tbuckley/cabot-search huggingface dataset:
Clinical impact of perioperative changes of serum p53 antibody titers in patients with esophageal squamous cell carcinoma
Authors: A. Takeda
Journal: Journal of Clinical Oncology (2008)

4583 Background: The p53 protein overexpression that usually results from genetic alterations has been reported to induce serum antibodies against p53 in patients with esophageal squamous carcinoma. The clinical features of serum p53 antibodies (s-p53 Abs) are early negative conversion after curative treatment and patients who do not seroconvert to negative having a small number of residual cancer cells that remain after surgery. However, there is little information about the clinical significance of perioperative changes of s-p53 Abs titers in esophageal carcinoma. Methods: Our domestically developed highly specific enzyme- linked immunosorbent assay kit (MESACUP anti-p53 TEST) was used to analyze s-p53 Abs in 110 patients with esophageal carcinoma before and after surgery. The cutoff level of 1.3 U/mL was used to indicate seropositive patients. One month after surgery, s-p53 Abs titers were followed up to evaluate clinical impact of changes of serum titers. After surgery, all patients were monitored until the end of October 2007 or their death by clinical examinations on a regular basis. Recurrent disease was treated according to the standard methods. Prognostic impact of postoperative s-p53 Abs was evaluated in univariate and multivariate analyses. Patients recruitment and sample collections were performed within the guideline of protocols by the institutional review board. Results: A total of 40 (36%) patients were positive for s-p53 Abs before surgery. Serum titers were significantly reduced after surgery (3.1±4.8 vs 2.7±4.6, P=0.05). One month after surgery, 12 converted to sero-negative and 28 remained sero-positive. The patients who remained sero-positive revealed worse prognosis (P=0.02). Multivariate analysis revealed that postoperative s-p53 Abs was an independent risk factor for worse overall survival (adjusted hazard ratio=3.05, 95%IC=1.11–8.33, P=0.03). Conclusions: Perioperative monitoring of s-p53 Abs titers was useful to identify high risk group for tumor recurrence and a poor prognosis in esophageal carcinoma. Our clinical research for s-p53 Abs over a decade proved to be approved to use it as a biomarker for esophageal, colorectal and breast cancer by Japanese Ministry of Health and Welfare from Nov.1. 2007 No significant financial relationships to disclose.
Healthcare utilization among cancer patients prior to hospice.
Authors: Emily Miller Ray, Richard F. Riedel, Christel N. Rushing, Anthony N. Galanos
Journal: Journal of Clinical Oncology (2016)

135 Background: The integration of palliative medicine in oncologic care has become increasingly recognized and supported. We have previously reported improved health system and quality of care outcomes for solid tumor patients admitted to our novel, fully-integrated palliative care (PC) and medical oncology inpatient service at Duke University Medical Center (DUMC). In this study, we explored healthcare utilization in patients specifically discharged to hospice pre- and post-PC integration. Methods: We conducted a retrospective cohort study of hospitalized patients on the solid tumor unit at DUMC who were discharged to hospice care between September 1, 2009-June 30, 2010 (pre-PC integration) and September 1, 2011-June 30, 2012 (post-PC integration). Cohorts were compared on the following outcome variables occurring within 30 days prior to discharge to hospice: number of hospitalizations, ICU days, ED visits, invasive procedures, subspecialty consultations, radiologic studies, medical oncology clinic visits, and use of chemotherapy or radiation. Wilcoxon rank-sum and Chi square tests were used for statistical analyses. Results: A total of 296 patients were included (133 pre-PC integration; 163 post-PC integration) in the analyses. Patient characteristics were well matched between cohorts. The overall mean age was 63 years (range 25-96), 62% were Caucasian, 51% were male, and 98% of patients had recurrent or metastatic disease. Of particular note, there were no significant differences noted between cohorts with regards to the resource utilization outcome variables assessed. Conclusions: Understanding healthcare utilization in this patient population is of great interest to clinical providers and policymakers alike. While we have previously demonstrated the benefit of integrating palliative care and medical oncology for reducing hospital readmissions and length of stay, this study shows no significant impact of an integrated approach on the utilization of healthcare resources measured within the 30 days prior to discharge to hospice. This may reflect the aggressive approach to management of symptoms for end-of-life patients, which often involves invasive procedures, use of imaging, and other resources to meet their needs.
