tbuckley/cabot-search huggingface dataset:
The impact of statin use on abiraterone acetate (AA) treatment duration in patients with castration-resistant prostate cancer (CRPC).
Authors: Lauren Christine Harshman, Lillian Werner, Mari Nakabayashi, Abhishek Tripathi, Rana R. McKay, Xiaodong Wang, Mark Pomerantz, Lorelei A. Mucci, Mary-Ellen Taplin, Christopher Sweeney, Gwo-Shu Mary Lee, Philip W. Kantoff
Journal: Journal of Clinical Oncology (2016)

196 Background: Statins compete with DHEAS for influx through the transporter SLCO2B1 and may prolong time to progression (TTP) on androgen deprivation therapy (ADT). The androgen biosynthesis inhibitor, AA, may also undergo SLCO-mediated transport. We hypothesized that statins may compete with AA for influx by SLCO2B1, which could negatively impact drug efficacy. Methods: We queried our institutional clinical database for patients treated with AA for CRPC. Data on statin use including on-therapy dates were retrospectively collected from the medical record. Time on AA was used as a surrogate for TTP. Duration of AA was defined as the time from AA initiation to time to when AA was discontinued or censored on the last known alive date. The association between statin use and AA duration was estimated using the Kaplan-Meier method. Multivariable Cox regression adjusted for known prognostic factors (e.g, prior docetaxel (D) or enzalutamide (E) use, and sites of metastases (mets) specifically bone or lymph node versus liver or other viscera. Results: Of the 224 patients eligible for analysis, the majority (96%) had metastatic disease at time of AA initiation. 26% had prior D and 7% E. Nearly half were statin users (41%). The median duration on AA was 10.7 months (mo) with a trend to longer duration in statin users: 14.2 vs. 9.2 mo (HR 0.79, 95% CI: 0.57-1.09, p = 0.14). Prior D and E was significantly associated with shorter AA duration while site of mets and age were not. Adjusting for prior use of D, E, and site of mets did not alter the relationship between statin use and AA duration (p = 0.18, HR 0.81, 0.58-1.11). Conclusions: Contrary to our initial hypothesis, there was a trend to longer AA duration in statin users. Given our prior work demonstrating a 10 mo prolonged TTP on ADT in men concurrently taking statins (adjusted HR 0.83), and in vitro findings of inhibition of DHEAS uptake by statins, we postulate that there could be an additive effect of statins and AA by blocking DHEAS uptake. Alternatively, statins may inhibit hepatic AA uptake prolonging drug exposure and increasing effectiveness. Ongoing analyses are evaluating the impact of SLCO SNPs on AA efficacy.
Randomized comparisons of IL-6 and lean body mass between open versus laparoscopic distal gastrectomy for gastric cancer.
Authors: Takaki Yoshikawa, Tsutomu Hayashi, Toru Aoyama, Junya Shirai, Hirohito Fujikawa, Takashi Ogata, Haruhiko Cho, Takashi Oshima, Yasushi Rino, Munetaka Masuda, Akira Tsuburaya
Journal: Journal of Clinical Oncology (2013)

55 Background: Laparoscopic distal gastrectomy (LA) for gastric cancer may reduce breakdown of the muscle protein due to less surgical stress, compared with open surgery (OP). Methods: This study was performed as an exploratory analysis of a phase III trial comparing OP and LA for stage I gastric cancer in KCCH by limiting the period between May and Dec of 2011. IL-6 was measured before and 12 hours after surgery. Prealbumin and body composition were examined before and 7 days after surgery. %LBM was defined as percentile of LBM at 7 days to LBM before surgery. Values were expressed as median and range. Results: Twenty-seven patients were randomized to OP in 14 and LA in 13. Baseline: Body weight, LBM, prealbumin, and IL-6 were similar between both. Surgery