tbuckley/cabot-search huggingface dataset:
Preliminary results of a prospective pilot study of cisplatin (C) and doxorubicin (D) as neoadjuvant chemotherapy (NACT) for locally advanced triple-negative breast cancer (TNBC).
Authors: Lyudmila Zhukova, Maria Okruzhnova
Journal: Journal of Clinical Oncology (2014)

e12011 Background: Till now chemotherapy is the only effective treatment options in patients (pts) with TNBC. The best regimen is critical for the patients outcome. This study was designed to assess efficacy and safety of cisplatin + doxorubicin in locally advanced TNBC. Methods: This single-arm, prospective pilot study enrolled pts with clinical stage III ER-negative, PR-negative, and HER2-negative BC. Neoadjuvant C (75 mg/m2; IV; D1) and D (50 mg/m2; IV; D1) were given every 21 days for 4-6 cyclesfollowed by definitive surgery and standard radiation therapy. The patients who had not achieved pathologic complete response (pCR) received an adjuvant course of taxanes based CT followed by standard radiation therapy. The primary endpoint is pCR, defined as no invasive and no in situ residual disease in the breast and axilla. Secondary endpoints are safety, clinical response, and progression free survival. Results: Among 34 eligible pts treated with 4-6 cycles, median age is median age 51.5 yrs (range 33-73 yrs) and clinical stage is T4 -28 pts and / or N2-3 – 7 pts. 30 of 34 enrolled pts received surgery. Pathologic complete response was achieved in 12 (35,3%) of 34 treated pts. 30 (88%) of 34 pts had a clinical complete or partial response (ORR). 2 pts had stable of disease and required a preoperative radiotherapy. 2 pts had a disease progression after 3 cycles of NACT and was treated with another chemotherapy regimen. At a median follow-up of 20,4 months (1-36 months) 23 of 34 pts (68%) are alive and disease free. Grade 3 anemia was observed in 4 patients, renal toxicity (decreased creatinine clearance less than 60 ml/min) – in 4 patients which required a cisplatin dose reduction. An early termination of NACT (after 4 cycles) was required in 2 patients due to toxicity. Conclusions: Neoadjuvant cisplatin + doxorubicin regimen has a high efficacy and acceptable toxicity in locally advanced TNBC (pCR – 35,3%, ORR – 88%). Long term results pending.
A population-based study of incidence and survival trends of 1,261 thymic malignancies (TM): Results from the California Cancer Registry (CCR).
Authors: Jonathan Riess, Yingjia Chen, Primo Lara, Heather A. Wakelee, Matthew A. Gubens, Rosemary Donaldson Cress
Journal: Journal of Clinical Oncology (2014)

1584 Background: TMs are rare with sparse population-based epidemiologic literature. Methods: We used data from the CCR, a comprehensive population-based state registry to examine TM incidence and survival trends in California from 1988 to 2011. Cases were specified by site (thymus), histology (thymic carcinoma and thymoma), and behavior (malignant). Primary endpoint was cause-specific survival (CSS). Hazard ratios (HR) for CSS were calculated using a Cox proportional-hazards model controlling for relevant baseline variables including age, gender, stage, and year of diagnosis, among others. Results: We identified 1,261 TM cases with an incidence of 0.17 per 100,000 person-years. Average annual increase was 2% (95% CI 1-3.1%). Earlier stage was associated with improved CSS in the crude (localized HR=0.17, 95% CI 0.11-0.28; regional HR=0.37, 95% CI 0.28-0.49) and multivariate models (localized HR=0.30, 95% CI 0.157-0.567; regional HR=0.44 (95% CI 0.29-0.67). Thymic carcinoma histology was associated with worse CSS in both the crude (HR=2.42, 95% CI 1.74-3.37) and multivariate models (HR=2.57, 95% CI 1.1-6.1). Patients diagnosed between 1995-2001 had improved CSS compared to 1988-1994 (crude HR=0.49, 95% CI 0.35-0.70), even in the multivariate model (HR=0.35, 95% CI 0.18-0.71). Radiotherapy was associated with improved CSS (multivariate HR=0.45, 95% CI 0.21-0.97) for patients treated with partial or total removal of tumor. Conclusions: This is the first population-based study of TMs from the CCR that identifies baseline variables significantly associated with CSS. TM incidence appears to be increasing over time: this was also associated with improving CSS over the same period. In addition to stage and non-thymic carcinoma histology, treatment with radiotherapy after partial or total removal of tumor was found to be associated with improved CSS. These findings provide a more contemporary database for future TM outcomes research and generate new hypotheses for clinical evaluation.
Is advanced imaging in early-stage breast cancer ever warranted? Exploring benchmarks for an ASCO Choosing Wisely quality measure.
Authors: Tian Zhang, Steve Power, Paul K. Marcom, Arif Kamal
Journal: Journal of Clinical Oncology (2014)

