tbuckley/cabot-search huggingface dataset:
Tumor c-Met expression and prognosis of advanced hepatocellular carcinoma patients treated with sorafenib.
Authors: Yu Yun Shao, Chi-Huang Hsiao, Ray Lee, Oscar Puig, Soa-Yu Chan, Yong-Shi Li, Chih-Hung Hsu
Journal: Journal of Clinical Oncology (2015)

317 Background: Overexpression of c-Met signaling has been associated with development and progression of hepatocellular carcinoma (HCC). We explored the prognostic role of tumor c-Met expression in patients with advanced HCC. Methods: Patients who had received sorafenib alone as first-line therapy for advanced HCC and had available archival tumor tissues were enrolled. Expression of total c-Met was determined by immunohistochemical staining using CONFIRM anti-total c-MET (SP44) rabbit monoclonal primary antibody (Ventana) on the BenchMark ULTRA staining platform. We evaluated c-Met expression by H scores and by a clinical score as defined in the table. Results: The study enrolled 62 patients, all with Child-Pugh class A status. The HCC etiology was hepatitis B in 48 patients, and hepatitis C in 12 patents; 57 had BCLC disease; 40 had extrahepatic metastasis, and 37 had macrovascular invasion. Clinical scores of c-Met were 0 in 30 (48%) patients, 1 in 31 (50%) patients, 2 in 1 (2%) patients, and 3 in 0 patients. Patients with different clinical scores of c-Met had similar PFS (p = 0.821) or OS (p = 0.533). The median membranous H score and cytoplasmic score were 32.5 and 5, respectively. Patients with higher (≥ median) and lower c-Met membranous H scores or cytoplasmic H scores also had similar PFS and OS. Conclusions: High c-Met expression was rare in this advanced HCC cohort. Tumor expression of c-Met had no obvious associations with the prognosis of advanced HCC. (This study was supported by National Science Council, Taiwan (NSC-102-2314-B-002-120, NSC-103-2314-B-002-181-MY2, NSC-103-2314-B-002-092)). [Table: see text]
Concurrent chemoradiotherapy with or without induction chemotherapy for locally advanced head and neck cancer.
Authors: J. J. Caudell, S. Spencer, R. Meredith, L. Nabell, J. A. Bonner
Journal: Journal of Clinical Oncology (2011)

5553 Background: Recent trials suggest that induction chemotherapy followed by concurrent chemotherapy and radiotherapy (SEQ) may improve outcomes for patients with locally advanced head and neck cancer (LAHNC) over concurrent chemotherapy and radiotherapy alone (CRT). SEQ and CRT have not been prospectively compared in a phase III trial, therefore we retrospectively compared these approaches with patients treated on prospective trials at the University of Alabama at Birmingham. Methods: From 1995 to 2007, 114 patients with LAHNC of the larynx, hypopharynx, oral cavity or oropharynx were treated with definitive SEQ or CRT on prospective trials. All patients who received SEQ (n = 38) were treated on one phase I/II trial with three cycles of docetaxel and cisplatin, followed by docetaxel concurrent with radiotherapy (RT). CRT was delivered on a variety of trials (n = 13) with weekly cetuximab (n = 19), carboplatin/paclitaxel (n = 4), carboplatin/paclitaxel and celecoxib (n = 14), cisplatin/paclitaxel (n = 1), or every three week cisplatin (n = 17), cisplatin/5-fluorouracil (n = 14) cisplatin/weekly cetuximab (n=6), or cisplatin/5-fluorouracil daily during the last 10 RT treatments (n = 1). Patient, tumor, and treatment factors were compared with Pearson chi square. Loco-regional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) were assessed via Kaplan-Meier survival analyses and multivariate regression analyses. Results: Median follow up for patients treated with SEQ was 33.5 months and 32 months for CRT. Patients in the SEQ group were more likely to have a Performance Status <90 (p = 0.04). Additionally, SEQ patients were more likely to have both altered fractionation RT (p < 0.001) and a shorter RT treatment time (p < 0.001). At 3 years there were no significant differences in LRC (69.7% v 71.2%, p = 0.84), DMFS (86.6% v 76.7%, p = 0.38), or OS (62.7% v 56.8%, p = 0.27) between CRT or SEQ, respectively. Use of SEQ therapy was not associated with improvements in LRC, DMFS, or OS on multivariate analyses. Conclusions: In this retrospective analysis of patients with LAHNC treated on prospective clinical trials, SEQ therapy was not associated with gains in LRC, DMFS, or OS compared with CRT.
Prospective analysis of toxicity of chemo-radiotherapy versus radiotherapy alone in HIV positive women with cervical cancer in the developing world
Authors: O. McArdle, A. Hamya Kaggwa, E. Nagudi Situma, J. Kigula-Mugambe
Journal: Journal of Clinical Oncology (2008)

