tbuckley/cabot-search huggingface dataset:
Systemic or hepatic arterial chemotherapy after curative resection of liver metastases from colorectal cancer. A meta-analysis of randomized controlled trials
Authors: P. Mariani, G. Des Guetz, B. Uzzan, P. Nicolas, K. Chouahnia, T. Bouillet, G. Perret, J. Morère
Journal: Journal of Clinical Oncology (2008)

4077 Background: Curative treatment of liver metastases from colorectal cancer (CRC) relies upon R0 surgery whenever feasible (5-year survival: 40 %). Whether or not addition of adjuvant systemic or hepatic arterial chemotherapy (CT) (5FU) to surgery improves survival (Overall Survival OS or Relapse Free Survival RFS) is still debated. Therefore, we performed a meta-analysis (MA) of all published randomized controlled trials (RCTs). Methods: PubMed query using several key-words simultaneously (CRC, liver metastases, curative surgery, CT, RCT). Cross-checking of references from all studies, reviews and MAs. Software: EasyMA available online). Participants: Our MA included 9 RCTs, representing 1147 patients (mean age: 61.4 years, range 25–79; 602 men, 369 women, 176 missing data; 264 colon, 225 rectum, 658 missing data). Results: Our MAs used a fixed-effect model, since there was no statistically significant heterogeneity between studies. Both OS and RFS significantly improved by addition of adjuvant or neo-adjuvant CT to surgery: HR OS = 0.81 (95 % CI: 0.67- 0.99; p = 0.04) and HR RFS = 0.84 (95 % CI: 0.75–0.94; p = 0.003). Five RCTs (443 patients) used intra-arterial CT (some were very small). Their results were similar to those of the 2 larger RCTs assessing systemic CT. The most recent multicenter RCT included in our MA (Nordlinger, 2007) used systemic CT (FOLFOX 4) and showed a trend towards a better RFS after surgery + CT (35.4 % vs 28.1 %; HR RFS = 0.79 [95 % CI: 0.62–1.02; p = 0.058]). A second recent RCT using 5FU IV bolus (Portier 2006) also showed that CT significantly improved RFS (but not OS). Jointly, these 2 RCTs included 537 patients (47 % of the global population). Conclusions: Addition of adjuvant CT to curative R0 surgery for liver metastases from CRC significantly improved OS and RFS. These encouraging results should be interpreted cautiously since they are based upon nine RCTs. The methodological quality of RCTs dealing with this issue considerably improved recently. The number of patients included in each RCT sharply increased. New RCTs of good quality are needed to draw more definite conclusions. No significant financial relationships to disclose.
Stratification of risk for patients with prostate cancer at biopsy using CCP score.
Authors: Neal D. Shore, Brian Abbott, Raoul S. Concepcion, Daniel Saltzstein, Rajesh R. Kaldate, Kelsey Moyes, Arletta van Breda, Christopher Clark, Jennifer Saam, Michael K. Brawer
Journal: Journal of Clinical Oncology (2013)

127 Background: In the US, most prostate cancers are treated with surgery or radiation, despite many having low malignant potential. If low cancer progression risk can be established, some men can be spared treatment. PSA, Gleason score and clinical stage work well for population risk assessment but lack precision for individuals. Molecular analysis can refine risk assessment as demonstrated by a cell cycle progression score (CCP) predictive of prostate cancer aggressiveness in 4 separate cohorts. In these studies, CCP typically ranged from −2 to +3 with each 1−unit increase corresponding to approximately a doubling of risk. We characterized the CCP distribution using recent samples from a typical US urology multi−centered clinical setting and determined the analytic success rate of the assay. Methods: Formalin fixed, prostate biopsy tissue from 300 patients diagnosed with adenocarcinoma within the last 12 months was analyzed. CCP is calculated by measuring the relative RNA expression of 31 cell cycle progression genes. Patients were recruited from 15 geographically diverse community urology practices. Results: CCP could be measured for 98% of samples (294/300). This study showed a normal distribution for the CCP ranging from −2 to 3.2 (median = −0.3, SD=0.92). There was little correlation of CCP with PSA, age, or body mass index. Correlation with Gleason score was similar to those in prior studies (r=0.494). A relative classification of cancer aggressiveness based on CCP of ~ 1200 patients from multiple cohorts has been developed. The 294 evaluable patients were cross−classified by AUA risk and cancer aggressiveness (see table). CCP further stratified patients within each AUA risk classification. Conclusions: CCP is a novel assay that can facilitate risk stratification for men with prostate adenocarcinoma. [Table: see text]
Clinical results at 3 years of the ACCORD 12 randomized trial in rectal cancer.
