tbuckley/cabot-search huggingface dataset:
A phase I study of DENSPM (N1, N11-diethylnorspermine) in patients with advanced hepatocellular carcinoma (HCC).
Authors: Lipika Goyal, Jeffrey G. Supko, Jordan Berlin, Lawrence Scott Blaszkowsky, Amanda Carpenter, Douglas M. Heuman, Keith E. Stuart, Scott Cotler, Neil N. Senzer, Carl L. Berg, Jeffrey W. Clark, Aram F. Hezel, David P. Ryan, Andrew X. Zhu
Journal: Journal of Clinical Oncology (2013)

260 Background: DENSPM, a synthetic analog of the naturally occurring polyamine spermine, offers a novel approach for treating HCC by inducing polyamine depletion and inhibiting cell growth. The objectives of this multicenter phase I study were to assess the safety, maximum-tolerated dose (MTD), pharmacokinetics (PKs), and preliminary antitumor activity of DENSPM in HCC. Methods: Forty-four patients with measurable advanced HCC, Child-Pugh A or B cirrhosis, CLIP score ≤ 3, and Karnofsky score ≥ 60% were enrolled in a dose escalation study of DENSPM given intravenously on days 1, 3, 5, 8, 10, and 12 of each 28-day cycle. The starting dose of 30 mg/m 2 was escalated at a fixed increment of 15 mg/m 2 until the MTD was identified. A sensitive LC-MS/MS assay with a 6.4 nM limit of quantitation was developed and validated to characterize the plasma PKs of DENSPM. Results: Thirty-eight patients (male 79%; median age 61years; Child A 84%; Asian 5%; ≥1 prior systemic therapy 45%) received at least one dose of DENSPM. The most common adverse events (AEs) were fatigue (53%), nausea (34%), diarrhea (32%), vomiting (32%), anemia (29%), and increased AST (29%). The most common grade 3/4 AEs were fatigue/asthenia (13%) and increased AST (13%), hyperbilirubinemia (11%), renal failure (8%) and hyperglycemia (8%). The MTD was 75 mg/m 2 and was not directly associated with major treatment-related safety concerns. DENSPM plasma levels decreased very rapidly during the initial 60 min post-infusion. The total body clearance, 66.7±35.8 L/h/m2 (mean±SD) for the initial dose was comparable to that in solid tumor patients with normal to near normal hepatic function. However, drug concentrations ≥10 nM persisted for several days after dosing and remained detectable in samples obtained before day 12 dosing in 11/16 (68.8%) patients. No responses were seen but 9/27 (33.3%) evaluable patients achieved stable disease. Conclusions: DENSPM toxicity was dose dependent, the 75 mg/m 2 MTD was relatively well-tolerated, and the PK behavior was favorable. Nevertheless, the study was terminated early because of insufficient evidence of clinical benefit in HCC patients. Further evaluation of DENSPM as a monotherapy for HCC does not appear to be justified. Clinical trial information: NCT00081900.
Percentage of sarcomatoid component as a prognostic indicator for survival in sarcomatoid renal cell carcinoma.
