tbuckley/cabot-search huggingface dataset:
Long term effects of once-only flexible sigmoidoscopy screening after 17 years of follow-up: the UK Flexible Sigmoidoscopy Screening randomised controlled trial
Authors: Wendy Atkin, Kate Wooldrage, D Maxwell Parkin, Ines Kralj-Hans, Eilidh MacRae, Urvi Shah, Stephen Duffy, Amanda J Cross
Journal: The Lancet (2017)

<h2>Summary</h2><h3>Background</h3> Colorectal cancer is the third most common cancer worldwide. Previous analyses have only reported follow-up after flexible sigmoidoscopy for a maximum of 12 years. We aimed to examine colorectal cancer incidence and mortality after a single flexible sigmoidoscopy screening and 17 years of follow-up. <h3>Methods</h3> In this multicentre randomised trial (UK Flexible Sigmoidoscopy Screening Trial), done between Nov 14, 1994, and March 30, 1999, 170 432 eligible men and women, who had indicated on a previous questionnaire that they would probably attend screening if invited, were randomly assigned (1:2) to an intervention group (offered flexible sigmoidoscopy screening) or a control group (not contacted). Randomisation was done centrally in blocks of 12, and stratified by trial centre, general practice, and household type. The nature of the intervention did not allow the staff to be masked to arm of the trial; however, randomisation was done in batches so that the control group and participants not yet randomised were unaware of their allocation status. The primary outcomes were incidence and mortality of colorectal cancer. Hazard ratios (HRs) and 95% CIs for colorectal cancer incidence and mortality were estimated for intention-to-treat and per-protocol analyses. The trial is registered with ISRCTN, number 28352761. <h3>Findings</h3> Our cohort analysis included 170 034 people: 112 936 in the control group and 57 098 in the intervention group, 40 621 (71%) of whom were screened and 16 477 (29%) were not screened. During screening and a median of 17·1 years' follow-up, colorectal cancer was diagnosed in 1230 individuals in the intervention group and 3253 in the control group, and 353 individuals in the intervention group versus 996 individuals in the control group died from colorectal cancer. In intention-to-treat analyses, colorectal cancer incidence was reduced by 26% (HR 0·74 [95% CI 0·70–0·80]; p<0·0001) in the intervention group versus the control group and colorectal cancer mortality was reduced by 30% (0·70 [0·62–0·79]; p<0·0001) in the intervention group versus the control group. In per-protocol analyses, adjusted for non-compliance, colorectal cancer incidence and mortality were 35% (HR 0·65 [95% CI 0·59–0·71]) and 41% (0·59 [0·49–0·70]) lower in the screened group. <h3>Interpretation</h3> A single flexible sigmoidoscopy continues to provide substantial protection from colorectal cancer diagnosis and death, with protection lasting at least 17 years. <h3>Funding</h3> National Institute for Health Research Efficacy and Mechanism Evaluation.
