tbuckley/cabot-search huggingface dataset:
Detection of lung cancer circulating tumor cells by combining immunomagnetic and size-based separation.
Authors: Shadia Ibrahim Jalal, ChunLi Chang, Wanfeng Huang, Daniela Matei, Cagri Savran
Journal: Journal of Clinical Oncology (2014)

e22034 Background: Background: Circulating tumor cells (CTCs) have multiple potential uses in lung cancer patients (pts) including possibly providing a window through which the disease can be constantly analyzed on a molecular level. Various platforms are currently available for CTC isolation with limitations restricting their widespread clinical utility. The aim of this pilot study is to develop and test a novel system that uniquely combines immune-magnetic separation, high speed microfluidics and size based filtration for isolation of CTCs in lung cancer pts. Methods: Pts with histological diagnosis of advanced lung cancer who are either therapy naïve or have received therapy ≥ 3 weeks prior to sample collection, were enrolled. Participating pts provided two (8ml) blood samples at a single time-point. Blood samples were kept at 4◦C and analyzed within 12 hours. Samples were processed to remove RBCs, washed then incubated with beads conjugated to antibodies against EPCAM, EGFR and vimentin. The mixture was pumped into a fluidic chamber that contained a microchip with apertures larger than individual beads but smaller than the targeted CTCs. The mixture flowed parallel to the microchip and circulated for 3-5 minutes to attract the magnetized CTCs to the chip surface and filter out the unbound free beads. CTCs were then analyzed on-chip using a combination of criteria including shape, size, and immunofluorescence. The study is currently ongoing with target accrual goal of 60 pts. Results: 10 pts have enrolled on the study, with adenocarcinoma of the lung as the histology in 9 pts, and squamous cell carcinoma in 1 pt. Median age of study population was 66 years (range 53-72). Results are available for 8pts with the number of CTCs isolated/8ml blood sample as follows: 4 (pt #1), 8 (pt#2), 30 (pt#3), 20 (pt#4), 120 (pt#5), 48 (pt#6), 84 (pt#7), 32 (pt#8). The average number of CTCs was higher in untreated pts (71 +/-std 39.2) as compared to treated pts (15.5 +/- std 11.8). Conclusions: Early results of a novel microchip system confirm its capacity to isolate CTCs. The system has the capability to target multiple surface antigens to maximize the number of CTCs captured.
Phase II study of dacarbazine for metastatic colorectal cancer with determined MGMT status.
Authors: Alessio Amatu, Andrea Sartore-Bianchi, Katia Bencardino, Catia Moutinho, Giovanna Marrapese, Alessandro Belotti, Alessandra Gambaro, Andrea Cassingena, Filippo Venturini, Felicia Giacobbe, Andrea Sporchia, Calogero Lauricella, Roberta Schiavo, Manel Esteller, Salvatore Siena
Journal: Journal of Clinical Oncology (2012)