Authors: Mehrad Adibi, Arun Z. Thomas, Leonardo Borregales, Megan M. Merrill, Kanishka Sircar, Pheroze Tamboli, Rebecca Slack, Hsiang-Chun Chen, Nizar M. Tannir, Eric Jonasch, Surena F. Matin, Christopher G. Wood, Jose A. Karam
Journal: Journal of Clinical Oncology (2015)

499 Background: Renal cell carcinoma with sarcomatoid component (sRCC) is characterized by the microscopic spectrum of spindle cells within a background of RCC. The presence of sarcomatoid elements is associated with higher stage of presentation and decreased patient survival. The objective of this study is to examine the clinicopathological characteristics associated with overall survival (OS), specifically examining the percentage of sarcomatoid component (PSC) to stratify risk. Methods: We retrospectively reviewed data for all radical nephrectomy patients with pathologically confirmed sarcomatoid component from 1987−2011. All slides were re−reviewed by a GU pathologist to ascertain PSC. Patient characteristics were tabulated overall and by disease status (metastatic vs. localized). Cutpoints in the percent sarcomatoid providing a meaningful difference in OS were identified by recursive partitioning analysis (RPA) as univariate and combined with patient characteristics. Factors selected included age, gender, race, clinical stage, tumor histology, and treatment. The Kaplan−Meier method and two−sided log−rank test was used to assess differences in OS. Results: Among 186 patients with sRCC, 64 (34%) had localized and 122 (66%) metastatic disease. Patients were primarily white (76%) males (63%) with clear cell histology (73%), and did not receive neoadjuvant or adjuvant therapy (87%). The median follow−up time was 12.1 months (range, 0.1 to 242.2 months). The median OS was 12.6 months (95% confidence interval (CI) 10.7−14.9 months). Two subgroups were identified with a cut−point of 12.5% for PSC after univariate RPA. Patients with PSC ≥ %12.5 were at higher risk of death compared to patients with &lt;%12.5 (45% vs. 61% 1 year OS; p value=0.04). Mutlivariate RPA revealed clinical stage and percent sarcomatoid were significantly associated with OS. Patients with localized disease were most likely to be alive at 1 year (74%). Among patients with metastatic disease with PSC&lt;%42.5 had 1−year OS of 44% vs. 27% for patients with ≥%42.5 cutoff (p&lt;0.001). Conclusions: The PSC appears to be a prognostic factor in the OS of patients with RCC, with larger percentage of involvement portending a worse survival.
Conditional probability of survival in gallbladder carcinoma as a prognostic tool for long term survivors.
Authors: Rahul Rajeev, Nicholas Gerard Berger, Abdulrahman Y Hammad, John Thomas Miura, Fabian McCartney Johnston, T. Clark Gamblin, Kiran Turaga
Journal: Journal of Clinical Oncology (2016)

455 Background: Gallbladder carcinoma (GBC) often presents in an advanced stage and despite radical resection and nodal harvest, prognosis remains poor. Conventional survival statistics do not account for time elapsed from diagnosis and may not carry relevant prognostic information for long term survivors. This study sought to estimate the conditional probability of survival (CS) in patients of GBC. Methods: Patients with GBC were identified from the Surveillance, Epidemiology and End Results (SEER) database (1988-2012). Overall probability of survival (OS) was estimated using Kaplan-Meier method. Cumulative incidence method was employed to calculate CS. Results: Of 15,046 GBC patients identified, Stage IV disease was the most common presentation (n = 5625). Surgical intervention was reported in 9,720(65%) patients with cholecystectomies (n = 8254) outnumbering radical resections (n = 1116). 3-year OS for all stages was 18% and conditional probability of surviving additional 3 years (CS 3 ) at 1, 2 and 3 years from diagnosis was 42%, 57% and 66% respectively. Stage III and IV disease had 3-year OS rates of 19% and 3% respectively while CS 3 increased progressively with each year survived(33% and 17% at 1 year, 51% and 34% at 2 years, 60% and 56% at 3 years). Conclusions: Conditional probability of survival is favorable in patients surviving one year from diagnosis and shows an increasing trend with time. Improvements in survival are more substantial in patients with adverse initial prognosis. Conditional survival provides valuable information on prognosis to patients after curative surgery and can be the basis of follow-up guidelines.
Cost-effectiveness of brentuximab vedotin in relapsed or refractory systemic anaplastic large cell lymphoma.
