tbuckley/cabot-search huggingface dataset:
MicroRNA-21 ISH analysis to predict DFS in pancreatic cancer patients undergoing adjuvant gemcitabine after curative surgery.
Authors: Soichiro Morinaga, Yoshiyasu Nakamura, Yusuke Katayama, Sho Sawazaki, Koji Numata, Kosei Higuchi, Teni Godai, Manabu Shiozawa, Yohei Miyagi, Shinichi Ohkawa, Kameda Yoichi, Makoto Akaike
Journal: Journal of Clinical Oncology (2014)

234 Background: Overexpression of microRNA-21(miR-21) in pancreatic cancer has been reported to be associated with tumor cell proliferation, invasion, and also resistance to gemcitabine (GEM) chemotherapy. The aim of this study was to evaluate whether miR-21 expression, determined by microRNA ISH, was associated with clinical outcomes of pancreatic cancer patients who underwent adjuvant gemcitabine chemotherapy after curative surgery. Methods: Expression levels of miR-21 were semi quantitatively analyzed for staining intensity and distribution of positive tumor cells, by microRNA ISH in formalin-fixed paraffin embedded tissue arrays from 41 pancreatic cancer patients who underwent adjuvant GEM chemotherapy after curative resection at Kanagawa Cancer Center. The staining intensity for the miR-21 was assigned a score from 1 to 3 based on staining with1+: weakly, 2+: moderately, and 3+: strongly positive. The percentage of positive tumor cells was scored as follows, 1+: &lt; 50% positive cells, 2+: 50-80% positive cells, and 3+: ³a 81% positive cells. A composite score was obtained by calculating the sum of these two scores. Results: 27 patients were assigned to low miR-21 expression group (score &lt;4) and 14 patients to high miR-21 group (score 4,5,6). High miR-21 expression group had a significantly shorter DFS (P = 0.039, by log-rank test). The median DFS was 9.8 months (95% CI, 6.9-12.6) in the low miR-21 group, and 7.9 months (95% CI, 6.1-9.8) in the high miR-21 group. The median OS was 19.6 months (95% CI, 6.3-32.8) in the low miR-21 group, and 15.1 months (95% CI, 11.7-18.5) in the high miR-21 group, but was not significant. Multivariate analysis including miR-21 expression, microscopic lymphatic invasion and microscopic perineural invasion, indicated that miR-21 expression (p = 0.024) and microscopic lymphatic invasion (p = 0.035) were the independent predictor for DFS. Conclusions: A high level of miR-21 expression in pancreatic cancer was significantly associated with shorter DFS in patients who received adjuvant GEM after curative resection. miR-21 ISH analysis may serve as a significant predictor for GEM resistance in adjuvant setting.
Runx1 Deficiency Produces Aberrant Progenitor Self-Renewal through Selective Compromise of Pu.1 Mediated Transactivation but Not Transrepression.
Authors: Zhenbo Hu, Soledad Negrotto, Kristine Marie Baraoidan, Vinzon Ibanez, Aron Shama, Fariborz Mortazavi, Steven Ackerman, Shrihari Kadkol, Giuseppina Nucifora, Yogen Saunthararajah
Journal: Blood (2008)
Caring for our deceased.
