tbuckley/cabot-search huggingface dataset:
Meta-analysis of effects of demographic and treatment variables on outcome for localized paratesticular rhabdomyosarcoma (PT RMS) in North America and Europe.
Authors: David Walterhouse, Donald A. Barkauskas, Andrea Ferrari, Ewa Koscielniak, Michael Stevens, Helene Martelli, Guido Seitz, David A. Rodeberg, Margarett Shnorhavorian, Roshni Dasgupta, John C. Breneman, James Robert Anderson, Douglas S. Hawkins, Veronique Minard-Colin
Journal: Journal of Clinical Oncology (2015)

10044 Background: Treatment recommendations for localized PT RMS differ based on clinical trials conducted by cooperative groups in North America and Europe. We conducted a meta-analysis to identify effects of demographic features and treatment choices on outcome for patients with localized PT RMS. Methods: We analyzed demographic and treatment variables from 12 studies conducted by the Children’s Oncology Group (COG; n = 416), Cooperative Weichteilsarkom Studiengruppe (CWS; n = 106), European paediatric Soft Tissue Sarcoma Group (EpSSG; n = 99), Italian Cooperative Group (ICG; n = 64), and SIOP Malignant Mesenchymal Tumor Group (MMT; n = 159) that enrolled 844 eligible patients with localized PT RMS from 1988-2013. Categorical and continuous variables were checked for association. Event-free survival (EFS) and survival (S) were compared among groups using univariate and multivariate analyses. Results: Mean patient age at enrollment differed among the cooperative groups (7 yrs [MMT] – 11 yrs [EpSSG]; p < 0.05). Patients ≥ 10 yrs were more likely to have tumors > 5 cm (60%; p < 0.05), enlarged nodes (N1) (17%; p < 0.05), and pathologically involved nodes (33%; p < 0.05) than younger patients. 89% of N1 nodes and 19% of N0 nodes were pathologically involved in patients ≥ 10 yrs. With a median follow-up of 7 yrs, 87.5% of patients were event-free and 94.9% were alive. Variables that impacted EFS (p < 0.05) were cooperative group, era of enrollment, age, IRS group, T-stage, tumor size, and surgical assessment of nodes in patients ≥ 10 yrs with tumors > 5 cm. Using a stepwise variable selection procedure on a proportional hazards regression model starting with all demographic and treatment variables, the EFS model selected era, age, size, and surgical assessment of regional lymph nodes (p < 0.05) and the S model selected era, age, size, and histology (p < 0.05). Conclusions: Localized PT RMS has a favorable prognosis using approaches of North American and European cooperative groups. Surgical assessment of regional nodes is important in boys ≥ 10 yrs as this impacts EFS (but not S), and in younger boys with N1 disease. Clinical lymph node staging is otherwise sufficient to guide therapy.
Design of a phase I clinical trial with PNT2258, a novel DNA interference oligonucleotide (DNAi), in patients with advanced solid tumors.
Authors: Drew Warren Rasco, Anthony W. Tolcher, Amita Patnaik, Kyriakos P. Papadopoulos, Alex Amaya, Shari Gaylor, Timothy David Moore, Robert Forgey, Neal Goodwin, Charles L. Bisgaier, Wendi V. Rodrigueza
Journal: Journal of Clinical Oncology (2012)

