tbuckley/cabot-search huggingface dataset:
Tinbergen's “four questions” provides a formal framework for a more complete understanding of prosocial biases in favour of attractive people
Authors: Ian D. Stephen, Darren Burke, Danielle Sulikowski
Journal: Behavioral and Brain Sciences (2017)

Abstract We adopt Tinbergen's (1963) “four questions” approach to strengthen the criticism by Maestripieri et al. of the non-evolutionary accounts of favouritism toward attractive individuals, by showing which levels of explanation are lacking in these accounts. We also use this approach to propose ways in which the evolutionary account may be extended and strengthened.
Phase I study of ABT-888 in combination with carboplatin and gemcitabine in subjects with advanced solid tumors.
Authors: Katherine M. Bell-McGuinn, Heidi J. Gray, Gini F. Fleming, Mihaela C. Cristea, Diane M. Medina, Hao Xiong, Matthew W. Dudley, Martin Dunbar, Vincent L. Giranda, Yan Luo, Mark D. McKee, Lainie P. Martin
Journal: Journal of Clinical Oncology (2013)

2584^ Background: Veliparib (V) is an oral inhibitor of poly(ADP-ribose) polymerases (PARP)-1 and -2, which are essential for base excision repair of ssDNA breaks. BRCA deficient tumors are more sensitive to PARP inhibitors when used as monotherapy or in combination with DNA-damaging agents. The objectives of this study were to determine the maximum tolerated dose (MTD), pharmacokinetic interactions, and safety/tolerability profile of V in combination with carboplatin (C) and gemcitabine (G). Methods: Eligibility criteria included patients (pts) with metastatic or unresectable solid tumors for which C/G was a treatment option. During the study, eligibility was amended to limit prior chemotherapy regimens to ≤ 2. C AUC 4 /G 800 mg/m 2 was given intravenously on Day 1 and G given on Day 8 of 21 day cycles. To assess tolerability of C/G prior to V, V was started in Cycle 2. When C/G was stopped, pts could stay on monotherapy V until progression. Dose-escalation used a Bayesian continual reassessment method. Results: 59 pts (51 female, median age 52) were enrolled. The most common tumor types were ovarian (n=39) and breast (n=10). Germline BRCA mutations were known in 24 ovarian pts. 58 pts had prior chemotherapy (1-6 regimens, median 2), and 51 had prior platinum. Grade 3/4 AEs in &gt;10% of pts were neutropenia, thrombocytopenia, anemia, and leukopenia. Dose limiting toxicities were thrombocytopenia (n=3) and neutropenia at V 310 mg twice daily (BID) and thrombocytopenia at 250 mg BID. Other frequent AEs were nausea, constipation, and fatigue. Preliminary results showed co-administration of V did not affect C or G pharmacokinetics. Treatment cycles (range, median) were 1-28, 5 for V; 2-10, 5 for C; and 2-10, 4 for G. Day 8 G was stopped in some pts to improve tolerability. 28 pts stayed on monotherapy V (1-23 cycles). Partial and complete responses were seen in 11 and 2 pts. Response rates were 47% (8/17) in known BCRA deficient ovarian, 25% (3/12) in other ovarian, and 13% (2/15) in other evaluable pts. Conclusions: V combined with C and G was tolerated with a safety profile similar to C and G alone. The MTD was V 250 mg BID, C AUC 4.0, G 800 mg/m 2 . Promising anti-tumor activity was observed in BRCA deficient ovarian pts. Clinical trial information: NCT01063816.
EXCAP exercise to improve fatigue, cardiopulmonary function, and strength: A phase II RCT among older prostate cancer patients receiving radiation and androgen deprivation therapy.