Authors: Jean-Pierre Gérard, David Azria, Sophie Gourgou-Bourgade, Thierry Conroy, Laurent Bedenne
Journal: Journal of Clinical Oncology (2012)

389 Background: The main end point of this trial was pathological response and published in 2010. We present the main clinical outcome after 3 years follow up. Methods: A total of 598 patients were included by 56 different French institutions between 2005 and 2008. Inclusion criteria were: resectable rectal adenocarcinoma accessible to digital examination and staged T3,4 Nx M0. Low anterior T2 were also eligible.Two neoadjuvant treatments were compared: CAP 45 (Radiotherapy 45 Gy/5 weeks with concurrent chemotherapy: capecitabine 1 600 mg/m2/day) versus CAPOX 50 (RT 50 Gy/5weeks with the same capecitabine plus oxaliplatin 50 mg/m2 /q week). Adjuvant chemotherapy was given to 253 patients and well balanced between both arms. All patients were analysed according to the intent to treat principle. Results: With a median follow up time of 36 months the main clinical results are presented in the table . There was no significant difference in local control, survival, toxicity and functional results. In an exploratory analysis, clinical complete response (24 pts) before surgery and pathological complete response (92 pts) were associated with an excellent disease free survival at 3 years respectively 92% and 90%. These results must be interpreted in reference with 3 other recent randomized trials involving the same patients: STAR 01 (Italy) NSABP R 04 (USA) (Table) CAO/ARO 04 (Germany). Conclusions: It is possible to conclude from this trial and the 3 other trials that: (1) oxaliplatin should not be included in the protocol (increased early toxicity and no effect on the pCR rate) (2) capecitabine is as efficient as fluorouracil (3) RT dose escalation to 50 Gy is improving pCR without increasing toxicity. A “CAP 50” regimen appears as safe and efficient in this neoadjuvant situation. [Table: see text]
Loco-regional treatment (LRT) for M1 at diagnosis prostate cancer (PCa) patients (pts) and impact on overall survival (OS): A retrospective analysis.
Authors: Diletta Bianchini, David Lorente Estelles, Pasquale Rescigno, Hazel 'O Sullivan, Michael Paul Kolinsky, Semini Sumanasuriya, Zafeiris Zafeiriou, Niven Mehra, Anurhada Jayaram, Joaquin Mateo, Raquel Perez, Nina Tunariu, Nicholas John Van As, Vincent Khoo, Alison Tree, Chris C. Parker, Rosalind Eeles, David P. Dearnaley, Gerhardt Attard, Johann S. De Bono
Journal: Journal of Clinical Oncology (2016)

280 Background: The optimal management of the primary tumour in pts with M1 at diagnosis PCa is not established. We aimed to evaluate the impact on OS of LRT (surgery or radiotherapy to the primary tumour) in de novo metastatic disease. Methods: PCa pts with M1 disease at diagnosis treated at the Royal Marsden between June 2003 and December 2011 were evaluated. LRT+ patients were defined as those that had received surgery or radiotherapy for the primary. Covariates analysed included age, diagnostic Gleason score, lines of CRPC treatment, PSA, burden of bone metastases ( ≥ 4 vs &lt; 4 bone