tbuckley/cabot-search huggingface dataset:
Interim results of a multicenter phase II trial of <i>nab</i>-paclitaxel (<i>nab</i>-P) plus gemcitabine (G) for patients (Pts) with locally advanced pancreatic cancer (LAPC).
Authors: Jill Lacy, Fabienne Portales, Pascal Hammel, Roberto A. Pazo Cid, Jose Luis Manzano Mozo, Edward Jae-hoon Kim, Scot D. Dowden, Christophe Borg, Javier Sastre, Venu Gopal Bathini, Eric Terrebonne, Daniel Lopez-Trabada, Fernando Rivera, Jamil Asselah, Azzurra Damiani, Jimmy J. Hwang, Teng Jin Ong, Thom Nydam, Jack Shiansong Li, Philip Agop Philip
Journal: Journal of Clinical Oncology (2017)

358 Background: Treatment options for pts with LAPC are limited and generally similar to those for metastatic PC (mPC). The phase 3 MPACT trial of pts with mPC demonstrated a &gt; 3-fold shrinkage of primary tumors with nab-P + G vs G, suggesting the potential of nab-P + G for LAPC treatment. Here, we present interim results on disease control rate (DCR), adverse events (AEs), and quality of life (QoL) from the international phase 2 LAPACT trial. Methods: Pts with treatment-naive unresectable LAPC and ECOG performance status of 0 or 1 received 6 cycles (C) of nab-P 125 mg/m 2 + G 1000 mg/m 2 on days 1, 8, and 15 of each 28-day C. After the initial nab-P + G treatment phase, pts without PD and unacceptable AEs were eligible for investigator’s choice (IC) of continued treatment with nab-P + G, chemoradiation, or surgery. Surgery could occur prior to completing 6 C in the case of a major response. Pt-reported QoL was assessed via EORTC QLQ-C30 and QLQ-PAN26 questionnaires at screening and prior to infusion on day 1 of each C. Results: As of Aug 17, 2016, 47 pts completed (28/47, 60%) or discontinued (19/47, 40%) the initial nab-P + G treatment (median, 5 C). Median age was 66 years (range, 44 - 86). The most frequent reasons for discontinuation were AE (10/47 [21%], with the most common being neutropenia and abnormal liver function [2 pts each]) and PD (3/47, 6%). The most common grade ≥ 3 AEs were neutropenia (34%) and anemia (11%). The DCR ≥ 16 weeks was 76% (34/45 efficacy-evaluable pts [defined as having evaluable baseline and ≥ 1 postbaseline scan]; PR, n = 13; SD, n = 21). Twenty-two pts (47%) were assigned by the investigators to an IC treatment: 4 (9%) to continue nab-P + G, 8 (17%) to chemoradiation, and 10 (21%) to surgical resection. Mean QoL scores remained stable during the study, with improved symptom scores for appetite and pain. During the initial nab-P + G treatment phase, most patients reported a complete resolution of certain limitations, including depression (≈ 80%), constipation (≈ 62%), and nausea (≈ 93%). Conclusions: These interim results suggest that for pts with LAPC, nab-P + G is tolerable and produces a promising DCR. On average, QoL scores remained stable during nab-P + G treatments. Clinical trial information: NCT02301143.
Erratum: Mutations in GDI1 are responsible for X-linked non-specific mental retardation (Nature Genetics (1998) 19 (134-139))
Authors: P. D'Adamo, A. Menegon, C. L. Nigro, M. Grasso, M. Gulisano, F. Tamanini, T. Bienvenu, A. K. Gedeon, B. Oostra, S. K. Wu, A. Tandon, F. Valtorta, W. E. Batch, J. Chelly, D. Toniolo
Journal: Nature Genetics (1998)
Results of the prospective T-DIS randomized phase II trial comparing interruption versus continuation of trabectedin after six cycles of treatment in patients (pts) with advanced soft tissue sarcoma (ASTS).