3570 Background: O 6 -methylguanine-DNA-methyltransferase (MGMT) is a DNA repair protein that removes mutagenic and cytotoxic adducts from O 6 -guanine in DNA. Roughly 40% of colorectal cancers (CRCs) display MGMT deficiency due to promoter hypermethylation leading to silencing of the gene. Alkylating agents exert their antitumor activity by DNA methylation at the O 6 –guanine site, inducing base pair mismatch; therefore, activity of these compounds may be enhanced in CRCs lacking MGMT (Esteller, 2004; Pegg, 1990). Despite anecdotal reports about activity of dacarbazine in CRC (Shacham-Shmueli, 2011) no clinical trials assessed monotherapy with dacarbazine for metastatic CRC. Methods: We conducted a phase II study of dacarbazine in CRCs who had failed standard therapies (oxaliplatin, irinotecan, fluoropyrimidines and cetuximab or panitumumab if KRAS WT), PS=0-1, with adequate organ function, and measurable disease as per RECIST criteria assessed by CT scans at baseline and every 8 weeks. All patients had tumor tissue assessed for MGMT as promoter hypermethylation. Patients received dacarbazine 250 mg/m 2 i.v. d1-4, q21 until PD or untolerable toxicity (with a maximum of 6 cycles in case of SD). We employed a Simon, two-stage design to determinate if the ORR of dacarbazine treatment would be ≥ 10%. Secondary endpoints were association of response/resistance with loss of expression of MGMT, PFS and disease control rate. Results: In the first stage, from June 2011 to November 2011 we enrolled 40 pts (male 68%, median age 67 y [range 29-81], PS=0 50%, KRAS mut 55%). Pts received a median of 3 cycles [range 1-11]. Toxicities included (All Grades/Grade 3-4 %): fatigue (58/5), constipation (38/0), nausea/vomiting (35/0), anemia (20/2.5), platelet count decrease (10/5). 36 pts were evaluable for objective response. Overall, 2 pts (5%) achieved PR and 5 pts (12.5%) had SD. All pts with PR had tumors with MGMT promoter hypermethylation. Conclusions: Having exceeded the boundaries of futility (at least 2 objective responses in the first stage), the trial proceeds to the second stage, enrolling 28 more patients. Analysis of MGMT promoter hypermethylation and association with sensitivity/resistance is performed at the end of the second stage.
Patient-reported cognitive impairments among women with breast cancer randomly assigned to hormonal therapy (HT) alone versus chemotherapy followed by hormonal therapy (C+HT): Results from the Trial Assigning Individualized Options for Treatment (TAILORx).
Authors: Lynne I. Wagner, Robert James Gray, George W. Sledge, Timothy Joseph Whelan, Daniel F. Hayes, Charles E. Geyer, Elizabeth Claire Dees, David Cella, Joseph Sparano
Journal: Journal of Clinical Oncology (2012)

9020 Background: Cognitive impairment is a complication of chemotherapy. Perceived cognitive impairments (PCI) were prospectively assessed among TAILORx participants randomized to HT alone versus chemotherapy followed by HT (C+HT). Methods: TAILORx participants with an OncoType DX Recurrence Score 11-25 were randomly assigned to HT or C+HT. PCI, fatigue, endocrine symptoms and health-related quality of life (HRQL) were assessed at baseline, 3, 6, 12, 24, and 36 months, using the Functional Assessment of Cancer Therapy (FACT) in 455 patients enrolled after 1/15/10. PCI change scores &gt; 4.5 from baseline were defined a priori as clinically meaningful. Linear regression (LR) was used to model PCI scores on baseline PCI, treatment and other factors. Results: PCI scores were significantly worse at 3, 6, and 12 months compared to baseline for both groups (Table). The decline was greater for C+HT than HT at 3 months, but scores were similar at 12 months. Tests of an interaction between menopausal status and treatment were non-significant. PCI correlated with fatigue (r = 0.57-0.64) but not FACT Emotional well-being (EWB; r = 0.28-0.38); controlling for EWB did not account for differences in PCI change scores between treatment arms. Conclusions: Our study is the first to examine PCI among breast cancer patients randomized to receive C+HT vs. HT alone. C+HT was associated with greater declines in PCI at 3 months, but at 12 months PCI was similar in the C+HT and HT groups. PCI was associated with fatigue but not EWB. Pre- and post-menopausal groups demonstrated the same pattern of change. Since this study did not include a control group of patients not treated with HT, further study is required to determine if and to what extent HT contributes to PCI. [Table: see text]
Doxorubicin, cisplatin, and ifosfamide (API) as first-line therapy for relapsed or metastatic uterine leiomyosarcoma.
Authors: Julien Hadoux, Annie Rey, Pierre Duvillard, Catherine Lhomme, Corinne Balleyguier, Christine Haie Meder, Philippe Morice, Sebastien Gouy, Catherine Uzan, Renaud Mazeron, Christine Larue, Patricia Pautier
Journal: Journal of Clinical Oncology (2012)