metastases) and ECOG PS. Kaplan-Meier analyses generated OS data. The association between LRT and OS was evaluated in univariate (UV) and multivariate (MV) Cox regression models. Results: Overall 234 pts with M1 at diagnosis were identified; 27 (11.53%) received LRT (25 XRT; 2 prostatectomy). Median time interval between diagnosis and LRT was 782 days (range 0-4130). Patients receiving LRT were younger (49 vs 61 yrs, p = 0.042), had lower baseline PSA values (68 vs 148; p &lt; 0.001), and were more likely to have lymph node only disease (26% vs 10%; p = 0.029) and a lower burden of bone metastases with &lt; 4 metastases (85% vs 34%;p &lt; 0.001). Patients receiving LRT had a significantly longer survival (74.2 vs 55.1 months; HR 0.39; p &lt; 0.001) in UV and MV cox-regression analysis (table). LRT+ remained highly prognostic, independently of disease volume at diagnosis and baseline PSA. Conclusions: LRT was associated with increased survival in patients with de novo metastatic disease, and in these analyses the prognostic utility of this LRT prognostic biomarker was independent of volume of metastatic disease at baseline and I'd baseline PSA. Other possible confounder factors may need to be taken into account when interpreting these results which require prospective validation from clinical trials such as STAMPEDE . [Table: see text]
Trends of multimodal therapy in high-stage penile cancer.
Authors: Elizabeth Kate Ferry, Hui Zhu
Journal: Journal of Clinical Oncology (2014)

370 Background: Penile cancer (PC) is associated with high mortality and treatment failure in higher stage disease. While no prospective data exists, small anecdotal reports advocate the use of perioperative chemotherapy and/or radiotherapy for advanced disease. The 2013 National Comprehensive Cancer Network (NCCN) guidelines advocate the use of multimodal therapy for advanced disease. This study aimed to examine the trend in the use of perioperative chemotherapy or radiotherapy for advanced stage PC in the U.S. from 2000 – 2011. Methods: The National Cancer Database (NCDB) Datalinks Portal was queried. Diagnosis by year, first course treatment by stage, in all hospitals from 2000 – 2011 was obtained. Percentages of men treated with surgery alone, surgery with radiation, and surgery with chemotherapy in stages III and IV by year were determined to assess trends. Results: From 2000 – 2011, there were 1,028 and 440 men diagnosed with stage III and IV PC, respectively, who were recorded as having either surgery alone, surgery with radiation (+XRT), or surgery with chemotherapy (+Chemo). Addition of radiation therapy was variable, but low. Addition of chemotherapy has gradually increased, most dramatically in stage III PC. Conclusions: Consistent with the 2013 NCCN guidelines on penile cancer, the use of multimodal therapy for higher stage PC has increased, though modestly. Surgery with chemotherapy is the most common multimodal therapy. Further studies are needed to determine if this corresponds to a change in PC mortality. [Table: see text]
Breast cancer in young women in a northern province of Tucuman, Argentina.