and pathology D1/D1+/D2 lymph node dissections were 0/9/5 in OP and 0/9/4 in LA (p=0.785). Blood loss (g, range) and operation time (minutes, range) were 160 (50-475) and 174.5 (85-276) in OP, respectively, and 40 (5-270) and 267 (168-360) in LA, respectively, which were both significantly different (p=0.009 and 0005, respectively). Pathological T and N were similar between both. Morbidity and mortality: Any complications &gt; grade 2 defined by Clavien-Dindo classification were 2 (14.3%) including grade 3B anastomotic stenosis and 3A pancreatic fistula in OP and 1 (7.7%) grade 2 transient ischemic attack in LA (p=0.586). Measurements: IL-6 (pg/ml, range) after 12 hours was 36.3 (14.4-405.0) in OP and 53.3 (24.1-217.0) in LA (p=1.000). Prealubumin (mg/dl, range) was 17.3 (11.7-23.7) in OP and 17.8 (10.5-28.7) in LA (p=0.680). %LBM (range) was 96.9 (93-101) in OP and 96.5 (93-100) in LA (p=1.000). When excluding the patients who developed morbidity &gt; grade 2, IL-6 (range) was 32.1 (14.4-405.0) in OP and 49.5 (24.1-217.0) in LA (p=0.356). Prealubumin (mg/dl, range) was 17.7 (13.7-23.7) in OP and 17.8 (10.5-28.7) in LA (p=0.729). %LBM (range) was 97.1 (93-101) in OP and 97.2 (94-100) in LA (p=1.000). Conclusions: Laparoscopic approach has no impact on surgical stress and breakdown of the muscle protein after distal gastrectomy.
Efficacy of sorafenib in combination with gemcitabine and fluorouracil in metastatic renal-cell carcinoma: Preliminary result of a multicenter phase II study.
Authors: J. Guo, C. L. Cui, H. Chen, X. D. Xie, J. Chen, J. Liang, F. Li, T. S. Liu, Z. H. Chi, L. Si, X. N. Sheng, S. M. Li
Journal: Journal of Clinical Oncology (2011)

e15042 Background: To investigate the efficacy in terms of the overall response rate and progression-free survival (PFS) time of the combination of gemcitabine, fluorouracil, and sorafenib for metastatic renal cell carcinoma (RCC) in a multicenter phase II clinical trial. Methods: Patients were enrolled at seven centers across China between November 2008 and April 2010. Patients were aged 18 years or older, had confirmed metastatic RCC with clear-cell histology, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had not undergone previous therapy. Treatment consisted of intravenous gemcitabine 800 mg/m2 (days 1,15), fluorouracil 1250 mg/m2 civ 48h (days 1,15), Q28d, and oral sorafenib 400 mg twice a day (days 1-28), for four cycles, followed by sorafenib monotherapy. The primary endpoint was median PFS analyzed in a population of all patients who received treatment. Results: Fifty-four patients enrolled in the study, and 52 received treatment. Median age was 54.18±11.57, with MSKCC status of 0-2. The 6-month PFS rate has reached 56.25%; however, the median PFS was not reached. Partial response or stable disease were achieved in 23 patients (44%) and 28 patients (54%), respectively, with a disease control rate was 98%. The effect of dose escalation of sorafenib remained evident in patients with disease progression. Most adverse events were grade 1 or 2, and included hand-foot skin reaction (n=32), rash (n=24), diarrhea (n=23), fatigue (n=13), and hypertension (n=4). Grade 3 adverse events included hand-foot skin reaction in 8, thrombocytopenia in 1, and neutropenia in 13 patients. One patient terminated treatment prematurely due to pulmonary edema possibly related to study drug. Conclusions: Improved response rates and PFS were achieved with the regimen of sorafenib in combination with gemcitabine and fluorouracil as compared to that was observed after sorafenib monotherapy in patients with metastatic RCC. In addition, the combination was well tolerated. Longer follow-up is needed, and further investigation preferably in a randomized trial may be warranted.