Authors: Margaret Hux, Denise Zou, Esprit Ma, Peter Sajosi, Andreas Engstrom, Ross Selby, Eugene Benson, Jeremy Teasell, Akshara Richhariya, Andrew Briggs, Vijayveer Bonthapally
Journal: Journal of Clinical Oncology (2016)

18 Background: Systemic anaplastic large cell lymphoma (sALCL) is a rare T-cell lymphoma. For patients who fail front-line therapy, outcomes are poor and there is no current defined standard of care. Brentuximab vedotin has demonstrated high objective response rates and is approved for patients with relapsed or refractory (R/R) sALCL. However, the cost-effectiveness of brentuximab vedotin compared with conventional chemotherapy has not been explored. Methods: A lifetime Excel-based partitioned survival model was used to compare survival outcomes from the pivotal phase-2 single-arm brentuximab vedotin trial of 58 R/R sALCL patients with good Eastern Corporative Oncology Group (ECOG) performance status after one or more prior therapies (SG035-0004); with 40 sALCL patients from a Canadian cancer registry receiving first-line conventional salvage chemotherapy (65% with ECOG 0 or 1) between 1980 and 2012 and followed for up to 20 years. Extrapolation of brentuximab vedotin survival after the trial period assumed the same rate of change as for conventional chemotherapy. A United Kingdom National Health Service perspective was adopted. Costs included drug acquisition and administration, and medical care for adverse events and pre- and post-progression. Utility values elicited by response and by progression, and disutilities associated with adverse events were applied to estimate quality-adjusted life years (QALYs). Results: The incremental cost-effectiveness ratio (ICER) for brentuximab vedotin was £35,390 per QALY gained versus conventional chemotherapy. ICERs were between £28,112 and £61,921 across a range of alternative model assumptions. Comparing only first-line salvage patients in both groups reduced the ICER to £26,766. Conversely, considering only patients with good ECOG performance status increased the ICER to £38,186. Using probabilistic sensitivity analysis, at willingness-to-pay of £38,000, the probability that brentuximab vedotin is cost-effective was &gt; 50%. Conclusions: Brentuximab vedotin may represent a cost-effective intervention compared to conventional chemotherapy for this patient population with limited therapeutic options.
Association of relapse in patients with esophageal and esophagogastric junction (E-EGJ) cancer with surgical stage after trimodality therapy (TMT): Implications for customized surveillance.
Authors: Maria-Claudia Campagna, Takashi Taketa, Arlene M. Correa, Kazuki Sudo, Mariela A. Blum, Roopma Wadhwa, Ritsuko Komaki, Jeffrey H. Lee, Manoop S. Bhutani, Brian Weston, Zhongxing X. Liao, David C. Rice, Stephen Swisher, Wayne Lewis Hofstetter, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2013)

95 Background: The surveillance strategy for E-EGJ cancer patients after TMT is currently not based on evidence and varies considerably. Literature does not provide guidance. Methods: Between 2000 and 2010, 579 patients with E-EGJ cancer who underwent TMT were analyzed. The type and timing of first relapse using 12-month intervals and their association the post-TMT surgical stage. Various statistical methods were utilized. Results: For 579 patients, the median follow-up time was 57.4 months (95% confidence interval [CI], 51.5-63.3 months). A total of 232 (40%) patients had a relapse. First relapses were: distant metastases (199 patients; 34.4%) and local-regional metastases (33 patients; 5.7%). Irrespective of the surgical stage, 95% of all relapses occurred within 36 months of surgery. The timing and frequency of relapses were significantly associated with the surgical stage (see Table; stage 0 or I vs. II or III; p= &lt;0.001). Conclusions: Our data suggest that customization of surveillance is possible based on the surgical stage after TMT. These data can contribute to the development of an evidence-based surveillance strategy. [Table: see text]
Accuracy of kidney cancer diagnosis and histological subtype within cancer registry data.