16541 Background: There are no prospective data available on the toxicity of chemo-radiotherapy in HIV positive women with cervical carcinoma in the developing world. We report the toxicity of treatment in women participating in a randomized controlled trial comparing overall survival after radiotherapy (RT) and chemo-radiotherapy (CRT) for the treatment of cervical cancer in this setting. Methods: The local ethics committee approved this IAEA-sponsored trial and all patients signed informed consent. RT consisted of 46 Gy in 23 fractions to a pelvic field delivered using ap/pa fields on a cobalt machine, followed by a single 30Gy brachytherapy insertion. Cisplatin was given at a dose of 30mg/m2 once weekly during external beam radiotherapy. Toxicity was recorded weekly using the RTOG acute toxicity score. Patient characteristics and toxicity scores were compared using the Chi square test. Inclusion criteria: biopsy proven cervical carcinoma, FIGO stage IB - IIIB, age >18 years, KPS > 60, Haemoglobin >10 mg/dL, Platelets >140,000/μL, white cell count >4,000/μL, HIV positive, creatinine <97 micromoles/L. Results: 16 women have received RT, 18 have received CRT. Patient characteristics including median age and FIGO stage are not significantly different between the two groups. Table 1 describes the frequency of grade 3 toxicity. No patient experienced grade 4 toxicity. There were no significant differences in the rates of skin toxicity between the two arms. Conclusions: The potential toxicity of CRT in the HIV positive population is currently in question. Preliminary toxicity data from our study indicates significant skin toxicity in both groups, in keeping with retrospective data. However, treatment was otherwise well tolerated with the only significant difference being increased hematological toxicity with CRT. Table 1. Grade 3 toxicity Toxicity RT alone n=16 no. (%) CRT n=18 no. (%) Skin 8 (50%) 5 (28%) Upper GI - - Lower GI - - Genitourinary - - White cell count - 5 (28%) Haemoglobin 1 (6%) 1 (6%) Platelets - 1 (6%) No significant financial relationships to disclose.
Creation of a standardized set of patient-centered outcomes for advanced prostate cancer: An international effort.
Authors: Alicia Katherine Morgans, Annelotte van Bommel, Caleb Stowell, David F. Penson
Journal: Journal of Clinical Oncology (2015)

282 Background: Clinical trials and international registries assess outcomes considered relevant to men with advanced prostate cancer (CaP). However, we lack a single standardized set of outcomes, making direct comparisons between populations and quality of care assessments challenging. We sought to create a minimum standardized set of outcomes relevant to men with advanced CaP. Methods: The International Consortium for Health Outcomes Measurement assembled a multi-disciplinary working group to create a minimum set of measures to collect for men with advanced CaP. We used a modified Delphi method to establish pertinent measures and case-mix characteristics. Results: Approximately 24 experts, including clinicians and patient advocates, from North America, Europe, and Australia participated. We defined the included population as men with metastatic prostate cancer or biochemical recurrence who failed or were ineligible for salvage therapy. Outcomes important to all men with advanced CaP, such as overall survival, and measures specific to subgroups, such as time to metastasis, were identified. Measures gathered from clinical data include risk-stratification characteristics and measures of disease control. Patient-reported outcome measures, like pain control, depression, and erectile, urinary, and bowel dysfunction, were also identified. Conclusions: Standardized outcome measures are necessary to assess quality of care across different populations, and are critical to ensure value in health care. Our international, multi-disciplinary team identified clinical data and patient-reported outcomes to provide a basis for international health outcome comparisons and future assessments of quality of care for men with advanced CaP.
Secondary cytoreductive surgery for recurrent mullerian adenocarcinomas: A comparison of serous and non-serous subtypes.
Authors: T. Goto, M. Takano, A. Watanabe, M. Miyamoto, N. Sasaki, K. Kudoh, T. Kita, J. Hirata, H. Sasa, K. Furuya
Journal: Journal of Clinical Oncology (2010)

