tbuckley/cabot-search huggingface dataset:
Second line axitinib in metastatic renal cell carcinoma: Evaluation of prognostic factors influencing outcome.
Authors: Helen Brooks, Amarnath Challapalli, Hannah Reed, Susan Masson, Serena Hilman, Amit Bahl
Journal: Journal of Clinical Oncology (2017)

495 Background: Axitinib has been approved for 2nd line treatment in the UK for patients with advanced renal cell carcinoma on the basis of the AXIS study, which showed improved progression free survival (PFS) and a trend towards overall survival (OS) benefit. There is no randomised data to support the use of Axitinib after first line Pazopanib. Hence, we compared the efficacy of Axitinib after first line Pazopanib or Sunitinib. The influence of Heng prognostic risk score (HPRS) at initiation of Axitinib, previous nephrectomy, and haemoglobin (Hb) rise during Axitinib treatment on outcome was also evaluated. Methods: Thirty one patients were commenced on Axitinib between May 2013-May 2016. Patient demographics, laboratory parameters, and survival data were collected retrospectively. Data were analysed in October 2016, which served as a censor date for patients who were alive. Analysis of PFS and OS was performed by Kaplan-Meier estimates and log-rank test. Results: All 31 patients received axitinib as 2nd line treatment. At the time of analysis, 14 patients were alive and 7 remained on axitinib. The prognostic factors influencing outcome are shown in the table. Conclusions: There was no significant difference in PFS or OS regardless of first line treatment, supporting the use of axitinib post pazopanib or sunitinib. Prior nephrectomy, and favourable HPRS significantly predict better PFS and OS. The impact of Hb rise needs further validation in a larger cohort.[Table: see text]
Needs assessment and utilization of an educational workshop and support group for Lynch syndrome patients.
Authors: Rohini Rau-Murthy, Christopher Anrig, Emily Glogowski, Erin E. Salo-Mullen, Megan Harlan Fleischut, Kara Sarrel, Marina Corines, Kate Niehaus, Mark E. Robson, Arnold Markowitz, Noah D. Kauff, Kenneth Offit, Zsofia Kinga Stadler
Journal: Journal of Clinical Oncology (2013)

e12536 Background: Lynch syndrome (LS) requires a lifelong commitment to multi-organ cancer surveillance and/or prophylactic surgery. Emotional and informational support for LS patients is not readily available. Through an LS Educational Workshop (LSEW) we assessed the need and interest in an educational and support group for LS families. Methods: LS patients identified at Memorial Sloan-Kettering Cancer Center (MSKCC) were sent LSEW invitations and a pre-workshop survey. All patients underwent prior genetic counseling. Though family members could attend, only index patients completed the surveys. All attendees were asked to complete both an evaluation of the LSEW and a needs assessment regarding implementation of a support group. Results: Invitations to 213 LS patients were mailed. Of 8 potential discussion topics, the most desired were chemoprevention and cancer screening recommendations. Thus, the 1 st hour of the LSEW was a didactic session by physicians on these topics and LS research. The 2 nd hour was a panel on patient experiences, family communication and Q&amp;A. Fifty-three patients (25% of those invited) and 22 family members attended. The LSEW evaluation was completed by 26 index attendees, with 88% overall satisfied or extremely satisfied. Common requests for improvement were better division of informational and support aspects, and more Q&amp;A. Of 23 who completed the needs assessment, 73% considered an LS support group as either somewhat or extremely useful. The group was equally divided on preference for a free-flow vs topic-focused approach; 57% felt a support group would have increased utility immediately after genetic testing. An in person venue was preferred by 87% over a virtual one, and 73% preferred every 3-6 month meetings. Respondents preferred a group inclusive of gender and cancer history. Based on this, the MSKCC Lynch Syndrome Patient Advocacy Network was created in 2012 with an in-person, every 4 month meeting facilitated by a social worker. Conclusions: Following genetic counseling, there is a continued need for informational sessions and support groups for LS patients/family members. Implementation of an in-person support group is feasible and responsive to the needs of our LS population.
Intraoperative conversion from partial to radical nephrectomy: Predictive factors and outcomes.
Authors: Firas G. Petros, Sarp K. Keskin, Kai-Jie Yu, Bryan M. Fellman, Michael J. Metcalfe, Surena F. Matin, Jose A. Karam, Christopher G. Wood
Journal: Journal of Clinical Oncology (2017)

