with different metastatic potential. The development of metastases may be correlated to a more mesenchymal transcriptomic subtype. However, for cancer cells to survive in a distant organ, metastatic sites need to be modulated into pre-metastatic niches. Proteomic studies identified the influence of exosomes on the Kuppfer cells in the liver, which could function to prepare this tissue for metastatic colonization. Phosphoproteomics adds an extra layer to the established omic techniques by unravelling key functional signaling. Future studies integrating results from these large-scale omic approaches will hopefully improve PDAC prognosis through identification of new therapeutic targets and patient selection tools. In this article, we will review the current knowledge on the biology of PDAC metastasis unravelled by large scale multi-omic approaches.
Second Autologous or Allogeneic Transplantation after the Failure of First Autograft in Multiple Myeloma.
Authors: Muzaffar H. Qazilbash, Rima Saliba, Marcos de Lima, Daniel Couriel, Chitra Hosing, Ana Aleman, X Lei, Richard E. Champlin, Sergio A. Giralt
Journal: Blood (2004)
Adverse prognostic impact of intratumor heterogeneous HER2 gene amplification in patients with breast cancer.
Authors: Carmen Criscitiello, Giuseppe Viale, Davide Disalvatore, Vincenzo Bagnardi, Luca Fumagalli, Lucia Gelao, Marzia Adelia Locatelli, Nicole Rotmensz, Aron Goldhirsch, Giuseppe Curigliano
Journal: Journal of Clinical Oncology (2013)

617 Background: There is increasing recognition of the existence of intratumoral heterogeneity of the human epidermal growth factor receptor (HER2), which affects interpretation of HER2 positivity in clinical practice and may have implications for patient prognosis and treatment. Only patients (pts) with HER2 positivity - defined as 3+ by IHC or FISH amplified defined as a HER2 gene to chromosome 17 (HER2/CEP17) ratio ≥ 2.0 - are eligible to receive trastuzumab treatment. Limited information is available on the prognosis of pts with HER2 2+ or FISH test with a HER2/CEP17 ratio &lt; 2.0. Methods: We retrospectively analyzed data from 455 consecutive early BC pts with HER 2+ and HER2/CEP17 ratio &lt; 2.0 who underwent surgery after 2007. The association between HER2/CEP17 ratio and other known prognostic factors was evaluated with multivariable linear regression models. The role of HER2/CEP17 ratio on recurrence free survival was assessed with multivariable Cox regression models. Results: Fifty-one percent of the evaluated pts were node negative, 51% were postmenopausal, 93% had ER positive BC and 85% had Ki-67 ≥14%. The mean HER2/CEP17 ratio was 1.27 (SD=0.3). A significant positive relationship between HER2/CEP17 ratio and Ki-67 was observed (p&lt;0.01). During a median follow-up time of 2.7 years, 40 recurrences were observed (15 locoregional events and 25 distant metastases). Overall, the association between HER2/CEP17 and the risk of recurrence was not significant. From subgroup analysis, a significant interaction between HER2/CEP17 ratio and nodal involvement emerged (p=0.02). Among pts with node-negative disease, pts with HER2/CEP17 ratio ≥1.27 were at higher risk of recurrence with respect to pts with HER2/CEP17 ratio &lt; 1.27 (adjusted HR 4.0, 95% CI 1.01-15.9). Conclusions: Among pts with BC and HER2 intratumoral heterogeneity, HER2/CEP17 ratio ≥1.27 could have a strong prognostic role in node negative HER2 2+ BC, thus suggesting potential future therapeutic approaches in this setting of pts.
A phase I dose-escalation study of enzalutamide in combination with the AKT inhibitor AZD5363 in patients with mCRPC.
Authors: Michael Paul Kolinsky, Pasquale Rescigno, Diletta Bianchini, Zafeiris Zafeiriou, Niven Mehra, Joaquin Mateo, Ruth Riisnaes, Mateus Crespo, Ines Figueiredo, Penelope Flohr, Nina Tunariu, Udai Banerji, Florence I. Raynaud, Karen E Swales, Holly Tovey, Nuria Porta, Rachel Slade, Lorna Leonard, Emma Hall, Johann S. De Bono
Journal: Journal of Clinical Oncology (2017)