A randomized phase III study of 72 h infusional versus bolus bleomycin in BEP (bleomycin, etoposide and cisplatin) chemotherapy to treat IGCCCG good prognosis metastatic germ cell tumours (TE-3)
Authors: J. Shamash, S.-J. Sarker, R. Huddart, S. Harland, J.K. Joffe, D. Mazhar, A. Birtle, J. White, K. Chowdhury, P. Wilson, M.R. Marshall, S. Vinnicombe
Journal: Annals of Oncology (2017)
Differential ICAM3 Gene Expression Correlates with Susceptibility to Natural Killer Cell-Mediated Lysis in Multiple Myeloma
Authors: Tarun K. Garg, Ricky D Edmondson, Shweta S. Chavan, Katie Stone, Justin M Stivers, Jessica I Warden, Veronica Macleod, Charles M Skinner, Joshuah D Lingo, Amy D Greenway, Junaid Khan, Donald Johann, Christoph Heuck, Bart Barlogie, Gareth J Morgan, Joshua Epstein, Frits van Rhee
Journal: Blood (2015)
Abnormalities in skin temperature and its 24-hour rhythm in patients with cirrhosis: sleep-wake and general clinical implications
Authors: M. Garrido, D. Saccardo, M. De Rui, E. Vettore, A. Verardo, P. Carraro, N. Di Vitofrancesco, A.R. Mani, P. Angeli, M. Bolognesi, S. Montagnese
Journal: Journal of Hepatology (2017)
Correlation between findings from comprehensive genomic profiling and targeted therapy response in metastatic renal cell carcinoma.
Authors: Thai Huu Ho, Toni K. Choueiri, Kai Wang, Jose A. Karam, Zachary Rockow Chalmers, Garrett Michael Frampton, Julia Andrea Elvin, Adrienne Johnson, Xueli Liu, Yulan Lin, Richard Wayne Joseph, Melissa L. Stanton, Vincent A. Miller, Philip J. Stephens, Jeffrey S. Ross, Siraj Mahamed Ali, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2016)

570 Background: Vascular endothelial growth factor- (VEGF-) and mammalian target of rapamycin- (mTOR-) directed therapies represent a standard of care in metastatic renal cell carcinoma (mRCC). However, these agents are not employed based on an assessment of predictive biomarkers such as genomic alterations (GA). We sought to determine if an association exists between GA detected by comprehensive genomic profiling (CGP) and the response to VEGFR and mTOR pathway targeted therapies in a cohort of mRCC treated in a clinical practice setting. Methods: The results of CGP performed in the course of clinical care on 31 consecutive mRCC obtained from patients who had received VEGFR- and/or mTOR-inhibitors were reviewed. Duration of treatment (DOT), extent and duration of clinical response was obtained from review of medical records. All classes of genomic alterations - base substitutions, short insertions, deletions, gene fusions, rearrangements and copy number - were assessed via CGP. Descriptive statistics were used to determine the frequency of GAs in groups segregated by the DOT with VEGF-directed agents. Results: The most common GAs detected in this series were in VHL (70%), PBRM1 (48%), SETD2 (32%), TSC1 (29%), MLL (19%), TERT (16%), ARID1B (16%) and KDM5C (16%). Across 61 administrations of VEGF-directed therapy in 27 patients, exceptional responses (DOT &gt; 21 months) were more frequent amongst patients with GAs in KDM5C, PBRM1, and VHL. Conversely, these patients also featured a lower frequency of GA associated with response to mTOR-directed therapy, such as TSC1. Conclusions: Multiple GAs are more prevalent in exceptional responders to VEGF-directed therapy. Prospective validation of these findings may lead to use of CGP to optimize therapeutic selection.