Authors: Axel Le Cesne, Jean-Yves Blay, Thomas Ryckewaert, Christine Chevreau, François Bertucci, Corinne Delcambre, Esma Saada, Sophie Piperno-Neumann, Jacques-Olivier Bay, Julien Domont, Isabelle Laure Ray-Coquard, Thibaud Valentin, Emmanuelle Tresch, Stephanie Clisant, Nadia Badri, Nicolas Penel
Journal: Journal of Clinical Oncology (2014)

10523 Background: Trabectedin (T) maintenance beyond 6 cycles (cy) of treatment in responding pts with ASTS is associated with improved outcomes (Retrospective on database analysis; ASCO 2013). Herein, the impact of T discontinuation on progression-free survival (PFS) and overall survival (OS) was prospectively analyzed by the French Sarcoma Group in a national non-comparative randomized phase II trial. Methods: After the initial 6 cy of T (1.5 mg/m² as 24-h infusion every 3 weeks), pts free from progressive disease (PD) were randomly assigned either to continuous treatment (C arm) or therapy interruption (I arm) with T. Pts who declined randomization could continue with T. Pts allocated to the I arm could restart T in case of PD. Primary endpoint was PFS rate at 6 months (m) weeks after randomization. Results: FromFebruary 2011 to March 2013, 178 pretreated pts have been enrolled. At inclusion, the pts had a median age of 57.5 years (range19-82) and a median performance status of 1 (range 0-3) and most had leiomyosarcoma (30%), liposarcoma (18%) or synovial sarcoma (12%). Among evaluable pts (n=178), the rate of non-progression after the initial 6 cycles of T was higher than expected (29.7%). After 6 cy of T, 27 and 26 non progressive pts were randomized to C and I arm, respectively (30% of included pts). After randomization, a median number of T cy were similar in both arms: 5 (range 2-17) for C arm and 5 (range 1-12) for I arm. In December 2013, the median PFS after randomization was 7.2 m in C and 3.7 m in I arm (p=0.05), respectively, with the 6-m PFS of 50% and 16% for C and I arm. The 12-m OS rate after randomization was 86% (62.4-95.3) and 74% (44.1-89.2) for C and I arm, respectively. T has been reintroduced in 19/21 pts who progressed in I arm. Conclusions: The rate of non-progression after 6 cycles of T was higher than previously reported, probably due to a better selection of ASTS pts in referral centers and a better management of T. Interruption of T resulted in a rapid PD in the vast majority of pts, independently of the response achieved after initial 6 cy of T. Therefore, T treatment has to be given until PD, intolerance or patient refusal. Clinical trial information: 2010-022613-26.
Impact of metformin on prostate cancer (PC) outcomes in the E3805 CHAARTED trial.
Authors: David Frazier Jarrard, Yu-Hui Chen, Glenn Liu, Michael Anthony Carducci, Mario A. Eisenberger, Yu-Ning Wong, Noah M. Hahn, Manish Kohli, Matthew M. Cooney, Robert Dreicer, Nicholas J. Vogelzang, Joel Picus, Daniel H. Shevrin, Maha Hussain, Jorge A. Garcia, Robert S. DiPaola, Christopher Sweeney
Journal: Journal of Clinical Oncology (2017)

181 Background: To evaluate whether metformin (Met) a widely-used, nontoxic oral antidiabetic drug with putative anticancer properties leads to improvements in prostate cancer (PC) outcomes in the CHAARTED trial. Methods: In the CHAARTED database where metformin use at baseline was recorded prospectively, we identified patients with metastatic PC who underwent either ADT alone or ADT and docetaxel (D) chemotherapy. Cox proportional hazards models were used to determine the effect of Metformin on outcomes. Results: A total of 788 patients (median age, 63 y) had complete data after randomization. Comparison of ADT+D+Met (n = 39) to ADT+D (n = 357) and ADT+Met (n = 29) to ADT alone (n = 363) revealed similar clinicopathologic characteristics. Cause of death was PC in 13(81%) of ADT+D+Met, 72(85%) ADT+D, 9(82%) ADT+Met and 105(84%) ADT alone groups. See table for PC outcomes and overall survival by metformin use. Cox regression analysis for overall survival stratified by stratification factors at randomization demonstrates Met use was associated with a trend for worse overall survival (HR 1.47 95%CI: [0.95,2.26], p = 0.08) with adjustment for treatment arm and prior local therapy. In contrast, ADT+D use (HR 0.62; 95%CI: [0.47,0.81]) and prior local therapy with surgery or radiation (HR 0.56; 95% CI: [0.38, 0.82]) were associated with improved survival. Conclusions: In this study, baseline metformin did not improve PC outcomes. Partial support and drug supply by Sanofi. Clinical trial information: NCT00309985. [Table: see text]
Expression of COX-2 and 15-PGDH in adenomas removed during pretreatment colonoscopy to predict chemopreventive efficacy of the selective COX-2 inhibitor, celecoxib.