Authors: Karen Michelle Mustian, Lisa Sprod, Michelle Christine Janelsins, Luke Joseph Peppone, Supriya Gupta Mohile, Lara Anne Trevino, Jennifer S. Gewandter, Kavita Dayal Chandwani, Charles E Heckler, Gary R. Morrow
Journal: Journal of Clinical Oncology (2012)

9010 Background: Radiation therapy (RT) and androgen deprivation therapy (ADT) result in cancer-related fatigue (CRF), decreased cardiopulmonary function (CPF) and decreased strength. Research suggests exercise can improve CRF during RT and ADT, through physical conditioning responses that improve CPF and strength. We explored the influence of an individually-tailored, home-based exercise intervention (EXCAP), including progressive resistance and aerobic training, on CRF, CPF and strength. Methods: Older prostate cancer patients (N=58; mean age=67), receiving RT (47%) or ADT (53%), were randomized to 6 wks of EXCAP (7 days/wk) or standard care (RT or ADT with no exercise). CPF (VO2 max) was assessed via graded exercise testing (GXT) or a 6-minute walk test when GXT was contraindicated. Muscular strength was assessed using multiple repetition maximum testing (chest press and leg extension). CRF was assessed via valid self-report questionnaires (BFI, POMS-FI, MFSI). All assessments were pre- and post-intervention. Results: ANCOVAs, controlling for baseline, revealed significant differences between groups in mean levels of CRF on the BFI and POMS-FI (all p&lt;0.05), and a trend toward differences on the MFSI (p&lt;0.10) with significant baseline interactions (all p&lt;0.05) post-intervention: exercisers decreased CRF while controls increased. ANCOVAs revealed a trend toward differences between groups in mean levels of CPF (VO2 max) and strength (all p&lt;0.10): exercisers improved while controls declined in performance. Pearson correlations revealed significant inverse associations between changes in CRF (BFI) and CPF (p&lt;0.05;r=-0.0.36), and CRF and strength (p&lt;0.05;r=-0.0.31). MANOVA revealed that changes in CPF and strength significantly predicted changes in CRF (p&lt;0.05, r=0.67) and accounted for 45% of the variance. Conclusions: Exercise improves CRF and these improvements may be mediated, in part, by improvements in CPF and strength. Future phase III RCTs with prostate cancer patients receiving RT and ADT are needed to confirm these relationships. Funding: DOD W81XWH-07-1-0341, NCI K07CA120025, NCI 1R25CA102618.
A phase II study of everolimus for advanced melanoma patients with mTOR mutations.
Authors: Lu Si, Yan Kong, Xuan Wang, Zhihong Chi, Chuanliang Cui, Xi Nan Sheng, Li Li Mao, Bixia Tang, BIN LIAN, Xieqiao Yan, Jun Guo
Journal: Journal of Clinical Oncology (2015)

e20007 Background: Everolimus, an oral mTOR inhibitor, has shown minimal activity as a single agent in patients with metastatic melanoma, unselected by potential predictive biomarkers (J Clin Oncol 24:463s, 2006). Selection of patients with melanoma harboring mTOR mutations may improve the efficiency of mTOR inhibitor in patients with melanoma (J Clin Oncol. 2012, 30(4):e37-40). This study (NCT01960829) aims to observe the efficacy of mTOR inhibitor in melanoma patients with mTOR mutations. Methods: Pts, who had unresectable melanoma harboring mutation in mTOR, who had measureable disease by RECIST, and who failed to systemic treatment (at lease 1), were enrolled. Pts received everolimus 10 mg daily continually until disease progression or unacceptable toxicity occurred. Response assessments were performed every 8 weeks. The endpoints were progression-free survival (PFS) and overall survival. Results: Of 396 pts screened, 10.3% had a mTOR mutation: 22/207(10.6%) acral, 15/104 (14.4%) mucosal, 2/28(7.1%) CSD and 3/57(5.2%) Non-CSD. Thus far, 8 pts have been treated, with 6 pts currently evaluable for response. The median age was 54 yrs (range: 38-65); the male:female ratio was 3:5; the median number of prior therapies was 2 (range: 1-4). 6 pts achieved stable diseases. The PFS were: 26 weeks+ (Exon 41: G5741C; acral melanoma; failed to DTIC, DDP and PTX), 18 weeks+ (Exon 41: A5794G; mucosal melanoma; failed to TMZ, bevacizumab, DDP and nab-PTX), 17 weeks+ (Exon 41: G1914R; acral melanoma; failed to DTIC), 12 weeks+ (Exon 46: C6520T; acral melanoma; failed to TMZ, carboplatin, bevacizumab, PTX and fotemustine), 11 weeks+ (Exon 47: C6637T; mucosal melanoma; failed to nab-PTX, DDP and TMZ) and 10 weeks+ (Exon 43: C6026T; CSD melanoma; failed to DTIC, DDP, bevacizumab and PTX). All the 6 pts showed median tumor shrinkage (12%, 10%, 9%, 23%, 1% and 5% respectively). Conclusions: While mTOR inhibitors show limited activity in a non-selected melanoma pt population, a substantial proportion of melanoma pts harboring mTOR mutation appear to respond. It may be expectable to identify appropriate pts prospectively for treatment with mTOR inhibitors. Clinical trial information: NCT01960829.