135 Background: Activation of the PI3K/AKT/mTOR pathway may contribute to resistance to androgen receptor targeted therapies in metastatic CRPC (mCRPC). The phase I/II RE-AKT trial (NCT02525068) investigates the safety and activity of enzalutamide (enza) in combination with the AKT inhibitor, AZD5363, in patients (pts) with mCRPC. Results of the phase I run-in are reported. Methods: mCRPC pts progressing after 1-2 lines of taxane chemotherapy and at least 12 weeks (wks) of abiraterone or enza were treated with enza (160mg od) and AZD5363 bid 4-days on, 3-days off, in a 3+3 dose escalation design. Co-primary endpoints were to assess toxicity (CTCAE), and identify the recommended phase II dose (RP2D) of AZD5363; antitumour activity and pharmacokinetics (PK) were secondary endpoints. Response was assessed by PSA, RECIST v1.1 and circulating tumor cell (CTC) conversion. Pts were considered evaluable for response if they completed 12 wks of treatment. Results: 16 pts were enrolled between 12/2014 &amp; 04/2016 with 15 receiving treatment. At the AZD5363 320mg dose 3 pts were treated with no dose limiting toxicity (DLT). At the AZD5363 480mg dose, 5 pts were treated with 2 DLTs of grade (G) 3 maculopapular rash (MPR) related to AZD5363. An intermediate dose level of AZD5363 400mg was selected with 7 pts treated. 1 pt withdrew consent prior to completing the DLT window. 1 DLT of G3 MPR occurred and this dose was selected as the RP2D. Non-DLT treatment related (TR) G3/4 adverse events (AEs) were hyperglycaemia (n = 4, 26.7%), neutropenia (n = 1, 6.7%) &amp; diarrhea (n = 1, 6.7%). All other TR AEs were G1 or G2, with diarrhea (n = 9, 60%), anorexia (n = 8, 53.3%) &amp; nausea (n = 7, 46.7%) being most common. Of the 10 pts who completed 12 wks of treatment, 3 met at least one of the criteria for response. 1 pt (AZD5363 320mg) who had previously progressed on enza exhibited RECIST v1.1 partial response, &gt; 50% PSA response, and CTC conversion by wk 13. Enza decreased AZD5363 PK exposure; robust modulation of pS6, pGSK3b and pPRAS40 was demonstrated. Conclusions: AZD5363 at the RP2D of 400mg bid 4 days on, 3 days off combined with enza 160mg od is safe and tolerable. Antitumor activity is reported, suggesting that AZD5363 may be able to overcome resistance to enza. Clinical trial information: NCT02525068.
Characteristics and treatment patterns of elderly patients with biliary tract cancers.
Authors: Ji Hyun Yang, In-Ho Kim, Joon Won Jeong, Sang Mi Ro, Myung Ah Lee
Journal: Journal of Clinical Oncology (2017)

459 Background: Biliary tract cancers do not respond well to multipmodal treatment and generally show poor prognosis, and this may be a reason to make elderly patient consider best supportive care only. Methods: We reviewed 108 elderly patients of 80 years of age or older who diagnosed as biliary tract cancers from 2008 to 2014 at Seoul St. Mary's Hospital, Korea. Results: The mean age was 83.76 years ranging from 80 to 100. The patients included 24 intrahepatic(22.2%), 17 common bile duct(15.7%), 21 perihilar(19.4%), 37 gall bladder(34.3%), and 9 Ampulla of Vater(8.3%) cancers. 47 patients (43.5%) was initially resectable and 19(40.4%) of them underwent curative surgery, 17(36.2%) had percutaneous or endoscopic biliay drainage, and 11(23.4%) had best supportive care only. Mean survival was 29.8 months, 15.1 months, and 12 months, following the above treatment, respectively(p = 0.004). The mean hospitalized time for the curatively resected patients was 9.8 days. One died of traumatic SAH after surgery, 2 underwent adjuvant chemotherapy, and 10 experienced recurrence. Unresectable patients included 13 (12%) with locally advanced disease and 48 (44.4%) with distant metastasis. Among them, 4(6.6%) received palliative radiotherapy or chemotherapy, 30(49.2%) had biliary drainage, and 27(44.3%) had just best supportive care. Mean survival was 10.2 months, 7.3 months, and 3.6 months, respectively(p = 0.109). One with radiotherapy did not completed his treatment course due to intolerance. Three received chemotherapy with dose reduction from 75% to 70% considering their old age and poor performance status. Among those patients, 1 patient with stage IV intrahepatic cholangiocarcinoma showed partial response at 1st line of chemotherapy and had received totally 3 lines of chemotherapy. He survived 16.4 months. Conclusions: Elderly patients with early stage cancers who undewent curative resection and some selected advanced stage patients with palliative chemotherapy showed good response and survival improvement. There should be careful decision making for the management for geriatric biliary tract cancer patients and further investigations are needed to find more predictive factors.
Quality of life evaluation of the effect of decapeptyl compared with zoladex preradiotherapy: Final results of randomised controlled trial.
Authors: Amit Bahl, Amarnath Challapalli, Rosemary Greenwood, Katrina Hurley, Rajendra Persad
Journal: Journal of Clinical Oncology (2017)

