tbuckley/cabot-search huggingface dataset:
Use of the Optimata Virtual Patient (OVP) to predict effects of sunitinib malate in advanced pancreatic cancer.
Authors: M. Kleiman, S. Shacham, M. Kushnir, E. Chapnik, Z. Agur
Journal: Journal of Clinical Oncology (2011)

341 Background: Pancreatic cancer is considered to be incurable by available treatment modalities, with 5-year survival rate &lt;4%. Sunitinib malate (Sutent) significantly increased progression-free survival in patients with advanced islet cell tumors (pancreatic); however, it demonstrated only modest single-agent effect in a phase II study in patients with metastatic pancreatic adenocarcinoma (PaC) that progressed after first-line therapy with gemcitabine. To improve the response of PaC patients to drugs, the interplay between biologic, pathologic, and pharmacologic processes underlying drug-patient interactions have been mathematically modeled, predicting efficacy responses, different toxicities, and long-term tolerability in clinical trials, allowing for improved dosing regimens and patient selection (OVP engine) (Agur Z., 2010). The OVP engine was used to predict Sunitinib malate single-agent activity in advanced PaC. Methods: OVP replicated the observed growth patterns of human PaC. Pharmacokinetics (PK) and pharmacodynamics (PD) of sunitinib malate were modeled based on literature (NDA 21-938). Effects of sunitinib malate on human PaC xenografts were scaled to model PK/PD in human. To evaluate drug efficacy in advanced PaC patient-population, a Virtual PaC Patient- Population was created by replacing the population averaged parameter values in the model by their distribution in the population. Using this procedure, a large set of virtual patients was generated. Model simulations with sunitinib malate therapy (50 mg QD/28 days; 14 days rest [1 cycle]) enabled the prediction and classification of patients' response according to RECIST criteria and compared with the actual clinical response (O'Reilly et al, 2008). Results: Simulations of the FDA-approved schedule, predicted a stable disease in 81% of the patients following one treatment cycle and 54% following two treatment cycles. Stable disease was predicted to be the best observed response, which was confirmed in the clinical study. Conclusions: Our model predictions are compatible with clinical results of a recent phase II trial with the same treatment regimen of sunitinib malate (O'Reilly et al, 2008) and further suggest the use of mathematical model during drug development. [Table: see text]
Shared decision-making in chronic lymphocytic leukemia: Preferences and perceptions of patients, providers, and navigators.
Authors: Gabrielle Betty Rocque, Emily Van Laar, Uma Borate, Karina I. Halilova, Pamela M. Peters, Bradford E. Jackson, Maria Pisu, Thomas Wayne Butler, Randall S. Davis, Amitkumar Mehta, Aras Acemgil, Sara J. Knight, Monika M. Safford
Journal: Journal of Clinical Oncology (2016)

221 Background: In recent years, new treatments for chronic lymphocytic leukemia (CLL) with excellent response rates and varying toxicity profiles have emerged. In the setting of multiple available options, shared decision-making is critical. Developing strategies to enhance shared decision-making requires better understanding of how patients and providers make treatment decisions. Methods: Patients with CLL and health care providers within the University of Alabama at Birmingham Health System Cancer Community Network were to assess how treatment decisions are made. Results: Forty-four patients with CLL completed telephone-based surveys. The median age was 69 years old. Thirty percent had completed ≤12 years of education, 20% had some college education. Seventy-three percent of patients preferred an active or shared role in decision-making (27% preferring to make decision, 23% making decision with physician input, and 45% a shared role). Only 2% of patients preferred the doctor select the treatment. Despite &gt;50% preferring an active role, only 20.5% perceived having an active role (Table 1). Thirty-three lay patient navigators, 26 oncologists, and 28 nurses (RN)/advanced care providers (ACP) completed web-based surveys. Navigators and nurses perceived a greater patient role in decision-making than physicians, who perceived that decisions were most often shared. Conclusions: Patients and providers have differing perceptions of their roles in decision-making in CLL treatment. Patients desire higher levels of participation in decision-making than they perceive that they receive, suggesting an opportunity for education of patients and providers to improve shared decision-making. [Table: see text]
Are hospital clinicians aware of legislation surrounding provision of palliative care?
