tbuckley/cabot-search huggingface dataset:
Radium-223 in metastatic castration-resistant prostate cancer: Effect of performance score and albumin levels.
Authors: Amarnath Challapalli, Sue Cowley, Dorothy Griffiths, Eleanor Compton, Rajendra Persad, Amit Bahl
Journal: Journal of Clinical Oncology (2017)

e594 Background: Radium-223 (Ra223) is a novel alpha-emitting radiopharmaceutical agent approved for use in patients with metastatic castration resistant prostate cancer (mCRPC) and bone metastases based on ALSYMPCA results. However, its optimal sequencing in the treatment of mCRPC remains unclear. We evaluated the relevance of albumin (A) levels to aid in optimal selection and timing for Ra223 treatment. Methods: Eighty-eight patients had completed treatment with Ra223 from Feb 2014 - Sep 2016. The patients were planned to receive 6 injections at a dose of 55 kBq/kg every 4 weeks. Visual analogue score (VAS) was used to assess pain. The effect of serum alkaline phosphatase (SAP), docetaxel chemotherapy, A levels and performance score (ECOG-PS) on progression free survival (PFS) and overall survival (OS) were evaluated. Results: At baseline (BL) median age was 74.5years; 68% of patients were ECOG-PS-0/1; median VAS was 4.5 &amp; median A level was 34g/dL. 48% had received prior docetaxel. 45 patients (51%) received all the scheduled 6 cycles with significant reduction in the pain scores after 6 cycles compared to the BL score (p &lt; 0.05). The reduction in pain scores was independent of the PSA response and ECOG-PS. A 34% reduction in the SAP levels was seen (p = 0.003). The treatment was well tolerated with no grade 3,4 toxicity. Discontinuation rate was 49% (43/88) due to disease progression. In PS-0/1 patients who completed 6 cycles, PFS &amp; OS were significantly longer compared to those who didn't (7.8vs.4.2&amp; 21vs.7.6 months, respectively). Patients with SAP ≤ 220 U/L &amp; A ≥ 34 g/dL also had significantly prolonged OS (16.2vs.8.6 &amp; 16.1vs.9.5 months, respectively). Patients with PS-2/3 also had significantly longer PFS and OS with completion of 6 cycles and prolonged OS with SAP ≤ 220 U/L, but not with A levels. Conclusions: Ra223 is a safe and effective treatment for mCRPC with bone metastases. Completion of 6 cycles improved outcome. Lower SAP and high A levels significantly prolonged OS in PS-1/2 patients. Whilst the level of SAP can be a reflection of disease activity, monitoring A levels and ensuring that Ra223 is started before A level goes below 34, especially in PS-1/2 patients will aid in the benefit from this treatment in mCRPC.
A phase II study of everolimus in patients with aggressive RAI refractory (RAIR) thyroid cancer (TC).
Authors: Jochen H. Lorch, Naifa Busaidy, Daniel T Ruan, Pasi A. Janne, Sewanti Atul Limaye, Lori J. Wirth, Justine A. Barletta, Guilherme Rabinowits, Levi A. Garraway, Eliezer Mendel Van Allen, Nikhil Wagle, Glenn J. Hanna, Krzysztof Misiukiewicz, Margaret Suda, Tyler C Haddad, Catherine E Devine, Amy Williams, Ghulam Warsi, Marshall R. Posner, Robert I. Haddad
Journal: Journal of Clinical Oncology (2013)

