tbuckley/cabot-search huggingface dataset:
Disparities in preoperative imaging for breast cancer: Not so black and white.
Authors: Richard J. Bleicher, Karen Ruth, Elin R. Sigurdson, Kathryn Evers, Margaret Lord Crivello, Yu-Ning Wong, Marcia Boraas, Brian Egleston
Journal: Journal of Clinical Oncology (2012)

6061 Background: Controversy exists about racial/ethnic differences in the care of breast cancer patients. Imaging plays a critical role in evaluation, but little national data exists on breast imaging by race. This study was performed to determine if imaging disparities exist in Medicare patients, when adjusting for socioeconomic (SE) factors. Methods: Surveillance Epidemiology and End Results (SEER) data linked to Medicare claims were reviewed for patients diagnosed with invasive nonmetastatic breast cancer between 2000 and 2005, undergoing surgery as their 1st treatment modality. Diagnostic imaging was reviewed during the interval between the 1 st physician visit and surgery (“preoperative interval”[POI]) and imaging use was defined as ≥1 imaging-specific claim. SE factors included rural/urban setting, and education, poverty, and median income per census tract. Results: Among 39,790 patients, there were 34,774 White (87%), 2,341 Black (5.9%), 1,459 Hispanic (3.7%), and 1,216 Asian/Pacific Islander (3.1%) patients. Univariate racial differences were noted for all imaging types (p’s &lt;0.0001 to 0.007). During the POI, when adjusting for demographics, tumor characteristics, and SE factors in multivariable analysis, use of mammogram, ultrasound (US), breast MRI, CT, and bone scan were not different between Blacks and Whites. Education level was a predictor for US (p=0.007), breast MRI (p&lt;0.0001), CT (p=0.006) and bone scan use (p=0.002), but not mammography (p=0.90). There were varying correlations between Hispanics or Asians vs Whites for all imaging types. Stage, histology, U.S. region, and comorbidity index were most consistently predictive of imaging use of all types. When evaluating 6 mos prior to the 1 st physician visit along with the POI, 96.4% of all patients had ≥1 mammogram, with 94.1% of Blacks having mammograms vs 96.5% of Whites (OR 0.7, 95% CI 0.6-0.9; p=0.001). Conclusions: There is little racial difference in imaging performed during the POI for Medicare patients having breast cancer, and efforts to determine causes of survival disparities in such patients should be focused elsewhere. Whether these findings apply to the privately insured or the uninsured requires additional exploration.
Alcohol and breast cancer risk in postmenopausal women: The PLCO experience.
Authors: Roni Falk, Paige Maas, Catherine Schairer, Saundra S. Buys, Nilanjan Chatterjee, Theresa Lee, Regina G Ziegler, Claudine Isaacs
Journal: Journal of Clinical Oncology (2012)