TPS3110 Background: With the knowledge that Bcl-2 facilitates drug resistance and cell survival, a DNA interference (DNAi) strategy was applied to silence Bcl-2 in cancer cells and promote apoptosis. DNAi differs from cytoplasmic mRNA targeting (antisense, RNAi, and miRNA targets) as it targets genomic DNA, blocking transcription. PNT100, a first in class DNAi, is a novel single-stranded 24-base unmodified DNA designed to bind to an upstream region of the Bcl-2 promoter. The drug product (PNT2258) is PNT100 encapsulated in a specialized pH tunable liposome and is being assessed for safety and tolerability in a phase I trial. PNT2258 avoids the toxicities associated with modified oligonucleotides and double-stranded RNAs; since the liposome formulation is anionic and contains no surface spacers, vehicle toxicities are minimal. Xenograft experiments demonstrated marked single agent activity in a diffuse large cell lymphoma, and therapy potentiation when combined with either rituximab in Daudi-Burkitt’s Lymphoma or docetaxel in A375 melanoma. Methods: An open-label, single-arm, first-in-man phase I dose-escalation study of PNT2258 in patients with advanced solid tumors was designed to evaluate safety, tolerability, dose-limiting toxicities, pharmacokinetics, and pharmacodynamics of PNT2258 to recommend a dose for phase II studies. In this phase I study, pharmacodynamic effects of PNT2258 will be evaluated through analyses of soluble serum and plasma markers and peripheral blood mononuclear cells. Patients will receive PNT2258 as an intravenous infusion over 2 hours once daily for 5 consecutive days (days 1-5) of each 21-day treatment cycle (3 weeks). The starting dose of 1 mg/m 2 with PNT2258 administered to one patient per cohort and dose-escalation will proceed by dose-doubling in each successive cohort until a dose level of 64 mg/m 2 is attained, provided no dose-limiting toxicities are observed in cycle 1. Thereafter, dose escalations shall proceed at 33% increments of the previous cohort dose-level to 85, 113, and 150 mg/m 2 with expansions of up to six patients per cohort as needed. The ten planned dose cohorts have been completed with all patients enrolled.
Quantitative measurement of HER2 expression and HER2 homo-dimerization in formalin-fixed paraffin-embedded (FFPE) breast cancer tissues using a novel proximity-based assay
Authors: W. Huang, Y. Tan, X. Jin, A. Mukherjee, J. Sperinde, H. Pannu, U. Prasad, E. Penuel, J. Winslow
Journal: Journal of Clinical Oncology (2007)

21023 Background: The best method to assess HER2 status remains controversial. Here we describe a novel assay that provides reliable quantitation of total HER2 (H2T) and HER2 homodimer (H22D) in FFPE tissues. The assay was cross-validated with conventional HER2 tests - immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Characteristics of the new assay and its potential application as predictive test were explored. Methods: Electrophoretic Tag (eTag) is a proprietary proximity-based technology that measures gene and protein expression. We have developed a novel application of the technology to quantify H2T and H22D in FFPE tissues. The validity of the assay was evaluated by analyzing its performance in cell lines and FFPE breast cancers. IHC (clone CB-11, Ventana) was performed in 174 breast cancers, scored according to standard IHC criteria and Histoscore (H-score), and HER2 gene amplification was evaluated by FISH (PathVysion, Vysis) in 19 breast cancers. eTag assays were performed on the same specimens and the results were compared with those of IHC and FISH. Results: H2T and H22D were proportional to the known expression levels in cell lines. H2T demonstrated a continuous measurement over a wide dynamic range (&gt;2 logs), in contrast with conventional IHC (0, 1+, 2+, 3+). The correlation between H2T and IHC categories was significant (correlation=0.84, p&lt;0.0001 by the Jonckheere-Terpstra test for trend), but overlap of H2T values in adjacent IHC categories was observed. H-score showed good correlation within the lower range of H2T, but plateaued at higher range of H2T. HER2 gene amplification (HER2/CEP17 ratio and gene copy #) by FISH was generally correlated with IHC categories and H2T values. There was a good correlation between H22D and H2T (r 2 = 0.7, P &lt; 0.001). Conclusions: eTag reliably measures H2T and H22D in FFPE tissues. The continuous measure of H2T over a wide dynamic range and the novel H22D measure provide data superior to conventional HER2 tests by IHC and FISH, but clinical utility of the eTag assay remains to be investigated. eTag has potential as a predictive test for targeted HER2 therapy in breast cancer. No significant financial relationships to disclose.
Multicenter retrospective analysis of 31 patients with aggressive angiomyxoma.
Authors: Roberta Sanfilippo, Nadia Hindi, Chiara Colombo, Isabelle Laure Ray-Coquard, Mehdi Brahmi, Marinella Micol Mela, Maria A. Pantaleo, Bruno Vincenzi, Angelo Paolo Dei Tos, Domenica Lorusso, Francesco Raspagliesi, Alessandro Gronchi, Paolo Giovanni Casali
Journal: Journal of Clinical Oncology (2014)

