tbuckley/cabot-search huggingface dataset:
Does the sequence of anthracycline and taxane matter? The NeoSAMBA trial.
Authors: Jose Bines, Fabiola Kestelman, Silvania B Siva, Roberta MB Sarmento, Isabele Avila Small, Fabiana R Rodrigues, Pedro S Maroun, Eduardo Millen, Martin H Bonamino
Journal: Journal of Clinical Oncology (2018)

575 Background: Taxanes usually follow anthracyclines in breast cancer neo/adjuvant treatment, likely due to its later introduction in clinical practice. However, there is no biological rationale that justifies this current standard-of-care. We compared an anthracycline-based regimen followed by a taxane (FAC-T) neoadjuvant chemotherapy with the reverse sequence (T-FAC) (NCT01270373). Methods: In this randomized, open-label, single center phase 2 trial, women with locally advanced (LABC) HER2 negative breast cancer, stratified by hormone receptor, were randomized to 3 cycles of fluorouracil, doxorubicin and cyclophosphamide followed by 3 cycles of docetaxel vs. docetaxel followed by fluorouracil, doxorubicin and cyclophosphamide. Surgery, radiotherapy and adjuvant hormonal therapy were given as per local guidelines. The primary endpoint was pathological complete response (pCR) and secondary endpoints included disease-free (DFS) and overall survival (OS). The expected baseline pCR was 15%. With 53 patients per arm, we had a 90% probability of selecting a schedule that had a true benefit of 25%. A 10% drop-out was anticipated. Results: Between September 2010 and November 2012, we randomly allocated 118 patients: 60 received FAC-T and 58 T-FAC. The median follow-up was 53.8 months (95% CI 51.9- 55.7). The median age was 50 years. Ninety-four patients (70.7%) had stage III tumors and 31 (26.3%) had triple negative disease. pCR was higher in triple negative patients: 21.4% vs 1.2%. Treatment sequence did not improve pCR of all patients operated (114): 3 (5.2%) and 4 (7.3%) in the FAC-T and T-FAC arms, respectively. Taxane-first when compared to anthracycline-first sequencing showed a 5y DFS of 78% and 45% (HR 0.31, 95% CI 0.16–0.59) and a 5y OS of 88% and 65% (HR 0.28, 95% CI 0.12–0.66), respectively. The relative dose intensity was similar between both arms. No unexpected toxicity was reported. Conclusions: We showed for the first time an improvement in DFS and OS with taxane-first when compared to anthracycline-first sequencing chemotherapy in HER2 negative LABC. Tumor and blood samples were collected for translational analyses at three time points. Clinical trial information: NCT01270373.
The impact of circulating tumor cells (CTCs) detection in metastatic breast cancer (MBC): Implications of “<i>indolent</i>” stage IV disease (Stage IV<sub>indolent</sub>).
Authors: Andrew A. Davis, Jean-Yves Pierga, Luc Yves Dirix, Stefan Michiels, Alfred Rademaker, James M. Reuben, Tanja N. Fehm, Elisabetta Munzone, Mario Giuliano, Jose Vidal-Martinez, Dimitrios Mavroudis, Salvatore Grisanti, Daniele Giulio Generali, Jose Angel Garcia-Saenz, Justin Stebbing, Sarah-Jane Dawson, Paola Gazzaniga, François-Clément Bidard, Massimo Cristofanilli
Journal: Journal of Clinical Oncology (2018)