Authors: Aaron Kee Yee Wong
Journal: Journal of Clinical Oncology (2016)

118 Background: Many deaths require medical treatment to be withheld or withdrawn. Patients or their substitute decision makers may disagree with these decisions, and sometimes refuse the right to appropriate palliative care. An awareness of legal frameworks surrounding end of life decisions is vital to navigate through these conflicts. Without this, patients suffer unnecessarily. Methods: 542 hospital doctors and nurses were recruited from a large metropolitan public tertiary teaching hospital network involving 5 campuses and 2 medical schools. A questionnaire examined their regarding legislation surrounding end of life care, both in adults with and without capacity. Results: Approximately a quarter of respondents did not believe that the “Not for Resuscitation Form” is legally a medical decision. Most doctors (68%), but not nurses, believed competent patients cannot demand futile treatment. Most clinicians (79% doctors and 85% nurses) erroneously believe that competent patients can refuse appropriate palliative care. There was significant confusion regarding the roles of substitute decision makers. Most clinicians could not find the advance directive. Groups with most correct answers were doctors, had 5-10 years experience, and were in palliative care and critical care specialties. Conclusions: This study confirms poor knowledge regarding legislation surrounding provision of palliative care. An unusually high proportion believed patients could refuse appropriate palliative care. Most clinicians could not locate advance directives. Most nurses believed patients could legally demand futile treatment. Both junior and senior staff had comparably poor knowledge in this area.
Results of toxicology studies with MPC-3100, an oral HSP90 inhibitor.
Authors: G. G. Mather, D. J. Scholl, V. L. Belcher, C. Bradford, D. I. Papac
Journal: Journal of Clinical Oncology (2011)

e13016 Background: MPC-3100, an orally bioavailable synthetic inhibitor of HSP90, has demonstrated efficacy in animal models and is currently in a phase I clinical study in cancer patients. Toxicology studies were conducted to support the long term safety of MPC-3100. Methods: MPC-3100 was administered to rats daily by gavage at 50, 100, or 200 mg/kg for 28 consecutive days or at 25, 50, or 100 mg/kg for 117 days. In cynomolgus monkeys, MPC-3100 was given daily at 10, 25, or 50/35 mg/kg for 28 days or at 6.25, 12.5, or 25 mg/kg for 113 days. Endpoints included weight gain, food consumption, clinical chemistries, hematology, urinalysis, pathologic, and histopathologic evaluation. ECGs were performed on monkeys and ophthalmoscopic examinations were conducted on all animals. Results: Daily doses of 200 mg/kg for 28 days or 100 mg/kg for 117 days exceeded the maximum tolerated dose in rats. Clinical observations were limited to gastrointestinal effects. Generalized lymphoid depletion, mild to moderate hepatobiliary effects, mild changes in hematology, electrolytes, AST/ALT, and changes in the nonglandular stomach and intestine were noted at doses ≥100 mg/kg/day. Toxicity was greater in males. All of the observations were reversible with cessation of treatment. The no observable adverse effect level (NOAEL) after 28 or 117 days was 100 and 50 mg/kg/day, respectively. In monkeys, mortality was noted following 4 days of treatment at 50 mg/kg and 20 days of treatment with dose reduction to 35 mg/kg. Inappetance and diarrhea were associated with gastrointestinal effects. Additional effects were lymphoid depletion, decreased erythrocytes, hemoglobin, hematocrit, and mild changes in electrolytes. Reticulocytes tended to be higher. There were no drug-related effects on clinical pathology parameters at doses up to 25 mg/kg for 113 days or changes to qualitative or quantitative ECG parameters in either study. The NOAEL was 25 or 12.5 mg/kg/day for 28 or 113 days of administration. There were no ocular findings in rats or monkeys. Conclusions: Long term administration of MPC-3100 to rats or monkeys at high doses may result in lymphoid depletion and mild changes in hematology and/or electrolytes. All adverse effects appeared to be reversible upon cessation of treatment.