Identification of a new subgroup of adult acute T-lymphoblastic leukemia (T-ALL) with a very favorable outcome using low ERG and BAALC expression
Authors: C. D. Baldus, P. Martus, T. Burmeister, S. Schwartz, N. Goekbuget, C. D. Bloomfield, D. Hoelzer, W. K. Hofmann, E. Thiel
Journal: Journal of Clinical Oncology (2007)

7014 Background: High expression of the oncogenic ETS transcription factor ERG is an independent adverse prognostic factor in T-ALL and acute myeloid leukemia (AML). The gene BAALC similarly shows high expression in hematopoietic progenitors, downregulation with onset of differentiation, and prognostic significance in AML. Therefore, we assessed whether combined expression of ERG and BAALC would better predict outcome in T-ALL. Methods: ERG and BAALC mRNA expression was determined by realtime RT-PCR in pretherapy bone marrow of 152 adults with newly diagnosed T-ALL treated on German ALL protocols (05/93, 06/99). Patients (pts) were designated low (n=76) or high (n=76) ERG expressers based on median ERG expression and as low (n=111) or high (n=37) BAALC grouping the lower quartiles 1–3 vs. quartile 4. HOX11 and HOX11L2 expression was determined and immunophenotyping differentiated 3 T-ALL groups (early, thymic, mature). Results: High BAALC expression correlated with immature T-ALL with a higher frequency of early T-ALL (P&lt;0.0001), CD34 positivity (P&lt;0.0001), co-expression of myeloid markers (CD13 and/or CD33; P=0.03), and high ERG expression (P=0.02). Pts with high BAALC had fewer complete remissions (73% vs. 89%, P=0.03) and a higher relapse rate (67% vs. 32%, P=0.01) than low BAALC pts. Excluding 33 pts that had received stem cell transplantation (SCT), high expression of ERG (P=0.002) and of BAALC (P=0.0004) was associated with inferior relapse-free survival (RFS) and overall survival (OS, ERG: P=0.004; BAALC: P=0.0001) compared to low expression of ERG and BAALC, respectively. In contrast, pts with low expression of both ERG and BAALC had the most favorable outcome (5y-RFS: low ERG/low BAALC 81% vs. high ERG and/or high BAALC 33%, P&lt;0.0001; 5y-OS: low ERG/low BAALC 69% vs. high ERG and/or high BAALC 26%, P=0.0001). On multivariable analysis low ERG/low BAALC expression was of independent favorable prognostic significance (RFS, HR: 0.18, P=0.0003; OS, HR: 0.3, P=0.001); the only other prognostic factor was the immunophenotype. Conclusions: Low expression of both ERG and BAALC identifies T-ALL pts with a distinctly favorable long term outcome, thus detecting pts that may not benefit from further treatment intensification including SCT. No significant financial relationships to disclose.