1019 Background: CTCs count has been validated as a prognostic biomarker in MBC. In primary breast cancer, diagnostic tools exist to select less aggressive treatments in patients with indolent disease. In the largest CTC analysis to date, we define an indolent subset of patients in MBC, Stage IV indolent, identified using CTC counts. Methods: We performed a combined pooled analysis of individual patient data in two large cohorts: the European Pooled Analysis Investigators (EPAC) cohort (N = 1,944) and the MD Anderson Cancer Center (MDACC) cohort (N = 492). For all patients (N = 2,436), CTC enumeration was performed using the FDA-approved CellSearch™ (Menarini Silicon Biosystems, LLC) with baseline samples collected before starting a new treatment. Overall survival (OS) data were collected from both cohorts. Patients were stratified based on 5 CTCs/7.5 mL blood (N = 1,336 with < 5 CTC or Stage IV indolent; ≥5 CTC, Stage IV aggressive). Proportional hazards regression model and stratified log rank tests were performed. Results: For all patients, CTC ≥5 identified patients with a worse outcome (HR 2.43, 95% CI 2.17-2.73, P < 0.0001), while the indolent CTC group had a median OS of 36.3 months (mts). Moreover, for patients with de novo MBC prior to treatment (N = 244), the indolent cohort demonstrated an OS greater than 5.5 years. The Stage IV indolent disease showed significantly longer OS across all disease subtypes compared to the aggressive cohort, HR+ (44 mts vs. 17.3 mts, P < 0.0001), TNBC (23.8 mts vs. 9.0 mts, P < 0.0001), and HER2+ (36.7 mts vs. 20.4 mts, P < 0.0001). Furthermore, Stage IV indolent consistently discriminated a less aggressive cohort among subtypes even in the refractory setting. Conclusions: CTC < 5 identifies an indolent subset of MBC, Stage IV indolent, independent of line of treatment and molecular subtype. A CTCs-based classification of MBC has tremendous implications and practical applications including, considerations for cost-effective single-agent therapy, particularly in the first-line setting, and the availability of a validated stratification tool in prospective efficacy clinical trials.
The prognostic role of CpG island methylator phenotype in metastatic colorectal cancer.
Authors: Kuo-Hsing Chen, Liang-In Lin, Li-Hui Tseng, Yu-Lin Lin, Jau-Yu Liau, Jia-Huei Tsai, Jin-Tung Liang, Been-Ren Lin, Ann-Lii Cheng, Kun-Huei Yeh
Journal: Journal of Clinical Oncology (2018)

667 Background: The prognostic role of CpG Island Methylator Phenotype (CIMP) in colorectal cancer (CRC) is still controversial, especially in metastatic CRC. Methods: We retrospectively analyzed the CpG island methylator phenotype (CIMP) in stage I to IV CRC specimens, which were diagnosed during 2005-2013. CIMP status was determined using a 5- gene MethyLight-based assay ( p16, MINT1, MINT2, MINT31, and MLH1). Tumors were designated as CIMP if 3 or more of 5 genes gave percent of methylated reference value ≧ 10. The clinicopatholoical characteristics, anti-cancer therapies, and the overall survival outcome were reviewed. Overall survival (OS) was compared between patients with CIMP CRC and those with non-CIMP CRC. Results: Among 450 patients with successfully determined CIMP status, 259 (57.56%) were male, 312 (70.31%) were stages I-III, 316 (70.69%) were left-sided CRC. In the survival analyses in stages I-IV patients, there was no significant difference in OS between those with or without CIMP (long rank test, p = 0.4526). Importantly, patients with metastatic CIMP CRC had poor OS than those with metastatic non-CIMP CRC (median survival, CIMP vs. non-CIMP: 1.36 vs. 3.11 years, log rank test, p = 0.0047). In a multivariate analysis, which adjusted prognostic variables such as: KRAS and BRAF mutations, microsatellite instability status, age, sex, grade, primary site, metastatic site number, chemotherapies and targeted therapies, CIMP remained an independent poor prognostic factor for OS (HR = 6.213, 95% confidence interval: 2.443 to 15.799, p = 0.0001) in metastatic CRC. In an exploratory analysis, there were more tumors with liver metastases at diagnosis in CIMP CRC than in non-CIMP CRC (94.4% vs. 71.3%, p = 0.0416). Conclusions: Our data demonstrated CIMP might independently predict poor survival in metastatic CRC in a large East Asian cohort.
Effect of a combined diet plus exercise intervention on weight loss, physical fitness, and cancer-related fatigue among Japanese women with breast cancer.
Authors: Koki Okumatsu, Takehiko Tsujimoto, Akina Seki, Teruo Yamauchi, Hideko Yamauchi, Kiyoji Tanaka
Journal: Journal of Clinical Oncology (2017)