Value of circulating epithelial tumor cells and circulating endothelial cells (CTCs/CECs) in patients with HER2-negative recurrent or metastatic breast cancer treated with bevacizumab (B) in combination with paclitaxel (P) and gemcitabine (G) as first-line therapy (AVALUZ trial).
Authors: Manuel Codes, Luis Manso, Eva M. Ciruelos, Juan De la Haba- Rodriguez, Antonio Galan, Jose Manuel Baena, Ana Jaen, Miquel Gil, Adolfo Murias, Isabel Blancas, Encarnacion Gonzalez, Diego Perez, Juan L. Bayo, Jose Ramón Mel, Elena Garcia-Martinez, Ricardo Cubedo, Javier Salvador
Journal: Journal of Clinical Oncology (2012)

e21088 Background: CTCs in peripheral blood are an ideal source for the detection of tumor dissemination. Their prognosis significance has been demonstrated in metastasic breast carcinoma (Cristofanilli, NEJM 2004). Beacizumab in combination with CT, improves progression free survival (PFS) of first line treatments, may modify CTC and CEC levels. Aims of this study are the evaluation of the prevalence and kinetics of CTCs and CECs before and after treatment with B in pts with MBC Methods: Pts received B 10mg/kg/q2w combined with P 150mg/m 2 and G 2000mg/m 2 d1,15/q28d therapy until disease progression, unacceptable toxicity or withdrawal. CTC/CEC were measured in 7.5ml of blood at baseline and after the 1 st cycle of treatment. Enumeration was performed by CellSearch System, Veridex Results: Data were available for 37 pts. Median of f-up was 16.2 m. The media of CTCs was 41 cells (min0-max845) in the 1st determination and 5 cells (min0-max99) in 2nd determination. Baseline CTCs&gt;2 was associated with statistic lower PFS 10.8 m (95%CI:7.66-16.91) compared to those with CTCs&lt;2, PFS 17.7m (95%CI:17.60-NA),p=0.046. Baseline CTCs&gt;10 vs CTCs&lt;10 was associated with statistic lower OS (14%vs45% of deaths), p=0.035. 92% (N=22) of pts that had stable disease/partial response, decreased or maintained CTCs value. CTC level was not correlated with CEC level, p=0.74. Media value of baseline CECs was 130 (min4-max1407) and 60.3 (min0-max349) in 2nd determination. Baseline CECs&gt;200 was associated with lower PFS 8.2m (95%CI:0.6-10.8) compared to those with &lt;200, PFS 16.9m (95%CI:8.78-NA),p=0.003. No difference was observed in OS. 74% of pts (N=14) that had stable disease/partial response, decreased or maintained CECs value. Baseline CTCs &gt;5 was associated with a median PFS of 15.2 m (95%CI:7.6-16.9) Conclusions: Our study suggests significant correlations between levels of baseline CTCs and CECs and poor prognosis. Addiction of B to 1st-line CT was related with high reduction of CECs and CTCs count.
Feasibility of salvage focal nodal SBRT or protracted elective nodal irradiation in <sup>18</sup>F fluoro-choline PET based nodal failures from prostate cancer.