Predictors for reclassification at repeat biopsy in active surveillance cohort for low-risk prostate cancer: From an interim analysis of PRIAS-JAPAN.
Authors: Mikio Sugimoto, Yoshiyuki Kakehi, Hiromi Hirama, Seiji Naito, Akito Yamaguchi, Hirofumi Koga, Nobuo Shinohara, Satoru Maruyama, Yoichi Arai, Koji Mitsuzuka, Shin Egawa, Hiroshi Sasaki, Yukio Homma, Hiroshi Fukuhara
Journal: Journal of Clinical Oncology (2017)

118 Background: The Prostate Cancer Research International: Active Surveillance (PRIAS) study is a large international prospective observational AS study that commenced in 2006. Japan has participated in the study (PRIAS-JAPAN) since 2010, and recruitment remains ongoing. The objective of this study is to define clinical and pathological factors predicting reclassification at the time of 1-year repeat biopsy (re-Bx) based on a Japanese cohort forming part of the PRIAS study. Methods: The inclusion criteria for the PRIAS study are as follows: clinical stage T1c/T2, PSA ≤ 10 ng/ml, PSA density (PSAD) &lt; 0.2 ng/ml per milliliter, one or two positive biopsy cores, and Gleason score (GS) ≤ 6 at initial diagnostic biopsy. Baseline clinical characteristics and prostate-specific antigen doubling time (PSADT) at the time of re-Bx were analyzed via multivariate logistic regression with respect to reclassification on the 1-year re-Bx. Results: A total of 711 patients were enrolled in PRIAS-JAPAN by September 2016. Of these, 409 underwent re-Bx at 1-year. The re-Bx acceptance rate was 83.3%. A total of 122 (29.8%) was reclassified whereas 150 (36.7%) had no cancer. Older age, a higher PSAD, a higher positive core rate, and a shorter PSADT were significant predictors of reclassification. Among them, the positive core rate was the strongest predictor for pathological reclassification at 1-year after starting AS. The AS remaining rates at 1, 2, 3, 4 and 5 years were 93.9%, 70.6%, 65.7%, 60.0% and 49.5% respectively Conclusions: An interim analysis of a Japanese AS cohort participating in PRIAS revealed that the positive core rate was strongly associated with reclassification at the 1-year re-Bx. Clinical trial information: UMIN000002874. [Table: see text]
Relationship of fusion protein status and outcome for children with intermediate-risk rhabdomyosarcoma: A Children's Oncology Group report.
Authors: Stephen Skapek, James Robert Anderson, Frederick G. Barr, Julia Ann Bridge, Julie M Gastier-Foster, David Parham, Erin R. Rudzinski, Timothy J. Triche, Douglas S. Hawkins
Journal: Journal of Clinical Oncology (2012)

9535 Background: Rhabdomyosarcoma (RMS) includes both alveolar (ARMS) and embryonal (ERMS) subtypes, with ARMS generally having a worse prognosis. Most ARMS express one of two fusion genes generated by balanced translocations fusing DNA binding domains of PAX3 or PAX7 with FOXO1 (P3F and P7F, respectively). The prognostic value of fusion gene versus histological subtype is not clear. We carried out a multi-institutional clinical trial through the Children’s Oncology Group (COG) to evaluate this molecular feature. Methods: All participants were enrolled on COG D9803 from 1999-2005 for children and young adults with intermediate risk ARMS or ERMS, and were treated with vincristine, dactinomycin, and cyclophosphamide (+/- topotecan), radiotherapy, and surgery. Diagnostic specimens were reviewed centrally and fusion gene was assessed by fluorescence in situ hybridization (FISH), RT-PCR, or both. Event-free (EFS) and overall survival (OAS) at 5 years (yr) was correlated with histology and fusion gene status. Results: Of 327 cases included in a re-review of the pathology, 295 could be classified biologically. Cases with ARMS but unknown trans status (N=23) and those with mixed or RMS-NOS histology without trans (N=17) and 12 with inadequate clinical data were excluded. ARMS cases with detectable fusion gene were defined as ARMS P3F+, ARMS P7F+, while ARMSn was reserved for those without detectable fusion. P3F and P7F were not observed in ERMS. An additional 189 pts with ERMS tumors not re-reviewed were also included in the survival analysis. There was a trend toward better EFS for those with ARMSn than for ERMS (p=0.15); EFS for ARMS P3F+ and P7F+ were worse than that for ERMS (p&lt;0.001). Only ALV P3F+ cases had poorer OAS (p=0.004). Conclusions: ARMSn has an outcome similar to ERMS and a superior EFS compared to ARMS with P3F or P7F, when given therapy designed for intermediate risk RMS. This analysis, from a single, prospective trial restricted to those with non-metastatic disease and with near universal molecular evaluation, supports incorporating fusion status into treatment allocation. [Table: see text]
Mucinous histology to predict disease-free survival in microsatellite stable stage III colon cancer patients treated with adjuvant FOLFOX chemotherapy.