Authors: Kimberly Tripp, Angela Hayes-Rodgers, Altrivice D. Revis
Journal: Journal of Clinical Oncology (2012)

145 Background: In spring 2010, Off-Shift Administration (OSA) at MD Anderson Cancer Center received a spike in inquiries from staff concerned about the lack of uniformity in processing patient deaths occurring on campus. Procedures were known within administration, but no formal policy existed to substantiate requirements. A core team from Medical Affairs, Nursing, and OSA joined forces to address deficiencies and enhance the quality of end-of-life care across the organization. The core team then assembled two multidisciplinary groups to contribute to outcomes. Specific project aims were to increase physician completion of a death note within one hour of death from 83% to 95% compliance by April 2011. Monitoring of the death note was selected because it is often the first action barrier that further hinders processing a patient death. Methods: Key activity was carried out from July 2010 to July 2011. The first working group met to consider all processes relevant to expirations and write a policy. A second convened to address needed updates to clinical documentation. CLN1084 Caring for the Deceased Policy was implemented in January 2011. Education to physicians occurred in March 2011 and to ancillary staff in July 2011. In-services were given and announcements were made in various institutional communiqué. Results: Results were tabulated following a randomized monthly audit of deceased inpatient medical records. Audit specifications included a) determining presence of a death note and b) verifying that the note was completed within one hour of pronouncement. A March 2011 audit revealed 100% compliance of death note completion within one hour of the death. After the target end date, the team continued to see a superior 96.6% compliance rate. Clinical and support staff alike have also expressed great appreciation for reference tools now available to guide activity following a death on campus. Conclusions: Monitoring for compliance will continue as deemed necessary. The policy will also be reviewed regularly to assure accuracy and ongoing compliance with state law and hospital requirements. Finally, the core group continues to consult with departments who express interest in outlining specific departmental procedures (Rotary House, Regional Care Centers, etc.) that align with policy.
Polycythemia vera in GIST patients.
Authors: D. Schoeler, C. Klühs, D. Pink, A. Reichardt, P. Reichardt
Journal: Journal of Clinical Oncology (2010)

e20520 Background: The coincidence of second or multiple malignancies in gastrointestinal stroma tumor (GIST) patients was reported by several authors. We here report 3 patients diagnosed with GIST and polycythemia vera (PV) what was to date not reported to our knowledge. Methods: This is a retrospective analysis screening our GIST database which includes 346 patients until January 2010. Results: Patient (P) 1, a male born in 1930, was diagnosed with high-risk (hr) GIST of gastric wall in 2008 and had a history with unclear splenomegaly since 2005. The hemoglobin level was below 12g/dl since 2005. The laparascopic wedge resection was complicated by a splenic hematoma. He refused an adjuvant treatment with imatinib. One year post OP he developed night sweat and his hemoglobin level reached 16.5g/dl, the max. spleen diameter was 27cm. The erythropoietin level was 2U/l and we were able to detect the JAK2-V617F-mutation in peripheral blood cells due to diagnosis of PV. P2 is a male born in 1941 who was simultaneously diagnosed with hr-GIST of the gastric wall, PV und essential thrombocytosis (ET) with thrombocytes of 2000/nl in 2007. A laparascopic wedge resection was performed and he remains free of GIST relaps or metastases since 2007. For ET und PV the patient is treated with ASS and hydroxyurea. He has a normal blood count since 2007. We detected the JAK2-V617F-mutation in bone marrow cells. P3 is a male born in 1938 with a history of ischemic insult of left a. cerebri interna in 2003 who was diagnosed by hr-GIST of the gastric wall in 2005. He underwent gastric wall resection and had an adjuvant treatment with imatinib for one year. Since 2003 thrombocytosis up to 950/nl was known. Bone marrow diagnostics showed no clear signs for myeloproliferative disorder and he was diagnosed with reactive changes in 2005. In 2008 the patient was diagnosed with PV and ET due positive JAK2-V617F-mutation. Conclusions: Due to the bleeding tendency of GIST it is possible that the diagnosis of PV is delayed. We assume that tumor bleeding works like “internal bloodletting” that typical symptoms of PV can be missing and the diagnosis of PV is therefore delayed. If the incidence of PV in GIST patients is higher than in normal population, were it is 2/100.000, further analyses will show. No significant financial relationships to disclose.
Survival trends in advanced gastrointestinal stromal tumor patients: A population-based study.