Authors: Alexis Lepinoy, Etienne Martin, Magali Quivrin, Mélanie Gauthier, Philippe Maingon, Francois Brunotte, Alexandre Cochet, Gilles Crehange
Journal: Journal of Clinical Oncology (2016)

290 Background: 1) To establish the feasibility of salvage nodal radiotherapy in patients with 18 F Fluoro-choline (FCH) PET+ nodal recurrence only from a prostate cancer. 2) To compare salvage focal FCH PET+ stereotactic radiation therapy (sf-SRT) with salvage elective nodal irradiation with a protracted FCH PET+ nodal boost (seni-PRT) . Methods: Between 2009 and 2014, 42 patients out of 102 patients with FCH PET for a rising PSA after RP or radiotherapy had positive lymph nodes only. Twenty nine patients had sf-SRT and 13 patients had seni-PRT in a curative intent. Acute and late genito urinary (GU) and gastro intestinal (GI) toxicities were assessed with CTCAE v4. Failure was defined as a rising PSA higher than the maximal pre-therapeutic PSA value followed by 2 consecutive rises or a nodal or distant metastatic failure or the initiation of any salvage therapy. Results: Seventy-six nodes were diagnosed with FCH PET/CT with a median PSA value of 2.8 [0.3 -29.2] at time of failure. Mean number of nodes was higher in the seni-PRT group than in the sf-SRT group (2.8 vs 1.6). The median prophylactic dose of WPRT and/or LA was 48.0 Gy [36.0-54.0] and the median dose delivered to involved FCH PET+ nodes was 66.0 Gy [46.0-70.0] with a median dose per fraction of 2.0 [1.8-2.2]. In the sf-SRT group, the median dose to the involved nodes was 36 Gy [18-45] with a median dose per fraction of 7.5 Gy [6-15]. After a median follow-up of 19.1 months [2.9-74.1], no difference was observed for GI or GU toxicities between the 2 groups (p = 0.26 and p = 0.19). One grade 4 GI and GU toxicity occurred in 1 patient in the seni-PRT group. The median freedom from failure (FFF) time was 14.8 months for sf-SRT and 37.6 months for seni-PRT with 2-year FFF rates of 47.8 % and 72.7 %, respectively. Conclusions: FCH PET+ node-targeted salvage radiotherapy is feasible with very low rates of toxicity. Freedom from failure was significantly improved with protracted elective nodal irradiation, suggesting that nodal disease diagnosed on FCH PET may not be an oligometastatic disease. Dose escalated seni-PRT is currently being investigated in a French phase II trial (Oligopelvis- GETUG P07).
Is adjuvant oxaliplatin (Ox) overutilized in colon cancer (CC): 408 cases from the practices of 102 oncologists.
Authors: Kathryn Ziel, Axel Grothey, Alan Paul Venook, Atif Mahmoud Hussein, Jonathan Moss, Neil Love
Journal: Journal of Clinical Oncology (2013)

e14564 Background: Recent long-term clinical trial follow-up suggests that adding Ox to a fluoropyrimidine (FP) may provide less benefit in adjuvant CC than originally believed (Tournigand JCO 2012). In addition, emerging data on tissue biomarkers such as microsatellite mismatch repair (MMR) and the 12-gene Recurrence Score (RS) suggest these assays may be helpful in better defining treatment benefit, and a new report provides evidence that RS may specifically predict the value of Ox (O'Connell ASCO 2012). In view of these developments we sought to document current use of adjuvant chemotherapy and physician perceptions about these decisions. Methods: U.S.-based oncologists were recruited to complete a survey and contribute treatment data for their last three patients (pts) with stage II disease and last pt with a stage III tumor. Results: 25 gastrointestinal cancer clinical investigators and 77 practicing oncologists participated, providing data from a total of 408 cases (92% treated since 2011). Findings from the two groups are similar and are presented in aggregate. A median of 9 and 15 pts annually were evaluated with Stage II and III tumors, respectively. Clinicians stated that they require a median of a 5% absolute reduction in relapse rate to use a FP alone and an additional 5% reduction to add Ox. Ox/FP was administered to 95 of 102 pts with stage III tumors (93%) and 85 of 306 pts with stage II disease (28%), particularly to those under age 70 or with T4 tumors (Table). MMR was evaluated in 127 pts (42%) with stage II and 20 pts (20%) with stage III disease. RS was obtained for 46 pts (15%) with stage II tumors, but only 2 pts (2%) with stage III. Conclusions: Adjuvant Ox is employed widely in spite of the fact that it may provide less benefit than many oncologists report requiring to initiate its use. However, several recent research developments may be laying the groundwork for a change in this treatment practice. [Table: see text]
Tumor cancer stem cell genetic profile as predictor of relapse in stage II and III radically resected colon cancer patients.