6023 Background: We present results of an open label phase II study of the mTOR inhibitor Everolimus in patients (pts) with RAIR TC. Methods: Pts with metastatic, incurable RAIR TC who had shown radiographic progression within 6 months prior to enrollment received Everolimus 10mg orally once daily. Responses were monitored by CT's every two months. The primary endpoint was progression free survival. Sequential biopsies were obtained in selected pts. Results: Enrollment to the differentiated TC (DTC) cohort finished in Jan 2013 and included 33 pts, among them 11 with Hurthle cell TC. Exploratory cohorts enrolled 10 pts with medullary [MTC] and 5 with anaplastic [ATC] with 2 added openings remaining for ATC. For the DTC cohort, median time on study to date is 10 months (mo) (&lt;1-23+). 31 pts are evaluable at this time. PFS in the DTC cohort by Kaplan-Meier (K-M) analysis is 16.0 mo (95%CI 10-NR). Currently, disease stability for 6 and 12 mo or more was achieved in 18 and 10/31 pts, respectively, 11 pts remain on study. Median OS was not reached but 1 year survival by K-M analysis was 76%. One pt achieved a PR. 3 pts with DTC underwent sequential biopsies which revealed activation of autophagy while markers for apoptosis were not detected. Among 10 MTC pts, one achieved a PR and 9 pts had stable disease for 6 mo or more (6-33+). Among 5 ATC pts, 3 progressed, one has ongoing disease stability for 5 mo. One patient achieved a complete response that lasted for 18 mo and whole exome sequencing revealed somatic loss of function mutation affecting the Tuberous Sclerosis 2 (TSC2) protein, a negative regulator of mTOR activity [TSC2 (Q1178*) and FLCN (R17fs)]. Most common treatment-related adverse events were as anticipated and included fatigue, stomatitis and infections. Grade (gr) 3 events included infection 5, weight loss 3, leukopenia 3, thrombocytopenia 3, fatigue 3, hypophosphatemia 2, stomatitis 2, pneumonitis 1 and thrombosis 1pts. One pt had gr 4 hypercholesterinemia and one pt had gr 4 leukopenia. Conclusions: Everolimus has significant anti-tumor activity in pts with advanced TC. Activation of autophagy could account for high rate of disease stability. Sequencing may identify mechanistic basis and predictive markers for treatment response. Clinical trial information: NCT00936858.
Familial breast cancer in Spain: A retrospective study of family history and clinical/pathologic characteristics from the GEICAM “El Álamo III” project.
Authors: Ivan Marquez-Rodas, Marina Pollán, Ana Lluch, Teresa Ramon y Cajal, Angel Guerrero-Zotano, Sonia Servitja, Miguel Martin, Ignacio Blanco, Purificacion Martinez del Prado, Santiago Gonzalez-Santiago, Ana Santaballa, Gemma Llort, Raquel Andres, Ana Laura Ortega Granados, Carlos Jara-Sanchez, Maria Jose Juan Fita, Rosalia Caballero, Maria Jose Escudero, Eva Maria Carrasco, Sara Lopez-Tarruella
Journal: Journal of Clinical Oncology (2013)

e12513 Background: Family history (FH) of breast cancer (BC), ovarian cancer (OC), and individual features (IF), like early age of onset, bilateral BC, coexistence of BC and OC, and triple negative BC (TNBC) younger than 50 years, are suspicion criteria of hereditary BC. Although it is assumed in the literature that 15-30% of BC cases can be familial BC (FBC), only 5-10% of BC are hereditary, explained by a germline mutation in BRCA1 or 2. Moreover, there is no international consensus to define FBC (e.g. number of relatives affected, age of onset), in contrast with, e.g. Lynch syndrome and Amsterdam/Bethesda criteria, in order to offer genetic counseling. In Spain, there are not population-based studies analyzing the real percentage of BC with familial and/or individual high risk features. Methods: A retrospective study based on 10,641 Spanish BC patients diagnosed from 1998-2001, collected in the “El Álamo III project”, was conducted. Specific data regarding FBC were analyzed: IF (age of onset, bilateral breast cancer, ovarian cancer and TNBC; and FH features (first and second degree relatives with BC and /or OC). Results: The Table summarizes the results. Conclusions: 21% of BC patients in Spain diagnosed from 1998 to 2001 have at least one relative with BC and/or OC. In addition, 2.8 % of patients with no FH of BC/OC fulfill high risk criteria. However, several study characteristics, such as 18% patients with no FH recorded, and lack of data regarding age of affected relatives, limit the interpretation of these results, being necessary to improve the family data collection in further “El Álamo” project studies. [Table: see text]
Outcomes of clinical testing for 50,000 patients utilizing a panel of 25 genes associated with increased risk for breast, ovarian, colorectal, endometrial, gastric, pancreatic, melanoma, and prostate cancers.
Authors: Eric T. Rosenthal, Heidi McCoy, John Kidd, Brent Evans, Krystal Brown, Jennifer Saam, Susan Manly, Richard J. Wenstrup
Journal: Journal of Clinical Oncology (2015)