Authors: Jiping Wang, Nancy L Cho, Ann G. Zauber, Meier Hsu, Dawn Dawson, Amitabh Srivastava, Kisha Mitchell-Richards, Sanford D. Markowitz, Monica M. Bertagnolli
Journal: Journal of Clinical Oncology (2017)

524 Background: The APC trial showed that patients at high risk for colorectal adenoma development experienced a 33-45% reduction in post-polypectomy adenoma detection when treated with the selective cyclooxygenase-2 (cox-2) inhibitor, celecoxib. Unfortunately, this study also found a small increased risk of cardiovascular toxicity among celecoxib users, preventing broad use of this agent for chemoprevention. Celecoxib inhibits expression of prostaglandin E 2 (PGE 2 ), an inflammatory mediator produced by fatty acid metabolism via cyclooxygenases, and degraded through the activity of 15-prostaglandin dehydrogenase (15-PGDH). Methods: Adenomas collected from APC trial participants prior to treatment were examined using immunohistochemistry (IHC) to assess expression of cox-2 (high vs. low) and 15-PGDH (present vs. absent). A combined variable to estimate tumor PGE 2 levels identified cases as PGE 2 low (Cox-2 low/15-PGDH present) or PGE 2 high (Cox-2 high/15-PGDH present; Cox-2 high/15-PGDH absent; or Cox-2 low/15-PGDH absent). Mantel–Cox test was used to evaluate whether markers of PGE 2 expression in these adenomas predicted benefit from celecoxib treatment for the primary study outcome of adenoma detection. Results: Biomarker determinations were achieved for 1295 cases, or 71% of patients with available outcome data. Patients whose baseline adenomas demonstrated elevated Cox-2 achieved the greatest overall reduction in adenoma risk with celecoxib treatment (RR 0.37; p = 0.0001). This risk reduction was less significant in the low Cox-2 category (RR 0.64). Patients with low estimated tumor PGE 2 did not benefit from celecoxib for adenoma prevention (RR 0.95; p = 0.83). This is compared to a 41% reduction in adenoma detection with celecoxib treatment for patients in the high PGE 2 category (RR 0.59; p &lt; 0.0001). Conclusions: IHC to determine expression of target enzymes in pre-malignant adenomas provides significant prognostic and predictive information in patients treated with celecoxib for prevention of colorectal adenomas.
Predictors of bilateral central neck lymph node dissection in unilateral papillary thyroid carcinoma.
