tbuckley/cabot-search huggingface dataset:
Safety and feasibility of adjuvant chemotherapy with S-1 and concurrent radiotherapy for Japanese patients with breast cancer after primary systemic chemotherapy.
Authors: Takashi Shigekawa, Akihiko Osaki, Nobuaki Sato, Chizuko Kanbayashi, Hiroshi Sano, Toshiaki Saeki
Journal: Journal of Clinical Oncology (2013)

165 Background: Advanced breast cancer can respond to S-1. Other oral fluoropyrimidine-based regimen, tegafur-uracil (UFT) was proven to be effective as adjuvant chemotherapy in Japanese breast cancer patients. Adjuvant chemotherapy with S-1 was useful in gastric cancer patients and S-1 with concurrent radiotherapy was safe and effective in several kinds of cancer patients. We tested S-1 and concurrent radiotherapy as adjuvant therapy in curatively resected breast cancer patients after standard primary systemic chemotherapy. Methods: Adjuvant chemotherapy with S-1 consisted of eighteen courses (2-week administration and 1-week withdrawal), at 80-120 mg/body per day. In cases judged to require postoperative radiotherapy, it was concurrently initiated on day1 of the study (a fractional daily dose of 1.8 Gy, up to a total dose of 50.4Gy). If estrogen receptor and/or human epidermal growth factor receptor 2 were positive, endocrine therapy and/or trastuzumab were permitted concurrently. Results: Among 45 patients enrolled between September 2007 and September 2009 from 3 institutions, 43 patients were eligible. 32 patients (74.4%) received concurrent radiotherapy. 22 patients (51.2%) completed the scheduled courses of chemotherapy. The most common reason for withdrawal of treatment was the request to discontinue in 8 patients (38.1%) between 6 courses of the beginning due to subjective symptoms, such as anorexia. It was followed by the detection of recurrence in 7 patients (33.3%). Among 36 patients without recurrence, the planned courses of S-1 were administered to 22 patients (61.1%), and the cumulative rates of administration for 365 days were 66.4% (95%CI: 50.8-79.1%). Although grade 3 neutropenia (8.9%), leukopenia (4.4%), and diarrhea (4.4%) were observed, they were manageable, and no grade 4 adverse effects appeared. Conclusions: Except for a relative many withdrawal of treatment due to subjective symptoms in early courses, adjuvant chemotherapy with S-1 and concurrent radiotherapy have an acceptable toxicity profile, and it seems feasible. A phase III trial investigating the usefulness of adjuvant S-1 is now ongoing in Japan.
Association Study of Ploidy Category with Mitotic Disruption In Multiple Myeloma
Authors: Elena Dementyeva, Fedor Kryukov, Sabina Sevcikova, Pavel Nemec, Smetana Jan, Henrieta Greslikova, Romana Zaoralova, Ivana Buresova, Miroslav Penka, Petr Kuglik, Roman Hajek
Journal: Blood (2010)
Clinical factors and outcomes in HPV-associated anal canal cancer.