Authors: S. Holgado, M. Sanchez Segura, A. Vinuales, V. Audi, F. Arrieta, D. Gonzalez, M. Jimenez, C. E. Lorente, R. Audi, A. d. C. Elias, J. J. Zarba
Journal: Journal of Clinical Oncology (2011)

e12022 Background: Breast Cancer (BC) in Argentina (A) is the most common cancer among women and the first cause of death by cancer (5,261 deaths in 2008, 6.98% in women under 44 years). Tucumán (T) has a predominantly urban population (79.46%), Census 2010, INDEC. BC mortality is 18.6/ 100,000 women (MSP, 2007) which means about 140 BC deaths /year and age-adjusted incidence 1994-96: 83/100 000/year (Herrera, Zarba et al). In 2008, 138 patients (pts) were diagnosed with BC in the public health subsector in T (PPCCMT). Women in T have an oncologic profile similar to those in developed countries. Pts under 45 with BC, have worse prognosis, an increased chance of dying from BC (5% yearly prior these age) and a significant reduction on life expectancy (Vinh-Hung et al, 2004). The young age of a patient is an independent indicator of poor survival. Objective: To analyze clinical-pathological features in pts with BC, diagnosed outside the range of screening in PPCCMT (< 40 years old). Methods: The features of 1016 pts with BC were studied reviewing the records of 4 diagnostic nodes, from January 2004 to July 2009. Pts with an age equal to or less than 39 years were selected. The variables studied included: age, tumor size, histological type and grade of the invasive carcinoma. An observational descriptive statistical method was applied. Results: We found reports of 84 (8,27%) pts with BC under 39 years old. Mean age: 34 years old (15 - 39). Median age: 35 years old. Invasive Ductal Carcinoma (IDC) was the most frequent histological type 58/84 (69%). Age frequency: <19: 1(1%); 20-24: 3 (4%); 25-29: 11 (13%); 30-34: 24 (29%); 35-39:45 (53%). Histological type: IDC: 41 (50%); IDC + DCIS:17 (20%); DCIS: 6 (7%); Invasive lobular carcinoma + LCIS: 6 (7%); Mixed: 3 (4%); Phyllodes: 4 (5%); Others: 5 (6.%). Size tumor: T1a: 2%; T1b:1%; T1c:11%; T2: 26%; T3:18% Unavailable (Core biopsies): 17%, Unregistered:25%. Histological Grade (Nottingham Score) Grade 1:5%, Grade 2:35%, Grade 3:17%, Unavailable: 43%. Conclusions: Our results showed a higher frequency of BC among women under 40 years old (8,27%) than in USA (7%). Diagnosing breast cancer in younger women is more difficult and it’s a challenge for the future. We must be careful with the “wait and see” concept in a young woman with a breast lump.
Comparative effectiveness of early-line <i>nab</i>-paclitaxel (<i>nab</i>-P) versus eribulin in patients (pts) with metastatic breast cancer (MBC): A U.S. real-world analysis.
Authors: Fadi S. Braiteh, Monika Parisi, Quanhong Ni, Si yeon Park, Claudio Faria
Journal: Journal of Clinical Oncology (2016)

293 Background: In a phase III study in MBC, nab-P demonstrated anti-tumor activity across lines of therapy. Eribulin is indicated for the treatment (Tx) of MBC in pts who have previously received ≥ 2 chemotherapeutic regimens. This analysis evaluated Tx patterns and effectiveness of nab-P and eribulin in pts with MBC in a real-world community-based setting. Methods: A retrospective cohort study was performed using fully de-identified data from a US electronic medical record platform of 1300 community oncology physicians. The analysis included women aged ≥ 18 years with MBC who started on nab-P or eribulin monotherapy as 1L or 2L Tx from 12/4/10 to 10/6/14 (≥ 1 cycle of nab-P or eribulin required). The primary objective was to examine duration of Tx (DOT, including time to Tx discontinuation [TTD]; censored if last administration &gt; 30 days from the last date in the database) and time to next Tx (TTNT; day 1 from drug 1 to drug 2). Incidence of adverse events (AEs) and supportive care used during Tx were also examined. Results: Pt characteristics were similar between groups. Mean age was 59 years. Most pts had hormone receptor + (62%), HER2− (82%) disease, and 1L therapy (60%). More pts received nab-P vs eribulin. Slightly more pts receiving nab-P vs eribulin were treated in 1L (63% vs 55%). DOT, TTNT, and TTD were significantly longer in the nab-P vs eribulin group (Table). Thrombocytopenia and anemia were numerically lower in the nab-P vs eribulin group (P = 0.11 for each). Nausea/vomiting was less common with eribulin vs nab-P (P = 0.009). Granulocyte-colony stimulating factor, hydrating agents, and antiemetics were used less often in pts receiving nab-P (P &lt; 0.01 for each). Conclusions: DOT, TTNT, and TTD were significantly longer for pts treated with nab-P vs eribulin. Moreover, pts receiving nab-P experienced fewer hematologic AEs and utilized fewer doses of supportive care. [Table: see text]
New-Generation Anti-CD20 Monoclonal Antibody (GA101) Evokes Homotypic Adhesion and Actin-Dependent, Lysosome-Mediated Cell Death in B-Cell Lymphoma.