1515 Background: Genetic assessment for inherited risk is a key tool for cancer prevention. Genetic testing strategies are evolving in response to expanding information about gene associations and available technologies for the cost-effective simultaneous screening of large numbers of genes. Here we provide outcomes data from clinical testing of a large, diverse cohort of US patients using a panel of 25 genes known to be associated with an increased risk for 8 common cancers with known genetic associations. Methods: Results are included from the first 50,000 patients tested with the 25-gene panel in a CLIA approved laboratory. All clinical information was obtained from test requisition forms completed by ordering healthcare providers. Results: 3750 (7.5 %) of tested patients were found to carry one or more pathogenic variants linked to an increased risk for cancer, distributed as shown in the table below. Clinical history review demonstrates that many patients had pathogenic variants in genes for which they most likely would not have been tested based on the reported personal/family history. Pathogenic variants in most genes were found in patients of all ancestries, indicating that the panel testing strategy can increase the sensitivity of testing in all populations. Conclusions: Testing with a 25 gene panel targeted at 8 common cancers significantly increases the number of patients identified as being at an increased cancer risk compared with testing targeted to a single gene or syndrome. This potentially benefits patients carrying pathogenic variants in genes for which testing was not widely available previously, and/or whose personal/family histories do not fit unambiguously with a single gene or syndrome. Distribution of pathogenic variants detected. Gene Pathogenic Variants Detected BRCA2 869 BRCA1 791 CHEK2 432 ATM 350 PALB2 255 PMS2 157 BRIP1 138 MSH6 124 MSH2 117 MLH1 83 NBN 91 RAD51C 80 BARD1 77 APC 73 TP53 43 CDKN2A (p16INK4A) 40 RAD51D 32 CDH1 28 MUTYH Biallelic 18 PTEN 14 EPCAM 8 STK11 6 SMAD4 5 BMPR1A 4 CDKN2A (p14ARF) 1 CDK4 0 Total 3854
A population-based study of incidence, diagnostic approaches and therapy of thymic epithelial tumors
Authors: M. Schaapveld, W. K. De Jong, W. Timens, T. J. Klinkenberg, J. L. Blaauwgeers, H. J. Groen
Journal: Journal of Clinical Oncology (2007)

18086 Background: Diagnostic and therapeutic approaches to thymic epithelial tumors are not standardized. Also, opinions differ on the biological behavior of thymomas. The purpose of this population-based study was to assess the incidence of the whole spectrum of thymomas and thymic carcinomas and to assess the diagnostic approaches, therapy, and survival of these tumors. Methods: The Dutch National Pathological Archives (PALGA) were used to evaluate the incidence of thymomas and other thymus neoplasms between 1994- 2003. Clinical and pathological characteristics were obtained from PALGA and the Netherlands Cancer Registry. Results: We identified 537 thymic epithelial tumors, male/female 262/275, median age 59 years (range 1–94). WHO classification was type A 12%, AB 21%, B1 16%, B2 18%, B3 12%, C 11%, unknown 10%. Clinical disease stage according to Masaoka was I in 26%, II 23%, III 13%, IV 12%, unknown 26%. Incidence of all thymic epithelial tumors in the Netherlands is 3.2/1,000,000 and of thymomas (WHO classes A-B2) is 2.2/1,000,000. Primary resection as first procedure for obtaining a diagnosis was performed in 56% of patients, and was associated with smaller tumors (p&lt;0.001), younger age (p=0.006), and the presence of myasthenia gravis (p&lt;0.001). Survival data were available for 232 patients. Five- year overall observed survival was 69%. Not only thymic carcinomas but also thymomas showed tumor-related mortality. The majority of patients (78%) was treated with resection, and had a better survival than non-operated patients (median survival more than 10 years versus 1.1 years, p&lt;0.001). Among the surgically treated patients (n=180), the completeness of resection was not prognostic (p=0.17). Conclusions: Thymic epithelial tumors are rare and the majority shows tumor-related mortality. Primary resection is the most frequently used procedure to obtain a definite diagnosis and is also advisable in cases with questionable resectability. No significant financial relationships to disclose.
Tumor progression and chemoradiosensitivity in relation to the expression of apoptosis related proteins in esophageal squamous cell carcinoma
Authors: S. Tsujitani, H. Saito, S. Tatebe, M. Ikeguchi
Journal: Journal of Clinical Oncology (2007)