483 Background: Predictive risk factors for intraoperative conversion from partial to radical nephrectomy (RN) are poorly quantified. We evaluated preoperative predictors of conversion in a cohort of patients undergoing planned partial nephrectomy (PN). Methods: A prospectively maintained database was reviewed to identify patients who were scheduled to undergo (open, laparoscopic, or robot-assisted) PN that were converted to RN between 1990 and 2015. Reasons for conversion were collected from the operative report. Patient demographics and perioperative variables were evaluated including body mass index (BMI), tumor size, nephrometry score, hilar tumors, procedure type, intraoperative complications, and oncologic outcome. Results: A total of 2298 patients underwent successful PN. The rate of conversion to RN was 4% (n=99) patients. The median patient age was 60 years and median BMI was 30 kg/m 2 . The median American Society of Anesthesiologists (ASA) score was 3 and median Charlson Comorbidity Index (CCI) was 2. The median tumor size for the converted cases was 4.5 cm (1.0-10.1) and median nephrometry score was 9. Histology was clear cell-RCC in 79% of the tumors. A total of 30 patients had completely endophytic tumors. The most common reasons for conversion were hilar/renal sinus extension of the renal mass in 38 (38%) patients, positive surgical margin on frozen section or gross assessment in 27 (27%) patients, insufficient renal remnant in 27 (27%) patients, and excessive intraoperative bleeding in 7 (7%) patients. RN was performed open in 79, laparoscopically in 9, and robot-assisted in 11 cases. Intraoperative complications occurred in 1 (1%) patient underwent an attempted robot-assisted PN resulted in an injury to a major renal artery branch requiring conversion to RN. Patients were followed up for a median of 33 months. In the converted cohort, evidence of disease at last follow-up was found in 13 (13%) patients. Conclusions: The rate of conversion to RN was low in patients undergoing PN in this series. The most common reason for conversion was hilar/renal sinus extension of these complex renal masses while positive surgical margin and insufficient renal remnant were contributing equally at lower rates.
Early post-therapy prescription drug usage among survivors of childhood cancers.
Authors: Andrew Brian Smitherman, Danielle Mohabir, Tania Wilkins, Julie Blatt, Hazel Nichols, Stacie Dusetzina
Journal: Journal of Clinical Oncology (2017)

147 Background: Childhood cancer survivors often develop treatment-associated morbidities. We hypothesized that emerging treatment-related medical morbidities would be reflected in patterns of prescription drug usage among survivors in the first three years after therapy completion. Methods: Using the Truven Health MarketScan Commercial Claims database, we identified survivors of childhood (0-21 years-old at diagnosis) leukemia, lymphoma, central nervous system (CNS), bone, or gonadal tumors who completed therapy during 2000 - 2011. Patients were identified using diagnosis codes and cancer-specific procedure codes for chemotherapy, surgery, or radiation therapy. Prescription fills during the first three years following therapy completion were examined and categorized by drug class. Median numbers of prescriptions per survivor were compared to age- and sex-matched children without cancer. Relative risks (RR) for any prescription and for prescriptions by drug class were calculated comparing survivors to children without cancer. Results: We identified 1,414 survivors and 14,140 children without cancer. The median number of unique drug class prescriptions among survivors ranged from 4 [gonadal] to 8 [CNS] in year 1 and from 2 [gonadal] to 6 [CNS] in year 3 compared to a median of 1 among children without cancer (p &lt; 0.001 for all comparisons). Increased risks for fills of antibiotics (RR in year 1: 1.5 [CNS, gonadal], 1.7 [bone], and 1.8 [leukemia, lymphoma]) and opioids (RR in year 1: 2.4 [lymphoma], 2.7 [gonadal], 4.0 [CNS], and 4.8 [leukemia, bone]) persisted throughout the three years among all cancer groups. Survivors of leukemia, lymphoma, CNS, and bone tumors had 2-4 times the risk for antidepressant prescriptions and 4-10 times the risk for anxiolytics. Survivors of leukemia, lymphoma, and bone tumors had 8-10 times the risk for ACE inhibitor prescriptions by the third year off therapy. Conclusions: Compared to children without cancer, childhood cancer survivors have higher rates of prescription drug use across many drug classes indicative of their higher burden of medical morbidities. Careful attention should be given to emerging morbidities during the early off-therapy period.
A phase IB, multicenter, open-label study to assess the safety, tolerability, and efficacy of the pleiotropic pathway modifier CC122 administered orally to patients with advanced HCC.
Authors: Robin Kate Kelley, Kent C. Shih, Fadi S. Braiteh, Drew W. Rasco, Antoine Hollebecque, Filippo de Braud, Anthony Goncalves, Andres Cervantes-Ruiperez, Xin Wei, Patrick Hagner, Anita K. Gandhi, Kristen Hege, Michael Pourdehnad, Armando Santoro
Journal: Journal of Clinical Oncology (2017)