Authors: Riccardo Giampieri, Mario Scartozzi, Cristian Loretelli, Alessandra Mandolesi, Alessandro Bittoni, Luca Faloppi, Maristella Bianconi, Italo Bearzi, Stefano Cascinu
Journal: Journal of Clinical Oncology (2013)

429 Background: Although disease stage is the most relevant factor influencing treatment choice in locally advanced radically resected colon cancer, it is not uncommon to observe disease relapse in patients with apparent low risk stage that are usually excluded from an adjuvant therapy. On the contrary we also know that some patients with high risk stage are not likely to relapse, independently from medical treatment received. Preclinical data suggested that cancer stem cells may influence the biological behaviour of many solid tumours including colorectal cancer, we then tested a panel of genetic markers of stemness in resected Dukes stage B and C colorectal cancer patients in order to define a prognostic profile. Methods: We performed k-means unsupervised clustering (K=2) using the mRNA expression data of 66 genes. The algorithm divided the patients into two groups (A and B). Most patients clustered in a manner consistent with relapse free survival, defined as the time between primary surgery and first radiological sign of metastatic involvement or patients death, whichever came first. Results: A total of 62 patients were analysed (36, 58% stage II and 26, 41% stage III), 36 (58%) patients relapsed during the follow-up period (range 1.63-86.5 months). Respectively 12 (19%) and 50 (81%) patients were allocated into group A and B. A significantly different median relapse-free survival was observed between the 2 groups (22.18 vs 42.85 months, p=0.0296). Interestingly, even if group A had a worse outcome in terms of risk of relapse, an higher proportion of stage II patients could be found in this group (83%) when compared with the group B (52%). Among tested genes, those with the highest capability in determining allocation into one of the two groups were CD44, ALCAM, DTX2, HSPA9, CCNA2, PDX1, MYST1, COL1A1 and ABCG2. Conclusions: This analysis supports the idea that, other than (or maybe more than) stage, biological variables, such as expression levels of colon cancer stem cell genes, may be relevant in determining an increased risk of relapse in resected colorectal cancer patients. Our findings may also be relevant for new treatment strategies targeting tumour stem cells genetic profile.
A NSQIP analysis of 30-day complications after bilateral versus unilateral mastectomy with immediate reconstruction.
Authors: Amanda Kathryn Silva, Brittany Lapin, Katharine Yao, David H. Song, Mark Sisco
Journal: Journal of Clinical Oncology (2014)

62 Background: Women with breast cancer are increasingly electing to undergo contralateral prophylactic mastectomy (CPM) despite questionable survival benefit and limited data on added risks. This study seeks to assess differences in perioperative complications between those who have bilateral mastectomy with reconstruction (BM/R) and unilateral mastectomy with reconstruction (UM/R). Methods: The American College of Surgeons National Surgery Quality Improvement Program Participant Use Files (2005-2012) were used to identify women with breast cancer undergoing UM/R or BM/R. 30-day complications after implant-based or autologous reconstruction were compared between UM/R and BM/R groups. Linear and logistic regression models were used to adjust for differences in age, obesity, smoking, diabetes, and hypertension between groups. Results: 18,229 patients were identified, of whom 6,502 (35.7%) underwent BM/R. Most patients underwent implant-based reconstruction (88.6% of BM/R and 79.4% of UM/R). Among patients with implant-based reconstruction, BM/R was associated with higher rates of implant loss (adjusted odds ratio [aOR] 1.55, p=0.02), transfusion (aOR 2.20, p&lt;0.001), and reoperation (aOR 1.14, p=0.05) than was UM/R. Patients who had BM/R with autologous reconstruction were more likely to require transfusion (aOR 2.34, p&lt;0.001) than those who had UM/R. BM/R was associated with a greater length of hospital stay (LOS) than was UM/R for implant and autologous reconstruction groups (aOR [for LOS ≥ 2 days] 2.22 and 2.25, respectively, p&lt;0.001). There were no significant differences in rates of medical complications, surgical site infection, or wound disruption between UM/R and BM/R groups for either type of reconstruction. Conclusions: Women who undergo implant-based BM/R have a greater risk of implant loss and reoperation then those who undergo UM/R. Those who have BM/R are also more likely to require a transfusion and have a longer hospital stay, regardless of reconstruction type. Women considering CPM with reconstruction should be educated about these increased risks.