e21658 Background: Weight gain, deterioration of physical fitness, and cancer-related fatigue often occur in the breast cancer patients mainly due to endocrine therapy. A number of previous studies have reported that obesity increases the risk of breast cancer recurrence and death, while exercise habituation improves physical fitness and fatigue among breast cancer patients. However, almost all studies have been conducted in the Western community and there are few studies focused on Asian women who may have lower BMI compared with the Western ones. Therefore, we investigated whether a combined diet plus exercise program affects weight loss, physical fitness and fatigue indices among Japanese breast cancer patients undergoing endocrine therapies. Methods: Thirty-two Japanese women with breast cancer undergoing endocrine therapy (age; 50±6 years, body weight; 57±10 kg) were voluntarily assigned to either intervention group (n = 21) or control group (n = 11). The intervention group completed a 12-week combined diet plus exercise program, consisting of weekly diet instruction classes aimed at maintaining a nutritionally well-balanced 1,200 kcal/d diet and a weekly 90-min exercise session. Anthropometric indices, physical fitness, blood sample and cancer-related fatigue were measured at baseline and after the 12-week program. Results: All of the 21 women completed the 12-week program. Mean weight loss was 8.7% of the initial weight in the intervention group and 0.1% in the control group ( P &lt; . 001). Significant improvements were observed in cardiorespiratory fitness ( P &lt; .01), flexibility ( P &lt; .01) and agility ( P &lt; .01) in the intervention group. Cancer related-fatigue scores decreased by 7.9 points (39%) among the intervention group ( P &lt; .001), while it remained essentially unchanged among the control group. No adverse events were reported in the intervention group. Conclusions: A combined diet plus exercise program may contribute to a decrease in body weight and improvement in physical fitness and cancer-related fatigue. Further study is needed to help reduce side effects due to endocrine therapy and enhance quality of life among Asian breast cancer patients. Clinical trial information: UMIN000025890.
Mutation-specific signaling profiles and kinase inhibitor sensitivities of juvenile myelomonocytic leukemia revealed by induced pluripotent stem cells
Authors: Sarah K. Tasian, Jessica A. Casas, David Posocco, Shilpa Gandre-Babbe, Alyssa L. Gagne, Ge Liang, Mignon L. Loh, Mitchell J. Weiss, Deborah L. French, Stella T. Chou
Journal: Leukemia (2018)
Survivorship care plans in safety net: Bridging the barriers.
Authors: Niharika Dixit, Piera Wong, Robin McBride, Ditas Hernandez, Barbara Cicerelli
Journal: Journal of Clinical Oncology (2018)