Phase II study of eribulin mesylate (E7389) in patients (pts) with locally advanced or metastatic breast cancer (MBC) previously treated with anthracycline, taxane, and capecitabine therapy
Authors: L. T. Vahdat, C. Twelves, M. K. Allison, J. A. Cortes, M. Campone, D. E. Shuster, J. Wanders, F. Fang, R. D. Gurnani, J. L. Blum
Journal: Journal of Clinical Oncology (2008)

1084 Background: Eribulin mesylate (E7389) is a non-taxane microtubule dynamics inhibitor with a novel mechanism of action. This study evaluated efficacy and safety of eribulin for locally advanced or MBC in pts previously treated with an anthracycline, a taxane, and capecitabine. Methods: This single-arm, open-label phase II study planned to recruit 300 breast cancer pts with measurable disease (RECIST), ECOG performance status 0–2 and neuropathy ≤ grade 2. Eligible pts had received 2–5 prior chemotherapy (CT) regimens, and progressed on or within 6 months of their last CT. Eribulin (1.4 mg/m2) was administered as a 2–5 minute intravenous (IV) infusion on Days 1 and 8 of a 21-day cycle. The primary efficacy endpoint was objective response rate (ORR) assessed by independent review (IR) using RECIST criteria. Results: Of 299 pts enrolled, 291 received eribulin (safety population): median age 56 (range: 26–80) years; ER+ or PgR+ (71%); HER2/neu+ (11%); triple ER, PgR, HER2 negative (21%); median of 4 prior CT regimens. Pts received a median of 4 eribulin cycles (range 1–27). Efficacy analysis was based upon 269 pts who met key inclusion criteria: ORR by IR was 9.3% (all PR; 95% CI 6.1–13.4%) and investigator-assessed ORR was 14.1% (1 CR; CI 10.2–18.9%). SD was 46.5% and the clinical benefit rate (CBR, defined as CR + PR + SD≥6 months) was 17.1% (95% CI 12.8–22.1%). Median duration of response was 3.5 mo (106 days; range 42+-258 days; +censored observation). Median PFS and OS were 2.6 mo (78; 1+-398 days) and 10.4 mo (315; 19–604 days), respectively. Six-month PFS and OS rates were 12.4% and 72.3%, respectively. The most frequently reported treatment-related grade 3/4 toxicities were neutropenia (54%; febrile neutropenia: 5.5%), leukopenia (14%), and asthenia/fatigue (10%; no grade 4). Grade 3 peripheral neuropathy occurred in 5.5% of pts (no grade 4). Conclusions: Eribulin demonstrated activity in heavily pretreated pts (median of 4 prior CT regimens) who had previously received an anthracycline, a taxane, and capecitabine (ORR, 9.3%; CBR, 17.1%). Eribulin had a manageable tolerability profile with a notably low incidence of grade 3/4 neuropathy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eisai Medical Research, Eisai UK Ltd Eisai Medical Research Eisai Medical Research Eisai Medical Research, Weill Cornell Medical College Eisai Medical Research
Meta-analysis of sentinel lymph node positivity in thin melanoma (≤ 1mm)
Authors: J. A. Zakrzewski, M. A. Warycha, Q. Ni, R. L. Shapiro, R. S. Berman, A. C. Pavlick, D. Polsky, M. Mazumdar, I. Osman
Journal: Journal of Clinical Oncology (2008)

20032 Background: Indications for sentinel lymph node (SLN) biopsy in patients with thin (≤1mm) primary melanoma are as yet undefined, with selection criteria varying among institutions. We performed a meta-analyses of published studies to estimate the risk of regional nodal disease in this group of patients. Methods: MEDLINE (January 1966 to July 2007), EMBASE (January 1980 to July 2007), and Cochrane databases were searched for published studies or abstracts which reported on the rate of SLN positivity in patients with thin melanomas. Searches were supplemented by scanning bibliographies of included articles. Two authors independently extracted data. Study quality was assessed using the MINORS criteria. A meta-analysis was performed using fixed and random effect models. Results: 3,651 patients enrolled in 34 studies met inclusion criteria. Meta-analysis resulted in a random effects pooled SLN positivity rate of 5.6%. Significant heterogeneity among studies was detected (p=0.005, test of non-combinability), suggesting high variation among study outcomes. There was no statistical evidence of publication bias (p=0.21, Begg-Mazumdar test). 18 studies had a primary focus on SLN biopsy in melanomas ≤1mm. These studies reported select clinical and histopathologic data limited only to SLN positive patients (n=113). Among the tumors from these patients 6/98 (6.1%) were ulcerated, 17/54 (31.5%) showed regression, and 48/101 (47.5%) were invasive to Clark’s level IV/V. Only 3 patients for whom recurrence and survival data were available died of melanoma at follow-up. Conclusions: These data indicate that nodal involvement, as detected by the highly sensitive SLN technique, is rare in melanomas ≤ 1mm in thickness. In addition, the lack of complete clinicopathologic data from SLN biopsy negative patients in most of the published literature precludes the identification of reliable criteria to select patients who might benefit from SLN biopsy. Therefore, the benefits of SLN biopsy among patients with melanomas ≤ 1mm in thickness appear marginal. Given the increasing diagnosis of thin melanomas as well as the cost and morbidity associated with this procedure, alternative strategies to identify patients at risk for nodal disease, including molecular prognostic factors, are critically needed. No significant financial relationships to disclose.