6503 Background: ASCO’s Choosing Wisely initiative recommends reducing certain low value services, including advanced imaging in early-stage (ES) breast cancer (BC). Few have explored baseline frequency of, or documented clinical reasons for, advanced imaging in ES BC. We analyzed data at an NCI comprehensive cancer center to characterize pt scenarios in which advanced imaging was ordered. Methods: We analyzed all pts with ES BC from January 2010 to June 2012 at the Duke Cancer Institute (DCI). We used the Choosing Wisely criteria for ES BC (clinical Stage IIb or less) and advanced imaging (nuclear bone scan, computed tomography (CT), positron emission tomography (PET), and brain magnetic resonance imaging). We then searched an administrative database for advanced imaging performed in the Duke Health System within 60 days after diagnosis. Three independent reviewers abstracted the medical charts of 40% of cases, randomly selected, to explore reasons for image ordering. Descriptive statistics and the chi-square test were performed. Results: Of 1,143 ES BC cases identified, 20.6% (235 pts) had at least one advanced imaging procedure performed. Imaging type varied widely (41% CT, 22% PET, and 36% bone scans, p<0.001). Pts with advanced imaging were more likely hormone receptor negative, HER2-negative, younger (age<50), and with higher stage (Stage IIb vs. Stage IIa or less) disease (all p<0.001). Of the 95 abstracted cases with imaging, 62% (59 pts) were obtained for further staging, 17% to evaluate a major concurrent disease (6 oncologic, 10 non-oncologic), and 19% for exam or history findings worrisome for distant disease. 15% (9/59 pts) of images ordered for staging were abnormal. Overall, 45% (43/95 pts) of advanced imaging ordered were for a major concurrent disease, worrisome findings, or staging which ultimately revealed an abnormality. Conclusions: Advanced imaging is ordered in a minority of ES BC cases. When ordered, almost half of images aid in clarifying a complex clinical decision. Our data highlight the benefit of quality measures in reducing low value services, while also acknowledging that allowances for measure non-adherence are needed to promote patient-centered cancer care.
Abstract 15374: Interaction of G-Protein Beta 3 Subunit (GNB3) and G-Protein Receptor Kinase 5 (GRK5) Genotypes Impacts Heart Failure Outcomes in African Americans
Authors: Amber E Johnson, Karen Hanley-Yanez, Clyde W Yancy, Anne L Taylor, Arthur M Feldman, Dennis M McNamara
Journal: Circulation (2017)