10098 Background: Uterine leiomyosarcomas (ULMS) are rare gynecologic malignancies characterized by a poor prognosis due to a high rate of local and metastatic recurrences. Chemotherapy (CT) with doxorubicin or ifosfamide or both is associated with a 10 to 30% objective response rate (ORR) and a cisplatin-based multiCT approach achieved a good response rate (DECAV therapy: API + dacarbazine + vindesine, 54% ORR in uterine sarcomas), though toxic. We aimed to determine efficacy and toxicity of doxorubicin, cisplatin and ifosfamide (API) combination as first line treatment of metastatic or relapsed ULMS (MRULMS). Methods: This monocentric study included MRULMS pts with a physiological age &lt; 65 y. CT consisted in doxorubicin 50 mg/m² d1, ifosfamide 3 g/m²/d d1d2 + mesna, cisplatin 75 mg/m² d3, + G-CSF; q 3 weeks. Results: Results in 38 pts with MRULMS were analyzed; median age was 51 (40-64), median cycles of CT was 5; 8 (21%) pts were treated for local relapse, 21 (55.3%) for metastatic disease and 9 (23.7%) for both. Metastatic sites were: lungs in 16 pts (42.1%), pelvis in 7 pts (18.4%), liver in 7 pts (18.4%), peritoneum in 6 pts (15.8%) and bone in 5 pts (13.2%); 14 pts (36.8%) had a multisite metastatic disease. Main grade 3-4 toxicities in 38 pts were neutropenia (74%), thrombopenia (60%), anemia (55%), fatigue (18%) and vomiting (13%). Febrile neutropenia was observed in 35% of pts and 1 patient died of septic shock after cycle 1. Thirty four pts were evaluable for response (4 pts had complete surgery at relapse) and 16 pts responded (4 CR + 12 PR) (ORR: 47%); 23.5% and 29.4% of the pts had respectively stable and progressive disease. For all pts (38) and evaluable pts (34), median PFS were 9.8 and 9.5 months and OS 27 and 25.3 months respectively. Conclusions: Despite toxicity observed, API is an effective treatment which compares favorably with other first line therapies for MRULMS pts.
Relationship between smoking, prognostic factors, and outcomes in patient (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving sipuleucel-T (sip-T): Preliminary analysis of the PROCEED registry.
Authors: Andrew J. Armstrong, Celestia S. Higano, Oliver Sartor, David F. Penson, Nicholas J. Vogelzang, Shaker R. Dakhil, Christopher Michael Pieczonka, Jeffrey L. Vacirca, Ronald F. Tutrone, Luke T. Nordquist, Nancy N. Chang, Matthew R. Cooperberg
Journal: Journal of Clinical Oncology (2017)

216 Background: Smoking is associated with poor treatment outcomes after definitive therapy for PC (Steinberger 2015 BJU Int; Joshu 2011 JNCI). However, there is a paucity of data on the effects of active smoking on pts with mCRPC. The PROCEED registry provides an opportunity to evaluate differences in disease characteristics and outcomes by smoking status in men receiving sip-T, an FDA-approved, autologous cellular immunotherapy for asymptomatic or minimally symptomatic mCRPC. Methods: Enrolled pts with mCRPC who never smoked (NS) or were current smokers (CS) were evaluated.Pt characteristics, time to first anticancer intervention (tACI; measured from last sip-T infusion to first ACI; agents: abiraterone, enzalutamide, docetaxel, cabazitaxel, radium-223), PC-specific survival, and OS were assessed. Results: Of 1956 enrolled pts with known smoking status, 904 were NS, 179 were CS; 873 were former smokers and not included in this analysis. Compared with NS, CS were younger, had lower BMI (p &lt; 0.001), higher hemoglobin (Hgb; p &lt; 0.001), lower lactate dehydrogenase (LDH; p = 0.05), and shorter time between PC diagnosis and first sip-T infusion (p = 0.01). Fewer CS pts had Gleason score &lt; 8 (p = 0.2) and prior radical prostatectomy (p = 0.07). CS and NS did not differ in pattern or extent of metastatic disease spread. CS was associated with shorter OS, PC-specific survival, and tACI (Table). Conclusions: CS were younger at enrollment and had shorter OS, PC-specific survival, and tACI. Higher Hgb in CS likely reflects reduced plasma volume and/or increased red cell production. A multivariate analysis of prognostic factors for survival outcomes including smoking status in mCRPC is planned. However, active smoking represents a possible modifiable risk factor in the mCRPC setting. Clinical trial information: NCT01306890. [Table: see text]
A randomized placebo-controlled phase II study with the cancer vaccine IGN101 in patients with epithelial solid organ tumors (IGN101/2–01)
Authors: H. Loibner, H. Eckert, N. Eller, F. Groiss, G. Himmler, F. Rosenkaimer, M. Salzberg, H. Samonigg, M. Schuster, A. Settaf
Journal: Journal of Clinical Oncology (2004)