379 Background: CC122 is a novel cereblon-modulating agent with multiple biologic activities including potent immunomodulatory and antiangiogenic effects. CC-122 binding to cereblon promotes ubiquitination and subsequent degradation of lymphoid transcription factors Ikaros and Aiolos resulting in activation of T cells. Methods: Following establishment of oral CC122 3 mg daily (QD) as the MTD in phase 1a (Blood 122:2905 2013), an expansion cohort of advanced Hepatocellular Carcinoma (HCC) subjects was enrolled. All subjects had progressed on or were intolerant to sorafenib. Efficacy was assessed per RECIST 1.1 criteria. Results: As of Jan. 13, 2016, 25 advanced HCC subjects were enrolled. The median age was 59.6 years, median Child-Pugh score was 5 (range 5-8) and all were ECOG 0-1. Viral status was HBV 28%, HCV 28%, HBV/HCV 12% and non-viral 32%. 52% had alpha-fetoprotein ≥ 200. CC122 was well tolerated. Two subjects discontinued due to AEs. Dose reductions occurred in 32% (n = 8). The most common ( ≥ 5%) grade 3/4 AEs were neutropenia, ALT elevation (each n = 4, 16%), AST elevation (n = 3, 12%), asthenia, ascites, anemia, hyperbilirubinemia, pneumonia, and rash (each n = 2, 8%). Drugrelated serious AEs included vomiting and rash. 19 subjects were evaluable for efficacy. ORR was 10.5% (n = 2 PR, 1 confirmed) and Disease Control Rate (CR+PR+SD &gt; 7 weeks) was 36.8%. The duration of response was 108 and 125 days in the 2 PRs. The median PFS was 57 days (MinMax: 28334, 95% CI: 45-135). CC122 treatment resulted in a median increase from baseline in peripheral blood activated and memory cytotoxic T cells by 64% (range: 17-213%, n = 6) and 78% (range: 30-111%, n = 6 (p &lt; 0.05), respectively, and activated helper T cells by 106% (range: 62-218%, n = 7 (p &lt; 0.05). CC122-activated T cells from the blood increased IFNg (2.73 fold; range: 0.45-26.1, n = 13) and IL2 (9.5 fold; range: 0.85-24.3, n = 11) production when compared to baseline (both P &lt; 0.05) upon ex-vivo stimulation. Conclusions: CC122 3 mg QD appears to be well tolerated and activates cytotoxic T cells in HCC patients. Combination studies with sorafenib or nivolumab are recommended and underway. Clinical trial information: NCT01421524.
Taste and prostate cancer: Preliminary data on a novel patient-reported outcomes.
Authors: Lydia D. Chow, Patrick Cotogno, Emma M. Ernst, Charlotte Manogue, Elisa M. Ledet, Oliver Sartor
Journal: Journal of Clinical Oncology (2017)

201 Background: Taste alterations are a common yet frequently under-assessed problem in cancer patients. Health-related quality-of-life (HRQOL) instruments for prostate cancer (PCa) patients (pts) do not assess taste despite these hypothetically being related to both appetite and weight loss. Herein we begin to assess taste using a novel instrument evaluating taste alterations with a focus on PCa. Methods: 61 PCa pts treated at Tulane Cancer Center were enrolled in this prospective study. An 18-item questionnaire assessed appetite, taste, smell, and diet. 127 questionnaires were completed (mean 2.1 responses/pt). In a subset of questionnaires, we compared self-reported taste, appetite, and weight loss over a 6-month period. In another subset, we compared taste and appetite to treatments with abiraterone, docetaxel, or enzalutamide. Non-parametric testing was performed. Results: Of the 61 participants with PCa, 18.0% reported poor taste, 17.1% reported poor appetite, and 6.6% reported nausea while eating. When asked to assess to what extent this was a perceived problem, 16.4% rated taste, 13.1% rated nausea, and 16.4% rated appetite as a “moderate” or “big” problem. Men with poor or very poor taste (1 or 2 on a 5 point Likert scale) had a significant association with poor appetite (OR = 7.9, P = 0.0002). There was no direct relationship observed between taste and weight loss. The population with poor appetite was more likely (OR = 21.25, P &lt; 0.0001) to have had ≥ 5% weight loss as compared to those without a poor appetite. Those reporting at least some nausea were also (OR = 8.645, P = 0.0007) more likely to have ≥ 5% weight loss. In the treatment subset, pts on docetaxel at time of survey were 15.17 fold more likely to have poor taste as compared to those on abiraterone (p = 0.0145). Conclusions: We observed that perceived problems with taste were associated with loss of appetite which in turn was associated with weight loss. Weight loss is a known adverse prognostic factor in pts with advanced PCa. Further studies are warranted on this important patient-centric assessment.
Phase 1 study to evaluate the safety and tolerability of MEDI4736, an anti-programmed cell death ligand-1 (PD-L1) antibody, in myelodysplastic syndrome (MDS) after treatment with hypomethylating agents.
Authors: Guillermo Garcia-Manero, Charles Alan Schiffer, Lucy A. Godley, Ronald Paquette, Uwe Platzbecker, Paul B. Robbins, Jonathan Norton, Joyson Joseph Karakunnel, Robert Coleman Lindsley
Journal: Journal of Clinical Oncology (2015)