LAPACT: An open-label, multicenter phase II trial of <i>nab</i>-paclitaxel (<i>nab</i>-P) plus gemcitabine (Gem) in patients (pts) with locally advanced pancreatic cancer (LAPC).
Authors: Philip Agop Philip, Jill Lacy, Scot D. Dowden, Javier Sastre, Venu Gopal Bathini, Dana Backlund Cardin, Wen Wee Ma, Alberto F. Sobrero, Sheryl L. Koski, Christophe Borg, Giuseppe Tonini, Fernando Rivera, Jimmy J. Hwang, Jeanna L. Knoble, Tareq Al Baghdadi, Wasif M. Saif, Eyal Meiri, Louis Kayitalire, Jack Li, Pascal Hammel
Journal: Journal of Clinical Oncology (2016)

TPS477 Background: In pts with LAPC, more effective systemic therapies may be associated with improved local control, delay of metastasis, and overall survival (OS). The phase III MPACT trial in pts with metastatic PC demonstrated longer OS (median, 8.7 vs 6.6 mos; HR, 0.72; P &lt; 0.001) and an ≈ 3-fold greater shrinkage of primary tumors with nab-P + Gem vs Gem alone (−22.15% vs −7.02%), raising the possibility of improved local PC control with nab-P + Gem. LAPACT will assess the efficacy and safety of nab-P + Gem in LAPC. Methods: LAPACT will enroll treatment-naive pts (planned n ≈ 110) in the United States, Canada, and Europe with Eastern Cooperative Oncology Group performance status ≤ 1, confirmed unresectable LAPC, no distant metastases, and adequate organ function. Pts with mixed-origin tumors, any other malignancy within 5 years, peripheral neuropathy grade &gt; 1, or clinically significant ascites are ineligible. Pts will receive nab-P 125 mg/m 2 + Gem 1000 mg/m 2 on days 1, 8, and 15 of each 28-day cycle. Pts without progressive disease (PD) or unacceptable toxicity after 6 cycles will receive investigator’s choice of surgery, chemoradiotherapy, or continued nab-P + Gem. If a major response is observed, surgery may occur prior to completing 6 cycles of nab-P + Gem. The primary endpoint is time to treatment failure (TTF; time from first therapy dose to discontinuation due to PD, start of a new non–protocol-defined anti-cancer therapy, or death). The study design allows for 80% power at a 1-sided α of 0.05 to detect a 30% increase over the 5.1-month median TTF observed for nab-P + Gem in the MPACT study. The secondary endpoints are disease control rate (DCR) after 6 cycles, overall response rate, progression-free survival, OS, safety, and quality of life. The exploratory endpoint is correlation of changes in circulating nucleic acids with PD and treatment response. An interim DCR analysis will occur after all pts have completed 6 cycles of nab-P + Gem, discontinued therapy due to PD, died, or started a new non–protocol-defined therapy before completing 6 cycles of therapy. Enrollment is ongoing (first pt enrolled in April 2015). Clinical trial information: NCT02301143.
Effect of AXIN2 expression on prostate cancer recurrence and an invasive, tumorigenic phenotype.