Authors: Rui Chen, Jingqiang Zhu, Tao Wei, Rixiang Gong, Zhihui Li, Xiuhe Zou, Feng Liu, Yu Ma
Journal: Journal of Clinical Oncology (2014)

e17012 Background: Study the predictors of bilateral central neck lymph node dissection (CND) in papillary thyroid carcinoma (PTC). Methods: A total of 322 patients (67 males and 265 females) with unilateral PTC who underwent total thyroidectomy (TT) and bilateral CND from West China Hospital of Sichuan University from June 2008 to June 2011were analyzed retrospectively. The median age at diagnosis was 43.3±12.7 years (ranging from 8 to 79 years). All patients had a preoperative diagnosis of PTC without clinically evident positive lymph nodes (LN) by ultrasonography, and 160 patients had underwent modified radicalneck dissection (MRND) at the same time. Results: One hundred and ninety-one (57.5%) of 332 patients had central neck lymph node metastatic including123 ipsilateral and 68 bilateral. CND upstage 76 patients in the present cohort, and modified the indication for radioiodine treatment in 20% of patients initially staged as T1N0.The bilateral central neck lymph node(CLN) metastases was significantly associated with the size of primary(>1cm) (P<.001), capsular invasion (P<.001), Pretracheal LN metastasis(P<.001), lateral LN metastasis(P<.001) and ipsilateral CLN metastasis (P<.001). Age, sex and tumor location were not found to be associated with bilateral CLN metastases. In multivariate analysis, the size of primary(>1cm)(P=0.013), capsular invasion (P=0.009), pretracheal LN metastasis(P=0.021) and lateral LN metastasis (P=0.002) were independent predictors of bilateral CLN metastases. Conclusions: Bilateral CND should be considered for PTC patients with the size of primary>1cm, capsular invasion, pretracheal LN metastasis and lateral LN metastasis.
Serial evaluation of lymphocyte subsets in patients with newly diagnosed high grade gliomas treated with standard radiation and temozolomide.
Authors: Anna F. Piotrowski, Jian Li Campian, Frances Hakim, Jeremy Rose, Xiao-Yi Yan, Ronald Gress, Stuart A. Grossman
Journal: Journal of Clinical Oncology (2015)

e22116 Background: The immune system plays a significant role in cancer prevention and outcome. In high grade gliomas (HGG), severe lymphopenia is associated with shortened survival due to tumor progression. Here we report the first comprehensive study of serial changes in lymphocyte subsets in HGG following standard radiation (RT) and temozolomide (TMZ). Methods: Adults (KPS > 60, HIV negative) with newly diagnosed HGG scheduled to receive standard RT and TMZ followed by adjuvant TMZ were eligible. Lymphocyte subsets were assessed by flow cytometry before beginning therapy and at weeks 6, 10, 18, and 26, and 3 months after completing adjuvant TMZ. Results: All 20 patients have enrolled. Their median age is 53 years; baseline dexamethasone dose is 0.5 mg/day, and follow-up time is 6.5 months. 15% had lymphocyte counts < 1000 cells/mm3 before starting therapy. As noted below the most significant T-cell reductions were in naïve CD4+ (60%) and CD4+ (49%) cells. Recovery in these subsets was not evident at 26 weeks. CD8, Tregs, CD3, CD8 effector, and NK cells were less affected. B cells were also markedly reduced. The CD4+/CD8+ ratio fell after RT/TMZ and remained low. Conclusions: This is the first study to report serial trends in T lymphocytes following RT+TMZ. CD4+ and naïve CD4+ T cells appear most affected. This data provides insight into potential therapeutic approaches (i.e. IL-7) and the optimal timing for immunologic interventions in this patient population. Lymphocyte subset Median cell counts (cells/mm3) % reduction week 0-26 P value Week 0 Week 10 Week 26 CD45RA+CD4+ Naive 214 63 86 60 0.008 CD4+ 755 323 382 49 0.007 CD8+ 368 248 238 35 0.395 Treg 64 22 47 27 0.067 ALC 1665 915 1240 26 0.029 CD3+ 1172 604 885 24 0.023 CD4+/CD8+ ratio 1.8 1.4 1.4 22 0.017 CD8+ effector 102 60 105 0 0.754 NK cell 154 119 124 19 0.130 B cell 173 63 62 64 0.013
The Human Cathelicidin Antimicrobial Peptide (CAMP) Gene Is a Direct Target of the Vitamin D Receptor and Is Strongly Upregulated in Myeloid Cells by 1,25(OH)2D3 Treatment.