Authors: Lori Wood, Jeff Himmelman, Kara Thompson, Jennifer Merrimen
Journal: Journal of Clinical Oncology (2016)

606 Background: Cancer registries are the mainstay for population-based cancer statistics including incidence and cancer type. In Canada, each province captures this data in provincial registries including the Nova Scotia Cancer Registry (NSCR).The goal of this study was to describe data from the NSCR about method of diagnosis and kidney cancer (KC) pathology and compare it to the actual pathology reports to determine the accuracy of diagnosis and histological subtype assignment. Methods: This retrospective analysis included patients with KC in the NSCR with an ICD-10-CM code C64.9 (malignant neoplasm of unspecified kidney, except renal pelvis) within the largest provincial metropolitan area from 2006-2010. Method of KC diagnosis (clinical, radiologic, histology, or autopsy) was recorded as was the pathological diagnosis based on WHO classification. All non-clear cell KC (nonccKC) diagnosis from the registry were compared to the actual pathology report (and pathology re-review when necessary) for comparison. Results: 733 pts make up the study cohort. 81.2% of patients were diagnosed based on nephrectomy, 11.5% on radiography, 6.5 % biopsy, and 0.8% autopsy. By registry data 53.1% had clear cell, 20.2% KC not otherwise specified (NOS), 12.7% papillary, 3.8% chromophobe, and many other nonccKC. By pathology reports, 62.2% had clear cell, 13.4% papillary, 4.4% chromophobe, only 2% KC NOS (because most radiological diagnosis were classified this way). A large number of pathological diagnoses make up the other nonccKC and discrepancies between registry data and pathology reports will be described and compared in detail. Conclusions: Registry data is commonly used to report cancer statistics. Registry data may not be accurate for the true incidence of KC since 11.5% were based on radiology alone. Clear cell KC made up 53% of registry diagnosis but 62% on pathology report review. Although papillary and chromophobe incidence did not vary a lot, other types of nonccKC did. This registry data did not differentiate between papillary type I and II. NonccKC should not be considered one entity. One must be aware of the gaps in registry data for KC statistics including overall diagnosis, clear cell and nonccKC subtypes.
Incidence and characteristics of BRAF V600E mutation in colorectal cancer (CRC) with mismatch repair (MMR) protein defect due to loss of MLH1: A prospective evaluation of 104 consecutive patients.
Authors: S. A. Mahesh, E. Hanna, M. S. Khan, P. Ravichandran, F. Slezak
Journal: Journal of Clinical Oncology (2011)

3539 Background: MMR protein deficient CRC (15-20% of all CRC) can be sporadic or genetic (due to Lynch Syndrome). Loss of MMR proteins can be detected by absence of staining on immunohistochemistry (IHC). Previously, all MMR-deficient CRC were tested for LS by sequencing. With the advent of BRAF testing, genetic testing for LS can be avoided in a large subset of MMR-deficient CRC. In addition, detection of BRAF mutations (mut) may have therapeutic implications. We sought to investigate the contribution of BRAF V600E mut to MLH1 deficient CRC and incidence of LS among all newly diagnosed CRC. Methods: All CRC between 3/2010-12/2010 were tested for MMR protein (MLH1, MSH2, MSH6 and PMS2) deficiency by IHC. Absence of MLH1 prompted BRAF mut (V600E) testing. If BRAF was mut, further testing was stopped. Absence of MSH2, MSH6 and MLH1 with normal BRAF prompted genetic sequencing of the absent protein. If patients had MMR-proficient tumors but met modified Bethesda criteria, LS genetic testing was pursued. Results: Results are shown in the table. Conclusions: BRAF was mutated in 77% of patients with absence of MLH1. These patients were elderly and solely women with right-sided CRC. Number (n) 104 Median age (years) 70 Stage (%) 0=5%, 1=20%, 2=31%, 3=32%, 4=12% MMR status Deficient 14%, Proficient 86% MMR deficient (n=15) Absence of MLH1 and PMS2 (n=13), MSH2 (n=1), MSH2 and MSH6 (n=1) MLH1 deficient (n=13) BRAF mut (10/13), BRAF wild (3/13) Characteristics of MLH1 deficient CRC Median age Sex Location BRAF mut (n=10) 80.5 10 females (F), 0 males (M) 10 right-sided (R), 0 left-sided (L) BRAF wild (n=3) 67 1/3 F, 2/3 M 2/3 R, 1/3 L LS genetic testing (n=7) Negative=4, 3 genetic sequencing pending
Evaluation of c-kit (CD 117) expression as a prognostic factor in testicular germ cell tumors: An Izmir Oncology Group (IZOG) study.