Authors: J. Nair, Y. Hu, W. M. Mendenhall, C. Liu, C. G. Morris, R. Zlotecki, J. Kirwan, L. H. Dang, S. Tan, E. Huang, C. J. Allegra, T. J. George
Journal: Journal of Clinical Oncology (2011)

4105 Background: HPV infection is a favorable prognostic factor in H&N squamous cell carcinomas. Some anal squamous cell carcinomas (ASCCA) are associated with HPV infection with limited data linking HPV status with other clinical risk factors or prognosis in ASCCA. Methods: Patients with non-metastatic ASCCA treated between 1979-2010 at the University of Florida were eligible. Risk factors, tumor characteristics and clinical outcomes were identified. Formalin Fixed Paraffin Embedded (FFPE) tissue samples were obtained and analyzed for Ki67%, p16 overexpression (p16ink+) and concurrent active high-risk HPV infection(HPV-ISH +/-). HPV status was correlated with clinicopathologic factors using descriptive statistics, contingency analysis and chi-squared tests. Results: 125 patients were eligible and included in the analysis. All patients received definitive radiotherapy (median 59Gy) with concurrent chemotherapy in 74%. 5 year PFS was 74%, OS was 81% with a 9% colostomy rate. Impact of known clinical risk factors is consistent with previous reports. 36 patients had FFPE available for analysis. All overexpressed p16ink with 23 (64%) demonstrating concurrent HPV-ISH +. Characteristics of the total patient group, FFPE available group, and HPV-ISH cohorts are in the table. Median follow-up of p16ink positive cases was 57 months. HPV-ISH + patients had higher incidence of N+ disease, history of condyloma, and less tobacco use. At 3 years, there were no significant differences in PFS (68 vs.73%;p=NS) or OS (90 vs 61%;p=NS) for HPV-ISH + patients. Conclusions: P16 overexpression was present in all samples analyzed. Concurrent active HPV infection may be associated with condyloma and N+ disease, but does not appear to impact PFS or OS in ASCCA. The prognostic impact of HPV infection in ASCCA may be limited. The p16 pathway may be a novel therapeutic target in ASCCA. p16ink positive Entire cohort (n=125) FFPE group (n=36) HPV-ISH + (n=23) HPV-ISH - (n=13) Median age (years) 58.8 58.3 58.6 53.3 Male (%) 36 22.3 22 24 T3/T4 tumor (%) 40 39 35 46 N+ (%) 22 25 30 15 Ki67 (%) — 80 80 70 Tobacco use (%) 56.8 58.3 47.8 76 History of condyloma (%) 21 — 30 15 HIV+ 6 — 1 1 Organ transplant 6 — 2 1
Phase II trial of gemcitabine, docetaxel, and cetuximab in advanced non-small-cell lung cancer (NSCLC)
Authors: J. R. Rubinsak, D. R. Spigel, J. D. Hainsworth, C. Webb, R. C. Inhorn, J. R. Infante, D. A. Yardley, H. A. Burris, E. R. Vazquez, F. A. Greco
Journal: Journal of Clinical Oncology (2008)

19045 Background: Disrupting epidermal growth factor receptor signaling is an effective treatment strategy in NSCLC. Cetuximab targets this receptor and is a standard treatment in colon and head and neck cancers. In this multicenter trial we evaluated cetuximab in combination with a non-platinum regimen in first-line advanced NSCLC treatment. Methods: This trial had a 2-stage design with a primary aim to achieve an objective response rate (ORR) of 25% (α .05, β .10). Patients (pts) with newly diagnosed unresectable stage III/IV NSCLC, measurable disease, ECOG PS 0–2, and signed informed consent were eligible. All pts received gemcitabine 1000mg/m2 IV and docetaxel 30mg/m2 IV days (D) 1, 8, and cetuximab 400mg/m2 D1, then 250mg/m2 weekly, every 21D up to 6 cycles. Pts were restaged every 2 cycles (per RECIST criteria). Results: 69 pts were enrolled from 7/05 to 9/07, with a median follow-up of 8 months (range 3 - 28 months). Enrollment was closed at one site (Nashville) due to a high rate of cetuximab hypersensitivity reactions (HSRs). Baseline characteristics: median age 69 years; male, 70%; ECOG PS 0 - 1, 88%; and adenocarcinoma / squamous / large cell / unspecified, 36% / 28% / 6% / 30%. The ORR was 18% (95% CI 10% - 30%). 34 pts (52%) had stable disease and 12 pts (18%) had progressive disease. 