Authors: Joong Bae Ahn, Se Hyun Kim, Sang Joon Shin, Kang Young Lee, Tae IL Kim, Hyuk Hur, Byung Soh Min, Nam Kyu Kim, Hyun Cheol Chung, Jae Kyung Roh
Journal: Journal of Clinical Oncology (2012)

e14084 Background: The prognostic role of mucinous histology of the colon cancer has been studied for decades and remained controversial. The aim of this retrospective study was to investigate whether mucinous adenocarcinoma (MA) is associated with a worse prognosis than that of non-mucinous adenocarcinoma (NMA) in patients with stage III colon cancer. Methods: This study enrolled unselected 402 patients with stage III colorectal cancer treated with adjuvant FOLFOX after curative resection (R0). Clinicopathological information was retrospectively reviewed. Tumors were analyzed for microsatellite instability (MSI) by polymerase chain reaction (PCR) to determine MSI-high (MSI-H) or microsatellite stable (MSS). Kaplan-Meier method, log-rank test, and Cox proportional hazards regression models were used. Results: Among 402 patients, 42 patients (10.4%) were MA and 26 patients (6.5%) were MSI-H. Compared with MSS tumors, MSI-H tumors was associated with a higher rate of MA (26.9% vs 9.3%, P=0.005). In MSS tumors (n=376), 3-year disease-free survival (DFS) rate was 79% and 55% in NMA and MA, respectively (log rank, P=0.014). In MSI-H tumors (n=26), no statistically significant difference of DFS between MA and NMA was found. In multivariate analysis, MA remained an independent significant poor prognostic factor for DFS (HR=1.9; 95% CI, 1.003-3.717; P=0.049) in MSS patients. Conclusions: Mucinous histology is an independent poor prognostic factor for DFS in patients with microsatellite stable stage III colon cancer after adjuvant FOLFOX chemotherapy. [Table: see text]
Chemotherapy-induced amenorrhea (CIA) risk associated with taxane/platinum-based chemotherapy in young (≤45 years) breast cancer patients.