2619 Background: IGN101 is a vaccine for therapeutic vaccination against cancers of epithelial origin. The immunogenic principle is the murine monoclonal antibody 17–1A.. The vaccine consists of 0.5 mg alum-adsorbed antibody for s.c. injection.. The antibody carries epitopes that structurally mimic epitopes of the pan-carcinoma glycoprotein EpCAM, and also binds to EpCAM. Repeated vaccinations induce antibodies against EpCAM which may lead to destruction of EpCAM+ tumor cells via activation of natural effector functions. The immunological hypothesis of induction of anti-EpCAM antibodies has been substantiated in phase I studies. Methods: IGN101/2–01 is a 1:1 randomized, blinded, placebo-controlled phase II trial with overall survival as primary endpoint. Secondary endpoints include safety, tolerability and immunogenicity. 240 patients with epithelial cancers stage III or IV, mainly colorectal cancer but also upper GI tract cancer or NSCLC have been recruited between Sept. 2001 and July 2003. Vaccinations with IGN101 or placebo are administered on days 1, 15, 29 and 57 followed by booster injections in weeks 16, 24, 32, 40 and 68. Serum samples are collected at days 1 and 57, in week 16, 32 and 52 and every 4 months thereafter for analysis of the humoral immune response against the vaccine antigen. Results: Almost 50% of patients in this placebo-controlled study mount an immune response to IGN101. An interim analysis concerning survival of 45 stage IV colorectal cancer patients has been conducted without unblinding the data. The two groups compared were the immune-responders and the non-responders. Since the two groups reveal a distribution of almost 50% each, they may reflect the two treatment arms. Data showed a significant survival benefit for patients having mounted an immune response. No unexpected toxicities were observed. Conclusions: The blinded preliminary correlation analysis of survival and immune response indicate a promising activity of IGN101 in metastatic colorectal cancer. Study end and final analysis of unblinded data is planned for July 2004. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Igeneon Igeneon Igeneon Igeneon Krebs-Immun- therapie Forschungs- und Entwicklungs-AG
A pilot study identifying cancer-associated macrophage-like cells in the blood of cancer patients.
Authors: Daniel Adams, Stuart S Martin, Monica Charpentier, Saranya Chumsri, Raymond C. Bergan, Irene M. Ogden, R. Katherine Alpaugh, Massimo Cristofanilli, Susan Tsai, Olga V. Makarova, Peixuan Zhu, Shuhong Li, Platte T. Amstutz, Cha-Mei Tang
Journal: Journal of Clinical Oncology (2014)

e22014 Background: Using a “liquid biopsy” to recover Circulating Tumor Cells (CTCs) has revealed an accompanying macrophage subset that may be a highly sensitive biomarker for solid tumors. This newly discovered cell type, defined as a circulating Cancer Associated Macrophage-Like cell (CAML), has been identified as a specialized cancer specific blood monocyte. We studied the peripheral blood of cancer patients to ascertain the prevalence of this cell in relation to CTCs. Here, we supply evidence that this previously unidentified circulating cell can be used in conjunction with CTCs to sequentially track cancer treatment and provide clinically relevant information in patients with solid tumors. Methods: Peripheral blood samples from 79 cancer patients were tested, with a patient distribution including, stage I - IV; breast, pancreatic, and prostate cancers; newly diagnosed/untreated patients; and patients undergoing systemic therapies. The study included 30 healthy controls. CellSieve microfilters were used to isolate both CTCs and CAMLs from 7.5 mL of whole peripheral blood. CTCs and CAMLs collected by this size exclusion technique were fixed, permeabilized, and stained with DAPI, antibody cocktail against cytokeratin 8, 18 and 19, EpCAM, and CD45. CAMLs were defined as enlarged, multinuclear cells with diffuse cytoplasmic cytokeratin, and CTCs were defined as filamentous cytokeratin cells that are not positive for CD45. Results: CAMLs were found in 97% patients with stage III/IV cancer, 83% with stage I/II and 92% of patients overall, regardless of cancer type. By comparison, CTCs were found in 54% of the same sample set. Specifically, CAMLs were found in 86% of prostate, 93% of pancreatic, and 97% of breast patient samples. CAMLs and CTCs were not found in controls. Conclusions: We present evidence that highly differentiated CAMLs can be found in the blood of most cancer patients, when tested by microfiltration. The presence of this cell expands the concept of using a “liquid biopsy” to indicate metastatic cancer and in sequentially tracking cancer treatment using circulating cells. Though preliminary, the presence of CAMLs in early stage patient samples suggests the possibility of using CAMLs as a biomarker for early stage cancer screening.
Targeting <i>ERBB2</i> mutations in urothelial carcinoma.
Authors: Francois Audenet, Sumit Isharwal, Maria E. Arcila, Samuel Funt, Jonathan E. Rosenberg, Dean F. Bajorin, Bernard H. Bochner, Michael F. Berger, Hikmat Al-Ahmadie, David B. Solit, Gopa Iyer
Journal: Journal of Clinical Oncology (2017)