4588 To study apoptosis related protein expression and their impact on patient’s survival time and sensitivity to postoperative chemoradiotherapy (CRT), we examined the expression of RB, mutant p53, MDM2 and Bax proteins using immunohistochemistry in 115 (CRT; 42) surgically resected esophageal squamous cell carcinoma (ESCC). We also investigated the survivin mRNA expression with quantitative analysis by real-time RT-PCR in 57 (CRT; 30) patients with ESCC. CRT contained 40–60 Gy radiation and continuous infusion of 5-FU (300mg/sqm, day1–5qw). Expression of RB, mutant p53, MDM2, Bax proteins and survivin mRNA were detected in 65%, 46%, 33%, 37% and 32% of patients, respectively. Patients with RB(+), MDM2(-), Bax(+) or survivin(-) tumor had significantly better survival rates than those with RB(-), MDM2(+), Bax(-) or survivin(+) tumor, respectively. However, there was no significant difference in survival between patients with and without mutant p53 expression. In patients not treated with CRT, those with RB(+) or survivin(-) tumor survived significantly longer than those with RB(-) or survivin(+) tumor, respectively. In patients treated with CRT, the expression of Bax protein and survivin mRNA was prognostic indicator. The 5-year survival rates of patients with Bax(+) and survivin(-) tumors were 65% and 39%, significantly superior to 21% and 0% of those with Bax(-) and survivin(+) tumors (P&lt;0.05 and P&lt;0.01, respectively). These results indicate that the expression levels of apoptosis related proteins are important for predicting the prognosis of ESCC patients. Furthermore, CRT may be effective in patients with Bax(+) or survivin(-) tumors. Further investigations are required for clarifying the relationship between the efficacy of postoperative CRT and apoptosis promoting status of ESCC. No significant financial relationships to disclose.
Soluble CD87 (s-uPAR) predicts bevacizumab-based first line treatment of metastatic colorectal cancer (mCRC): Results from a prospective multi-center study.
Authors: Matthias Unseld, Gabriele Kornek, Andreas Gleiss, Svitlana Demyantes, Jost Schwarzwald, Daniela Bianconi, Johannes Andel, Christoph Tinchon, Martin Pecherstorfer, Wolfgang Eisterer, Björn Jagdt, Andreas Kretschmer, Armin Gerger, Richard Greil, Adelheid Seebacher, Peter Krippl, Friedrich Laengle, Christoph Zielinski, Werner Scheithauer, Gerald W. Prager
Journal: Journal of Clinical Oncology (2017)