1521 Background: Moderate alcohol consumption is an established breast cancer (BC) risk factor. Invasive BC is a heterogeneous disease comprised of several histological subtypes with distinct biological features that suggest etiologic differences. Several studies show the alcohol link may be stronger for estrogen receptor-positive tumors (ER+/PR+ and ER+/PR-) and for lobular BC. Few have evaluated the role of alcohol consumption by BC histology and hormone receptor status combined. Methods: We evaluated the risk of BC by baseline alcohol consumption in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial cohort (54649 participants, 1786 incident invasive breast cancers) by histology and hormone receptor status. Histologic subtype-specific associations were evaluated using a recently developed Cox proportional hazards model to calculate multivariate hazards ratios (HR) and 95% confidence intervals (CI). Results: 1444 ductal (81%), 233 lobular (13%) and 109 mixed ductal lobular (6%) cases were identified. The majority were ER+/PR+ (ductal: 959 ER+/PR+, 136 ER+/PR-, 229 ER-/PR-; lobular: 179 ER+/PR+, 37 ER+/PR-, 6 ER-/PR-; mixed ductal/lobular: 88 ER+/PR+, 6 ER+/PR-, 5 ER-/PR-). For ductal and lobular BC, risks for alcohol consumption were modestly elevated; compared to never drinkers, women consuming 7-14 drinks/week had a 40% increase in HR in both histologic subtypes. Risks for mixed ductal lobular cancer were significantly higher, particularly for women consuming 7-14 drinks per week (HR=3.0; 95% CI=1.5, 6.1). For all histologies combined, alcohol risks were confined to ER+/PR+ cancers with HR=1. 6 (95% CI=1.3, 2.1) for women consuming 7-14 drinks/ week; p trend=0.0005. Similarly, for each histologic subtype, the risk for alcohol consumption was limited to ER+/PR+ tumors, and notably, very few cases with pure lobular or mixed ductal lobular cancer were either ER+/PR- or ER-/PR-. Conclusions: Moderate alcohol consumption is associated with risk of ER+/PR+ BC in each of the predominant histologic subtypes, but not with hormone receptor-negative cancer. Unlike other studies, we did not find a link between alcohol consumption and ER+/PR- BC.
Central nervous system relapse in adults with acute lymphoblastic leukemia.
Authors: Muhamed Baljevic, Hagop M. Kantarjian, Dasarathula Jyothsna, Deborah A. Thomas, Michael E. Rytting, Gautam Borthakur, Jan Andreas Burger, Farhad Ravandi, Elias Jabbour, Marina Konopleva, Sherry Pierce, Mark Brandt, Susan Mary O'Brien, Jorge E. Cortes
Journal: Journal of Clinical Oncology (2014)

7080 Background: Recurrence of acute lymphoblastic leukemia (ALL) in the central nervous system (CNS) in adults is associated with poor outcome. Few reports have analyzed the impact of contemporary ALL regimens on outcome of patients (pts) with CNS recurrence. This report provides single institution experience in adults with ALL and CNS relapse. Methods: The records of 555 (89%) consecutive pts with newly diagnosed ALL with no CNS disease treated at MDACC between 2001 and 2013 were reviewed. Pts were treated with HCVAD ± tyrosine kinase inhibitors (TKIs) and/or Rituximab (R) or with augmented BFM (AUG-BFM). Among 519 (94%) pts who achieved complete remission (CR), 33 (22%) had a CNS relapse: 8 were treated with HCVAD+R, 11 with HCVAD+TKI, 2 with HCVAD+R+TKI, 1 with HCVAD+Nelarabine, 2 with HCVAD and 9 with AUG-BFM. Results: Three groups of pts were identified: (A) with isolated CNS relapse (n=17), (B) with CNS relapse after bone marrow (BM) relapse (n=7), and (C) with simultaneous CNS and BM relapse (n=9). The median age (range) at diagnosis was 39 (15-75) yrs. Only LDH 1463 (335-33811) was significantly different compared to pts without CNS recurrence (p=0.05). The median CR duration prior to CNS recurrence was 15.8 months (mo) (2.5–92.6). Intrathecal chemotherapy was effective in achieving CNS CR in 26 (79%) pts. The median overall survival (OS) was statistically different among the 3 groups: median for group A 55.9 mo, 100% alive at 1-year and 30% at 4-years; group B median 25.6 mo, 78% alive at 1-year and 28% at 4-years; and group C median 16.6 mo, 86% alive at 1-year and 0% at 4-years (p=0.01). Entire cohort OS was 41.3 mo; 91% alive at 1-year and 38% at 4-years. Outcome has improved substantially compared to period before yr 2000, when median OS was 6 mo, with 38% alive at 1-year and 6% at 4-years (Surapaneni et al. Cancer 2002). Conclusions: Adults with CNS ALL recurrence have a poor prognosis despite effective treatment, particularly those with combined systemic and CNS relapses. However, outcome of these pts has improved significantly in the last decade. Still, effective CNS prophylaxis remains the single best approach for treating patients with CNS leukemia.
Explanations for attractiveness-related positive biases in an evolutionary perspective of life history theory
Authors: Bin-Bin Chen
Journal: Behavioral and Brain Sciences (2017)