Targeting PPARγ in the epigenome rescues genetic metabolic defects in mice
Authors: Raymond E. Soccio, Zhenghui Li, Eric R. Chen, Yee Hoon Foong, Kiara K. Benson, Joanna R. Dispirito, Shannon E. Mullican, Matthew J. Emmett, Erika R. Briggs, Lindsey C. Peed, Richard K. Dzeng, Carlos J. Medina, Jennifer F. Jolivert, Megan Kissig, Satyajit R. Rajapurkar, Manashree Damle, Hee-Woong Lim, Kyoung-Jae Won, Patrick Seale, David J. Steger, Mitchell A. Lazar
Journal: Journal of Clinical Investigation (2017)

Obesity causes insulin resistance, and PPARγ ligands such as rosiglitazone are insulin sensitizing, yet the mechanisms remain unclear. In C57BL/6 (B6) mice, obesity induced by a high-fat diet (HFD) has major effects on visceral epididymal adipose tissue (eWAT). Here, we report that HFD-induced obesity in B6 mice also altered the activity of gene regulatory elements and genome-wide occupancy of PPARγ. Rosiglitazone treatment restored insulin sensitivity in obese B6 mice, yet, surprisingly, had little effect on gene expression in eWAT. However, in subcutaneous inguinal fat (iWAT), rosiglitazone markedly induced molecular signatures of brown fat, including the key thermogenic gene Ucp1. Obesity-resistant 129S1/SvImJ mice (129 mice) displayed iWAT browning, even in the absence of rosiglitazone. The 129 Ucp1 locus had increased PPARγ binding and gene expression that were preserved in the iWAT of B6x129 F1-intercrossed mice, with an imbalance favoring the 129-derived alleles, demonstrating a cis-acting genetic difference. Thus, B6 mice have genetically defective Ucp1 expression in iWAT. However, when Ucp1 was activated by rosiglitazone, or by iWAT browning in cold-exposed or young mice, expression of the B6 version of Ucp1 was no longer defective relative to the 129 version, indicating epigenomic rescue. These results provide a framework for understanding how environmental influences like drugs can affect the epigenome and potentially rescue genetically determined disease phenotypes.
PathWell: The development of a triage center and access hub for comprehensive palliative care in oncology.
Authors: Kavitha Ramchandran, Erika Lauren Tribett, Marcy Winget, LaTisha Webster, Dorothy Valmayor, Jenna Lunger, Patricia Falconer
Journal: Journal of Clinical Oncology (2016)

162 Background: Routine screening to identify palliative care (PC) needs, followed by assessment and management of needs is critical for high-quality cancer care. Our current healthcare system there is poor screening for PC needs, low referral rates to PC services, and unmet needs. In response to these gaps, we developed a dedicated triage center to streamline the assessment of PC needs and better connect patients with appropriate supportive care services. Methods: We identified 24 services at our academic cancer center that provide PC and supportive services. Examples include PC, psycho-oncology, survivorship, nutrition, and social work. Representatives from these groups convened to map service overlap and develop referral structures based on patient need and acuity. A triage hub (PathWell) was established to complete uniform assessments of patient needs and determine appropriate referrals. The hub utilized a centralized scheduling platform, new patient coordinators, and an oncology nurse for assessment and triage. Referrals to the hub were made via EHR, direct patient contact, or prompted by routine distress screening. Results: PathWell launched on February 1, 2016. Referral volume to the hub was 54 in February, 91 in March and 74 in April. Referrals from PathWell were distributed amongst the 24 services, the majority of referrals going to PC, psycho-oncology and nutrition. All programs that were part of the triage center experienced growth in volume; PC 41%, psycho-oncology 14%, nutrition 16%. Conclusions: Partnerships between specialist services and dedicated triage staff can improve early access to resources for PC needs. Early data from PathWell reveals improved assessment and management of patient needs via referrals to appropriate services. The hub has also unveiled important resource gaps (e.g. physical therapy, integrative medicine). These gaps were not previously quantified, and thus not prioritized by leadership. Future state for PathWell includes reporting operational and health-related outcomes, optimizing distress screening, establishing care pathways for patient subtypes (e.g., metastatic disease), and hosting interdisciplinary tumor boards for complex distress management.