Authors: Tarik Salman, Elif Yildiz, Ibrahim Yildiz, Dilek Yavuzer, Mehtat Unlu, Umut Varol, Murat Akyol, Yasar Yildiz, Vedat Bayoglu, Yuksel Kucukzeybek, Ahmet Alacacioglu
Journal: Journal of Clinical Oncology (2016)

476 Background: Little progress has been made in the management of testicular germ cell tumors (TGCTs). c-kit (CD 117) is a good target for cancer treatment and possesses an impressive role in the current oncological practice. We aimed to evaluate c-kit expression in early stage TGCTs as a prognostic factor. Methods: Patients with TGCTs who were referred to the Medical Oncology Clinic were included in our study before starting chemotherapy. Immunohistochemistry was performed on formalin-fixed and paraffinembedded three-micrometer thick sections with CD 117 Rabbit Anti c-kit in vitro gene kit. Biochemically, we utilized AFP and β-HCG Immunlite 2000 device with solid phase chemiluminescent immunometric method, and LDH Roche models with the DP-standardized UV method. AFP 0-15 ng/ml, β-HCG &lt; 0.1 mlu/ml and LDH 240-480 mg/dl were considered as normal values. Results: Sixty-five patients were included in our study. Forty-one (63%) patients had nonseminoma tumors (NSGCTs) and 24 (37%) had seminoma. Statistically significant c-kit expression was found in patients with seminoma (p&lt;0.0001). There was no difference between negative or positive c-kit expression in terms of clinicopathological characteristics, including preoperative serum levels of AFP, β-HCG, LDH, lymph node involvement, distant metastasis, and IGCCCG risk classification. No correlation was found between these parameters and 5-year progression free survival (PFS) rate except for tumor stage, presence of lymph node metastasis and IGCCCG score (p=0.001, p=0.04, and p=0.0001, respectively). Five-year PFS rate of patients with positive CD 117 was 72.2% (95% CI, 54.6-89.8), and6.6% (95% CI, 31.2-82.1) for those without CD 117 expression involvement (p=0.12). Conclusions: So far, there has been no significant breakthrough in the treatment of cisplatinrefractory TGCTs in the era of targeted therapies. No prognostic importance of c-kit expression has been found in our study. However, we believe that c-kit expression, in numerical terms, can be considered as a good prognostic factor for patients with TGCTs. The fact that all seminoma cases displayed positive c-kit expression is what we think has driven this result.
Evaluation of patient characteristics that are associated with response to a survivorship care planning intervention.
Authors: Elizabeth Ann Kvale, Chao-Hui Huang, Sejong Bae, Wendy Demark-Wahnefried, Karen Meneses, Casey Ballentine Azuero, Christine Ritchie
Journal: Journal of Clinical Oncology (2016)

8 Background: Appropriate targeting of survivorship care planning interventions to patient need is essential, but little evidence exists to support systematic triaging according to survivor needs. We demonstrated the positive impact of a self-management focused survivorship care planning (SCP) intervention on patient outcomes including wellbeing and depressive symptomology; herein we report how patient characteristics predict response to that intervention. Methods: Newly-diagnosed breast cancer survivors (Stage 0-IIIB) were randomized to receive the patient owned survivorship care planning intervention (n = 40) or usual care (n = 39). The intervention arm demonstrated improvements from baseline to 3-month follow-up in self-reported health and depressive symptom burden as measured with SF-36 Health Survey and Personal Health Questionnaire Depression Scale. We examined patient characteristics associated with response to the intervention. Results: Baseline characteristics including younger age, lower perceived finance adequacy, higher medical comorbidity, burden of depression, as well as anxious/preoccupation coping were significantly associated with greater self-reported health change (p &lt; 0.05). Additionally, higher levels of cancer symptom severity, fatigue, lower social functioning and mental health status at baseline were significantly correlated with greater reductions in depressive symptoms (p &lt; 0.05). Race, education, health literacy level, and cancer stage were not associated with improved outcomes. Conclusions: While SCP is an important step to improving care for cancer survivors, it is likely that some cancer survivors may need a robust intervention to support self-management of survivorship issues. Our preliminary findings suggest that younger patients with higher perceived financial, emotional, and cancer symptom burden may benefit from a focused SCP intervention to a greater extent than patients without these characteristics. A larger scale pragmatic study is needed to further confirm the associations, investigate the mechanism of effective interventions, and develop pragmatic strategies that target survivors who need robust SCP support.