68 Background: Survivorship care plans (SCPs) are considered an important tool in survivorship care. SCP should include treatment summaries and follow up care plans and are intended to improve survivorship care. Despite the institute of medicine (IOM) recommendation regarding SCPs, the uptake has been low in community cancer centers. The safety net hospitals face additional challenges to SCPs including patient who may have low health literacy and limited English proficiency. In addition, resources and personnel constraints can be important barriers for implementation of SCPs. Methods: Zuckerberg San Francisco General Hospital is a safety net hospital in the City and County of San Francisco. We created SCPs for breast cancer survivors, as it is our largest group of cancer survivors. Patients, who were within 5 years of completion of treatment with curative intent for breast cancer were candidates for receiving SCPs. We used ASCO survivorship template to create a survivorship care plan. ASCO breast cancer SCP was discussed in the focus groups and modified to match the needs of our patients. SCP committee and patient advisory board evaluated the SCP prior to a pilot of the SCPs in the clinic. We piloted the SCPs initially in English and Spanish to assess feedback from clinic providers. After requested modifications SCP was then translated in to simplified Chinese. The SCP delivery was embedded in the clinic flow and was done at time of routine clinic visit to reduce the burden of additional visits. Results: 104/175 eligible patients have already received the SCP over one year period. All providers in the clinic participated in delivery of SCPs. Conclusions: SCP in multiple languages can be implemented successfully in safety net setting in a patient population with low health literacy and limited English proficiency. Availability in multiple languages, provider buy–in and embedding SCPs in clinic flow appears to be important factors in implementation. We are evaluating the optimal process of SCP delivery with an ongoing randomized pilot study of SCPs with and without navigation with breast cancer related quality of life and self-efficacy measures. We are also evaluating the usefulness of SCPs in meeting the informational needs of primary care providers.
SGLT-2 Inhibitors and Cardiovascular Risk
Authors: Matthew A. Cavender, Anna Norhammar, Kåre I. Birkeland, Marit Eika Jørgensen, John P. Wilding, Kamlesh Khunti, Alex Z. Fu, Johan Bodegård, Betina T. Blak, Eric Wittbrodt, Marcus Thuresson, Peter Fenici, Niklas Hammar, Mikhail Kosiborod, Mikhail Kosiborod, Matthew A. Cavender, Alex Z. Fu, John P. Wilding, Kamlesh Khunti, Anna Norhammar, Kåre I Birkeland, Marit Eika Jørgensen, Reinhard W. Holl, Niklas Hammar, Peter Fenici, Hungta Chen, Johan Bodegård, Betina T. Blak, Eric T. Wittbrodt, Markus F Scheerer, Filip Surmont, Kyle Nahrebne, Hanne Løvdal Gulseth, Bendix Carstensen, Marcus Thuresson, Esther Bollow, Luis Alberto García Rodríguez, Lucia Cea Soriano, Oscar Fernándex Cantero, Ellen Thiel, Brian Murphy
Journal: Journal of the American College of Cardiology (2018)

Prior studies found patients treated with sodium-glucose co-transporter-2 inhibitors (SGLT-2i) had lower rates of death and heart failure (HF). Whether the benefits of SGLT-2i vary based upon the presence of cardiovascular disease (CVD) is unknown. This study sought to determine the association between initiation of SGLT-2i therapy and HF or death in patients with and without CVD. The CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors) study was a multinational, observational study in which adults with type 2 diabetes were identified. Patients prescribed an SGLT-2i or other glucose-lowering drugs (GLDs) were matched based on a propensity score for initiation of an SGLT-2i. Hazard ratios (HRs) for the risk of death, HF, and HF or death in patients with and without established CVD were estimated for each country and pooled. After propensity score matching, 153,078 patients were included in each group. At baseline, 13% had established CVD. Compared with therapy using other GLDs, initiation of an SGLT-2i was associated with lower risk of death in patients with and without CVD (HR: 0.56; 95% confidence interval [CI]: 0.44 to 0.70; and HR: 0.56; 95% CI: 0.50 to 0.63, respectively). There were also associations between SGLT-2i and lower risk of HF (HR: 0.72; 95% CI: 0.63 to 0.82; and HR: 0.61; 95% CI: 0.48 to 0.78, respectively) and the composite of HF or death (HR: 0.63; 95% CI: 0.57 to 0.70; and HR: 0.56; 95% CI: 0.50 to 0.62, respectively) observed in patients with and without established CVD. In this large, multinational, observational study, initiation of SGLT-2i was associated with lower risk of death and HF regardless of pre-existing CVD. Ongoing clinical trials will provide further evidence regarding the benefit of SGLT-2i in patients without established CVD. (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors [CVD-REAL]; NCT02993614)
Two-year follow-up of pretreatment anti-mullerian hormone (AMH) to predict for resumption of mense after chemotherapy in premenopausal hormone-receptor (HR+) positive early breast cancer (eBC).
Authors: Cong Xue, Ye Cao, Xin An, Zhongyu Yuan, Shusen Wang, Fei Xu, Jia Jia Huang, Wen Xia, Ruoxi Hong, Jun Tang, Xi Wang, Weidong Wei, Yanxia Shi
Journal: Journal of Clinical Oncology (2018)