62 Background: Hormone therapy in combination with radiotherapy is a curative treatment option for prostate cancer (CaP). There is paucity of data regarding quality of life (QoL) evaluation of neoadjuvant Decapeptyl. We reported on the equivalence of cytoreductive efficacy of neoadjuvant Decapeptyl and Zoladex previously. Here we present the final QoL evaluation of the effect of Decapeptyl compared with Zoladex preradiotherapy. Methods: Seventy-one patients with localised CaP who have chosen radical radiotherapy had been randomised by stratified block design, toreceive either Decapeptyl (D: n = 37) or Zoladex (Z: n = 34) with bicalutamide cover. All the patients had subsequent radical radiotherapy and followed up as per departmental protocol. The effect of Decapeptyl and Zoladex on QoL was assessed using EQ5D, QLQ-PR25, QLQ-C30 questionnaires, which were completed at baseline, 6, 10 &amp; 14 weeks after start of therapy. QoL scores were analysed as mean scores over the 4 treatment time points for all domains, controlling for baseline scores using Analysis of Covariance. Results: There was no clinically significant difference or trend towards worsening QoL with either Z or D in the global (EQ5D) and cancer-specific (QLQ-C30) domains. The cancer-specific (QLQ-C30) symptom score also showed no trend towards worsening QoL with either Z or D. Symptom scores in the QLQ-PR25 questionnaire did not show a significant difference between Z and D arms with the exception of hormone symptoms. The hormone symptoms showed an increasing trend over the 4 treatment time points, with those in the Z arm significantly (p = 0.02) more affected (3 points higher on average) than patients in the D arm, despite equivalence in cytoreductive effect and achieving castrate levels of testosterone. Conclusions: There were no clinically significant differences in QoL domains between Zoladex and Decapeptyl, apart from hormones symptoms which were worse with Zoladex. Further validation is required with affect on hormone symptoms as the primary outcome measure. To our knowledge this is the first reported prospective randomised data demonstrating the effect of Zoladex and Decapeptyl, on QoL in the neoadjuvant setting. Clinical trial information: EduraCT: 2008-007028-25.
Theranostics: Radiolabelled Polymeric Materials for Imaging and Treatment of Cancer: Quo Vadis? (Adv. Healthcare Mater. 6/2017)
Authors: Kritee Pant, Ondřej Sedláček, Robin A. Nadar, Martin Hrubý, Holger Stephan
Journal: Advanced Healthcare Materials (2017)

The utilization of polymeric nanomaterials in combination with imaging- and/or therapy-related radionuclides holds a promising potential for cancer diagnosis and treatment. In article number 1601115, Holger Stephan, Martin Hrubý, and co-workers review the recent advances and emerging opportunities of tumour-targeted radiolabelled polymeric nanomaterials for both non-invasive imaging and treatment of cancer.
Factor V Leiden Is Associated with Premature Myocardial Infarction.
Authors: Flora Peyvandi, Marta Spreafico, Luisa Foco, Luisa Bernardinelli, Stefano Duga, Rosanna Asselta, Diego Ardissino, Sekar Kathiresan, Pierangelica Merlini, Pier M. Mannucci
Journal: Blood (2008)
Distinct but complementary contributions of PPAR isotypes to energy homeostasis
Authors: Vanessa Dubois, Jérôme Eeckhoute, Philippe Lefebvre, Bart Staels
Journal: Journal of Clinical Investigation (2017)