Abstract The mating-related evolutionary explanation that Maestripieri et al. offer does not apply to (1) infants' positive biases toward attractive individuals and (2) adults' positive biases toward attractive infants and children. They are best understood when integrated into an evolutionary life history framework. I argue that the life history of positive biases toward attractive individuals is driven by fundamental trade-offs made throughout development.
A phase I dose-escalation study of intratumoral herpes simplex virus-1 mutant HSV1716 in pediatric/young adult patients with refractory non-central nervous system solid tumors.
Authors: Timothy P. Cripe, John M Racadio, Joe Conner, Alexander Towbin, Marianne M Brunner, Beth A Stockman, Mark Currier, James I. Geller
Journal: Journal of Clinical Oncology (2013)

10047 Background: HSV1716 is a mutant herpes simplex virus type 1 deleted in the RL1 gene which encodes the protein ICP34.5, a specific determinant of virulence. Mutants lacking the RL1 gene are capable of replication in actively dividing cells but not in terminally differentiated cells – a phenotype exploited to selectively kill tumor cells. Studies in adult patients with high grade glioma, melanoma and squamous cell carcinoma report that HSV1716 is safe when administered by intra-tumoral injection. This is the first study of HSV1716 in pediatric/young adult patients. Methods: The primary endpoint of the study is to assess safety of intratumoral HSV1716 in pediatric/young adult patients, and to determine any dose-limiting toxicities (DLT) at the doses given. Patients undergo long-term follow up in accordance with FDA guidelines for viral vectors. The secondary endpoints of the study are to measure: (i) antiviral immune response; (ii) systemic viremia and viral shedding and (iii) the antitumor activity of HSV1716 by radiological response within the confines of a Phase I study. Patients aged 7 to 30 with solid non-CNS tumors refractory to standard therapy (or for which no therapy exists) are eligible for the study provided the target lesion is accessible to image-guided injection. Eligible patients receive a single dose of HSV1716 (Virttu Biologics Limited) at either 10 5 or 2x10 6 plaque forming units (pfu) HSV1716 administered directly into the tumor via ultrasound or CT-guided injection by an interventional radiologist. Tumor response between baseline and day 28 is assessed by modified RECIST criteria. Patients showing at least stable disease may receive up to a 3 additional doses of HSV1716. Results: Recruitment of the first cohort of 3 patients has been completed without DLT or procedure related severe adverse events. In the second cohort, 2 patients have been treated without DLT or procedure related SAE. Conclusions: The trial is in progress and the study is open to recruitment. Clinical trial information: NCT00931931.
Development of a prognostic nomogram for liver toxicity in patients treated with pazopanib.
Authors: Michael W. Kattan, Winette T.A. Van Der Graaf, Thomas Powles, Simon Lam, Qasim Ahmad, Luca Dezzani, Jackie Han, Cora N. Sternberg
Journal: Journal of Clinical Oncology (2017)