10585 Background: Aggressive angiomyxoma is a rare mesenchymal neoplasm of perineum and pelvic region. Surgery is the main treatment, but local recurrences are frequent. Responses to hormonal therapy have been anecdotally reported. Methods: Aggressive angiomyxoma patients (pts) treated since August 1999 at two institutions (Istituto Nazionale Tumori, Milan, Italy, and Centre Léon Bérard, Lyon, France), and within the Italian Rare Cancer Network (RTR) were reviewed. Data regarding surgical and systemic therapy and survival were collected. Results: We identified31 patients (mean age: 43 years; F/M= 25/6). Anatomic site of occurrence was the perineum in 11/31 pts (35%) and the pelvis in 20/31 (65%) pts. Twenty-nine pts (93%) underwent at least one surgical procedure (R0/R1= 19; R2=9). Following complete surgery (R0 and R1), the local relapse rate at 2 yrs was = 21% (4/19 pts), with a median relapse-free survival (RFS) of 39 mos, Eleven patients (35%) received hormonal therapy for locally advanced disease. Eight patients received GnRH agonist as first-line therapy (6 pts as a single therapy and 2 patients in combination with tamoxifen). Seven were evaluable for response, with 2 CR, 3 PR and 2 SD, and a median PFS of 22 mos. One of these 8 pts, stopped her treatment while in CR and restarted treatment at the time of progression, obtaining a new CR. Two pts treated with GnRH agonist as first-line therapy were added an aromatase inhibitor after progression and reached a CR and a PR, respectively. Two patients received aromatase inhibitors as first-line therapy and reached a SD as their best response. One pt received tamoxifen as first-line therapy, with a PR as her best response. Median overall survival has not been reached, since all patients were alive at the time of this analysis. Conclusions: This is a large series of pts with aggressive angiomyxoma. Our results confirm the high rate of local recurrences after surgery. Hormonal therapy is an effective therapeutic option, which is able to result in sustained CRs in a fraction of pts. Treatment strategy of this disease needs to be defined.
Telephonic Advance Care Planning (ACP) with Medicare patients with advanced cancer: Interim program results.
Authors: Marcus A. Neubauer, J. Russell Hoverman, Jad Hayes, Kathryn Eagye, Melissa Jameson, Mitra Abdullahpour, Cynthia Taniguchi, Michael A. Kolodziej, Maria Sipala, Amy Supraner
Journal: Journal of Clinical Oncology (2015)

e17712 Background: Patient-provider discussion of future healthcare decisions in accordance with patient values—ACP—is especially relevant for metastatic cancer patients. Extending survival is the primary goal, but maximizing quality of life, including avoiding hospitalizations, is also essential. Innovent is an oncology disease management program which includes ACP counseling by a trained nurse. We measured hospitalizations, hospice use, chemotherapy within 14 days of death and total claims cost for patients who had died by the midpoint of the 3-year program. Methods: Aetna Medicare patients with metastatic cancer treated at Texas Oncology and managed by Innovent from 6/1/2013 to 9/30/2014 were eligible (n = 231); of these, n = 50 had EMR-documented dates of death as of 12/31/2014. All patients were offered all Innovent services, including ACP counseling, which they could accept or decline. We divided non-survivors into 2 cohorts: participated in ACP; did not participate (No ACP). Characteristics and outcomes were obtained from claims and EMR data and compared by Chi-Square and Wilcoxon Rank Sum tests (α = .05). Results: Karnofsky Performance Score at intake was higher for ACP (p = .05); other characteristics did not differ. Results are listed in the table. Non-significant trends favor ACP vs. no ACP; enrollment is ongoing. Conclusions: ACP addresses patient wishes involving end of life care. Our interim results suggest that when ACP counseling takes place early in the continuum of advanced cancer for those who ultimately die of their disease, outcomes related to quality of life appear to be enhanced and there is a trend towards lower claims cost. No ACP Had ACP Counseling (n = 31) (n = 19) p-value (No., % of total) or (Median [Min, Max]) Entered hospice 10, 32.3% 7, 36.8% 0.740 Days in Hospice 9.5 [3, 89] 9.0 [2, 69] 0.769 Ever admitted 27, 87.1% 13, 68.4% 0.109 Average Length of Stay 4.7 [0, 24] 2.0 [0, 16] 0.185 Chemo w/in 14 days of death 6, 19.4% 2, 10.5% 0.409 Died in Hospital 7, 26.9% 3, 21.4% 1.000 Total Claims Cost $38,658 [$7,124, $118,200] $32,505 [$4,551, $124,825] 0.6173
The effect of race on recommendation and acceptance of surgical resection for non-metastatic non-small cell lung cancer (NSCLC)
Authors: C. S. Lathan, B. A. Neville, C. C. Earle
Journal: Journal of Clinical Oncology (2004)