604 Background: Bevacizumab-combined chemotherapy is well established in the induction treatment of metastatic colorectal cancer (mCRC). Despite tremendous efforts, no valid predictive marker for anti-VEGF treatment has so far been defined. CD87, the urokinase plasminogen activator receptor (uPAR), is centrally regulating VEGF-induced angiogenesis via adapting endothelial cell migration and invasion (Unseld et al.; ThrombHaem,2015, Brunner et al.; Blood 2011, Prager et al; Blood 2009; Prager et al; Blood 2004). Preoperative plasma s-uPAR levels were shown to independently predicted survival of patients resectable colorectal cancer. This study aimed to identify any prognostic or predictive value of s-uPAR in front-line bevacizumab-treated mCRC patients. Methods: In this prospective multi-center trial (NCT02119026), patients were either treated with bevacizumab plus FOLFOX or bevacizumab plus FOLFIRI. Baseline s-uPAR levels were assessed in 80 patients (40 ea. group) using respective CE-certified electro-chemiluminescence immunoassay (ECLIA). Biomarkers were explored using Kaplan-Meier curves and were log transformed for survival analysis by Cox proportional hazards models. All P values reported are two-sided. Results: Data from eighty patients were available for analysis. Progression free survival (PFS) and overall survival (OS) were assessed. Data indicate significance for the angiogenic biomarker uPAR to determine prognostic (HR = 3.06, CI 1.45 - 6.53, p = 0.003) and predictive (HR = 3.41, CI 2.03 - 5.74, p &lt; 0.001) value in the treatment of Bevacizumab. Conclusions: This is the first prospective analysis of baseline s-uPAR. High baseline-s-uPAR levels were an independent predictive marker for worse bevacizumab-based first-line treatment response.
2008 WCC Poster Presentations
Authors: M Irurita, C Culebras, E Bosch, R Chirino, J Irurita, L Suarez, B Saiz, P Rosique, R Guerra, V Nieto
Journal: Circulation (2008)

continuous variable-predictor.Achieved LDL-C level at 3 months among all TNT patients was predictive of benefit in the risk reduction in major CV events.This association held true when on-treatment LDL-C was co-varied for or stratified by randomized treatment, and when LDL-C values in individual treatment groups were analyzed separately.Drug dose effect on major CV events, however, was lost when adjusted for 3-month LDL-C level.The reverse was true for eGFR, i.e., drug dose effect was apparent and unaffected by achieved LDL (Table ).Thus the statin benefits on eGFR, perhaps representing small vessel effects, appear to be independent of the LDL effects of atorvastatin.This suggests that the search for clinically important non-LDL effects of statins might be usefully directed to diseases involving blood vessels smaller than those affected by atherosclerosis.
<i>Salmonella typhimurium</i> A1-R prolongs survival of aggressive pancreatic cancer in orthotopic nude mouse models.
Authors: Ali Maawy, Yong Zhang, Michael Bouvet, Robert M. Hoffman, Ming Zhao
Journal: Journal of Clinical Oncology (2013)

e22013 Background: Salmonella typhimurium A1-R has been previously shown to target multiple tumor types in various mouse models. The aim of this study was to test the efficacy of S. typhimurium A1-R against a high aggressive pancreatic cell line in an orthotopic nude mouse model. Methods: Human MiaPaCa2 pancreatic cancer cells, expressing red fluorescent protein (RFP), were implanted subcutaneously in nude mice. After tumor engraftment, the mice were subjected to intravenous therapy with S. typhimurium A1-R (5×10 7 CFU) once a week for 3 weeks. The tumors were harvested and weighed after the treatment period. MiaPaCA2-RFP was subsequently surgically implanted orthotopically and S. typhimurium A1-R treatment was initiated 2 weeks later. Mice were treated with intravenous A1-R (5×10 7 CFU) once a week for 6 weeks, after which survival and tumor growth were recorded. Results: In the subcutaneous tumor model, significant decreases in the rate of tumor growth (p = 0.049) and tumor size (p = 0.004) were observed upon termination. In the orthotopic model, a significant decrease in the rate of tumor growth (p = 0.01) and increased survival was observed (p = 0.014). None of the mice showed any adverse events or weight loss from bacterial therapy. Conclusions: The results suggest further investigation S. typhimurium A1-R, including in combination with chemotherapy, with the goal of cure of pancreatic cancer.
A novel multiple biomarker assay for the detection of ovarian carcinoma
Authors: R. G. Moore, A. K. Brown, C. M. Miller, D. Badgwell, Z. Lu, T. Verch, K. H. Lu, J. W. Allard, C. O. Granai, R. Bast
Journal: Journal of Clinical Oncology (2006)