455 Background: Potential liver toxicity associated with pazopanib treatment has provided a challenge for decision-making regarding patient selection and monitoring. The goal of this study was to develop a tool for predicting liver toxicity for patients receiving pazopanib. Methods: Data was pooled from several clinical trials in patients with renal cell carcinoma, soft tissue sarcoma, or ovarian carcinoma; the dataset consisted of 2,051 patients treated with pazopanib in these trials. Liver toxicity was defined as an ALT level &gt; 3 times the upper limit of normal (ULN) and a bilirubin level &gt; 2 times ULN. Predictors of hepatotoxicity included were age, gender, race, hypertension, performance status, indication (tumor type), prior antineoplastic treatment, concomitant treatment with CYP450, P-gp, or BCRP inhibitors, and baseline clinical characteristics of weight, ALT, AST, ALP, and bilirubin. The statistical modeling was performed using logistic regression. Continuous predictors were modeled with restricted cubic splines to permit potentially nonlinear effects. The performance of the model was evaluated using discrimination (measured by concordance index) and calibration (assessed graphically). Results: Calibration plots suggested adequate congruence between predicted probabilities and actual proportions of liver toxicity. The model had a bootstrap corrected concordance index of 0.739. The calibration of the model was excellent for predicted probabilities up to 30% (Table). The prediction model was represented as a nomogram. Conclusions: This appears to be the first nomogram that predicts, with reasonable accuracy, liver toxicity in patients receiving pazopanib based on their baseline clinical characteristics. Although nomograms are limited by the degree of uncertainty that is inherent in the estimates of probability, the findings may aid clinicians in selecting patients for treatment and monitoring. Validation in a separate dataset is needed to confirm the nomogram’s accuracy. [Table: see text]
Survival outcomes in patients with early-stage, resectable pancreatic cancer: A comparison of gemcitabine and 5-fluorouracil based chemotherapy and chemoradiation regimens.
Authors: Sani Haider Kizilbash, Kevin Ward, Ishmael A. Jaiyesimi, Joseph Lipscomb
Journal: Journal of Clinical Oncology (2012)

e14608 Background: Beyond curative surgery, the optimal treatment for early stage pancreatic cancer is still a matter of debate. We conducted a comparative survival analysis between patients with resectable pancreatic cancer who received adjuvant treatment with either gemcitabine or 5-fluorouracil based chemotherapy and chemoradiation regimens. Methods: The Surveillance, Epidemiology and End Results (SEER)-Medicare database was used to identify patients with pancreatic cancer diagnosed from 1998 to 2005 who received curative surgery and adjuvant chemotherapy with either 5-fluorouracil or gemcitabine. These groups were subdivided by treatment with radiotherapy. Patients were followed until death, study endpoint or a maximum of five years after diagnosis. Results: 359 patients received 5-fluorouracil and 346 received gemcitabine. Compared to chemoradiation with 5-fluorouracil, outcomes for patients who received chemoradiation with gemcitabine did not differ. Patients who received gemcitabine without radiation had increased hazards (hazard ratio (HR) = 1.50 for high grade tumors (HGT), HR = 1.32 for low grade tumors (LGT)). However, outcomes of patients who received 5-fluorouracil without radiation varied with tumor grade. In LGT, patients had better outcomes with 5-fluorouracil when compared with chemoradiation with 5-fluorouracil (HR = 0.43). In HGT, the opposite was true (HR 2.10). Conclusions: Patients with low grade resectable pancreatic cancer may have better outcomes with 5-fluorouracil based chemotherapy without radiation when compared to 5-fluorouracil with radiation.
Combined treatment with TLR7/8 agonists and carbon ion radiation induces local and abscopal immune responses in gastrointestinal tumor models.
Authors: Peter E Huber, Nils H Nicolay, Ramon Lopez
Journal: Journal of Clinical Oncology (2017)