6018 Background: Black patients with early stage NSCLC have previously been found to have worse overall survival than White patients. Decreased likelihood to undergo resection has been implicated. To isolate the effect of decision-making from access to care, we used receipt of recommended surgical staging as a proxy for access, and examined treatment patterns and outcomes. Methods: We examined registry and claims data of Medicare-eligible patients with non-metastatic NSCLC living in areas monitored by the Surveillance, Epidemiology, and End Results (SEER) program between 1991–1996. Surgical staging was defined as bronchoscopy, mediastinoscopy, or thoracoscopy. We used logistic regression and Cox modeling to calculate the odds of having surgical staging, resection, and survival outcomes. Results: Among 23,943 patients, 15,162 underwent surgical staging and 7,014 had a resection. Survival for Black patients was worse than Whites (HR 1.08, P<0.0009). Black patients were less likely to undergo surgical staging (Odds Ratio (OR) 0.84, 95% Confidence Interval (CI) 0.76–0.93) or resection (OR 0.55, CI 0.49–0.62). Black patients once staged were still less likely to have a resection (OR 0.60, CI 0.53–0.69). Survival for Blacks and Whites was equivalent after resection. In patients who were staged but did not have surgery, Black patients had better overall survival when compared to Whites (40% vs. 37.7% at 1 year, 16.8% vs. 15.8% at 2 years, HR 0.92, P<0.028). Black patients who had surgical staging were less likely to have resection recommended (44.6% vs.56.4 %), but twice as likely to decline resection. (3.2% vs. 1.4%) Conclusions: Finding that Black patients who were surgically staged but did not have resection had a superior survival to White counterparts suggests that there are Black patients who may benefit from resection who are not receiving it. Barriers to resection may include Black patients being less likely to be offered resection in borderline cases, or being less accepting of recommendations for resection. Further examination of patient and provider attitudinal determinants is needed. No significant financial relationships to disclose.
Blood neutrophil-lymphocyte ratio at diagnosis to predict treatment response in gastric cancer.
Authors: Dr. Consuelo Diaz, German Caderillo-Ruiz, MaryTere Herrera, Erika B. Ruiz Garcia, Manuel Flores Castro, Horacio Noe López-Basave, Itzel Vela Sarmiento, Alejandro Padilla, Jose Luis Aguilar, Angel Herrera Gomez
Journal: Journal of Clinical Oncology (2015)

e15005 Background: Previous studies have shown that the neutrophil to lymphocyte ratio (NLR) in peripheral blood is a prognostic factor of various neoplasm. Some biomarkers have been associated with prognosis in gastric cancer (GC) identify depends specimens on biopsies and limits their use in clinical practice.Pheripheral blood tests at the time of diagnosis can reflect evolution within the tumor. We evaluated whether the NLR can predict response to treatment in patients with gastric cancer receiving chemotherapy. Methods: Is a retrospective analysis of 190 patients with GC (2011-2013) in National Cancer Institute Mexico. 73 patients received chemotherapy neoadjuvant, 30 chemoradiotherapy neoadjuvant and 117 patients palliative chemotherapy. NLR were calculated from complete blood counts in laboratory test at diagnosis, cut of values for the NLR were > 2.5 and < 2.5 using median values reported in previous studies. Results: Characteristics of Patients: male 107, female 83, mean age 54 (20-81). The response evaluation by tomography was after four cycles of treatment.The response rate was partial 20.5%, stable disease 36.3% and progression 43.2%.The median NLR :2.9 (1.1-15.2).84 patients were detected with NLR < 2.5 and 106 patients with NLR greater 2.5. Low NLR group patients had a better disease control (partial response and stable disease) in 68 % vs. 47.1% than high NLR( p = 0.028). Progression of disease was reported in 32 %( n = 27) with low NLR and 52.9 %( n = 56) of group high NLR (P = 0.002). There are more advanced disease in patients greater 2.5 NLR than < 2.5 80 vs 56 (p = 0.036) .Response pathological complete after surgery was 2 patients with a lower value. Overall survival with 2 years follow up for group low NLR is longer than NLR > 2.5, 14.5 vs. 10.1 months (p = 0.039) Conclusions: In this retrospective study, we found that lower NLR at initial clinical presentation of gastric cancer could be a predictive clinical marker of response and prognosis in patients with GC undergoing palliative chemotherapy. The routine laboratory work is available in comparison to the sophisticated methods, however further studies are needed for validation and consider stratification by stage and treatments.
Survival surrogates in gastric cancer after first- and second-line chemotherapy treatment: A Spanish retrospective study from one institution.
Authors: Federico Longo, Enrique Grande, Carmen Guillen, Vanessa Pachon, Mercedes Rodriguez Garrote, Reyes Ferreiro, Maria Angeles Vaz, Rebeca Alcalde, Ana Gomez, Eduardo Roberts, Patricia Cortez, Alfonso Cortes, Jacobo Munoz, Marisa Garcia De Paredes, Carme Guerrero, Julie Earl, Maria Eugenia Olmedo Garcia, Pilar Garrido, José Palacios, Alfredo Carrato
Journal: Journal of Clinical Oncology (2014)