Peroxisome proliferator–activated receptors (PPARs) regulate energy metabolism and hence are therapeutic targets in metabolic diseases such as type 2 diabetes and non-alcoholic fatty liver disease. While they share anti-inflammatory activities, the PPAR isotypes distinguish themselves by differential actions on lipid and glucose homeostasis. In this Review we discuss the complementary and distinct metabolic effects of the PPAR isotypes together with the underlying cellular and molecular mechanisms, as well as the synthetic PPAR ligands that are used in the clinic or under development. We highlight the potential of new PPAR ligands with improved efficacy and safety profiles in the treatment of complex metabolic disorders.
Phase I/II study of dianhydrogalactitol in patients with recurrent malignant glioblastoma multiforme (GBM).
Authors: Kent C. Shih, Manish R. Patel, Nicholas A. Butowski, Jeffrey A. Bacha, Dennis Brown, William J. Garner, Anne Steino, Richard Stephen Schwartz, Sarath Kanekal, Lorena Lopez, Howard A. Burris
Journal: Journal of Clinical Oncology (2014)

TPS2109 Background: Median survival for patients with recurrent GBM is < 6 months. Front-line systemic therapy is temozolomide but resistance due to O6-methylguanine-DNA-methyltransferase (MGMT) activity is implicated in poor outcomes. Dianhydrogalactitol (VAL-083) is a structurally unique bi-functional DNA alkylating agent that accumulates in brain tumor tissue. Previous clinical studies suggest that VAL-083 has anti-tumor activity against a range of cancers including GBM. In in vitro studies VAL-083 demonstrated activity in pediatric and adult GBM cell lines, as well as GBM cancer stem cells. Notably, VAL-083 overcomes resistance to MGMT in vitro. In light of extensive safety data from clinical trials and promising efficacy in CNS tumors, DelMar initiated a new clinical studyto establish the maximum tolerated dose (MTD) and identify a dose and dosing regimen for future efficacy trials in GBM. Dose limiting toxicity is expected to be myelosuppression, the management of which has improved in recent years. Early in the development of VAL-083, a cumulative IV dose of 125 mg/m2 delivered in a 35 day cycle in combination with radiation was shown superior to radiation alone in brain cancer (Eagan, et al. 1979). In the present study, the cumulative dose in a 33 day cycle ranges from 9 mg/m2 (cohort 1) to 240 mg/m2 (cohort 7). Five dose cohorts, with the highest 33 day cycle cumulative dose of 120 mg/m2, have completed the trial with no drug-related serious adverse events: MTD was not yet reached. Enrollment for cohort 6 (33 day cumulative dose: 180 mg/m2) has been initiated. The final cohort of this study, cohort 7 (33 day cumulative dose: 240 mg/m2), will be initiated subject to no DLT in cohort 6; the results will determine the design of the safety and efficacy registration trial. Methods: Open-label, single-arm Phase I/II dose-escalation study in patients with histologically-confirmed initial diagnosis of malignant GBM. The study utilizes a 3+3 dose-escalation design. Patients receive VAL-083 IV on days 1, 2, and 3 of a 21 day cycle. GBM patients previously been treated with surgery and/or radiation, if appropriate, must have failed both bevacizumab and temozolomide, unless contraindicated. Clinical trial information: NCT01478178.
Retrospective analysis of the safety and efficacy of vandetanib as systemic treatment for patients with advanced and progressive medullary thyroid cancer (MTC).
Authors: Jaume Capdevila, Javier Martinez-Trufero, Elsa Dalmau, Cristina Alvarez-Escola, Miguel Beltran, Manuel Duran, Isabel Gallegos, Jose Luis Manzano, Ricard Mesia, Isabel Pajares, Jose Fuentes Pradera, Juan J. Grau, Òscar Reig, Jose Manuel Trigo, Enrique Grande
Journal: Journal of Clinical Oncology (2014)