Authors: Binay Kumar Shah, Nibash Budhathoki
Journal: Journal of Clinical Oncology (2015)

136 Background: In February 2002, imatinib was approved by US FDA for treatment of patients with advanced gastrointestinal stromal tumor (GIST). This study was performed to evaluate survival trends in patients with advanced GIST in pre- (1992-2001) and post- (2002-2008) imatinib era in the United States. Methods: We selected adult patients (≥18 years) with advanced GIST (regional and distant metastasis based on SEER’s LRD staging) from the Surveillance, Epidemiology, and End Results 18 database diagnosed during 1992-2008. We excluded patients diagnosed at autopsy or from death certificate only, or those without survival date. We analyzed 1- and 3- year relative survival (RS) rates of the patients by age (all ages,18-64yrs,64+yrs), race [White, Black and Others (American Indian/AK Native, Asian/Pacific Islander)], and gender in pre-imatinib (1992-2001) and post-imatinib (2002-2008) eras. We used Z-test in SEER*Stat to compare RS rates. Results: There were total of 1,734 cases of advanced GIST (regional and distant metastasis) during the study duration. Of the total population, 744 were females and 990 were males. The 1- and 3- year RS rates were significantly higher for patients diagnosed in post-imatinib era compared to those in pre-imatinib era (83.8±1.1% vs 72.5±2.3%; Z 4.47 at one year and 68.8±1.4% vs 51.0± 2.6%; Z 6.25). The survival rates in younger patients (18-64 years) improved significantly in post-imatinib era compared to pre-imatinib era (88.60±1.2% vs 74.20±2.9%; Z 5.19 at 1 year and 75±1.6% vs 56.1±3.4%; Z 5.81 at 3 years). Among older patients, there was improvement in 3- year survival rate (76.90±2% vs 70.40±3.5%; Z 1.22 at 1 year and 59.80±2.5% vs 44.9±4%; Z 2.82 at 3 years). Survival rates improved for both sexes and for Whites and Blacks (1 year RS: 83.80±1.3% vs 73.40±vs2.6%; Z 3.45 for Whites and 85±2.4% vs 68.80±6%; Z 2.53 for Blacks; 3 year RS: 68.60±1.7% vs 51.20±3.1%; Z 5.02 for Whites and 69.10±3.3% vs 42.6±6.6%; Z 3.76 for Blacks). There was no improvement in survival rates for Others. Conclusions: Overall, survival rates of advanced GIST patients have improved significantly in post-imatinib era compared to pre-imatinib era. There was no improvement in survival rates of Others.
Favorable Transplantation Outcomes Associated with Early Recovery of Lymphocytes and CD8+ Cells Following Allogeneic Stem Cell Transplantation.
Authors: Joon Ho Moon, Yoon Young Cho, Byung Woog Kang, Shi Nae Kim, Soo Jung Lee, Yun Jeong Kim, Jang Soo Suh, Kun Soo Lee, Jae Hoo Park, Sang Kyun Sohn
Journal: Blood (2009)
Epoetin alfa (EPO) 60,000 U every 2 weeks (Q2W) in patients (pts) with cancer not receiving chemotherapy (CT) or radiotherapy (RT)
Authors: D. Shasha, D. H. Henry, D. Williams
Journal: Journal of Clinical Oncology (2005)

8229 Background: The efficacy of EPO in anemic pts receiving CT and RT is well established. Less is known about the efficacy of EPO in anemic pts with cancer not receiving CT or RT, particularly in regimens less frequent than QW. Methods: This open-label, multicenter, pilot study is fully enrolled and ongoing. 57 pts with nonmyeloid malignancy; Hb ≤11 g/dL; and who had not received CT, RT, or pRBC transfusion (TFN) in the previous 8 weeks (wks), 4 wks, or 28 days, respectively, nor planned to receive these therapies, were enrolled. Hormonal, androgen deprivation, or immunotherapies were allowed. Pts were to receive oral iron daily. EPO was administered 60,000 U SC Q2W; escalation to 80,000 U Q2W after 4 wks if Hb increased <1 g/dL. The dose was titrated or held to maintain Hb ∼12 g/dL. Pts were treated up to 12 wks. The primary efficacy endpoint was hematopoietic response (HR; Hb increase ≥2 g/dL from baseline [BL] or Hb ≥12 g/dL on study) exclusive of Hb obtained within 28 days of TFN. Hb change from BL and TFN were also measured. Efficacy analyses were performed on the modified intent-to-treat population (MITT; pts who received ≥1 dose of EPO and had ≥1 postBL Hb or TFN). Results: Mean age, 70 yrs; mean BL Hb, 10.2 ± 0.76 g/dL (MITT population, N=45). Preliminary results showed 32/45 (71%) pts achieved HR. Hb increased 1.6 ± 0.8 g/dL (n=37) after 4 weeks, and 2.0 ± 1.2 g/dL (n=27) after 8 weeks on study. 