Introduction: G-protein receptor kinases (GRK) are central to beta adrenergic receptor inactivation. A polymorphism of GRK5 (A122T), in which the T allele substitutes leucine for wild-type glutamine (A allele) at amino acid 41, is common in African Americans. GRK5 with leucine at position 41 attenuates adrenergic signaling, impacting heart failure survival. The G-protein beta 3 subunit (GNB3) also contributes to beta adrenergic signaling. The GNB3 825 T genotype is common in African Americans, is linked to a truncated subunit, and increases adrenergic signaling. Hypothesis: The interaction of GNB3 and GRK5 polymorphisms will impact heart failure outcomes in a cohort from the African American Heart Failure Trial (AHeFT). Methods: The AHeFT genetic sub-study, Genetic Risk Assessment of Heart Failure in African Americans (GRAHF1), included 348 patients genotyped for GRK5 A122T and GNB3 T825C polymorphisms. Patients were followed to either death or heart failure hospitalization. Event free survival was compar...
A triplet combination with irinotecan, oxaliplatin, continuous infusion 5-fluorouracil and leucovorin (FOLFOXIRI) plus cetuximab as first-line treatment in <i>RAS</i> wild-type, metastatic colorectal cancer: A phase 1 dose finding study.
Authors: Shigenori Kadowaki, Toshiki Masuishi, Takashi Ura, Seiichiro Mitani, Yukiya Narita, Kyoko Kato, Kazunori Honda, Hiroya Taniguchi, Masashi Ando, Kei Muro
Journal: Journal of Clinical Oncology (2018)

856 Background: The FOLFOXIRI regimen (irinotecan, oxaliplatin, 5-fluorouracil and leucovorin) improves the response rate and overall survival compared to FOLFIRI in pts with metastatic colorectal cancer (mCRC), and addition of cetuximab to chemotherapy increases efficacy in pts with RAS wild-type mCRC. We conducted a phase 1 study of FOLFOXIRI plus cetuximab to determine the maximum-tolerated dose (MTD) and recommended dose (RD) and to assess its safety and efficacy in Japanese pts with RAS wild-type mCRC. Methods: Main eligibility criteria were: histologically confirmed colorectal adenocarcinoma; KRAS and NRAS wild-type status; measurable metastatic disease according to Response Evaluation Criteria in Solid Tumors version 1.1; age 20-74 years; Eastern Cooperative Oncology Group performance status 0 or 1. Pts with UDP-glucuronosyltransferase 1A1*6/*6, *28/*28 and *6/*28 genotypes were excluded. Pts received an escalating dose of intravenous irinotecan (100, 120, and 150 mg/m 2 in the dose levels 0, 1, and 2, respectively) and a fixed dose of intravenous oxaliplatin (85 mg/m 2 ), continuous infusion 5-fluorouracil (2400 mg/m 2 ) plus l-leucovorin (200 mg/m 2 ), and cetuximab (an initial dose of 400 mg/m 2 followed by 250 mg/m 2 per week). Results: A total of 9 Japanese pts were treated (3 and 9 in the dose levels 1 and 2, respectively). No patients experienced a dose-limiting toxicity (the MTD was not reached), and the dose level 2 (irinotecan 150 mg/m 2 ) was established as the RD. With a median 8 cycles per patient, the most common grade 3 or 4 adverse events included neutropenia (44%), paronychia (22%), and acne-like rash (11%). No febrile neutropenia and treatment-related death were observed. Among 9 pts, 1 pt had complete response, 7 pts had partial response, and 1 pt had progressive disease, for an overall response rate of 89%. As of September 24, 2017, median progression free survival was 14.0 (95% CI 7.2-20.7) months. Conclusions: The combination of cetuximab and FOLFOXIRI has shown a favorable toxicity profile and promising antitumor activity in pts with RAS wild-type mCRC. Clinical trial information: UMIN000018217.
Insights on Multiple Myeloma Treatment Strategies
Authors: María‐Victoria Mateos, Heinz Ludwig, Ali Bazarbachi, Meral Beksac, Joan Bladé, Mario Boccadoro, Michele Cavo, Michel Delforge, Meletios A. Dimopoulos, Thierry Facon, Catarina Geraldes, Hartmut Goldschmidt, Roman Hájek, Markus Hansson, Krzysztof Jamroziak, Merav Leiba, Tamás Masszi, Larisa Mendeleeva, Michael O’Dwyer, Torben Plesner, Jesús F. San‐Miguel, Christian Straka, Niels W.C.J. van de Donk, Kwee Yong, Samo Zver, Philippe Moreau, Pieter Sonneveld
Journal: HemaSphere (2018)