Umbilical Cord-Derived Mesenchymal Stem Cells for Treatment of Steroid-Resistant Severe Acute Graft-Versus-Host Disease
Authors: Guanghua Chen, Ting Yang, Chengcheng Fu, Miao Miao, Zhengming Jin, XiaoWen Tang, Yue Han, Guangsheng He, Xuhui Zhang, Xiao Ma, Feng Chen, Xiaohui Hu, Shengli Xue, Ying Wang, Huiying Qiu, Aining Sun, Wu Depei
Journal: Blood (2011)
Impact of carboplatin plus weekly docetaxel as salvage chemotherapy in docetaxel-resistant and castration-resistant prostate cancer (DRPC) on free testosterone levels.
Authors: C. W. Reuter, M. A. Morgan, M. Fenner, P. Ivanyi, V. Gruenwald, A. Ganser
Journal: Journal of Clinical Oncology (2011)

4593 Background: Recent data suggest that carboplatin may be effective in combination with docetaxel in DRPC. Platinum(II)-complexes interfere with steroid biosynthesis, lowering testosterone levels by inhibiting 3β-hydroxysteroid dehydrogenase and 17α hydroxylase (Schertl et al. J Cancer Res Clin Oncol. 2007;133:153-67). Methods: Docetaxel failure/resistance was defined according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Since February 2005, 59 consecutive DRPC pts gave informed consent and were treated with at least two cycles of carboplatin AUC5 iv for 30 min on day 1 every 4 weeks (q4w), docetaxel at a dose of 35 mg/m2 iv for one hour on days 1, 8, 15 plus prednisone 2x5mg/day orally until disease progression or occurrence of intolerable adverse effects. Efficacy was measured following PCWG2 recommendations. Free testosterone levels were measured before and during carboplatin/docetaxel chemotherapy. Results: Response of prostate-specific antigen (PSAR; ≥50% PSA) was observed in 29/59 (49.2%) patients. At the time of the current analysis, the median follow-up time was 12.9 months and 36/59 patients had died. Median progression-free survival (PFS) for all patients was 7.2 months (CI 95% 6.1, 8.4) and median overall survival (OS) was 18.6 months (CI 95% 11.6, 25.6). In PSAR, PFS was 15.7 (CI 95% 7.3, 24.1) months and OS was 27.0 months (CI 95% 20.4, 33.6). This regimen was reasonably well tolerated, with leukopenia/neutropenia as the most common reversible grade 3/4 toxicities (44.2/40.4%). Median free testosterone levels were 1.15 pg/ml before and 0.255 pg/ml during carboplatin/docetaxel treatment (testosterone nadir; n=24; p<0.01). While free testosterone levels before DC treatment were associated with lower PSAR (HR 5.582 CI 1.105, 28.195; p=0.037), free testosterone levels <0.3 pg/ml during DC treatment were associated with higher PSAR, PFS and OS (HR 11.7 CI 1.49, 91.5; HR 0.2 CI 0.05, 0.78; HR 0.129 CI 0.02, 0.8; p<0.03, respectively). Conclusions: These data suggest that carboplatin plus weekly docetaxel may be an important second-line treatment option for DRPC patients by inhibiting testosterone biosynthesis.