A novel plasma amino acid profile-based biomarker for early detection of ovarian cancer.
Authors: E. Miyagi, R. Numazaki, Y. Ihata, T. Muramatsu, A. Imaizumi, H. Yamamoto, M. Yamakado, N. Okamoto, M. Asai-Sato, F. Hirahara
Journal: Journal of Clinical Oncology (2011)

5069 Background: Plasma amino acid profile could change depending on metabolic states. It has been reported that amino acid concentrations in plasma change in several cancers including non-small cell lung, breast, colorectal, gastric and endometrial cancer. Here, we evaluate the diagnostic performance of the biomarker based on plasma amino acid profile in patients with ovarian cancer. Methods: Amino acid levels in plasma were measured using liquid chromatography and mass spectrometry for 64 patients with ovarian cancer, 154 patients with gynecologic disease and no malignant conditions, and 192 age- and BMI-matching controls. (Patients are still being accrued to the study reported in this abstract until the end of March, 2011.) For multivariate analysis, we applied multiplexed model, based on plasma amino acid profile, to discriminate between patients with ovarian cancer and controls by using logistic regression analysis. And leave-one-out cross validation method (LOOCV) was applied to avoid overfitting model. The diagnostic performance was evaluated compared with CA125. Results: Univariate analysis revealed that several plasma amino acid levels significantly changed in ovarian cancer patients. The areas under the ROC curves (AUCs) of the model to distinguish ovarian cancer from controls and patients with gynecologic disease and no malignant conditions were 0.97 (p<0.001) and 0.74 (p<0.001) respectively. The AUC for controls was corrected by using LOOCV. The AUCs of the model were equivalent to those of CA125 for controls (AUC=0.96) and gynecologic disease and no malignant conditions (AUC=0.73). In addition, the AUCs for early stage (stage I) ovarian cancer from controls and patients with gynecologic disease and no malignant conditions were 0.94 (p<0.001) and 0.64 (p<0.001) respectively. Conclusions: We describe the novel multiplexed plasma biomarker, which is a useful tool with high accuracy and disease-specificity for early detection of ovarian cancer.
A sequential doublet chemotherapy regimen in patients (pts) with advanced endometrial adenocarcinoma (EC) and gynecological mixed müllerian tumors (MMT). Maintaining activity with tolerability?