Bleeding in Patients with Atrial Fibrillation Treated with Different Doses of Direct Oral Anticoagulants and Vitamin K Antagonists: A Population-Based Study
Authors: Martin H. Ellis, Orly Avnery, Estela Derazne, Erez Battat, Sari Greenberg Dotan, Ariel Hammerman, John Eikelboom, Jeffrey S. Ginsberg, Jack Hirsh
Journal: Blood (2016)
Inhibition of angiogenesis: Thalidomide or low-molecular-weight heparin? Authors' reply
Authors: Metin Ozkan, Bulent Eser, Ozlem Er, Gamze Gokoz Dogu, Mustafa Altinbas, William D. Figg, Avi Retter, Seth M. Steinberg, William L. Dahut
Journal: Journal of Clinical Oncology (2005)
Experience with adjuvant single-agent carboplatin therapy for clinical stage I seminoma
Authors: R. Morales-Barrera, M. Chilaca Rosas, C. Molina-Calzada, O. G. Arrieta, M. Alvarez-Avittia, J. de la Garza, G. Calderillo, M. A. Jimenez-Rios, E. Calvo-Aller, J. L. Aguilar-Ponce
Journal: Journal of Clinical Oncology (2008)

16131 Background: Testicular cancer accounts for only 1% of all male malignancies. Worldwide, an estimated 49,000 cases are diagnosed and 9,000 men die of the disease annually. In 2002, 1,265 new cases and 339 deaths were reported in Mexico. More than 90% of patients are cured. Standard treatment of these patients involves radical orchiectomy and routine adjuvant radiation therapy (RT) to the retroperitoneal and ipsilateral pelvic lymph nodes. Relapse rates range around 3% to 5%, and overall survival approaches 100%. Methods and Patients: Patient selection: Data from a retrospective chart review of all patients diagnosed with stage I seminoma and treated with adjuvant carboplatin at the Instituto Nacional de Cancerologia from September 2004 to June 2007 were analyzed. The patients were enrolled into the study if all of the following eligibility criteria were met: histological diagnosis of seminoma; radical inguinal orchiectomy was performed; no clinical and radiological evidence of nodal or distant metastasis found. Adjuvant Chemotherapy: Adjuvant chemotherapy consisted of single-agent carboplatin. Carboplatin doses were given intravenously and calculated by a formula based on the area- under-the-curve (AUC) estimate of drug clearance from the body. Results: A total of 67 patients with stage I seminoma were treated between September 2004 and January 2007. All patients underwent inguinal orchiectomy for testicular seminoma. The median tumor diameter, available in 37 patients, was 60 mm and 16% of patients had a tumor 4 cm long in its largest dimension. At the time of the present analysis, median follow-up time was 14 months. Relapses: Relapses were observed in 3 patients (4.4%). Recurrence was observed more in the older aged patients (> 30 years). All patients are currently alive. Conclusion: Adjuvant chemotherapy is a safe standard of care in controlling microscopic retroperitoneal disease in patients with clinical stage I seminoma. About 4% of patients undergo relapses. Overall survival rate is 100%. No significant financial relationships to disclose.