292 Background: Radiotherapy is a mainstay of local tumor treatment for rectal and pancreatic carcinoma. Radiation has local and abscopal immunological effects, and may beneficially be combined with immune therapies. Photon radiotherapy can favorably be combined with a TLR7/8 agonist to induce strong immune responses in gastrointestinal tumors in mice. Here we investigated carbon ion particle radiation, which has superior physical radiation dose precision and a higher relative anti-tumor effect strength (relative biological effect, RBE, compared with photons), because it was unclear if carbon ions can also favorably be combined with immunotherapies such as TLR agonists. Methods: Therefore we investigated the effects of 3M-011, a TLR7/8 agonist (that was systemically given), and carbon ions in vivo in gastrointestinal tumors in mice in subcutaneous and orthotopic mouse models of colorectal and pancreatic cancer. In vitro, cytotoxicity assays were applied to identify the immune cell populations involved in the therapy-induced immune reaction. The tumor specific T cell immune reaction was demonstrated by ELISPOT assays. Results: We found that the carbon ions and the TLR7/8 agonist 3M-011 induced strong immune responses in s.c. and orthotopic colorectal and pancreatic cancer models in mice. The TLR agonist dramatically enhanced the carbon ion effects in both local and distant antitumor activity. Depletion experiments showed that NK and CD8 T cells mediated the cytotoxic effects of the TLR agonist and in vivo depletion of CD11c + cells using a transgenic mouse carrying the diphteria toxin receptor showed that DCs are the necessary cell population inducing the detected antitumor immunity for monotherapies and combination treatment. Conclusions: Our findings suggest that TLR7/8 agonists are potent adjuvants not only to photon radiotherapy but also to particle radiation with carbon ions, and that the combination induced local and relevant systemic immune responses. In conclusion our preclinical proof of concept data supports the notion that TLR7/8 agonists may be favorably combined with particle radiation to treat GI tumors including pancreatic and rectal cancer.
Immunohistochemistry-based subtypes and gene expression signatures as predictors of prognosis in metastatic breast cancer.
Authors: Claudette Falato, Nicholas Tobin, Julie Lorent, Linda Sofie Lindström, Jonas C. S. Bergh, Theodoros Foukakis
Journal: Journal of Clinical Oncology (2015)

e22090 Background: Molecular subtypes and gene signatures are widely used in early breast cancer but their role in metastatic disease is unexplored. Methods: 187 patients diagnosed with primary breast cancer and subsequent relapse in Stockholm, Sweden between 1997-2006 were identified and their primary tumor was assessed for PAM50 risk of recurrence (ROR) score, 21-gene recurrence score and Amsterdam 70-gene profile using Affymetrix array (GPL10379). Clinical and pathological data were retrospectively collected and vital status was updated in July 2012. The relationship of immunohistochemistry (IHC)- based subtypes and gene signatures to survival after systemic relapse was investigated using Kaplan-Meier and Cox regression analysis. The prognostic contribution of gene signatures in addition to clinical factors was evaluated by the Likelihood Ratio test (LR-χ2). Results: IHC classified 49 (27%), 45 (24%), 67 (36%) and 23 (13%) patients as luminal A, luminal B, HER2+ and triple negative, respectively. Triple negative tumors had a significantly shorter median survival in comparison with luminal (10 vs 23 months; HR 0.53; 95%CIs, 0.33-0.87; P 0.008) but overall, IHC subtypes were not significantly prognostic in a model adjusted for primary tumor size, grade, metastasis free interval and site of systemic relapse (P 0.64). PAM50 categorized 41 (22%), 44 (24%), 49 (26%), 41 (22%), 12 (6%) tumors as luminal A, luminal B, HER2 enriched, basal and normal. PAM50 significantly correlated with survival in the univariate (P 0.03) but not in the multivariate analysis (P 0.58). Low and medium ROR groups had a longer survival compared with the high-risk group independently from classical prognostic factors (23 vs 10 months; low-risk: HR 0.59; 95%CIs, 0.34-1.01; medium-risk: HR 0.58; 95%CIs, 0.37-0.91; P 0.04). ROR provided significant prognostic information when added to a clinical model (LR-χ2= 32.78 vs 25.98; P 0.04). No significant association with survival emerged for 21- gene and 70- gene profiles (P 0.2 and P 0.64, respectively). Conclusions: ROR score from primary tumor represents an independent prognostic factor of post- relapse survival beyond classical clinicopathological variables.
Pembrolizumab (pembro) plus low-dose ipilimumab (ipi) for patients (pts) with advanced renal cell carcinoma (RCC): Phase 1 KEYNOTE-029 study.
Authors: Toni K. Choueiri, F. Stephen Hodi, John A. Thompson, David F. McDermott, Wen-Jen Hwu, Donald P. Lawrence, Nancy Ann Dawson, Deborah Jean Lee Wong, Shailender Bhatia, Marihella James, Xinxin Shu, Blanca Homet Moreno, Nageatte Ibrahim, Rodolfo F. Perini, Antoni Ribas, Michael B. Atkins
Journal: Journal of Clinical Oncology (2017)