Authors: Brian Robin Hu, Adrian S Fairey, Anisha Madhav, Dongyun Yang, Meng Li, Susan G. Groshen, Craig Stephens, Philip Kim, Navneet Virk, Lina Wang, Sue Ellen Martin, Nicholas Erho, Elai Davicioni, Robert B. Jenkins, Robert Benjamin Den, Tong Xu, Yucheng Xu, Inderbir S Gill, David I. Quinn, Amir Goldkorn
Journal: Journal of Clinical Oncology (2015)

29 Background: Better biomarkers are needed in prostate cancer (PCa) to predict disease recurrence and guide optimal therapy. We investigated whether genes associated with a highly tumorigenic, drug resistant, progenitor cancer phenotype impact PCa biology and clinical outcomes in localized disease. Methods: Genes associated with self-renewal, drug resistance, and tumorigenicity were analyzed by qRT-PCR on PCa mRNA from radical prostatectomy (RP) specimens (+/- disease recurrence). Wilcoxon rank sum two-sample test, multivariable recursive partitioning, and bootstrap internal validation measured and confirmed associations with recurrence. Further validation was conducted in external cohorts and in-silico, as well as in vitro and in vivo using siRNA knockdown and lentiviral overexpression to determined the effect of gene expression on PCa proliferation, invasion and tumor growth. Results: Four candidate genes were differentially expressed in PCa recurrence, and of these, low AXIN2 expression was internally validated. Validation in external cohorts demonstrated low AXIN2 expression was associated with more aggressive prostate cancer and was independently associated with biochemical recurrence (BCR) and metastasis-free survival (MFS) after RP. In vitro, low AXIN2 expression was associated with a cancer stem-like cell-surface signature, and siRNA knockdown of AXIN2 resulted in significantly greater invasiveness. Conversely, ectopic overexpression of AXIN2 significantly reduced cell proliferation and tumor growth in mice. Conclusions: Low AXIN2 expression was associated with PCa recurrence after RP in our test population as well as in external validation cohorts. AXIN2 expression levels in PCa cells significantly impacted invasiveness, proliferation and tumor growth. AXIN2 represents a putative biomarker and potential therapeutic target in early prostate cancer.
Updated survival results of the randomized phase II study of S-1, oral leucovorin, and oxaliplatin combination therapy (SOL) versus mFOLFOX6 in patients with untreated metastatic colorectal cancer (mCRC).
Authors: Toshio Otsuji, Kentaro Yamazaki, Hitoshi Ojima, Hiroyuki Kuwano, Takeshi Kato, Ken Shimada, Tadamichi Denda, Taito Esaki, Ichinosuke Hyodo, Narikazu Boku
Journal: Journal of Clinical Oncology (2012)

586 Background: We previously reported short term results of a randomized phase II study comparing SOL with mFOLFOX6 in terms of progression-free survival (PFS) by central review. The median PFS for SOL and mFOLFOX6 was 9.6 and 6.9 months (HR= 0.83; 95%CI, 0.49-1.40) with median follow-up time 14 months (Ojima et al, ESMO 2011). Here, we report updated overall survival (OS) results with 29 months follow-up. Methods: The inclusion criteria were; 1) histologically proved adenocarcinoma of colon or rectum, 2) age ≥ 20 years, 3) no prior treatment, 4) at least one target lesion by RECIST ver1.0 criteria, 5) ECOG Performance Status 0-1. Patients (Pts) were randomized to receive either S-1 (40-60 mg bid) and oral LV (25 mg bid) for one week and L-OHP (85 mg/m 2 ) on day 1, repeated every 2 weeks (SOL; Group A) or L-OHP (85 mg/m 2 ), l-LV (200 mg/m 2 ), and 5-FU (400 mg/m 2 , bolus) on day 1, followed by 5-FU (2400 mg/m 2 , ci, 46 hours), repeated every 2 weeks (mFOLFOX6; Group B). This trial was supported by Taiho Pharmaceutical CO., LTD and Yakult Honsha CO., LTD. ClinicalTrials.gov Identifier: NCT00721916 Results: From July 2008 to July 2009, 107 pts were randomized, and 105 were eligible (56 to Group A and 49 to Group B). When survival data were updated 2 years after the last patient’s enrollment, with no lost cases, median OS for Group A and Group B was 28.5 and 25.9 months (HR= 0.76; 95%CI, 0.45-1.31), 2-year survival rate was 71.4% and 59.2%, respectively. The incidences of grade 3/4 adverse drug reactions were; neutropenia (19.6% Group A, 41.2% Group B), lymphopenia (14.3% and 5.9%), sensory neuropathy (19.6% and 2.0%), anorexia (12.5% and 7.8%), fatigue (10.7% and 5.9%) and diarrhea (10.7% and 3.9%). Post treatments with or without molecular target agents were performed for 80.4 % of Group A, and 75.5 % of Group B. Conclusions: The results of the present analysis show that SOL might be more effective than mFOLFOX6 in terms of both PFS and OS as the first line chemotherapy for mCRC. Further investigation of the SOL regimen, a phase III trial of its combination with molecular target agents should be considered.