The introduction of new agents and management strategies over the past decade has resulted in a major step change in treatment outcomes with deepening responses and increased survival for patients with multiple myeloma. In daily clinical practice, healthcare professionals are now faced with challenges including, optimal treatment sequencing and changing treatment goals. In light of this, a group of experts met to discuss diagnostic and treatment guidelines, examine current clinical practice, and consider how new clinical trial data may be integrated into the management of multiple myeloma in the future.
Immunogenetic Studies on X-Irradiated Mice Treated With Hematopoietic Cells and Grafted With Tumor Tissues&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Michael Feldman, David Yaffe
Journal: JNCI Journal of the National Cancer Institute (1959)

A study was made of the behavior of tumor grafts in the radiation chimera to analyze the immune reactivity of the donor's hematopoietic cells and the influence on tumor cells of the radiation chimera. The regression of homografts of Sarcoma C10 and Sarcoma MCIM (of C3H origin) in irradiated C57BL animals treated with C57BL cells and their progressive growth in irradiated animals treated with C57BL fetal hematopoietic cells gave evidence of the ability of donor cells to form transplantation immunity against foreign antigens, thus substantiating the graft versus host theory as the basis for “homologous secondary disease.” Tumor grafts produced metastases in irradiated animals, and irradiation and immunogenetic factors were shown to influence their development. The transplantation of Sarcoma SBLI into various types of genetic chimeras was accompanied by immunogenetic changes in the tumor, which were manifested by the loss of strain specificity. The effect of total-body irradiation of the host and the absence of isologous C57BL cells were shown to he the main factors determining this change. Their analysis provided definite indications that the acquired homotransplantability of SBLx sublines is basically a result of immunogenetic transformation induced by the host and not a result of selection of pre-existing compatible cell variants.
Large granular lymphocyte (LGL) subsets in smoldering multiple myeloma (SMM): Immunophenotypic profiles that predict progression to multiple myeloma (MM).
Authors: Talib Dosani, Neha Korde, Elisabet Esteve Manasanch, Manisha Bhutani, Nishant Tageja, Sham Mailankody, Mark J. Roschewski, Mary Kwok, Dickran Gano Kazandjian, Ola Landgren, Irina Maric
Journal: Journal of Clinical Oncology (2014)

8597 Background: SMM is an asymptomatic precursor condition to MM. The immune system is known to play an important role in progression of SMM to MM. However, current risk-stratification schemes are often discordant, and there are presently no reliable biomarkers to predict progression to MM. In this study, we quantified various LGL subsets of SMM patients and identified potential LGL markers that may predict progression. Methods: Flow cytometric analysis was used to quantify LGL subsets in the peripheral blood (PB) of SMM patients (N=80) enrolled in the NCI Natural History of SMM/MGUS prospective clinical trial. PB samples were collected at enrollment and at every 12 months, in addition to regular 3-6 month clinical follow-ups. We conducted an analysis of LGL subsets using samples collected at diagnosis or follow-up on patients who progressed to MM at a subsequent 6-month or 12-month follow-up (N=8, median age 64) versus patients who had not progressed at 12 months of follow-up (N=72, median age 60). Two-tailed Mann-Whitney U test was used for all statistical analyses. Results: SMM patients who progressed to MM demonstrated a distinct LGL profile 6-12 months before progression. These patients had decreased levels of both relative and absolute numbers of CD3(-) CD16(+) CD57(-) NK cells (p=.03 and .09, respectively) and decreased levels of both relative and absolute numbers of CD56(+) CD57(-) lymphocytes (p=.003 and .02, respectively). Furthermore, there was an increase in relative numbers of total CD57(+) lymphocytes and CD57(+) CD8(-) NK cells (p=.23 and .13, respectively). There were no statistically significant differences in total WBCs, absolute lymphocyte counts, CD3(-) CD16(+) CD56(+) NK cells or CD3(+) CD16(+) CD56(+) NKT-like cells between the cohorts. Conclusions: SMM patients who progressed to MM possessed a distinct LGL immunophenotypic profile that was characterized by a decrease in CD57(-) lymphocyte subsets and a mild increase in CD57(+) lymphocyte subsets. These results suggest an LGL immunophenotypic profile that may be used as a marker of progressive disease in SMM patients.
Abstract 16388: Validation of Neointimal Coverage Classification After Stent Implantation by Coronary Angioscopy; ex vivo Histological Study
Authors: Kenji Kawai, Takahiro Imanaka, Rika Kawakami, Hirokuni Akahori, Kojiro Miki, Nagataka Yoshihara, Koji Yanaka, Seiichi Hirota, Tohru Masuyama, Masaharu Ishihara
Journal: Circulation (2017)