Authors: Adrian F. Gombart, Ook Kim, Dih-Yen Chen, Niels Borregaard, H. Phillip Koeffler
Journal: Blood (2004)
Evolution of number of lymph nodes identified by pathology in colorectal cancer from 1998-2010: A review of the National Cancer Data Base.
Authors: Sukamal Saha, Lindsay Berbiglia, Michael Hicks, Jill Gernand, Mohammed Shaik, Gerard Paez, Madan L. Arora, David Wiese
Journal: Journal of Clinical Oncology (2015)

e14633 Background: The most important prognostic criterion for treatment planning in colorectal cancer (CRCa) is the lymph nodes (LN) status, making LN yield (LNY) critical for accurate staging. In 2007, a national consensus of minimal LNY of 12 was established. Hence, we analyzed the National Cancer Data Base (NCDB) to determine the trend of LNY and LN status for CRCa patients (pts) before and after the consensus was established. Methods: From 1998-2010, 295,554 colon (C) Ca and 56,913 rectal (R) Ca pts from NCDB were analyzed. Data included year of diagnosis, LNY, LN status, surgery, neoadjuvant treatment (NeoAdj) and survival. Statistical significance was evaluated using Spearmans’s rho correlation coefficient. All pts with inadequate data and without surgery were excluded. Results: From 1998 – 2010, for both CCa and RCa pts, LNY progressively increased with average LNY in 1998 12.57 vs 18.54 in 2010 for CCa and 11.02 vs 14.98 for RCa. After NeoAdj for RCa, the LNY was decreased, but the trend of higher LNY over time persisted, 7.85 in 1998 vs 14.25 in 2010 for NeoAdj and 11.57 in 1998 vs 16.99 in 2010 for no NeoAdj. Increased LNY correlated with increased LN positivity in both CCa (rho 0.2796, p-value <0.001) and RCa (rho 0.2799, p-avlue <0.001). (Table) Conclusions: From 1998-2010, LNY and LN positivity in CRCa steadily increased across the country, suggesting better staging. Further prospective study should be done to find its effect on survival. Correlation between LNY and LN positivity over time in NCDB CRCa patients. Year of Diagnosis Colon Cancer Rectal Cancer Avg No LN examined Avg No Positive LN Avg No LN examined Avg No Positive LN 1998 12.57 3.87 11.02 4.13 1999 12.68 3.93 11.01 4.06 2000 12.95 3.85 11.09 4.20 2001 13.29 3.89 11.34 4.24 2002 13.76 3.97 11.45 3.93 2003 13.17 5.37 11.20 4.01 2004 13.54 5.88 11.90 4.02 2005 14.30 5.85 12.09 4.16 2006 15.39 6.24 13.45 4.20 2007 17.21 6.44 14.32 4.22 2008 17.84 6.6 14.80 4.28 2009 18.36 6.57 14.79 4.32 2010 18.54 5.81 14.98 4.02 rho/p-value year vs. no LN examined: 0.1836/<0.001 0.1989/<0.001 rho/p-value year vs. LN positivity: 0.1850/<0.001 0.0030/0.6235 rho/p-value no LN examined vs. LN positivity: 0.2796/<0.001 0.2799/<0.001
Retrospective analysis of gene expression profiling and TTF-1 staining in cancer of unknown primary (CUP).