High Dose Sequential (HDS) Followed by Autologous Hematopoietic Stem Cell Transplantation (AHSCT) for Salvage Treatment of Hodgkin’s Disease (HD): A Brazilian Experience.
Authors: Bruno K.L. Duarte, I.S. Valente, Afonso C. Vigorito, Francisco J.P. Aranha, Gislaine B. Oliveira, Eliana C.M. Miranda, Irene Lorand-Metze, Katia B.B. Pagnano, Carmino A. De Souza
Journal: Blood (2007)
Primary, resectable gastrointestinal stromal tumors (GISTs) originating from stomach and small intestine as different prognostically subtypes of disease
Authors: P. Rutkowski, Z. I. Nowecki, W. Michej, J. A. Siedlecki, W. Ruka
Journal: Journal of Clinical Oncology (2008)

10559 Background: The stomach (G) and small bowel (SB) are the most common primary sites of GISTs. However, the prognostic criteria for these GIST subtypes are still debatable. The aim of the study was to analyze the factors influencing the disease-free survival (DFS) in subgroups of G-GIST and SB-GIST patients based on the large prospectively collected registry. Methods: In group of 440 primary GISTs CD117(+) treated surgically (resection R0/R1) with curative intention we identified 208 G-GISTs (47%) and 168 SB-GISTs (38%) and in these subgroups we analyzed factors influencing on DFS (from date of radical surgery to date of relapse/last follow-up). Median follow-up was 33 months. Results: G-GISTs as compared with SB-GISTs were significantly smaller (median size: 5 and 9 cm, respectively; p<0.0001), with less mitotic activity (median: 3/50 vs. 5/50 HPF; p=0.01) and patients were older (median age: 62 vs 56 years; p=0.02). The most common mutations in G-GISTs were exon 11 KIT (56%) and exon 18 PDGFRA (18%), and in SB-GIST - exon 11 KIT (65%) and exon 9 KIT (14%). The prognosis of G-GISTs was significantly better than SB-GISTs (5-year DFS rate: 64% [SD±5%] vs. 31% [SD±5%], respectively; p<0.0001). In G-GIST group the following factors demonstrated negative impact on DFS in univariate analysis: primary tumor size >5 cm and >10 cm (p<0.0001), mitotic index >5/50 and >10/50 HPF (p<0.0001), male gender (p=0.01), resection R1/tumor rupture (p<0.01) and high or intermediate NIH risk group (p<0.0001). In SB-GISTs group the following factors demonstrated negative impact on DFS in univariate analysis: primary tumor size >5 cm (p<0.001), mitotic index >5/50 HPF (p<0.001), resection R1/tumor rupture (p<0.01), epithelioid-cell or mixed-cell pathologic subtype (p=0.01), and high or intermediate NIH risk group (p<0.0001). According to multivariate analysis in both groups primary tumor size and mitotic activity or NIH risk group (+additionally gender in G-GIST) demonstrated independent influence on DFS. Conclusions: GISTs originating from small bowel have worse prognosis than primary tumors located in the stomach. In both groups primary tumor size and mitotic activity are the most important factors in relation to disease recurrences. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis, Pfizer
Gynecologic cancer screening in women at high risk of Lynch syndrome.