Clinical Applications of the Genomic Landscape of Aggressive Non-Hodgkin Lymphoma
Authors: Andrea B. Moffitt, Sandeep S. Dave
Journal: Journal of Clinical Oncology (2017)

In this review, we examine the genomic landscapes of lymphomas that arise from B, T, and natural killer cells. Lymphomas represent a striking spectrum of clinical behaviors. Although some lymphomas are curable with standard therapy, the majority of the affected patients succumb to their disease. Here, the genetic underpinnings of these heterogeneous entities are reviewed. We consider B-cell lymphomas, including Burkitt lymphoma, diffuse large B-cell lymphoma, Hodgkin lymphoma, and primary mediastinal B-cell lymphoma. We also examine T-cell lymphomas, including anaplastic large-cell lymphoma, angioimmunoblastic T-cell lymphoma, cutaneous T-cell lymphoma, adult T-cell leukemia/lymphoma, and other peripheral T-cell lymphomas. Together, these malignancies make up most lymphomas diagnosed around the world. Genomic technologies, including microarrays and next-generation sequencing, have enabled a better understanding of the molecular underpinnings of these cancers. We describe the broad genomics findings that characterize these lymphoma types and discuss new therapeutic opportunities that arise from these findings.
Comparison of HER-2 expression in diagnostic biopsies and surgical specimens of gastric and esophageal adenocarcinoma: Influence of neoadjuvant chemotherapy.
Authors: Sarah Watson, Pierre Validire, Pascale Cervera, Nabila Zorkani, Aurelie Scriva, Frederic Lemay, Marie Line Garcia, Mostefa Bennamoun, Christophe Tournigand, Stanislas Ropert, Magali Svrcek, Christophe Louvet
Journal: Journal of Clinical Oncology (2013)

18 Background: HER-2 is overexpressed in 15 to 20% of gastric and esophageal adenocarcinoma (ADK), and is a target for trastuzumab in metastatic patients (Bang YJ et al, Lancet 2010). The main objective of this study was to compare HER-2 expression between diagnostic biopsies and surgical specimens of gastric ADK, and to determine the influence of non-trastuzumab containing neoadjuvant chemotherapy (NAC) on this expression. Methods: Pathological specimens and biopsies of patients operated on with a curative aim in two French hospitals (Institut Mutualiste Montsouris and Saint-Antoine hospital) between 2004 and 2011 were collected; two cohorts treated or not with a NAC were constituted. Blind HER-2 analyses on biopsies and on surgical specimens were performed using IHC and ISH methods, with two independent pathological readings. HER-2 overexpression was defined by a score 3+ in IHC, or by a score 2+ in IHC with a positive ISH test. Results: Paired samples of 201 patients wereanalyzed. HER-2 overexpression rates were 16.4% on biopsies and 19.4% on surgical specimens. HER-2 positive tumors were mainly cardial or esophageal tumors, with a well-differentiated, intestinal histological type. Surgical specimens seemed to allow better identification of HER-2 positive tumors than diagnostic biopsies for patients that had not received NAC (13.5% of HER-2 positivity on biopsies versus 24.3% on surgical specimens), whereas this trend was reversed for patients with NAC (18.1% of HER-2 positivity on biopsies versus 16.5% on surgical specimens). HER-2 status differed between biopsies and surgical specimens in 10% of patients. Conclusions: The determination of HER-2 status on biopsies provides results that completed those obtained with the analysis of surgical specimens. Analyzed only on surgical specimens, HER-2 status is underestimated in particular after NAC. This study suggests the interest of repeating HER-2 evaluations to optimize the identification of patients that can benefit from trastuzumab treatment.
Overcoming Resistance to 5-Azacytidine in Acute Myelogenous Leukemia
Authors: Piyanuch Sripayap, Tadashi Nagai, Mitsuyo Uesawa, Hiroyuki Kobayashi, Tomonori Tsukahara, Ken Ohmine, Kazuo Muroi, Gary Baley, Keiya Ozawa
Journal: Blood (2012)
Comprehensive genomic profiling of rare tumors in a dedicated community clinic.