1 pt received pRBC TFN after day 28. Most common adverse events were peripheral edema (8.9%), nausea (6.7%), and dizziness (6.7%). No deaths or clinically relevant thrombovascular events reported. Conclusion: Preliminary results suggest that EPO 60,000 U Q2W is effective and safe in anemic pts with cancer not receiving CT or RT. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ortho-Biotech/ Johnson & Johnson Johnson & Johnson/ Ortho-Biotech, Ortho-Biotech Ortho Biotech/ Johnson & Johnson Johnson & Johnson/ Ortho-Biotech, Ortho-Biotech Johnson & Johnson/ Ortho-Biotech, Ortho-Biotech Ortho-Biotech/ Johnson & Johnson
Risk factor migration and survival: Analysis from international dataset of 3,748 metastatic renal cell carcinoma (mRCC) patients treated on clinical trials.
Authors: S. Patil, J. Manola, P. Elson, W. Bro, S. Negrier, B. Escudier, R. M. Bukowski, R. J. Motzer
Journal: Journal of Clinical Oncology (2011)

4554 Background: Temporal shifts in the distribution of risk factors recorded at diagnosis can have a direct impact on clinical trial design and interpretation of outcome. Shifts may be a result of earlier more precise detection and diagnosis of metastatic disease. This analysis aims to investigate shifts in the frequency of known risk factors for mRCC patients in a multicenter, international experience of patient data collected to examine prognostic factors (Clin Cancer Res. 10[18 Pt 2]). Methods: An international database of 3748 patients with no prior systemic therapy and who were treated from 1975 to 2002 was constructed by pooling patient data from clinical trials conducted in the United States and Europe who met entry criteria. Systemic therapy included cytokines, chemotherapy, or various investigational agents. Proportions of known risk factors (low performance status, low HGB, high LDH, high corrected calcium, greater than 1 site of metastasis at diagnosis, nephrectomy, high neutrophils) were examined over six cohorts (1975 to 1980, 1981 to 1985, 1986 to 1990, 1991 to 1995, 1996 to 2000, 2001 to 2002). Overall survival for each cohort was examined using the Kaplan-Meier method. Results: Median overall survival increased with recently treated cohorts (Table). An increasing proportion of patients had prior nephrectomy (p=.0005). The proportions of patients with low performance status, high LDH, high adjusted calcium and high neutrophils have decreased over study year cohorts (all p<.01). The proportions of patients with low HGB and < 1 year from diagnosis to treatment have remained constant (p=.95, p=.35). There has been an increase in the proportion of patients with more than 1 site of metastasis (p=.0006). Conclusions: Pretreatment prognostic factors for shorter survival have decreased in proportion during more recent years. Higher representation of favorable risk factors may contribute to improvement in survival observed in recent years on clinical trials. Overall survival with 95% CI. Median (yrs) 95% CI 1975-1980 0.50 0.43 0.57 1981-1985 0.64 0.53 0.73 1986-1990 0.87 0.78 0.96 1991-1995 1.03 0.97 1.09 1996-2000 1.16 1.06 1.30 2001-2002 1.63 1.28 1.79
Promotion of gemcitabine resistance in pancreatic cancer cells by three-dimensional collagen I through HMGA2-dependent histone acetyltransferase expression.