e15019 Background: Overall survival (OS) is considered the traditional endpoint for assessing the efficacy of first-line treatments in clinical trials with advanced gastric cancer. Progression free survival (PFS) has not been established as a valid surrogate endpoint for OS in the first-line setting so far. Nowadays, a range of agents like ramucirumab, taxanes or irinotecan have shown significant activity as second-line. There is scarce information about OS surrogate endpoints in the second line setting for advanced gastric cancer. Methods: We retrospectively analyzed the outcome of 47 metastatic gastric cancer patients who had received at least two consecutive chemotherapy lines of treatment at our institution from Jan 2003 to Jan 2013. We sought for overall survival surrogates by correlating first and second line overall survival (1L-OS and 2L-OS) with first and second line progression free survival (1L-PFS and 2L-PFS). We also investigated if 2L-PFS could be predicted by 1L-PFS. Spearman coefficient was used to determine the existence of correlation. Results: With a median age of 65 (31 to 87) years at the start of 1L treatment, 70% of the patients received platinum-based treatment. Irinotecan- (64%) and taxane-based chemotherapy (21%) were the most frequent schemes used for 2L. There were 6 HER2+ patients (13%). Median 1L-OS and 1L-PFS were 16 months and 7 months respectively. Likewise, 2L-OS and 2L-PFS reached 8 months and 3 months respectively. The Spearman correlation coefficient between 1L-PFS and 1L-OS was 0.642 (95%IC 0.435 to 0.784; p<0.01); between 2L-PFS and 1L-OS was 0.521 (95%IC 0.274 to 0.702; p<0.01) and between 2L-PFS and 2L-OS was 0.537 (95%IC 0.295 to 0.714; p<0.01). The correlation coefficient between 1L-PFS and 2L-PFS was 0.202 (95%IC -0.090 to 0.462; p=0.206). Conclusions: Our retrospective study found that both 1L-PFS and 2L-PFS might become a surrogate endpoint for 1L-OS. In addition, 2L-PFS may also serve as a surrogate endpoint for 2L-OS. We found no significant relationship between 1L-PFS and 2L-PFS in our study. The results of our exploratory analysis need to be confirmed in prospective trials.
Role of HSF1 expression for tumor microenvironment in intrahepatic cholangiocarcinoma.
Authors: Yu Saito, Yuji Morine, Chie Takasu, Shuichi Iwahashi, Jun Higashijima, Tetsuya Ikemoto, Satoru Imura, Mitsuo Shimada
Journal: Journal of Clinical Oncology (2017)

249 Background: Heat shock factor 1 (HSF1) is a master regulator of heat shock response. HSF1 is recently identified to play a multifaceted role in cancer progression. However, the clinical significance and biological effect of HSF1 in intrahepatic cholangiocarcinoma (IHCC) remain unknown. The aim of this study was to investigate the relationship between HSF1 expression and clinicopathological factors in IHCC patients after hepatic resection, and its possible mechanism for malignant behavior. Methods: Forty-nine patients with IHCC who undergo hepatic resection were enrolled in this study. HSF1 expressions in tumor tissue were determined by immunohistochemistry. Patients were divided into two groups, the HSF1 high and low expression group. Clinicopathological factors including prognosis were compared between the high group (n = 20) and low expression groups (n = 29) in tumor tissues. Furthermore, the correlation between HSF1 with Fbxw7 or Ki-67 expressions was also examined. Results: HSF1 expression in tumor tissues was significantly higher than that in normal tissues. HSF1 expression was not significantly correlated with any clinicopathological characteristics, including age, sex, tumor markers, maximum tumor size, tumor number, and tumor staging curability . The overall survival rate in the HSF1 high expression group was significantly worse than that in the HSF1 low expression group ( p= 0.018). On multivariate analysis, HSF1 high expression was detected as the independent prognostic factor. There was a significant inverse correlation between HSF1 and Fbxw7 expression ( p= 0.008). Ki67 labeling index was significantly higher in the high than in the low HSF1 expression group ( p= 0.030). Conclusions: HSF1 high expression in tumor tissues may be prognostic biomarker in IHCC. Targeting the Fbxw7/HSF1 axis might be a critical therapeutic strategy in IHCC.