e15544 Background: The aim of the study was to evaluate the effects of secondary cytoreductive surgery on survival in patients with recurrent epithelial ovarian, tubal, and peritoneal cancer. Methods: Among all patients who underwent primary therapy for epithelial ovarian, tubal, and peritoneal cancer between 1994 and 2006 at our insitution, the medical records of all patients who were submitted to secondary cytoreductive surgery were retrospectively investigated. Survival analysis was estimated by Kaplan-Meier methods. Results: In total, 34 patients met the inclusion criteria, of whom, 26 had serous, 4 had endometrioid and 4 had clear cell type adenocarcinomas. Median age at treatment for recurrence was 57 years (range 47-76). Following primary surgical and systematic treatment, recurrence was diagnosed after a median treatment free interval of 10 months (range 2-137). Complete cytoreduction was achieved in 24 of the patients (75%). At the end of a median follow-up of 36 months after treatment for recurrence, 12 patients were alive and well, 6 alive with disease and 16 were dead and median post-recurrence survival was 60 months. When compared between histological subtypes, overall post-recurrence survival of serous adenocarcinoma was significantly worse than that of non-serous (p = 0.048). Conclusions: In the present study, the impact of secondary cytoreductive surgery on a significant survival benefit was identified especially for non-serous type. Further analyses are needed to better define the role of surgery in these patients. No significant financial relationships to disclose.
Computer-assisted outreach by patient care navigators using laptop wireless communication.
Authors: M. Castaldi, T. N. Elrafei, M. Broderick, H. Delany
Journal: Journal of Clinical Oncology (2011)

6136 Background: “Patient navigation” in cancer care refers to the assistance offered to patients, survivors, families, and caregivers to help them access and then chart a course through the healthcare system and overcome barriers to quality care. Jacobi Medical Center is a municipal hospital and is the largest safety net hospital for underserved and uninsured patients in the Bronx. The department of breast surgery, in conjunction with information technology, developed a remote access system to provide outreach, education, screening, and diagnostic services for women’s health within the community as a means to early detection and prevention of breast disease. Methods: From 2006, three patient navigators were trained to provide breast health education and awareness within the community. The navigators were equipped with wireless laptop enabled with live, off-site connectivity to access the hospital-based patient registration and appointment system. Communication was enabled with the hospital MISYS electronic medical record system. Navigator’s conducted patient intake interviews off-site, registered patients directly into the hospital system, generated a hospital medical record number, and scheduled appointments for mammograms, breast exams, and gynecologic examinations within minutes of the initial encounter. Results: There were 1124 community encounters generated from local health fairs, church functions, senior centers, libraries, nursing homes, and community organizations to provide teaching, education, demonstrations, and answer questions pertaining to breast health. 716 patients received education. 306 Screening Mammograms were scheduled via wirelessly, of which 270 were performed. 58 patients were given breast clinic appointments, of which 24 patients were seen and had breast exams. In addition 29 patients were given GYN appointments. Conclusions: The Patient Navigation Program is a critical component to accessing the Breast Center. With the use of remote access and off-site connectivity directly into the hospital registration system, the navigators were able to provide services for early detection and prevention of breast disease that would have otherwise been delayed or not done at all.
Final toxicity results of a phase I dose-escalation trial of tremelimumab (CP-675206) in combination with gemcitabine in chemotherapy-naive patients (pts) with metastatic pancreatic cancer.
Authors: M. Aglietta, C. Barone, M. B. Sawyer, M. J. Moore, W. H. Miller, C. Bagalà, D. A. Ferraro, F. Colombi, C. Cagnazzo, L. Gioeni, K. D. Fly, B. Huang, F. Leone
Journal: Journal of Clinical Oncology (2011)