Authors: Waleed Alduaij, Sandeep Potluri, Andrei Ivanov, Jamie Honeychurch, Stephen A Beers, Claude Chan, Kazayuki Shimada, Martin J. Glennie, Mark S Cragg, Tim Illidge
Journal: Blood (2009)
Impact of obesity on outcomes after definitive dose escalated intensity modulated radiation therapy for localized prostate cancer.
Authors: Lora S Wang, Karen J. Ruth, Marc C. Smaldone, Alexander Kutikov, Mark L. Sobczak, Rosalia Viterbo, Eric M. Horwitz
Journal: Journal of Clinical Oncology (2014)

50 Background: Multiple retrospective studies have investigated the association between body mass index (BMI) and biochemical failure (BF) after definitive external beam radiotherapy (EBRT) of localized prostate cancer (CaP) prior to the dose escalation era, with conflicting results. The purpose of this study is to determine whether increasing BMI is associated with CaP outcomes in patients treated with dose escalated radiotherapy. Methods: From 2000 to 2010, we identified 1,291 patients with localized (T1b-T4N0M0) CaP who were treated with definitive intensity modulated radiation therapy (IMRT). BMI was categorized using World Health Organization classification. Multivariable competing risk and Cox proportional hazards regression models were used to assess the risk of BF, distant metastasis (DM), cause-specific mortality (CSM) and overall mortality (OM). BF was defined as prostate-specific antigen (PSA) greater than or equal to nadir + 2 ng/mL. Covariates included age, androgen deprivation therapy (ADT), pre-treatment PSA (iPSA), Gleason score, and T stage. For OM, self-reported history of diabetes, heart disease, and hypertension were included. Results: Of the 1,291 patients identified, there were 20% normal (BMI&lt;25 kg/m 2 ), 47% overweight (BMI 25-29.9), 23% obese class I (BMI 30-34.9), 6% obese class II (BMI 35-39.9), and 4% obese class III (BMI &gt;40). Median follow-up was 43.7 months (range 1.1-127) with median age of 68 (range 36 to 88). Median dose was 78 Gy (range 76-80) and 33% of patients received ADT. Increasing BMI was inversely associated with age (p&lt;0.0001) and iPSA (p=0.047). There were 128 BF, 51 DM, 15 CSM, and 119 OM. Risk of BF, CSM, and OM were increased for obese class II and III compared to normal (all p&lt;0.05). On multivariable analysis, for BF, HR was 2.1(p=0.057) for obese class II and 2.5 (p=0.043) for class III. For CSM, HR was 5.1 (p=0 .028) for class II and 5.15 (p=0.014) for class III. For OM, HR was 2.3 (p=0.022) for class II and 2.6(p=0.023) for class III. There was a trend toward increased DM for class III (p=0.057). Conclusions: For CaP patients receiving IMRT, those with higher levels of obesity may be at increased risk of BF and prostate cancer mortality, and should be considered for more aggressive treatment.
Structure of the Transcriptional Regulatory Network Correlates with Regulatory Divergence in Drosophila
Authors: Bing Yang, Patricia J. Wittkopp
Journal: Molecular Biology and Evolution (2017)

Transcriptional control of gene expression is regulated by biochemical interactions between cis-regulatory DNA sequences and trans-acting factors that form complex regulatory networks. Genetic changes affecting both cis- and trans-acting sequences in these networks have been shown to alter patterns of gene expression as well as higher-order organismal phenotypes. Here, we investigate how the structure of these regulatory networks relates to patterns of polymorphism and divergence in gene expression. To do this, we compared a transcriptional regulatory network inferred for Drosophila melanogaster to differences in gene regulation observed between two strains of D. melanogaster as well as between two pairs of closely related species: Drosophila sechellia and Drosophila simulans, and D. simulans and D. melanogaster. We found that the number of transcription factors predicted to directly regulate a gene ("in-degree") was negatively correlated with divergence in both gene expression (mRNA abundance) and cis-regulation. This observation suggests that the number of transcription factors directly regulating a gene's expression affects the conservation of cis-regulation and gene expression over evolutionary time. We also tested the hypothesis that transcription factors regulating more target genes (higher "out-degree") are less likely to evolve changes in their cis-regulation and expression (presumably due to increased pleiotropy), but found little support for this predicted relationship. Taken together, these data show how the architecture of regulatory networks can influence regulatory evolution.