Authors: William Jeffery Edenfield
Journal: Journal of Clinical Oncology (2015)

6540 Comprehensive genomic profiling of rare tumors in a dedicated community clinic W. Jeffery Edenfield1, Ryan Fields1, Siraj M. Ali2, W. Larry Gluck1, Julian Chmielecki2, Jeffrey S. Ross2, Phillip J. Stephens2, Vincent A. Miller2, Ki Chung1 1Greenville Health System Cancer Institute, Greenville,SC. 2Foundation Medicine, Boston, MA Background: Rare tumors by European Union (EU) definition are uncommon ( < 6/100,000 patients), but aggregately number more than all other solid cancers. With few prospective trials to guide treatment, therapy is based on minimum merit by case reports and small series. Comprehensive genomic profiling (CGP) may provide insight into tumor biology and identify rational therapeutic choice. Methods: In March 2014, the rare tumor clinic began evaluating 4-6 patients/month using CGP. DNA was extracted from 40 micron FFPE sections from 39 patients. All classes of genomic alterations were evaluated. Important alterations identified links to marketed drugs available or agents under evaluation in mechanism driven trials. Results: Patients were diverse. Of the 39, 6 each of biliary origin or sarcomas, 5 each neuroendocrine or glandular head and neck, and 3 mixed mullerian tumors. Nearly half had commercial drug options (18/39); 15/39 had available trial choices matched to their alteration. 61% of patients derived actionable information. 9 patients had both off-label and trial options. Marked clinical response to pazopanib in a patient with metastatic hemangioendothelioma and VHL mutation as well as a novel melanoma ALK-OTAF fusion will be reported separately. 3 potential germ line mutations were identified. Conclusions: CGP of tumors from 39 patients with rare cancers provided relevant information in the majority of cases. Although outcomes data are premature, this approach represents a reasonable standard for patients with rare cancers. The potential discovery of germline associated malignancy identifies the need for genetic consultation.
Long-term follow-up of advanced gastric cancer patients who achieved a pathologic complete response with neoadjuvant chemotherapy.
Authors: Haruhiko Cho, Takaki Yoshikawa
Journal: Journal of Clinical Oncology (2014)

133 Background: Adjuvant chemotherapy (AC) after D2 gastrectomy has become a standard treatment for stage 2/3 gastric cancer in Japan and Korea; however, the results remain unsatisfactory due to insufficient risk reduction in patients with stage 3 disease and low compliance. Although the administration of neoadjuvant chemotherapy (NAC) is a promising approach associated with a high rate of compliance and a downstage effect, the long-term survival benefits of this modality are unclear. Moreover, the impact of the pathological response on survival has not been evaluated. Based on the hypothesis that the pathological response grade is associated with survival, we conducted a search for reports of a pathological complete response (pCR) obtained with NAC. Methods: A total of 27 gastric cancer patients who achieved a pCR following NAC therapy were identified using PubMed and the Japanese medical search engine “Ichu-shi,” with the search words “gastric cancer,” “NAC,” and “pCR.” A questionnaire regarding the patients’ prognoses was posted in 23 institutions in Japan in July 2013. Results: Answers regarding 22 patients were obtained from 20 institutions. The subjects included 13 males and nine females. The mean age was 67.5 years. Tumors with stage 3/4 (95.4%: 21/22) and a diffuse-type histology (61.9%: 13/21) were dominant. S1/CDDP was the most frequently selected NAC regimen. A total of 77.2% (17/22) of the patients required combined resection of adjacent organs, and all patients underwent R0 resection and D2 lymphadenectomy. At present, 86.3% (19/22) of the patients are alive without recurrence; none of the ten patients who received postoperative AC demonstrated any recurrence, while three of twelve patients who did not receive postoperative AC developed recurrence, and two patients died of the disease after surgery (at 71 months and nine months, respectively). The overall and recurrence-free survival rates at three/five years were 95.5%/85.1% and 90.9%/75.1%, respectively. Conclusions: Patients with gastric cancer who achieve a pCR with NAC are rare; however, their prognoses are excellent. It is therefore important to develop a NAC regimen focusing on a high pCR rate.
Molecular characterization of primary breast cancer in older women using partitional clustering and correlation with long-term clinical outcome.