4081 Background: Tremelimumab (CP-675206) is a fully human monoclonal antibody that binds to cytotoxic T lymphocyte-associated antigen 4 (CTLA4) on T lymphocytes and T regulatory cells. It is thought to stimulate the immune system to attack tumor cells by blocking the CTLA4-negative regulatory signal. The primary objective of this phase I study was to determine the maximum tolerated dose and evaluate the safety of tremelimumab plus gemcitabine in pts with previously untreated metastatic pancreatic cancer. Methods: In Part A of the study, pts received gemcitabine only during a 1-mo lead-in period. Gemcitabine (1,000 mg/m2) was administered on days 1, 8, and 15 of a 4-wk cycle. Escalating doses of tremelimumab (6 mg/kg, 10 mg/kg, and 15 mg/kg) were then administered intravenously on day 1 of each 12-wk cycle. In Part B, tremelimumab at 2 dose levels (10 mg/kg and 15 mg/kg) was administered simultaneously with gemcitabine. Dose-limiting toxicities (DLTs) related to tremelimumab were evaluated during the first 6 wk after the first dose of tremelimumab. Results: A total of 34 pts (M/F = 22/12; median age 59; range 29-76) received at least 1 dose of tremelimumab. The median number of cycles was 1 (range, 1-5). No DLTs related to tremelimumab were observed at any dose level. Most frequent grade (G) 3-4 toxicities were neutropenia (n=8), fatigue (n=5), transaminases increase (n=4), nausea (n=3), and diarrhea (n=3). Two cases of G3 diarrhea, 1 case of G3 nausea, and 1 case of G3 transaminases increase were considered related to tremelimumab. Other toxicities related to tremelimumab were G2 diarrhea (n=6), G2 thrombocytopenia (n=1), G2 rash (n=1), and G2 vitiligo (n=1). Two of 25 evaluable pts had confirmed partial responses (PR), and 5 had stable disease (SD) at 7 wk (defined by measurements demonstrating neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify as progressive disease after the start of treatment). One pt with SD as best result remains progression free after 14 mo of therapy. Conclusions: Tremelimumab (up to 15 mg/kg every 12 wk) plus gemcitabine was well tolerated in pts with metastatic pancreatic cancer.
The effect of oncology massage in the treatment and prophylaxis of patient-reported distress during cancer treatment.
Authors: Alvaro G. Menendez, Alejandro Ramon Carvajal, Regina Cobb, Kathi Healey, Diane D'Ambra, Maria Soriano-Pisaturo
Journal: Journal of Clinical Oncology (2016)

191 Background: Distress (DS) levels are usually elevated across the disease course of cancer patients. Massage Therapy (MT) can improve patient-reported DS levels. We characterize the effect of MT on DS prevention and treatment, and compare the outcomes between single and multiple treatment sessions. Methods: This was a prospective single arm intervention with pre/post assessment using the validated NCCN DS Thermometer for patients on active chemotherapy who agreed to receive at least one MT session over a 10-week period. Results: 62 pts were included. 34/62 (55%) had DS when accruement started (X = 3.82, 6±4, M = 3, SD 2.32). 33/34 (97%) had improvement of DS after 1st session regardless of the type of DS on an average of 25% (p &lt; 0.05). From 1st MT session to beginning of 2nd MT session (5±3 wks), DS had improved in 78% (14/18) of pts on an average of 31% (p &lt; 0.001). 4/18 (22%) reported DS worsening chronically (X = 3.5, M = 3.5). 28/28 (100%) who had no DS reported initially did not develop it by the end of their participation. Conclusions: DS is prevalent among cancer patients and can affect treatment outcomes and overall quality of life. Regardless of type and source of DS, MT resulted in relief of patient-reported DS in a cumulative manner. MT may even appear to delay or prevent the onset of DS. Further studies are needed to determine if the improvement in DS is singularly from the MT intervention the patients received or from the emotional support that the therapist provided. A randomized study is also necessary to determine frequency and total duration of optimal treatment to confirm MT’s prophylactic and therapeutic ability for DS.
Comparision of the risk of cardiovascular events and death in patients treated with degarelix compared with LHRH agonists.
Authors: Peter C. Albertsen, Jan Nilsson, Laurence Klotz, Heather Payne, Egbert van der Meulen, Bo-Eric Persson, Tine Kold Olesen, Joshua Beckman
Journal: Journal of Clinical Oncology (2013)