Authors: Vaibhav Sahai, Surabhi Dangi-Garimella, Kazumi Ebine, Krishan Kumar, Hidayatullah G. Munshi
Journal: Journal of Clinical Oncology (2013)

172 Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with a pronounced stromal reaction that has been shown to contribute to chemo-resistance. We have previously shown that PDAC cells are resistant to gemcitabine chemotherapy in the collagen microenvironment due to increased expression of the chromatin remodeling protein high mobility group A2 (HMGA2). Methods: Pancreatic TMAs were stained with trichrome and for histone H3K9, H3K27 acetylation (Ac), and histone acetyltransferase (HAT) expression. PDAC cells were plated onto tissue culture plastic or in three-dimensional (3D) collagen gels and protein expression assessed by Western blotting. DNA damage response was assessed by comet and clonogenic assays. Results: PDAC tumors display higher levels of H3K9Ac and H3K27Ac in fibrotic regions. Moreover, PDAC cells upregulate H3K9Ac and H3K27Ac along with GCN5, PCAF and p300 HATs in 3D collagen compared to tissue culture plastic. Knocking down HMGA2 attenuates the effect of collagen on H3K9Ac, H3K27Ac and p300, PCAF and GCN5 expression. We also show that human PDAC tumors with HMGA2 expression demonstrate increased H3K9Ac and H3K27Ac. Additionally, we show that cells in 3D collagen gels demonstrate reduced tailing with the comet assay, increased clonogenic potential and increased γH2AX following gemcitabine treatment, suggesting an increased response and repair to damaged DNA in the 3D collagen microenvironment. Significantly, down-regulation of HMGA2 or p300, PCAF and GCN5 HATs decreases gemcitabine-induced γH2AX detected and attenuates clonogenic potential. Conclusions: Collagen microenvironment limits the effectiveness of gemcitabine through HMGA2-dependent HAT expression. HMGA2 expression is associated with histone acetylation and HAT expression in human PDAC tumors, particularly in area of fibrosis, suggesting that fibrosis may contribute to chemo-resistance through increased HMGA2-HAT signaling. Overall, our results increase our understanding of how the collagen microenvironment contributes to chemo-resistance and identify HATs as potential therapeutic targets against this deadly cancer.
A phase I/II study of S-1 plus oxaliplatin combined with radiation (SOX/RT) for preoperative locally advanced rectal carcinoma (JACCRO CC-04: SHOGUN trial).
Authors: Toshiaki Watanabe, Satoshi Matsusaka, Soichiro Ishihara, Keisaku Kondo, Hisanaga Horie, Keisuke Uehara, Masahiko Oguchi, Keiko Murofushi, Masashi Ueno, Nobuyuki Mizunuma, Daiki Kato, Yojiro Hashiguchi, Taiju Shimbo, Junji Okuda, Masanori Nakazawa, Eiji Sunami, Kazushige Kawai, Hideomi Yamashita, Tohru Okada, Yuichi Ishikawa
Journal: Journal of Clinical Oncology (2014)

602 Background: Previous western trials of preoperative chemoradiation (CRT) in patients with locally advanced rectal carcinoma (LARC) have been shown to increase the chance of sphincter preservation and local control, and has become the standard of care in western countries. In Japan, preoperative CRT has not been utilized in LARC and its value is unconfirmed. Thus, we conducted a phase I/II study of preoperative CRT with S-1, which is widely used oral fluoropyrimidine in Japan to treat gastrointestinal cancer, plus oxaliplatin in patients with LARC. Methods: Patients with histopathologically confirmed LARC (cT3-T4, any N) were eligible. A total radiation dose of 50.4 Gy was delivered in 28 fractions over 5 weeks, and S-1 was orally administered 40mg/m 2 twice a day for 5 days a week at 1st, 2nd, 4th and 5th week. Oxaliplatin was administered at a dose of 40 mg/m 2 (level 1), 50 mg/m 2 (level 2) or 60 mg/m 2 (level 3) on day 1, 8, 22 and 29. Surgery was performed within 6-10 weeks after CRT. The primary endpoint of phase I part was to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of oxaliplatin. Primary endpoint of phase II was evaluated pathologic complete response (pCR) rate at RD. Results: 13 patients were enrolled in the phase I part, 2 dose-limiting toxicities (DLTs, skipping oxaliplatin due to the grade 2 neutropenia) occurred in the dose level 3, and the MTD was not reached. In phase II, 45 patients were treated at the RD of oxaliplatin (60 mg/m 2 ) and 44 patients (97.8%) underwent surgery. A pCR was observed in 12 patients (27.3%). The relative dose intensity of radiation, S-1, oxaliplatin was 98.4%, 94.0%, and 94.3%, respectively. The incidence of grade 3-4 diarrhea and neutropenia was 8.9% and 2.2%, respectively. Postoperative complications of any grade occurred in 27.3% of patients. Conclusions: Preoperative CRT with S-1 plus oxaliplatin showed promising results in pathological responses and favorable toxicities profiles. Clinical trial information: NCT01227239.