A Dose Intensified Pediatric-Like Regimen Using Multiple Doses of Intravenous Pegylated Asparaginase in Adults with Newly Diagnosed Acute Lymphoblastic Leukemia.
Authors: Dan Douer, Kristy Watkins, Lisa Mark, Ann Mohrbacher, Allen S. Yang, Prakash N. Tiwari, Vassilos I. Avramis
Journal: Blood (2007)
Long-standing diabetes and its effects on outcomes in colon cancer.
Authors: J. Tiwana, S. Ortman, T. Davies, W. Gonsalves, T. Tashi, J. Krishnamurthy, R. Thota, M. Abu Hazeem, A. Ganta, A. R. Sama, I. T. Aldoss, A. K. Ganti, P. T. Silberstein, S. Subbiah
Journal: Journal of Clinical Oncology (2011)

e14019 Background: Diabetes mellitus 2 (DM2) is associated with increased colon cancer risk and is thought to be secondary to carcinogenesis induced by increased insulin and insulin growth factor-1 (IGF-1) levels. However, the effects of DM2 on outcomes in colon cancer pts remain uncertain. Methods: Retrospective analysis of pts with colon cancer diagnosed between 1995 and 2008 was done via the Veterans Affairs Central Cancer Registry. Age, gender, race, smoking hx, Charlson Comorbidity Index (CCI), tumor grade, stage, site of tumor, no of lymph nodes retrieved, positivity of nodes, treatment and survival data was obtained. Results: Of the 15,086 pts with colon cancer analyzed, 3091 (20%) had DM without end-organ damage (DM w/o EOD) and 257 (2%) had DM with end organ damage (DM w/ EOD). Median survival was 7.68 years in DM w/o EOD, 6.57 years in pts with DM w/ EOD and 7.03 years in non-diabetics. Older age, DM w/ EOD, higher CCI, poorly differentiated grade, current tobacco use, higher number of lymph nodes involved and lack of chemo adversely affected survival outcomes in a multivariate model (Table). Conclusions: Long-standing diabetes or DM w/ EOD appears to be an independent, negative prognostic marker in advanced stage (stage III and IV) colon cancer pts. This may be related to increased tumor proliferation from higher IGF-1 and insulin levels leading to chemoresistance. Future prospective analysis of survival outcomes and cancer recurrence with measurements of HbA1C, insulin, IGF-1 and chemotherapy doses administered would help confirm our hypothesis. Stage No Survival(yrs) Univariate Multivariate I p = 0.279 N/A No DM 3.377 10.96 DM w/o EOD 1.075 9.03 DM w/ EOD 17 8.90 IIA p = 0.469 N/A No DM 2.912 9.84 DM w/o EOD 774 8.03 DM w/ EOD 88 7.45 IIB p = 0.796 N/A No DM 357 5.24 DM w/o EOD 69 6.01 DM w/ EOD 5 5.32 III p < 0.001 No DM 2.361 4.10 Ref DM w/o EOD 489 3.62 HR = 1.13, 95% CI: 0.95 -1.34; p = 0.160 DM w/ EOD 48 3.02 HR = 2.55, 95% CI: 1.88 -3.45; p < 0.001 IV p = 0.035 No DM 2.731 0.90 Ref DM w/o EOD 684 0.72 HR = 1.08, 95% CI: 0.98 -1.21; p = 0.132 DM w/ EOD 99 0.43 HR = 1.27, 95% CI: 1.01-1.51; p = 0.047