Introduction: Coronary angioscopy allows to visualize directly neointimal coverage (NIC) after stent implantation. However, histological comparison with qualitative NIC classification by angioscopy...
Preliminary Results from a Phase II Study of the Combination of Azacitidine and Pembrolizumab in Patients with Higher-Risk Myelodysplastic Syndrome
Authors: Kelly S. Chien, Jorge E. Cortes, Gautam Borthakur, Courtney D. DiNardo, Naval G. Daver, Nitin Jain, Kiran Naqvi, Elias J. Jabbour, Kimberly B. Sheppard, Sherry A. Pierce, Hagop M. Kantarjian, Guillermo Garcia-Manero
Journal: Blood (2018)
Abstract P244: Relations Between Residential Fast-food Environment and Individual Risk of Cardiovascular Disease
Authors: Ilonca Vaartjes, Ilonca Vaartjes, Maartje Poelman, Maartje Poelman
Journal: Circulation (2018)

Background: The food environment has been hypothesized to influence cardiovascular diseases (CVD) such as hypertension and coronary heart disease (CHD). This study determines the relation between fast-food outlet density (FFD) and the individual risk for CVD, among a nationwide Dutch sample. Methods: After linkage of three national registers , a cohort of 2,472,004 adults (≥35 year), free from CVD at January 1 st 2009, and living at the same address for ≥15 years was constructed. Participants were followed for one year to determine incidence of CVD, including CHD, stroke and heart failure. FFD within 500m, 1000m and 3000m from residential addresses was related to CVD using logistic regression, stratifying models by degree of urbanisation and adjusting for age, sex, ethnicity, marital status, comorbidity, neighbourhood-level income and population density. Results: In urban areas, fully adjusted models indicated that the incidence of CVD and CHD was significantly higher within 500m buffers containing one or more fast food outlets compared to areas without outlets. An elevated FFD within 1000m was associated with a significantly increased incidence of CVD and CHD. Evidence was less pronounced for 3000m buffers, or for stroke and heart-failure incidence. Conclusions: Elevated FFD in the urban residential environment (≤1000m) was related with an increased incidence of CVD and CHD. To better understand how FFD is associated with CVD, future studies should account for a wider range of lifestyle and environmental confounders than was achieved in this study.
Everolimus plus bicalutamide in men with castration-resistant prostate cancer (CRPC): Final results of a phase II trial.
Authors: Chong-xian Pan, Helen Chow, Paramita Ghosh, Ralph deVere White, Christopher P. Evans, Marc A. Dall'Era, Stanley A Yap, Judy Li, Laurel A. Beckett, Primo Lara
Journal: Journal of Clinical Oncology (2014)