Phase I/II Study of Escalating Doses of Idarubicin in Combination with Methotrexate, Vindesine and Prednisolone in Patients with Primary Central Nervous System Lymphoma: Results of the GOELAMS LCP99 Multicenter Trial.
Authors: Gaelle Olivier, Martine Gardembas, Vincent Delwail, Annie Le Mevel, Martine Escoffre-Barbe, Annie Brion, Jean Michel Boulet, Philippe Solal-Celigny, Pierre Ingrand, Philippe Colombat
Journal: Blood (2009)
Pruritus as an unmet palliative care need in cancer patients: A retrospective cohort study of a Duke patient-reported outcomes database.
Authors: Kathryn Elizabeth Hudson, Steven Paul Wolf, Mary Ruth Pupa, Danielle Grace King, Susan C. Locke, Amy P Abernethy, Thomas William LeBlanc
Journal: Journal of Clinical Oncology (2015)

97 Background: For cancer patients, the impact of pruritus is not well known, and may be increasing in incidence and severity for those receiving targeted agents. We aimed to describe pruritus in patients with solid tumors, assessing the incidence, pattern, treatments, and associations with cancer types and therapies. Methods: From 2009-2011, patients seen in the Duke Cancer Institute solid tumor clinics directly reported their symptoms on electronic tablets as part of routine care, using Patient Care Monitor 2.0. Of the resulting 17,338 encounters, &gt;1,000 patients reported moderate-severe itching (score of &gt;3 out of 10). The analysis cohort included 215 patients who reported severe itching (&gt;6 out of 10) on at least one visit (total visits = 536). We reviewed charts to abstract demographics, diagnosis, stage, cancer therapy, comorbidities, anti-pruritus therapy, and provider response, and applied descriptive statistics and chi-square analyses. Results: Most patients had advanced disease (56% stage IV), and had breast (36%), lung (23%), kidney (8%), colorectal (6%), or prostate cancer (5%). Thirty percent were not on active therapy, 27% were receiving a targeted therapy, 29% were receiving cytotoxic chemotherapy, and 14% were receiving both. Pruritus persisted in 56% of patients, and resolved but recurred in 10%. Patients receiving chemotherapy were more likely to have severe rather than moderate pruritus (p 0.01), while those receiving targeted drugs were more likely to have persistent pruritus (p 0.03). Potentially high-risk targeted therapies including EGFR inhibitors, multi-kinase inhibitors, and mTOR inhibitors were not associated with severity or persistence of pruritus. Only 20% of patients were receiving an anti-pruritus treatment. Clinicians documented discussing pruritus in just 28% of cases, and addressed it directly only 10% of the time. Only 5% of patients were started on a new anti-pruritus treatment. Conclusions: Pruritus is common among patients with advanced cancer, and occurs across a range of cancer types and treatments. Pruritus is frequently not recognized or addressed by clinicians, and appears to be an unmet palliative care need in oncology.