Authors: C. Guillen-Ponce, C. Martinez-Sevila, R. Perea, M. Arenas, M. J. Molina-Garrido, M. Goicoechea, D. Salas, A. Carrato
Journal: Journal of Clinical Oncology (2011)

1559 Background: Endometrial cancer is the most frequent extracolonic tumor in women with Lynch syndrome (LS). The aim of this study was to assess adherence to screening of gynecological tumors by women with LS and determine the impact of monitoring and prophylactic surgery in these women. Methods: Between 2005-2008, 91 women with LS were subjected to gynecological examination (GE), transvaginal ultrasound (TVS) and endometrial aspirate (EA). The implementation of screening, its results and prophylactic surgery information were evaluated annually and verified with documentation. We analyzed factors associated with adherence: socioeconomic, clinical, genetic and family history, and the results of screening. Results: Of the 91 women with gynecological follow-up, 78 (85.71%) were performed at least once (GE and ETV). EA was zero, except in 3 women (3.3%) with abnormal TVS. 48 underwent a gynecological screening only once. The average gynecological screening examinations (EG + ETV) performed was 1.4 ± 1.07 (range 0-4). Women at risk without cancer adhered better (58.3% vs 52.5% vs 30.8%, p = 0.028). In addition, there was greater compliance if ≥ 2 first degree relatives were affected with endometrial cancer (80% vs 56.3 and 35.4%, p = 0.009). Socioeconomic status, educational, employment and mutational status had no effect on compliance. 3 (3%) women were diagnosed with endometrial cancer. 2 patients suspected diagnosis of endometrial cancer with the first GE including ETV, and confirmed with EA. The third case was detected by a prophylactic hysterectomy in a woman newly diagnosed with two synchronous colon cancers by screening colonoscopy. This was in the one case who underwent prophylactic surgery, and her endometrial cancer was at an early stage (stage IA). Conclusions: Compliance with the recommendations of gynecological screening was 44%. EA is not performed for screening of endometrial cancer. The number of relatives with endometrial cancer increases the likelihood of adhering to gynecological screening. The identification of a mutation has no effect. The first gynecological screening examination detects a significant number of endometrial cancers; and, in addition, prophylactic hysterectomy detects early stage tumors in women with LS.
Hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer: Sequencing of chemotherapy and endocrine therapy.
Authors: Nicole M. Engel-Nitz, Yanni Hao, Jaqueline Willemann Rogerio, James D. Turnbull, Gabriel Gomez Rey, Jane Sullivan, Arthur H. Rossof
Journal: Journal of Clinical Oncology (2013)

164 Background: National Comprehensive Cancer Network breast cancer guidelines suggest sequencing of systemic therapy. This study examined sequencing of endocrine and chemotherapy treatments to better understand real-world treatment patterns for HR+/HER2- advanced breast cancer. Methods: A proprietary clinical cancer database with physician-reported clinical data on patients with breast cancer was linked to medical and pharmacy claims (2008-2012) from a national US health plan. Study patients had HR+ and HER2- status. Advanced cancer cohorts were defined: stage III (SIII) or IV (SIV) at initial diagnosis, or developed metastases following initial diagnosis (MET). Index date was the first date of advanced cancer diagnosis or date of metastases following initial diagnosis. Health plan enrollment for 3 months pre- and ≥ 3-months post- index date was required; patients who died within 3 months after index date and were continuously enrolled were retained. A 3-month baseline period assessed prior treatment; a variable follow-up (until disenrollment or 31 Oct 2012) assessed patterns of endocrine and chemotherapy treatments following index date. Results: A total of 954 breast cancer patients met study inclusion criteria and were HR+/HER2- with ≥ 3 months of continuous enrollment after index date, with 369 of the 954 (38.68%) SIII, 117 (12.26%) SIV, and 469 (49.16%) MET patients. In the study population, 83.65% were treated with endocrine therapy, starting an average of 179 days after index date. A total of 80.29% were treated with chemotherapy, starting an average of 53 days following the index date; 65% of patients initiated chemotherapy after index date without prior endocrine treatment. Rates varied by cohort: 90% of SIII, 57% of SIV, and 48% of MET patients had no evidence of endocrine treatment prior to initiating chemotherapy. Conclusions: This study found large proportions of HR+/HER2- advanced breast cancer patients initiated chemotherapy without prior endocrine therapy. Further investigation of patient characteristics and outcomes by therapy sequencing patterns will help illuminate the extent to which patterns adhere to NCCN guidelines.