11 pts were not evaluable: pt decision, 2; treatment-related toxicity, 4; data unconfirmed, 1; and comorbidity, 4. The median time to progression was 4.5 months. Median overall survival and 1-year survival were 8 months (95% CI 5 - 10.5 months) and 35%, respectively. Grade (G) 3/4 non-hematologic toxicity in >5%: dyspnea (11%), fatigue (9%), hyperglycemia (6%), infection (11%), pain (9%), and rash (20%). G3/4 hematologic toxicity included neutropenia (20%) and thrombocytopenia (15%). There were 4 G3 and 1 G5 cetuximab HSRs for a severe HSR rate of 8%. Notably, 4 events occurred in the 12 pts enrolled in Nashville (33% severe HSR rate.) There were 3 (non-HSR) treatment-related deaths (infection, 1; respiratory failure, 2). Conclusions: Cetuximab does not appear to add to treatment efficacy when combined with gemcitabine and docetaxel in advanced NSCLC. A high rate of severe cetuximab HSRs necessitated trial closure at our Nashville site. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Genentech Bristol-Myers Squibb, Eli Lilly and Company, Genentech, GlaxoSmithKline, GPC Biotech, sanofi-aventis
Skin Lesions in Melanoma and Kaposi’s Sarcoma
Authors: Daniele Santini, Giuseppe Tonini, Bruno Vincenzi, Raffaele Murace, Giulio Ferranti, Alfonso Baldi
Journal: Journal of Clinical Oncology (2002)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.5.1411 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11870187 Skin Lesions in Melanoma and Kaposi’s Sarcoma Case 1. Detection of Circulating Malignant Cells by RT-PCR in a Case of Cutaneous Melanoma in Complete Regression Daniele SantinixDaniele SantiniSearch for articles by this author , Giuseppe ToninixGiuseppe ToniniSearch for articles by this author , Bruno VincenzixBruno VincenziSearch for articles by this author , Raffaele MuracexRaffaele MuraceSearch for articles by this author , Giulio FerrantixGiulio FerrantiSearch for articles by this author , Alfonso BaldixAlfonso BaldiSearch for articles by this author Show More Università Campus Bio-Medico, Centro Diagnostico, and Istituto Dermopatico dell’Immacolata, Rome, and Seconda Università di Napoli, Naples, Italy https://doi.org/10.1200/JCO.2002.20.5.1411 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Supportive care plans: Harnessing technology and patient-reported outcomes to drive quality care across the cancer continuum.
Authors: Jeannine Brant, Carrie Tompkins Stricker, Paul B. Jacobsen
Journal: Journal of Clinical Oncology (2014)

167 Background: Cancer care is increasingly complex. Clinicians lack time to stay current on evolving evidence and resources to implement quality standards. Health information technology solutions have proliferated, including electronic patient-reported outcome (ePRO) and care pathway technologies, but adoption has been slow. The goal of this study is to explore feasibility, usability, and acceptability of incorporating a novel supportive care planning technology into clinic workflow. The On Q Care Planning System (CPS) collects ePRO and clinical data to generate a personalized supportive care plan aligned with quality care standards and current evidence. Plans promote self-management and patient-provider communication. Methods: Prospective, multi-center pilot study at 2 NCI-affiliated centers (a comprehensive community cancer program [NCCCP] in the Western U.S., and a NCI-designated comprehensive cancer center [NCCC] in the Southeastern U.S.). 100 patients and their providers will participate; 50 women with gynecological cancers on chemotherapy; 50 women post-active treatment for breast cancer. Patients complete an ePRO assessment and are given an electronically generated, personalized supportive care plan by their providers during office visit(s) over a 3-month period. Study outcomes evaluated at baseline and 6 weeks include feasibility/usability of the platform (patient/provider, post-test only; surveys/platform statistics), patient satisfaction with care (pre/post-test; CG-CAHPS), and adherence to care plan recommendations (post-test survey). Results: To date, 10 patients have enrolled at the NCCCP and 7 completed baseline and 6 week measures; 5 at the NCCC have completed baseline measures. Four providers each at the NCCCP and the NCCC are scheduled for post-test assessments. Updated enrollment and results will be presented at the meeting. Conclusions: The On Q CPS is a novel supportive care planning technology developed to improve care processes and patient outcomes through the delivery of personalized electronic care plans. Feasibility, usability, acceptability, satisfaction and exploratory outcome data will be presented.