TPS7103 Background: Myelodysplastic syndrome (MDS) is a group of clonal bone marrow disorders associated with an increased risk of transformation to acute myeloid leukemia (AML). Despite recent progress in the treatment of MDS, therapeutic options are still limited, particularly for patients who fail to respond or relapse during treatment with hypomethylating agents and thus have poor survival rates. The programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway is an important checkpoint used by tumor cells to block antitumor responses. PD-L1 is present on myeloblasts during progression from MDS to AML, and its expression is enhanced by hypomethylating agents, providing the rationale for targeting PD-L1 in MDS. MEDI4736 is a human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80 with high affinity and selectivity. Methods: This Phase 1, multicenter, open-label, dose-escalation, and dose-expansion study (NCT02117219) evaluates the safety/tolerability of IV MEDI4736 in patients with pathologically confirmed MDS and Eastern Cooperative Oncology Group performance status of 0-2 who failed to respond, relapsed after an initial response, or were unable to tolerate hypomethylating agents. The primary objective is to assess the safety and tolerability of MEDI4736. Secondary objectives include: evaluation of clinical outcome in patients with MDS (International Working Group 2006 MDS response criteria), analysis of pharmacokinetics and immunogenicity of MEDI4736, and effect on patient-reported outcomes. Recruitment is ongoing, with a target enrollment of approximately 70 patients across 11 centers (United States, Germany, and United Kingdom). Clinical trial information: NCT02117219.
Metabolic syndrome and breast cancer: Effects of a 16-week combined exercise intervention.
Authors: Christina Marie Dieli-Conwright, Debu Tripathy, E. Todd Schroeder, Joanne E. Mortimer, Leslie Bernstein
Journal: Journal of Clinical Oncology (2013)

TPS9648 Background: Current evidence suggests that breast cancer treatments such as chemotherapy lead to excessive weight gain, fatigue, physical inactivity, and negative alterations in components of metabolic syndrome (MetS). MetS is associated with increased risk of cancer recurrence, cardiovascular diseases and type 2 diabetes, and is defined by visceral adiposity, insulin resistance, hyperglycemia, hyperinsulinemia, low serum high-density lipoprotein cholesterol, and hypertension. MetS is highly prevalent and present in 25% of American and European adults and higher in minorities. Given that chemotherapy for breast cancer induces many of the components of MetS, an effort to offset these consequences of cancer therapy using exercise/lifestyle intervention could improve breast cancer, cardiovascular and endocrine outcomes. Methods: Our study seeks to determine whether a 16-week exercise intervention induces changes in prognostic components of MetS (waist circumference, blood pressure, serum levels of glucose, insulin, lipids, C-reactive protein and HbA1c) among breast cancer survivors if initiated within 3 months of completion of chemotherapy or radiation therapy. We are currently recruiting women diagnosed with Stage I-III breast cancer from the USC Norris Comprehensive Cancer Center and Los Angeles County Hospital, which cares for a high proportion of minority/underserved patients. Participants are randomized to either the Control (usual care) or the Exercise group. The Exercise group participates in aerobic and resistance exercise sessions 3 times a week for 16 weeks supervised by an exercise specialist at the USC Clinical Exercise Research Center. At baseline and following the study period, all participants are tested for MetS components, muscle strength, body composition, bone density, cardiorespiratory fitness, quality of life, fatigue and shoulder function. We will recruit an additional 85 patients (at present time n=15) over the next 3 years. It is expected that this intervention will improve components of MetS and physical fitness in breast cancer survivors when compared to the Control group, thus defining intervention and biomarker variables for more definitive trials. Clinical trial information: NCT01140282.
Identification of pSTAT5 gene signature in hematologic malignancy.
Authors: Dmitriy Sonkin, Catherine Regnier, Xianhui Rong, Christie Fanton, Michael Palmer, Jocelyn Holash, Matthew Squires, L. Andres Sirulnik, Thomas Radimerski, Robert Schlegel, Michael Morrissey, Z, Alexander Cao
Journal: Journal of Clinical Oncology (2013)