e17015 Background: Vandetanib is a multikinase inhibitor (MKI) directed against VEGFR2-3, RET, RET/PTC and EGFR that has demonstrated significant efficacy in advanced MTC in a large phase III trial (NCT00410761). However, little evidence is available on safety and efficacy in a subgroup of patients (pts) with worse prognosis in the community setting. Methods: Pts with advanced, unresectable MTC with previous radiologicaly documented disease progression were included in a compassionate use program in Spain. Pts received vandetanib 300 mg qd as the initial dose, allowing dose reductions as per toxicity. Primary endpoint was response rate (RR) by RECIST and secondary endpoints were toxicity profile, progression-free survival (PFS) and correlation of RR and biomarkers. The program was validated by regulatory authorities and all patients signed an informed consent form. Results: 22 pts were enrolled (med age: 56 y; male: 50%). Vandetanib was given as first-line MKI in 59%, second-line in 23% and third-line in 18% of pts. Dose reductions were needed in 40% of patients to manage toxicity. Main side effects were grade 1-2 including fatigue (32%), diarrhea (32%), rash (32%), hand-foot syndrome (13%), mucositis (13%), AST/ALT elevation (13%) and hypertension (9%). The most frequent grade 3-4 side effect was rash in 13% of pts. 18 pts were evaluable for efficacy. Overall RR was 28%, disease stabilization was 55% and 17% had progressive disease. No significant differences were found regarding treatment lines and previous exposure to MKIs. Median PFS was 15.4 months (range 7.7-23.1 months) with 50% of patients still on treatment at the time of analysis. No correlation was found between calcitonin reduction and disease control rate (RR + SD). However, CEA level variation (30% increase or decrease versus baseline levels) appeared to predict tumor growth control or progression in 78% of cases (p=0.333). Conclusions: Vandetanib showed meaningful activity with an acceptable safety and toxicity profile in refractory and progressive MTC in a cohort of patients with a worse prognosis than previously reported. Activity is seen regardless of treatment line.
A phase II study of S-1 in gemcitabine-refractory metastatic pancreatic cancer
Authors: C. Morizane, T. Okusaka, J. Furuse, H. Ishii, H. Ueno, M. Ikeda, M. Najima, S. Hirokawa, K. Nakachi, T. Ogura
Journal: Journal of Clinical Oncology (2006)

4115 Background: Gemcitabine (Gem) monotherapy or Gem-containing chemotherapy is the standard first line therapy for advanced pancreatic cancer. After disease progression, there is no standard regimen available. In a previous phase II trial (J. Furuse et al, Proc ASCO 2005: # 4104), S-1 has been reported to show considerable efficacy, achieving a response rate of 37.5% in chemo-naïve patients with pancreatic cancer. This study evaluated the efficacy and toxicity of S-1 in patients with Gem-refractory metastatic pancreatic cancer. Methods: Eligibility criteria were pathologically-proven pancreatic cancer with confirmation of progressive disease while receiving Gem-based chemotherapy, Karnofsky performance status 80 to 100%, age 20 to 74 years, with measurable metastatic lesions, adequate hematological, renal and liver functions, and written informed consent. S-1 was administered orally at 40 mg/m 2 twice daily for 28 days with a rest period of 14 days as one course. Administration was repeated until the appearance of disease progression or unacceptable toxicity. The primary study end point was objective response, secondary end points included toxicity, progression-free survival (PFS) and overall survival, as well as clinical benefit response in symptomatic patients. Results: Forty patients (pts) from two institutions were enrolled between September 2004 and November 2005. Thirty-three pts are currently evaluable for response in this ongoing trial. There have been 5 confirmed partial responses (12.5%), and 14 pts (35%) with stable disease. Median survival has not been reached. Median PFS was 2.1 months. Toxicity data were available for 28 patients. Grade 3 and 4 toxicities were anemia (1 pts), appetite loss (2 pts), and fatigue (2 pts). Conclusions: Preliminary results demonstrated the safety and activity of S-1 in Gem-refractory metastatic pancreatic cancer. Efficacy and toxicity analysis are ongoing. Final results will be presented at the meeting. No significant financial relationships to disclose.