T-cell redirected killing and cure of pancreatic and gastric cancer xenografts by targeting Trop-2.
Authors: David M. Goldenberg, Edmund A. Rossi, Diane L Rossi, Thomas M. Cardillo, Chien-Hsing Chang
Journal: Journal of Clinical Oncology (2015)

262 Background: Trop-2 [also called tumor-associated calcium signal transducer 2 (TACSTD2), EGP-1 (epithelial glycoprotein-1), GA733-1, or M1S1]is a 35 kDa transmembrane glycoprotein that is overexpressed relative to normal tissues in a variety of human cancers, including pancreatic and gastric carcinomas, where increased expression correlates with poor prognosis. Trop-2 appears to be more tumor-specific than the related molecule, EpCAM (Trop-1). MT110, the EpCAM antibody x CD3 bispecific T-cell engager (BiTE), is currently undergoing a Phase I study in various solid tumors, including lung, gastric, colorectal, breast, prostate, and ovarian cancers. We produced a similar T-cell redirecting bispecific tandem scFv, E1-3, using the variable domains of hRS7 (humanized anti-Trop-2 mAb) and Okt-3 (anti-CD3 mAb). Methods: T-cell activation, cytokine induction and cytotoxicity were evaluated ex vivo using PBMCs or purified T cells with human pancreatic (Capan-1 and BxPC3) and gastric (NCI-N87) cancer cell lines as target cells. In vivo activity was assayed with NCI-N87 xenografts that were inoculated s.c. in a mixture with twice the number of human PBMCs and matrigel. Results: In the presence of target cells and PBMCs, E1-3 potently induced T-cell activation, proliferation, and dose-dependent cytokine production of IL-2 (&gt;2 ng/mL), IL-6 (&gt;1 ng/mL), IL-10 (&gt;7 ng/mL), TNF-α (&gt;1 ng/mL) and IFN-γ (&gt;50 ng/mL). In vitro, E1-3 mediated a highly potent T-cell lysis of BxPC3 [IC 50 =0.09(±0.04) pM], Capan-1 [IC 50 =1.2(±1.1) pM] and NCI-N87 [IC 50 =1.2(±1.2) pM] target cells. In vivo, two 50-µg doses of E1-3 given three days apart cured all of the mice (N=8) bearing NCI-N87 xenografts (P=0.0005; Log-Rank). Tumors in the control group (PBMCs only) reached the endpoint (TV&gt;1 cm 3 ) with a median of 39.5 days. All mice remained tumor-free in the E1-3 group at 78 days. Conclusions: Trop-2 is an attractive target for T-cell-mediated killing of pancreatic, gastric and other epithelial cancers.
Evaluation of oral chemotherapy prescribing at an outpatient oncology clinic.