7111 Background: The JAK/STAT pathway is an important signaling pathway downstream of multiple cytokine and growth factor receptors. Receptor-associated JAKs are activated following receptor-ligand binding. Activated JAKs phosphorylate STAT proteins, which then dimerize and translocate to the nucleus where they modulate the expression of target genes. Dysregulated JAK/STAT signaling has been implicated in the pathogenesis of multiple human malignancies. Activating mutations in JAK2 and the associated activation of STAT5 in myeloproliferative neoplasia is one example of the involvement of this pathway in human cancer. Additionally, overactivated JAK/STAT signaling has been suggested as a survival mechanism in several human cancers. Given the importance of JAK/STAT dysregulation in human diseases, it is important to identify patients with an overactivated JAK/STAT pathway for possible treatment with JAK inhibitors. Thus, we developed a gene signature assay to detect overactivated JAK/STAT5 signaling. Methods: The cancer cell line encyclopedia (CCLE) and associated gene-expression data were used to correlate the activation status of STAT5 with the induction of a set of STAT5 target genes. First, we used 27 tumor cell lines of hematologic lineage, with predetermined phosphorylated STAT5 (pSTAT5) status, to derive STAT5 activation gene signatures. Next, the putative gene signatures were validated against a different set of 13 hematologic tumor cell lines. Results: With this approach, a collection of 7 target genes were identified (PIM1, CISH, SOCS2, ID1, LCN2, EPOR, and EGR1) whose expression significantly correlated with pSTAT5 status in the 40 hematologic tumor cell lines (P &lt; .0001), either together or in specific subsets of 4 and 6 genes (Table). Conclusions: These 4-, 6-, and 7-gene signatures can be used to stratify or select for a patient population with activated JAK/STAT5 signaling that could potentially benefit from treatments targeting the JAK/STAT5 signaling pathway. [Table: see text]
Effect of availability of oral iron chelation therapy (ICT) on initiation, duration, and dose adequacy in patients with myelodysplastic syndromes (MDS) and transfusional iron overload (TIO).
Authors: Steven Gore, Amy J. Davidoff, Franklin Hendrick, Vu Duong, Bruce C. Stuart, Maria R. Baer, Rahul Shenolikar, Amer Zeidan
Journal: Journal of Clinical Oncology (2013)

e17584 Background: Most patients with MDS do not receive ICT despite evidence of TIO. Till 2005, the only approved ICT was Deferoxamine (DFO), a drug which requires daily prolonged parenteral administration. In addition to therapeutic equipoise of its efficacy, the logistics of administration of DFO may limit ICT use in MDS. We sought to assess whether the approval of an oral ICT (Deferasirox, DFX) in November 2005 has changed ICT use rates, dose adequacy and adherence in MDS patients with TIO. Methods: Using 100% Medicare enrollment and claims data from 2005-2008, we selected beneficiaries with MDS who were enrolled in Medicare Parts A, B, and D and were ICT-eligible based on RBC transfusions ≥ 20 units. Cox proportional hazard models examined the effect of time period relative to DFX market entry on the probability of ICT initiation and the effect of DFX vs. DFO use on duration and dose adequacy. Results: Of 3,843 ICT-eligible patients, 13.8% received ICT, with 81.6% of those receiving DFX, and 29.5% receiving DFO. Relative to the latter half of 2005, the probability of ICT initiation increased beginning in 2007, with a hazard ratio of 1.793 (CI,1.13-2.84; P=0.012) associated with cohort entry in the latter half of 2008. Treatment duration was longer for beneficiaries using DFX (mean 29.7, median 22 weeks) compared to DFO (mean 19.43, median 9 weeks). Only 7.1% of DFO-users received an adequate dose, compared to 72.8% of DFX-users. Conclusions: Use of oral ICT (DFX), following its approval, was associated with increased use, duration and dose adequacy of ICT, compared to DFO, among Medicare beneficiaries with MDS and TIO. The dramatic increase in use associated with availability of an oral formulation may have implications for other new oral chemotherapy and supportive care drugs.