5028 Background: We previously reported that the mammalian target of rapamycin (mTOR) pathway was upregulated in CRPC, and that inhibition of mTOR was ineffective in killing prostate cancer cells likely due to its effect on upregulating the androgen receptor (AR) pathway (Wang et al. Oncogene. 2008; 27:7106). We hypothesized that simultaneous blockade of both AR and mTOR pathways would be effective against CRPC. Methods: Eligible patients (pts) must have progressive CRPC with serum testosterone <50 ng/dl. No prior bicalutamide (except to prevent flare) or everolimus was allowed. Treatment regimen included bicalutamide 50 mg and everolimus 10 mg po, both qd. Primary endpoint was prostate specific antigen (PSA) response (≥30% reduction). Sample size of 23 pts would have the power of 0.8 and α error of 0.05 (one-sided) if the combination had a PSA response rate of 50% vs. a historical rate of 25% with bicalutamide alone. Molecular correlative studies were performed. Results: Twenty four pts were enrolled. Mean age was 71.1 years (range: 53.0-87.0). Mean PSA at the study entry was 43.4 ng/dl (2.5-556.9). Mean number of treatment cycles was 7.9 (1.0-23.0). Of 24 pts, 18 had a PSA response (75%, 95% CI: 0.53-0.90). Of these, 15 had a PSA decrease of ≥ 50% (62.5%, 95% CI 0.41-0.81). Median overall survival was 28 months (95% CI 14.1-42.7). Fourteen pts (54%, 95% CI 0.37, 0.78) developed Grade 3 (13 pts) or Grade 4 (1 pt with sepsis) adverse events attributable to the treatment. Serum ErbB3 increased by 5.16 folds in non-responders vs a 60% decrease in responders (p<0.001). Conclusions: The combination of bicalutamide and everolimus has very encouraging efficacy in men with bicalutamide-naïve CRPC. These results are contrary to the results of a similar phase II trial that predominantly enrolled pts previously treated with bicalutamide, and reported limited efficacy for this doublet (Nakabyashi, BJU Intl 2012; 110:1729). A substantial number of pts experienced everolimus-related toxicity. ERBB3 appears to be a candidate marker of response to therapy and deserves further study. A randomized Phase III trial of bicalutamide +/- everolimus in bicalutamide-naïve CRPC is warranted. Clinical trial information: NCT00814788.
The potential role of <sup>18</sup>F-FDOPA PET imaging in low-grade gliomas.
Authors: Carmine Maria Carapella, Veronica Villani, Agostino Chiaravalloti, Francesca Piludu, Irene Terrenato, Antonello Vidiri, Alessandra Fabi, Orazio Schillaci, Andrea Pace, Roberto Floris
Journal: Journal of Clinical Oncology (2014)

2091 Background: Brain tumors have been widely evaluated with 3,4-dihydroxy-6-18F-fluoro-L-phenylalanine (18F-FDOPA) PET examination, that demonstrated higher sensitivity and specificity for gliomas than 18F-FDG PET imaging. The aim of the present study is to evaluate the potential role of 18F-FDOPA PET in low grade glioma (LGG). Methods: We enrolled 56 patients (35 males and 21 females) affected by LGG; 23% were newly diagnosed, 45% were studied during chemotherapy, and 32% were observed out of treatment during a periodic follow-up. The mean age at diagnosis was 44.5 years. All patients underwent 18F-FDOPA PET and MRI examinations. Both FLAIR and contrast-enhanced T1 sequences were considered for the assessment of therapeutic response according to RANO criteria. PET images were considered as positive when the lesion definitely presented 18F-FDOPA accumulation taking into account background and controlateral site. The slices with a maximal 18F-FDOPA uptake in the ROI were chosen for quantitative measurement of metabolic activity of the tracer [standardized uptake value (SUV)]. In order to evaluate the concordance between diagnostic test 1 (MRI) and diagnostic test 2 (18F-FDOPA) we calculated the unweighted kappa statistic and its relative 95% Confidence Interval (CI). This value was interpreted in a qualitative manner on the basis of Landis and Koch criteria. Results: The Kappa statistic for the whole sample was equal to 0.301 (95% CIs from 0.21 to 0.40) showing a fair concordance between the two tests in terms of diagnostic ability. We found a good correlation between residual volume and SUV max (r=0.435, p=0.002 by Spearman Rank Correlation Coefficient), indicating that greater the residual volume, higher is the SUV max. Also multivariate analysis showed that a SUV max greater than 1.65 was the only independent predictor of tumor progression (HR=4.59, 95% CIs from 0.99 to 21.31, p=0.054). This implies that a patient with a SUV max higher than 1.65 had an almost 5-fold increased risk of progressive disease, regardless of its clinical and MRI characteristics. Conclusions: Our results confirm that 18F-FDOPA PET imaging could assume a relevant role mainly in the prognostic assessment of patients affected with primary and recurrent LGG.