Authors: R. N. H. Shah, M. Everard, C. Keyzor, K. Hall, R. A’Hern, P. Blake, M. E. Gore, S. B. Kaye
Journal: Journal of Clinical Oncology (2005)

5079 Background: Carboplatin (C), doxorubicin (D) and paclitaxel (P) have significant activity in advanced EC and MMT. Concurrent 3 drug regimens are associated with high activity but also significant toxicity. Sequential doublet regimens combining all three drugs may retain high levels of efficacy with acceptable levels of toxicity. Methods: Pts with Stage III-IV advanced EC or MMT received first line treatment, from 2001–2004, with 4 cycles of CD (C=AUC5, D=50mg/m2, d1q21) followed by 4 cycles of CP (C=AUC5, P=175mg/m2, d1q21). The primary endpoint was the % of pts completing all planned treatment. Results: 25 pts have completed treatment (19 EC, 6 MMT, median age 59) of whom 72% competed all 8 cycles of treatment (primary endpoint reached). 86% of all planned cycles of chemotherapy were delivered (172 out of a max possible of 200). Toxicity: 20% of cycles were delayed (85% by 1w, 12% by 2w and 3% by 3w), all for hematological toxicity (90% neutropenia, 10% thrombocytopenia). Non hematological toxicity ≥Gd3 was myalgia (1 pt), parasthesia (2pt) fainting and nausea (1pt). 8 consultations (in 7 pts) resulted in dose reduction (cause; 5 neutropenia, 2 parasthesia, 1 myalgia). Response: Of 18 radiologically evaluable patients; 3 had a complete response (17%), 10 partial response (55%), 1 differential response (5%), 3 progressive disease (17%) and 1 taken off trial due to toxicity (5%). Median duration of response was 5.8 months (1.5–29.4 months). 5 deaths have occurred all due to PD (2 on treatment, 1 after 3m and 2 after 6m follow-up). Conclusions: The sequential doublet as described is a feasible and highly active regimen (72% overall response rate) in the first line treatment of EC and MMT. This schedule should be considered for more formal evaluation using larger studies in both diseases. No significant financial relationships to disclose.
Sorafenib and pegylated interferon-alpha-2b in advanced metastatic melanoma: A multicenter phase II DeCOG trial.
Authors: A. Hauschild, R. Gutzmer, S. Ugurel, U. Trefzer, F. Egberts, J. Hassel, D. Schadendorf, C. Mauch, C. Garbe, M. Weichenthal
Journal: Journal of Clinical Oncology (2010)

8526 Background: There is no standard of care for advanced metastatic melanoma (MM). Therefore the combination of a multi-kinase inhibitor such as sorafenib, and pegylated interferon alfa-2b (PegIFN), as previously used in renal cell cancer with some success, could potentially lead to an improved anti-tumoral response. Methods: Patients (pts) with previously untreated (excluding immunotherapy in the adjuvant setting), stage IV MM without brain metastasis, ECOG performance status 0-1 were eligible. All pts received PegIFN 3 μ g/kg weekly once per week, and sorafenib 400 mg BID until progressive disease (PD). The primary endpoint was disease control rate (DCR) defined as CR+PR+SD after 8 weeks of treatment. Results: From February 2008 to February 2009, 55 pts were enrolled (ITT population). The median age was 64 years (range: 20-85); Pts were categorized as following: stage IV M1a/b/c = 3/9/43. 41 pts (75%) received at least 8 weeks of treatment. Prior to 8 weeks evaluation, 9 pts withdrew due to toxicity, 2 revoked consent, and 3 had overt PD. At 8 weeks, 3 pts (5.5%) had a PR, 14 (25.5%) had a SD, resulting in a 31% DCR. Median PFS in these pts was 2.1 months (95%CI: 1.9–2.3). The toxicity of this combination was mainly haematological. Serious brain and GI bleeding complications occurred in 4 pts, where 2 had a fatal outcome. Other grade ¾ toxicities were fatigue and flu- like symptoms. Conclusions: The combination of sorafenib and PegIFN showed modest clinical activity and some serious side effects including fatal bleeding complications. Due to these findings further testing of this combination is not warranted. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Health Care, Schering-Plough Bayer Health Care, Schering-Plough Bayer Health Care, Schering-Plough
Gemcitabine plus cisplatin versus gemcitabine plus vinorelbine in the treatment of advanced non-small cell lung cancer (NSCLC)