Authors: Priyanka Sharma, Lindsay Rock, Bruce F. Kimler, Qamar J. Khan, Carol Sue Connor, Marilee McGinness, Jamie Lynn Wagner, Joshua Mammen, Claire Ward, Jennifer R. Klemp, Carol J. Fabian
Journal: Journal of Clinical Oncology (2014)

9592 Background: Twenty-five percent of women with breast cancer (BC) are premenopausal and 15% are diagnosed in reproductive age group (≤45 years), thus at risk of CIA. Although CIA rates with alkylating agents/topoisomerase inhibitors (Alk/Topo) are well documented, there is inadequate data addressing the impact of newer Docetaxel/Carboplatin(TP) regimen on menstrual function. The objective of this study was to determine the incidence of long-term (>12 months) CIA related to different chemotherapy regimens in BC patients < 45 years. Methods: We identified 283 premenopausal women with BC ≤ 45 years treated with at least 4 cycles of Neo/adjuvant chemotherapy at University of Kansas from 2005 to 2012. Menstrual status information was extracted from medical records. Standard statistical methods were used to assess the association of CIA with variables of interest. Results: 165 patients met eligibility criteria and had sufficient follow up. Median age: 39 years(24–45 yrs), 62%:<41 years and 38%:41-45 years. 41%:HR+, 20%:HER2+/HR+, 12%:HER2+/HR-, 27%: TNBC. 79%(130/165) received Alk/Topo regimens (AC+/-T= 113, TAC=8, TC=9) and 21%(35/165) received TP regimen. Median ages of patients receiving Alk/Topo and TP regimens was similar. The overall rate of CIA was 34%. BMI, smoking, parity & Tamoxifen use did not impact CIA. Rates of CIA were lower in younger patients and in patients receiving TP chemotherapy. When examined by age at diagnosis CIA rates were 17% (<41yrs) and 63% (>41yrs), respectively (P<0.001). When examined by chemotherapy type the rates of CIA were 42% (Alk/Topo group) and 6% (TP group), respectively (p<0.001) in all patients and 22% (Alk/Topo group) and 0% (TP group) in patients <41 years (p=0.010). Conclusions: Risk of long term CIA with TP regimen is much lower (6%) compared with Alk/Topo regimens (42%) in premenopausal women ≤ 45 years. Premature menopause is associated with considerable side effects like menopausal symptoms, loss of fertility, risk of osteoporosis and cardiovascular disease. Information regarding CIA rates of different chemotherapy regimens is of value to young patients and physicians to aid in adjuvant chemotherapy regimen decision making.
Utilization of minimally invasive versus open colectomy for colon cancer and perioperative/short-term oncologic outcomes: Are we there yet?
Authors: Jillian K. Smith, Nestor F. Esnaola
Journal: Journal of Clinical Oncology (2017)

733 Background: Randomized controlled trials (RCTs) in highly-selected patient populations demonstrated equivalent outcomes following minimally invasive colectomy (MIC) versus (vs) open colectomy (OC) for colon cancer. The purpose of this study was to evaluate utilization of MIC and compare perioperative/short-term oncologic outcomes after MIC vs OC in a large, generalizable, national sample. Methods: We identified adult patients with invasive colon adenocarcinoma who underwent elective surgical resection between 2010 and 2012 using the National Cancer Data Base. Univariate associations between patient/tumor/facility/treatment characteristics and surgical approach were analyzed using chi-square tests. Multivariable logistic regression was used to identify independent predictors of receipt of MIC, as well as to evaluate independent associations between surgical approach and outcomes. Results: Among 111,372 patients identified, 48,393 (43.5%) underwent MIC; the proportion who underwent MIC increased between 2010 (37.8%) and 2012 (49%; p &lt; 0.001). High education level (adjusted odds ratio [aOR] 1.13) and increasing income level (aOR 1.09-1.36) were independently associated with receipt of MIC, whereas black race (aOR 0.85), Medicare (aOR 0.86)/Medicaid (aOR 0.67)/uninsured status (aOR 0.57), non-metropolitan residence (aOR 0.92), and community (aOR 0.63) or other (aOR 0.58) cancer programs were independently associated with potential underuse. Mean length of stay was shorter following MIC vs OC (6.07 vs 7.68 days; p &lt; 0.001). Use of MIC was independently associated with reduced 30-day (aOR 0.6) and 90-day (aOR 0.62) mortality, as well as lower rate of positive surgical margins (aOR 0.69) and higher rate of regional lymph nodes examined &gt; = 12 (aOR 1.14). Conclusions: This study confirms that MIC is associated with favorable perioperative/short-term oncologic outcomes (compared to OC), as demonstrated in RCTs. Although utilization of MIC for colon cancer continues to rise, implementation studies are warranted to enhance access to optimal surgical care and eradicate persistent disparities in receipt of MIC among historically underserved populations.