510 Background: The CTLA-4 antibody ipi and the PD-1 antibody pembro have demonstrated efficacy in pts with advanced malignancies. While these immune checkpoint inhibitors have shown robust activity as monotherapy, combination therapy may further improve outcomes. KEYNOTE-029 (NCT02089685) is a phase 1/2 study designed to assess the safety and efficacy of pembro + ipi or pegylated interferon alfa-2b (IFN-α) in pts with advanced melanoma or RCC. Here we report data from the phase 1 portion of the study in pts with RCC treated with pembro + ipi. Methods: Pts ≥18 years with advanced/unresectable or metastatic clear cell RCC who received ≥1 prior therapy for metastatic disease, had ≥1 measurable lesion per RECIST v1.1, and ECOG PS 0-1 were enrolled. Pts received pembro 2 mg/kg Q3W + low-dose ipi (1 mg/kg Q3W for 4 doses) until disease progression, unacceptable toxicity, investigator/patient decision, or 2 years of pembro treatment. AEs were monitored throughout treatment and for 30 days thereafter and graded per NCI CTCAE v4.0. Primary end point was safety; primary efficacy end point was ORR assessed per RECIST v1.1 by independent central imaging vendor review. Results: As of the March 17, 2016, data cutoff, 10 pts with RCC received pembro + low-dose ipi. 60% were male, 70% were white, median age was 61 years (range, 48-70 years), 40% received 2 prior lines of therapy, and 40% received prior immunotherapy. With a median follow-up of 17.4 months (0.9-23.5 months), 70% of pts experienced treatment-related AEs (TRAEs) of any grade, most commonly fatigue (30%); and 50% experienced grade 3/4 TRAEs, most commonly increased lipase (20%). 50% of pts discontinued pembro because of TRAEs, most commonly increased lipase (40%). There were no treatment-related deaths. ORR was 20% (2 partial responses); median duration of response was not reached (14.1+-17.1 months+). An additional 3 pts had stable disease; disease control rate was 50%. Conclusions: The combination of pembro + low-dose ipi for 4 doses, followed by pembro monotherapy, demonstrates a manageable toxicity profile and preliminary antitumor activity in pts with advanced RCC. Clinical trial information: NCT02089685.
A Research Agenda for Malaria Eradication: Modeling
Journal: PLoS Medicine (2011)

Malaria modeling can inform policy and guide research for malaria elimination and eradication from local implementation to global policy. A research and development agenda for malaria modeling is proposed, to support operations and to enhance the broader eradication research agenda. Models are envisioned as an integral part of research, planning, and evaluation, and modelers should ideally be integrated into multidisciplinary teams to update the models iteratively, communicate their appropriate use, and serve the needs of other research scientists, public health specialists, and government officials. A competitive and collaborative framework will result in policy recommendations from multiple, independently derived models and model systems that share harmonized databases. As planned, modeling results will be produced in five priority areas: (1) strategic planning to determine where and when resources should be optimally allocated to achieve eradication; (2) management plans to minimize the evolution of drug and pesticide resistance; (3) impact assessments of new and needed tools to interrupt transmission; (4) technical feasibility assessments to determine appropriate combinations of tools, an associated set of target intervention coverage levels, and the expected timelines for achieving a set of goals in different socio-ecological settings and different health systems; and (5) operational feasibility assessments to weigh the economic costs, capital investments, and human resource capacities required.