Authors: B. M. Syed, A. R. Green, D. Soria, E. C. Paish, J. Garibaldi, D. A. L. Morgan, I. O. Ellis, K. Cheung
Journal: Journal of Clinical Oncology (2011)

10549 Background: Recent advances in molecular classification of breast cancer have given more insights into management strategies and outcome. However, most of the reported studies are focused on younger patients. We now report its application in a series of older women managed in a single centre with long-term follow-up. Methods: Over 36 years (1973-2009), 2,000+ older (≥70 years) women with early operable primary breast cancer were managed in a dedicated clinic. Of these 831 underwent surgery as primary therapy (and received adjuvant therapies as per unit protocol at the time of diagnosis) and 575 had good quality tumour samples available for tissue microarray (TMA) analysis using indirect immunohistochemistry. H-scores of 19 markers (ER, PR, HER2, Ki67, p53, CK5,5/6,7/8,14,17,18,19, EGFR, bcl2, E-Cadherin, MUC1, CD44, HER3, HER4) were clustered using R (2.11.1, USA). Results: Unsupervised clustering showed 6 clusters. Following identification of their main drivers, 12 markers were selected and the same 6 clusters were reproduced, using K-means and Partitioning Around Medoids (PAM) methods, in 367 patients. Using Predictive Analytics Software (PASW 18, Chicago, Illinois), the following correlation with their clinical outcome was obtained, at a median follow-up of 60 months (longest=106) (Table). Conclusions: When compared with known molecular classification, the cluster with low hormone receptors and high luminal cytokeratins (“low ER luminal”) appears unique to older women, associated with different clinical outcome. Cluster (N/%) Pattern of key markers Breast cancer-specific survival Hormone receptors Luminal markers Basal markers p53 and HER2 5-year (%) 10-year (%) Luminal A (139/37.9) High High Low Low 95 76 Luminal B (92/25.1) ER=High PR=Low High Low Low 90 68 “Low ER luminal” (56/15.3) Low High Low Low 83 63 Basal (30/8.2) Low CK18=Low CK19=High CK7/8=Moderate High p53=High HER2=Low 73 73 Normal like (22/6.0) Low Low Low Low 84 47 HER2 overexpressive (28/7.6) Low High Low High 73 65
A phase II study of Chinese patients (pts) treated with <i>nab</i>-paclitaxel (<i>nab</i>-P) plus gemcitabine (Gem) for metastatic pancreatic cancer (MPC).
Authors: Lin Shen, Xianjun Yu, Jihui Hao, Liwei Wang, Hongming Pan, Guohong Han, Jian-Ming Xu, Yanqiao Zhang, Shujun Yang, Jia Chen, Jieer Ying, Guanghai Dai, Mingyu Li, Damir Begic, Brian D. Lu, Ruihua Xu
Journal: Journal of Clinical Oncology (2016)

327 Background: nab-P + Gem demonstrated significantly better overall survival (OS; median: 8.7 vs 6.6 mo; HR 0.72; P &lt; 0.001) than Gem alone as first-line treatment for pts with MPC in the MPACT study. This phase II bridging study evaluated efficacy and safety of nab-P + Gem in Chinese pts with MPC. Methods: Efficacy and safety of nab-P 125 mg/m 2 + Gem 1000 mg/m 2 on days 1, 8, and 15 every 4 weeks was evaluated in a 3-part sequential study. In part 1, safety was examined. In part 2, efficacy was evaluated by the Simon optimal 2-stage design. If there were &gt; 2 responses in 28 pts in stage 1 of part 2, an additional 54 pts would be treated in stage 2. The study would be completed if &gt; 9 responses were observed. If there was an insufficient number of responses in either stage of part 2, part 3 would be triggered to compare nab-P + Gem vs Gem alone. The primary endpoint was overall response rate (ORR). Secondary endpoints included duration of response (DOR), OS, and safety. Correlation of OS and baseline neutrophil-to-lymphocyte ratio (NLR) was also analyzed. Results: Eighty-three pts were treated. Median age was 57.0 y; 19% were aged &gt; 65 y; baseline Karnofsky performance status was 90 - 100 in 70% of pts and 70 - 80 in 30%. Combining results for stages 1 and 2, ORR was 35% by independent assessment, median DOR was 8.9 mo (95% CI, 6.01 - 8.94), median OS and PFS were 9.2 mo (95% CI, 7.60 - 11.10) and 5.5 mo (95% CI, 5.29 - 7.16), respectively (Table). Baseline NLR ≤ 5 was associated with a nonsignificant trend toward longer OS vs NLR &gt; 5 (median, 10.0 vs 8.3 mo; HR 0.62; P= 0.148). The most common grade ≥ 3 adverse events included neutropenia (37%), leukopenia (31%), and fatigue (14%). Grade ≥ 3 peripheral neuropathy occurred in 7% of pts. Part 3 was not triggered per study design. Conclusions: nab-P + Gem demonstrated efficacy in Chinese pts with MPC. The OS and ORR were numerically better than those of the phase III MPACT trial (Table). A trend toward longer OS in pts with baseline NLR ≤ 5 vs &gt; 5 confirmed previous findings from the MPACT study. No new safety signals were identified. Clinical trial information: NCT02135822. [Table: see text]
Randomized, multicenter phase II trial of CAP7.1 in patients with advanced biliary tract cancers.
Authors: Ulrich-Frank Pape, Stefan Kasper, Marianne Sinn, Karel Caca, Jan Kuhlmann, Ulrich Keilholz, Arndt Vogel, Nalan Utku
Journal: Journal of Clinical Oncology (2016)

441 Background: Non-resectable biliary tract cancers (BTC) have poor prognosis, but are chemosensitive. CAP7.1 is a new chemical entity that releases etoposide in the presence of carboxylesterases, leading to higher intra-tumor etoposide (E) with improved safety and efficacy. Methods: The primary objective of this trial is to determine the rate of disease control (DCR) (stable disease, SD; partial response, PR and complete response, CR) according to Recist 1.1. of CAP7.1 in patients (pts) with BTC. Secondary objectives are progression free survival (PFS), overall survival (OS) and safety. Pts with adenocarcinoma arising from bile ducts or gallbladder were randomized (1:1) to either CAP7.1 or best supportive care (BSC) group (institutional palliative treatment). Pts in CAP7.1 arm subjected to a 3-week cyle (cy) with CAP7.1 on days 1-5 in 3-week cy was given with either 200 or 150mg/m2. until progression. At progression BSC pts were allowed to cross over to CAP7.1. Safety was assessed with CTCAE v 3.0 and efficacy after 2 cy of treatment. 18 /50 pts (9 in each study arm) finalized 1st stage and analyzed for efficacy and safety. Results: DCR in the CAP7.1 arm was 56%, with 5/9 of pts with SD (including tumor shrinkages), while all pts in the BSC arm progressed. The median PFS time was 3.5 months (95% CI, 1.9 to 8.4 months) in the CAP7.1 arm. 5 pts crossed over to the CAP7.1 arm. 2/3 pts continued CAP7.1 treatment up to 5 and 8 cycles as SD, respectively, while one pts achieved PR. The median OS time from first treatment with CAP7.1 was 5.9 months (95% CI, 2.6 to 15.3 months) over all evaluable pts, including BSC after crossing to CAP7.1. Commonly observed drug related adverse events (AE) are hematoxicity/myeolosuppression, various events of infection, alopecia, fatigue, nausea and abdominal pain, which were in general well managed. G3-4 neutropenia occurred in 4/10 pt at a dose of 150 mg/m²/d and in 6/11 pts at 200 mg/ m2/d; uncomplicated g 3-4 thrombocytopenia occurred in 2/11 pt at 200 and in 1/10 at 150 mg/ m2/d. Non-hematological AE were mainly mild or moderate e.g. abdominal pain and alopecia as most frequent AEs. Conclusions: CAP7.1 showed promising activity in therapy refractory advanced BTC patients.