Authors: George W. Carro, Bruce Brockstein, Thomas A. Hensing, Patrick Joseph Fleming, Shannon Maureen Gavin, Wayne Spath, Abigail Harper, Wendy Hui, William J. Uhlig, Brad Hughes
Journal: Journal of Clinical Oncology (2013)

191 Background: Oral chemotherapy’s exponentially increasing role in the treatment of malignancies continues to pose unique challenges to oncology. The American Society of Clinical Oncology (ASCO) and Oncology Nursing Society (ONS) drafted measures in the Chemotherapy Administration Safety Standards that help address some of these issues concerning oral chemotherapy. There is a lack of data describing the prescribing process for oral chemotherapy. In a retrospective chart review, prescriptions at a hospital-based outpatient oncology center were evaluated for completeness of prescribing and follow up measures. Methods: A retrospective chart review of ten oral chemotherapy medications from May 2012 to July 2012 was conducted. The primary outcome measure was compliance with ASCO and ONS Chemotherapy Administration Safety Standards. A secondary outcome was frequency of pharmacist interventions on oral chemotherapy prescriptions. Results: 412 prescriptions were evaluated. Prescriptions were graded on a scale from 1 to 8. One point was given for inclusion of each of the following: prescribing physician, patient name, drug name, dose, dosing methodology, quantity, refills, and accurate directions. Of all the prescriptions, 23% contained all aspects of a complete prescription. The most common reasons for point deductions were contradictory or unclear directions and allowing refills for oral chemotherapy which should not be refillable. Four percent of prescriptions had a documented pharmacist intervention. Conclusions: This study revealed areas for improvement in the prescribing process of oral chemotherapy. Targeting directions and refill fields within prescription templates will improve compliance with ASCO and ONS standards. This can be accomplished by implementing customized oral chemotherapy prescription templates within treatment plans in the electronic medical record system. Unlike chemotherapy administered in the clinic setting, oral chemotherapy prescriptions are not generally reviewed by oncology trained pharmacists. With the collaboration of medical and nursing staff, a new work flow was implemented which includes pharmacist review of electronic oral chemotherapy prescriptions.
Safety and pharmacokinetics of AMG 706 in patients with advanced solid tumors
Authors: L. Rosen, R. Kurzrock, E. Jackson, L. Wathen, M. Parson, M. Eschenberg, M. Mulay, M. Purdom, L. Yan, R. S. Herbst
Journal: Journal of Clinical Oncology (2005)

3013 Introduction: AMG 706 is a potent, oral, multi-kinase inhibitor with anti-angiogenic and antitumor activity achieved by selectively targeting all known vascular endothelial growth factor (VEGF) receptors, platelet-derived growth factor (PDGF) receptor, kit, and Ret. The safety and pharmacokinetics (PK) of AMG 706 were assessed in patients (pts) with advanced solid tumors in an open-label phase 1 study. Methods: Pts with advanced solid tumors, refractory to standard therapy or with no standard therapy available, were enrolled in this ongoing AMG 706 study. After establishing the maximum tolerated intermittent dose (21 days of therapy followed by 7 days without dosing) in 31 pts, an additional 34 pts were orally administered AMG 706 125 mg once daily (QD) in a continuous dosing pattern. Pts remained on study until disease progression or unacceptable toxicities occurred. Tumor response (modified RECIST) was evaluated at week 8 and every 12 weeks thereafter. Tumor vascular permeability was evaluated by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in 18 pts. Results: AMG 706 was generally well tolerated up to 125 mg QD using the intermittent and continuous dosing schedules, with 3 pts continuing on study for > 1 year. Most adverse events were mild to moderate in severity and reversible. Across all cohorts, the most frequent medication-related adverse events were hypertension (31%), fatigue (29%), and headache (25%) that were primarily of mild to moderate severity. Among 56 evaluable pts, best responses were 2 (4%) partial responses and 34 (61%) stable disease (including 17 pts with decreases ranging up to 29% in the sum of the longest diameter of target lesions). DCE-MRI showed reductions up to 37% in initial area under the curve on day 3 and up to 61% on day 21 of treatment. Conclusions: The continuous once daily dosing regimen of AMG 706 appeared safe at daily doses up to 125 mg, demonstrated vascular changes, stabilized disease in the majority of pts, and is recommended for phase 2 study. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen Amgen