5023 Background: Studies show that ovarian cancer patients operated on by gyn oncologists are more often adequately staged and debulked than those operated on by non-gyn oncologists. Many benign gynecologic conditions will elevate the CA125 tumor marker decreasing its specificity. An accurate test is needed to help triage patients with a pelvic mass to centers with expertise in treating ovarian cancer. This project examined several novel tumor markers to develop a multiple biomarker assay to predict the risk of ovarian cancer in patients with an ovarian cyst or pelvic mass. Methods: Data from two separate IRB approved prospective trials from two institutions were collected. After obtaining informed consent, serum samples were obtained preoperatively from women undergoing surgery for an adnexal mass and analyzed for levels of CA125, SMRP, HE4 and CA72–4. All pathology results were compared to the tumor markers. Sensitivities at set specificities of 90, 95 and 98% were determined using logistic regression for each marker individually and all combinations of 2, 3, &amp; 4 markers. Results: 448 samples were analyzed. There were 267 benign cases and 181 ovarian cancers (27 stage I, 20 stage II, 115 stage III and 19 stage IV). Median values for HE4, SMRP, CA125 and CA72–4 all differed significantly between benign masses and cancer (p &lt; 0.001). In the differentiation of benign masses and stage I malignancies, the addition of HE4 to CA125 increased the sensitivity by 22.2% at a specificity of 90%. The combination of HE4 and CA125 for all stages was superior to HE4 or CA125 alone (p ≤ 0.003). Conclusions: The improvement in sensitivity shown by the addition of HE4 to CA125 suggests that this biomarker combination can be used to provide an accurate risk assessment for the presence of ovarian cancer in patients with an ovarian cyst or mass. This multiple biomarker assay is now undergoing validation in a multicenter prospective study. [Table: see text] [Table: see text]
Predictive markers for clinical outcome after neoadjuvant radiochemotherapy in breast cancer patients.
Authors: Christiane Matuschek, Edwin Boelke, Hans Bojar, Werner Audretsch, Hans Bernd Prisack, Wilfried Budach, Carolin Nestle-Kraemling
Journal: Journal of Clinical Oncology (2014)

3041 Background: Neoadjuvant radiochemotherapy (NRT-CHX) in locally advanced noninflammatory breast cancer (LABC) is still under debate. Proliferation markers are the majority of genes included in RNA-based prognostic gene signatures applied for breast cancer patients. Methods: During 1991-1998, a total of 315 LABC patients (cT1-cT4/cN0-N1) were treated with NRT-CHX. Preoperative radiotherapy (RT) consisted of external beam radiation therapy (EBRT) of 50 Gy (5 × 2 Gy/week) to the breast and the supra-/infraclavicular lymph nodes combined with an electron boost in 214 cases afterwards or -in case of breast conservation- a 10-Gy interstitial boost with (192)Ir after loading before EBRT. Chemotherapy was given prior to RT in 192 patients, and concomitantly in 113; 10 patients received no chemotherapy. The impact of age, tumor grade, nodal status, hormone and growth factor receptor status (ER, PR, EGFR), p53, ki-67, HER2/neu, and bcl-2 on pathological complete response pCR and disease-free survival were examined in uni- and multivariate terms. Results: Hormone receptor status, proliferative activity, bcl-2, EGFR-status and clinical tumor size had a significant impact on clinical outcome. Age, cN, grading, p53, and HER2/neu status failed to reach a significant correlation to complete remission. All examined immunohistochemical factors with the exception of EGFR, and all clinical factors displayed an univariately significant impact on DSF. Particularly, while HER-2/neu had no predictive value for pCR it displayed the highest impact on DSFafter complete response (n=92) , even in a multivariate setting with clinical tumor size and nodal status. Complementary, p53 was the most superior immunhistochemical factor for prognosis after neoadjuvant incomplete remission (n=223). Conclusions: Her2/neu is a predictive marker for overall survival independent from the pCR. Furthermore it has no predictive value for the pCR. P53 is a prognostic marker for patients with incomplete remission. Prospective studies are needed to evaluate their use for decisions to further individualize adjuvant treatment after neoadjuvant radiochemotherapy.