42 Background: LHRH agonists are used to treat patients (pts) with advanced prostate cancer and have been associated with an increased risk of cardiovascular (CV) events and related deaths. Degarelix is a GnRH antagonist that appears to mitigate this risk. Methods: Results were pooled from 2328 pts participating in 6 prospective randomised trials. Most pts (n=1,686) received 1 year of GnRH antagonist or LHRH agonist treatment; the remainder (n=642) had 3–7 months’ treatment. Data were classified based on the MedDRA system and analysed using Kaplan Meier plots and a Cox proportional hazard model. Event analysis was based on death from any cause or CV event defined as arterial embolic/thrombotic; haemorrhagic or ischemic cerebrovascular; myocardial infarction or other ischemic heart disease. High risk pts were defined as men with a baseline CV disease (CVD) history. Results: Treatment groups (GnRH antagonist, n=1,491 [degarelix]; LHRH agonist, n=837 [goserelin, n=458; leuprolide, n=379]) were balanced for baseline characteristics and CVD history (31% vs. 29%). Characteristics associated with CVD (e.g. statin medication, elevated blood pressure, diabetes, cholesterol &gt;6.2 mmol/L) were similar between groups. The risk of a CV event or death was significantly lower in pts receiving degarelix during the first year of treatment (see Table). In pts with baseline CVD the findings remained significant. In pts with no baseline CVD, there was no difference in subsequent CVD events or death in either group. In analysis by time to CV event only in all pts and pts with baseline CVD (see Table), men receiving GnRH antagonist had a significantly lower risk of CV events. Conclusions: In all pts treated with a GnRH antagonist (degarelix) risk of a CV event or death was significantly lower than in pts receiving an LHRH agonist over a treatment period of up to 1 year. In pts with baseline CVD, risk reduction remained significant at ~50%. [Table: see text]
Only Time Before the Beginning of Treatment and Time to Achieve CCyR Influence the Stability of CCyR In CML-CP Patients On Imatinib Therapy.
Authors: Kudrat Abdulkadyrov, Elza Lomaia, Alla Abdulkadyrova, Vera Udalieva, Dgariyat Shikhbabaeva, Elena Usacheva, Irina Zotova, Elena Machulaitene, Maria Ivanova, Ekaterina Poznyak, Elena Koryagina, Natalia Ilina, Tatiana Shneider, Svetlana Stepanova, Ekaterina Romanova, Evgenia Salamatova, Natalia Lazorko, Irina Martynkevich, Vasiliy Shuvaev, Andrey Zaritskey
Journal: Blood (2010)
A comprehensive molecular characterization of aggressive variant prostate cancer (PC).
Authors: Ana Aparicio, Li Shen, Elsa Li Ning Tapia, Jing-Fang Lu, Hsiang-Chun Chen, Jiexin Zhang, Guanglin Wu, Xuemei Wang, Patricia Troncoso, Bradley McIntosh Broom, Keith A. Baggerly, Christopher Logothetis, Sankar N. Maity
Journal: Journal of Clinical Oncology (2015)

149 Background: Unusually aggressive PC behavior is linked to small cell carcinoma (SCC) morphology. We observed SCC clinical features in association with morphologically heterogeneous PC and, in a prospective clinical trial (NCT00514540), also with chemotherapy responsiveness. Our previous studies in patient derived xenografts (PDX) revealed a distinct molecular profile for SCC. Here we sought to support the hypothesis that clinically defined aggressive variant PCs also share relevant biology with SCC. Methods: 59 PC samples, and 8 PDX, from 42 men registered to NCT00514540 were stained for RB, p53, AR, NKX3-1, ASCL1, AURKA, UBE2C and Ki67. Labeling indices (LI) were calculated as the ratio of positive epithelial cells to total of epithelial cells, at 200x. We determined copy number alterations (CNA) by Onco Scan® in 36 of 59 samples and 8 PDX lines. We used Western Blot and qRT-PCR to expand pathway analyses and their associations in PDX models. Results: Donor patients were similar to non-donor patients except for higher ECOG PS and LDH values. Strong positive correlations between nuclear AR (AR-N) and NKX3.1, AR-N and RB, AR-N and nuclear AURKA (AURKA-N), NKX3.1 and RB, p53 and nuclear UBE2C (UBE2C-N), Ki67 and UBE2C-N, Ki67 and cytoplasmic UBE2C (UBE2C-C) as well as a strong negative correlation between NKX3.1 and Ki 67 were observed. Frequent copy number losses were found for PTEN (largely gene-specific) and RB1 (often associated with regional-CNA). Gene-specific AURKA amplifications were not observed. Only RB1 CNA showed a positive correlation with its LI. Samples were segregated by quantity of CNA. PDX models shared these features and showed that only AR-negative tumors expressed pro-neural transcription factors, albeit heterogeneously. Conclusions: Our results support the hypothesis that clinically defined aggressive variant PC (including SCC and non-SCC morphologies) are characterized by frequent Rb, p53 and PTEN alterations, aberrant expression of mitotic, neural development and AR-signaling pathways, and high rates of CNA. Ongoing studies will confirm whether these molecular features distinguish this variant from the more common bone-homing, bone-forming, AR-driven adenocarcinomas of the prostate.