Authors: Wendy M. Chiang, Gary M. Strauss, J. Scott Nystrom
Journal: Journal of Clinical Oncology (2012)

10579 Background: CUP involves extensive use of immunohistochemical (IHC) stains because no individual marker is highly both site specific or sensitive. IHC algorithms lack standardization and may even eliminate actual primary sites. Extensive validation studies with gene expression profiling (GEP) has shown it be a new diagnostic technique that further contributes tumor site location in CUP. Thyroid transcription factor-1 (TTF-1) IHC stain is commonly used to identify the pulmonary origin of CUP (particularly adenocarcinoma) and is often used to exclude lung primary in CUP patients. This study evaluates the utility of TTF-1 staining in lung primaries (specifically non-small cell lung carcinoma - NSCLC) of CUP to GEP testing. Methods: This retrospective study contains data obtained from a registry of physicians who received the GEP-based Tissue of Origin (TOO) test (Pathwork Diagnostic, Sunnyvale, CA) between 07/2009 and 12/2009 on CUP cases. Sixty-six physicians contributed 111 TOO test cases. Only cases that had TTF-1 done were included for analysis and these were compared to TOO NSCLC results. Results: Out of 111 cases, there were 73 analyzable TTF-1 results with 12 cases of NSCLC and 61 cases of non-NSCLC by TOO (see TABLE). Assuming that the results of TOO testing accurately indicated the true primary site, the sensitivity and specificity of TTF-1 was 50% and 90%, respectively. The false negative rate was 50%, indicating that half of the identified NSCLC cases in this series had negative TTF-1. On the other hand, 10% of the 61 cases with primaries other than NSCLC (none of whom had thyroid cancer), had positive TTF-1. The “false positive” TTF-1 cases comprised 4 ovarian, 1 breast and 1 colorectal as the site of origin. Conclusions: TTF-1 has limited utility in identifying NSCLC in the setting of CUP. Half of NSCLCs identified by TOO testing had negative TTF-1, and 10% of non-lung primaries were TTF-1 positive. Negative TTF-1 should not be used to exclude NSCLC in the workup of CUP. [Table: see text]
MiRNA profiling by NGS in resectable non-small cell lung cancer: Prognostic implications.
Authors: Sandra Gallach, Eloisa Jantus-Lewintre, Silvia Calabuig, David Montaner, Marta Usó, Elena Sanmartin, Rafael Sirera, Ana Blasco, Ricardo Guijarro, Miguel Martorell, Carlos Camps
Journal: Journal of Clinical Oncology (2014)

7559 Background: MicroRNAs (miRNA) regulate gene expression, and are implicated in several processes like tumorogenesis. Here, we applied a multiplexed NGS approach to study differentially expressed miRNAs (tumor/ normal) in a cohort of resectable NSCLC patients and its correlation with clinical outcome. Methods: RNA was isolated from frozen lung specimens (tumor/ normal) from 33 patients. High-quality samples were analyzed and enriched in the miRNA fraction. Libraries were prepared according to manufactured instruction (SOLID), and miRNAs were sequenced. Data analysis was carried out using CLCbio software. First, raw data were annotated using miRBase and normalized by total reads followed by differential expression analysis. Results validation were performed by RTqPCR in an independent cohort (n= 195). Functional studies of differentially expressed miRNAS were done using in silico tools. Statistical significance was considered at p<0.05. Results: 28 miRNAs were significantly up-regulated and 11 were down-regulated in tumor samples compared with normal lung. Most of them were validated by RTqPCR in an independent cohort of samples obtaining the same results (Wilcoxon test). Survival analysis were done for those validated miRNAs. We found that patients with overexpression (2.0X tumor/ normal) of miR21, miR196b and miR188-5p had worse clinical outcome (Table). In silico functional studies showed several GO terms and KEGG pathways related to cell cycle, apoptosis, angiogenesis, among others, that were significantly overrepresented among the miRNAs differentially expressed in NSCLC. Conclusions: 25 miRNAs were found differentially expressed and validated in NSCLC. These miRNAs were found to regulate important KEGG and GO process involved in carcinogenesis. Prognostic analysis showed that higher levels of miR21, miR196b and miR188-5p were related to shorter PFS and OS in our cohort of resectable NSCLC. PFS OS Median Survival (months) p Median Survival (months) p miR188-5p (high vs low) 22.1 - 81.2 0.005 42.6 - NR 0.015 miR196b (high vs low) 25.6 - NR 0.031 42.6 - NR 0.006 miR21 (high vs low) 37.9 - NR 0.015 81.2 - NR 0.023