Authors: Y. Zhang, L. Zhang, N. Li, F. Xu, Z. K. Pan, Z. Z. Guang
Journal: Journal of Clinical Oncology (2005)

7329 Background: To evaluate efficacy and safety of combination of Gemcitabine plus Cisplatin(GP regimen) and combination of Gemcitabine plus Vinorelbine(GN regimen) in the treatment of advanced non-small cell lung cancer in Chinese patients. Methods: Eighty-two patients with stage III or IV NSCLC were enrolled, 42 patients randomized into GP group and other 40 patients into GN group. Gemcitabine 1000 mg/m2 d1, d8, Cisplatin 80mg/m2 d1 were administered to patients in GP group, while Gemcitabine 1000 mg/m2 d1, d8, Vinorelbine 25mg/m2 d1, d8 were given to patients in GN group, both of these two regimen were repeated every 3 weeks, no more than 6 cycles for each patient. Results: The median survival time (MST) was 9.8 months for GN arm and 8.8 months for GP arm. An objective response rate of 28.6% was observed in GP arm versus 25% in GN arm, 1-year survival rate was 64% in GP arm and 66% in GN arm with no significant difference in statistical analysis (Figure 1). Nausea and vomiting were the major dose-limiting toxicity. The incidence of leukopenia was similar between two groups (p=0.135). The incidence of grade III/IV nausea and vomiting were significantly higher in the GP arm than in the GN arm (Table 1, p=0.0005). Conclusions: Both of GP regimen and GN regimen were effective regimens when used in Chinese advanced NSCLC patients, however in GN regimen the grade III/IV nausea and vomiting was significant lower than that of platinum chemotherapy. No significant financial relationships to disclose.
Does the revised TNM staging system for lung cancer better estimate actuarial rates of local/regional recurrence after surgery?
Authors: J. M. Pepek, J. P. Chino, M. W. Onaitis, L. B. Marks, N. Ready, J. Crawford, T. A. D'Amico, J. L. Hubbs, C. R. Kelsey
Journal: Journal of Clinical Oncology (2010)

7072 Background: The International Association for the Study of Lung Cancer (IASLC) recently recommended changes to the TNM classification of lung cancers. For early-stage disease, increasing tumor size and nodal status are of primary prognostic relevance for overall survival. However, the ability of the old and the new staging system to predict the risk of local/regional recurrence (LRR) has not been evaluated. Therefore, we examined whether the proposed changes in AJCC 7 would refine the risk of LRR in patients who undergo surgery for early-stage NSCLC. Methods: The medical records and pertinent radiographs for all patients who underwent surgery for early-stage (N0-N1) NSCLC at Duke between 1995 and 2005 were reviewed. Patients undergoing suboptimal surgery (sublobar resections, positive margins), or those who received any preoperative therapy or postoperative radiation therapy were excluded. Disease recurrence at the surgical margin, ipsilateral hilum, and/or mediastinum was considered a LRR. Stage was assigned based on both AJCC 6 and AJCC 7. Actuarial rates of LRR were estimated using the Kaplan-Meier method. Results: Of 975 patients who underwent surgery during the time interval, 741 were eligible for this analysis. Surgery consisted of lobectomy in 91% (n=672) and pneumonectomy in 9% (n=69) of patients. 82% (n=605) of patients were pathologic N0 (pN0) and 18% (n=136) were pN1. Adjuvant chemotherapy was administered to 7% (n=52). Median follow-up was 35 months. Conversion from AJCC 6 to AJCC 7 resulted in 25% stage migration (upstaging in 15%; downstaging in 10%). For all patients, the 5-year actuarial risk of LRR was 20% (95% CI 17%-24%). 5-year rates of LRR for stage IA, IB, IIA, and IIB disease using AJCC 6 were 12%, 26%, 40%, and 27%, respectively. Using AJCC 7, corresponding rates were 12%, 21%, 34%, and 38%, respectively. Conclusions: The risk of LRR increases monotonically with stage in the new AJCC 7 system, but not for the older AJCC 6 system. Thus, the newer staging system is better in predicting the risk of LRR. This information will be valuable when designing future studies of postoperative RT. No significant financial relationships to disclose.