Expression of Wnt gene family and frizzled receptors by quantitative real time PCR in head and neck human carcinomas
Authors: R. Garcia Campelo, M. Valladares Ayerbes, S. M. Díaz Prado, V. Medina Villaamil, J. López Cerdrún, M. Reboredo López, G. Aparicio Gallego, M. Haz Conde, I. Santamarina Caínzos, L. M. Antón Aparicio
Journal: Journal of Clinical Oncology (2008)

17035 Background: Genes of the Wnt and Fz class have an established role in cell morphogenesis, cellular differentiation and also in oncogenesis properties. It is known that Wnt and Fz proteins are expressed in head and neck small cell carcinoma (human tissue and cell lines).The aim of this analysis is study Wnt and Fz expression in cancer tissue samples obtained from the HNSCC patients. Assess possible correlation between the expression levels obtained in cancer samples in relation to clinicopathological data. Methods: A total of 22 unique freeze samples from 22 oncologic patients, which underwent surgical therapeutic removed, were analyzed. All tumour samples were confirmed by histopathological studies. Quantitative Real Time PCR (qPCR) experiments were performed on a LightCycler 480 Instrument (Roche) using LightCycler 480 SYBR Green I Master (Roche). A constitutively expressed gene, HPRT, was used as internal control. Each assay was done at least in triplicate and included marker-positive and marker-negative controls. At least one PCR product coming from each qPCR experiment was verified by DNA sequencing. Statistical analyses were performed using SPSS 12.0 for Windows. Results: Of the Wnt genes, WNT-1 is not expressed in the majority of the HNSCC studied; only 3 cases expressed Wnt-1. Wnt10B were the most strongly expressed by the malignant tumors. Among all Wnt genes, WNT10B expression levels were related with higher grade of indifferentiation. Related to Fz genes, Fz-5 showed more expression levels in advanced stages and in no-affectation of regional lymph nodes. Conclusions: Real Time PCR assays confirmed that Wnt and Fz genes are frequently expressed in HNSCC and they could represent attractive targets to drug therapy. Support: Merck Farma y Quimica S.L. (Spain). S. Díaz Prado is beneficiary of an Isidro Parga Pondal contract from Xunta de Galicia (Spain). No significant financial relationships to disclose.
Validation of differential expression of microRNA profiles in prostate cancer specimens.
Authors: Nikhil Waingankar, Nicholas Broccoli, Soroush Rais-Bahrami, Kevin Smith, Michaela Oswald, Houman Khalili, Annette Lee, Theresa Chan, Oksana Yaskiv, Peter Gregersen, Manish Arvind Vira
Journal: Journal of Clinical Oncology (2014)

203 Background: MicroRNAs (miRNA) are small, noncoding nucleic acids that regulate expression of genes. Altered expression of miRNA has been implicated as a factor in carcinogenesis. We previously demonstrated 27 miRNA with differential expression that varied greater than two-fold between areas of benign and cancerous prostate glands in 64 patients. The goal of this study was to validate these findings in a selected group. Methods: RNA was extracted from prostate cancer foci and areas of benign glands from paraffin embedded prostatectomy specimens from 29 selected patients. Five patients each were selected with Gleason 3+3, 3+4, 4+3, and 4+4 or higher. The remaining nine selected patients went on to develop metastatic disease. Expression profiles for 577 miRNA were analyzed using Taqman OpenArray. Data analysis was performed using the mean-centering method for normalizing miRNA across the original and validation cohorts. Results: Significant overlap was found between the original and validation cohorts for miRNA that were upregulated at least two-fold between benign and cancerous glands (p&lt;0.05). There were no differences in miRNA expression between T2 and T3 cases. Comparison of Gleason 6 vs Gleason 8+ showed significant difference in expression of mir-185, mir106b, and mir-181a. Interestingly, among the subset of patients that developed metastatic disease, the benign prostate glands demonstrated significant overexpression of mir-21 as compared to the benign glands of the localized cohort. Mir-21 is a known oncomir shown to be overexpressed in other metastatic tumors. Conclusions: This study validates our findings on differential expression of miRNA between cancerous and benign glands. There was a significant difference in expression of three miRNAs between Gleason 6 and 8 cancers, and no differences were found between T2 and T3. miRNA may represent a unique signature in the benign glands of patients with metastatic disease.