e12511 Background: Menses status is commonly used to measure ovarian function after chemotherapy, but its retrospective pattern limits the prospective application in endocrine therapy plan making of hormone receptor-positive (HR+) early breast cancer (eBC). We reported that prechemothearpy anti-mullerian hormone (AMH) was associated with the one-year resumption of menses in 2016 (ASCO abstract e12032). Here, we present the data of two-year follow-up. Methods: Between August 2013 and December 2014, 120 premenopausal patients younger than 50 years old with HR+ eBC were included retrospectively. We tested the relationship between prechemotherapy AMH, follicle-stimulating hormone (FSH) and estrogen (E) with two-year menses status. Results: After a median follow up of 1074 days (range, 182-1502 days) after chemotherapy, 54 patients (45%) experienced resumption of menses in two-year after chemotherapy. Pretreatment AMH was significantly lower in women with amenorrhoea than those with menses at two-year (0.68±0.92 ng/ml vs 2.99±2.65, p< 0.0001), which was consistent at one-year and six-month follow-up. In adjusted analyses, AMH levels was associated with the two-year resumption of menses(p< 0.0001), independent of age, whereas FSH and E levels were not related. AMH < 1.89 ng/ml resulted in classification of resumption of menses in two-year with AUC 0.791. Conclusions: In premenopausal patients with HR+ eBC, prechemothearpy AMH was associated with the two-year resumption of menses, independent of age. The two-year follow-up data confirms the role of prechemotherapy AMH as predicting future recovery of menses.
Renal immune surveillance and dipeptidase-1 contribute to contrast-induced acute kidney injury
Authors: Arthur Lau, Hyunjae Chung, Takanori Komada, Jaye M. Platnich, Christina F. Sandall, Saurav Roy Choudhury, Justin Chun, Victor Naumenko, Bas G.J. Surewaard, Michelle C. Nelson, Annegret Ulke-Lemée, Paul L. Beck, Hallgrimur Benediktsson, Anthony M. Jevnikar, Sarah L. Snelgrove, Michael J. Hickey, Donna L. Senger, Matthew T. James, Justin A. Macdonald, Paul Kubes, Craig N. Jenne, Daniel A. Muruve
Journal: Journal of Clinical Investigation (2018)

Radiographic contrast agents cause acute kidney injury (AKI), yet the underlying pathogenesis is poorly understood. Nod-like receptor pyrin containing 3–deficient (Nlrp3-deficient) mice displayed reduced epithelial cell injury and inflammation in the kidney in a model of contrast-induced AKI (CI-AKI). Unexpectedly, contrast agents directly induced tubular epithelial cell death in vitro that was not dependent on Nlrp3. Rather, contrast agents activated the canonical Nlrp3 inflammasome in macrophages. Intravital microscopy revealed diatrizoate (DTA) uptake within minutes in perivascular CX3CR1+ resident phagocytes in the kidney. Following rapid filtration into the tubular luminal space, DTA was reabsorbed and concentrated in tubular epithelial cells via the brush border enzyme dipeptidase-1 in volume-depleted but not euvolemic mice. LysM-GFP+ macrophages recruited to the kidney interstitial space ingested contrast material transported from the urine via direct interactions with tubules. CI-AKI was dependent on resident renal phagocytes, IL-1, leukocyte recruitment, and dipeptidase-1. Levels of the inflammasome-related urinary biomarkers IL-18 and caspase-1 were increased immediately following contrast administration in patients undergoing coronary angiography, consistent with the acute renal effects observed in mice. Taken together, these data show that CI-AKI is a multistep process that involves immune surveillance by resident and infiltrating renal phagocytes, Nlrp3-dependent inflammation, and the tubular reabsorption of contrast via dipeptidase-1.
Prostate Power Play: Does <i>Pik3ca</i> Accelerate <i>Pten</i>-Deficient Cancer Progression?
Authors: Joanna Triscott, Mark A. Rubin
Journal: Cancer Discovery (2018)

Abstract Summary: PI3K pathway alterations are frequently recurrent in metastatic prostate cancer and are associated with the development of currently incurable castration-resistant disease. Candidate inhibitors that target single PI3K pathway members lack efficacy as demonstrated in multiple clinical trials. In this issue, Pearson and colleagues examine the functional importance of co-occurring PIK3CA and PTEN aberrations using a novel mouse model and demonstrate a synergistic acceleration of tumorigenesis that may be responsible for de novo metastatic prostate cancer. Cancer Discov; 8(6); 682–5. ©2018 AACR See related article by Pearson et al., p. 764.
Time to deliver: report of the WHO Independent High-Level Commission on NCDs
Authors: Sania Nishtar, Sauli Niinistö, Maithripala Sirisena, Tabaré Vázquez, Veronika Skvortsova, Adolfo Rubinstein, Festus Gontebanye Mogae, Pirkko Mattila, Seyyed Hassan Ghazizadeh Hashemi, Sicily Kariuki, José Narro Robles, Isaac F Adewole, Adboulaye Diouf Sarr, Kim Yong Gan, Saia Ma'u Piukala, Abdul Rahman Bin Mohammed Al Owais, Eric Hargan, George Alleyne, Ala Alwan, Arnaud Bernaert, Michael Bloomberg, Katie Dain, Tom Frieden, Vikram Harshad Patel, Annette Kennedy, Ilona Kickbusch
Journal: The Lancet (2018)
Is there a survival benefit from adjuvant chemotherapy for patients with liver oligometastases from colorectal cancer after curative resection?
Authors: Zhizhong Pan, Jianhong Peng, Junzhong Lin, Gong Chen, Xiaojun Wu, Zhenhai Lu, Yuxiang Deng, Yujie Zhao, Qiaoqi Sui, Desen Wan
Journal: Cancer Communications (2018)

Abstract Background Although colorectal oligometastases to the liver can potentially be cured with aggressive local ablation, the efficacy of adjuvant chemotherapy (ACT) for such metastasis remains unclear. The present study explored the effects of ACT on patients with colorectal liver oligometastases (CLO) after curative resections and aimed to identify patients who could benefit from ACT. Methods We retrospectively analyzed 264 eligible patients with CLO who underwent curative resection between September 1999 and June 2015. Recurrence‐free survival (RFS) and overall survival (OS) were analyzed using the Kaplan–Meier method and log‐rank test; prognostic factors were a by Cox regression modeling. Results Among 264 patients, 200 (75.8%) patients received ACT and 64 (24.2%) did not receive ACT. These two groups did not significantly differ in clinicopathologic characteristics, and had comparable 3‐year OS and RFS rates (RFS: 42.1% vs. 45.7%, P = 0.588; OS: 69.7% vs. 62.7%, P = 0.446) over a median follow‐up duration of 35.5 months, irrespective of preoperative chemotherapy. ACT markedly improved 3‐year OS in high‐risk patients with Memorial Sloan‐Kettering Cancer Center clinical risk scores (MSKCC‐CRS) of 3–5 (68.2% vs. 33.8%, P = 0.015), but presented no additional benefit in patients with MSKCC‐CRS of 0–2 (72.2% vs. 78.6%, P = 0.834). In multivariate analysis, ACT was independently associated with improved OS in patients with MSKCC‐CRS of 3–5. Conclusions ACT might offer a prognostic benefit in high‐risk patients with CLOs after curative liver resection, but not in low‐risk patients. Therefore, patients’ risk status should be determined before ACT administration to optimize postoperative therapeutic strategies.
Correction to: Discovery and preclinical characterization of the antagonist anti-PD-L1 monoclonal antibody LY3300054
Authors: Yiwen Li, Carmine Carpenito, George Wang, David Surguladze, Amelie Forest, Maria Malabunga, Mary Murphy, Yiwei Zhang, Andreas Sonyi, Darin Chin, Douglas Burtrum, Ivan Inigo, Anthony Pennello, Leyi Shen, Laurent Malherbe, Xinlei Chen, Gerald Hall, Jaafar N. Haidar, Dale L. Ludwig, Ruslan D. Novosiadly, Michael Kalos
Journal: Journal for ImmunoTherapy of Cancer (2018)

Unfortunately, after publication of this article [1], it was noticed that corrections to the legends of Figs.&nbsp;1 and 2 were not correctly incorporated. The correct legends can be seen below.