354 Background: ERBB2 encodes human epidermal growth factor receptor 2 (HER2), a member of the EGFR family of receptor tyrosine kinases that signal through the pro-oncogenic MAP- and PI3K-kinase pathways. ERBB2 is altered by amplification and/or overexpression in various cancers, including urothelial carcinoma (UC). These alterations could confer sensitivity to ERBB2 kinase inhibitors in selected patients with UC. Methods: Patients diagnosed with UC were enrolled onto an institutional review board approved prospective sequencing protocol. Tumor and matched germline DNA were analyzed using the MSK-IMPACT assay that detects alterations in 410 oncogenes and tumor suppressor genes, including ERBB2. Results: Overall, 449 samples from 429 patients were sequenced from 2013 to August 2016. Genetic alterations in ERBB2 were found in 78 samples (17%). At the time of sample collection, 24 patients (31%) had non-muscle invasive bladder cancer (NMIBC), 30 patients (38%) had muscle-invasive bladder cancer (MIBC), 18 (23%) had metastatic disease and 7 (8%) had upper tract urothelial carcinoma (UTUC). Sixteen samples (21%) came from metastatic specimens. Of the observed 78 ERBB2 alterations, 20 samples had amplifications (26%) and 58 samples had mutations (74%). Seven samples (9%) had both. We identified 71 missense, 2 inframe and 1 fusion alteration, corresponding to a somatic mutation rate of 13.1%. Thirty-seven mutations (50%) were functionally characterized hot spots that are potentially actionable. Of note, the hot spot mutation S310F/Y was found in 29 samples (37%). Its mutation allele frequency varied significantly. There was a trend towards a higher mutant allele frequency of S310F/Y in higher stage disease without reaching statistical significance (Table). In our cohort, 3 patients were enrolled in clinical trials with ERBB2 kinase inhibitors based upon the presence of an ERBB2alteration. Conclusions: ERBB2is a frequent mutation at different stages of UC. In higher stage disease, clonal selection of the S310F/Y hot-spot mutation may occur and requires further study. [Table: see text]
PROBABILIDAD DE RECIDIVA TRAS DSE EN NEOPLASIAS EPITELIALES. ¿IMPORTA LA AFECTACIÓN DEL MARGEN LATERAL SI LA RESECCIÓN SE HA LOGRADO EN BLOQUE?
Authors: JC Marín-Gabriel, J Díaz-Tasende, P Cancelas-Navia, S Rodríguez-Muñoz, AJ Del Pozo-García, M Pérez-Carreras, M Alonso-Riaño, Y Rodríguez-Gil, G Castellano-Tortajada
Journal: Endoscopy (2015)

Introducción: Recientemente se ha publicado que el riesgo de recidiva tras DSE en neoplasias colorrectales extirpadas en bloque y con márgenes laterales no valorables se halla sólo levemente incrementado (2,2%) comparado con los casos con margen horizontal libre (0%).
Community that pays together stays together: Sharing of resources for colorectal cancer screening and treatment of the underserved population.
Authors: Katie E Dowd, Aparajita Mishra, Michelle Marsh, Dawn Cox, Nail Aydin, Derek Yang, Subhasis Misra
Journal: Journal of Clinical Oncology (2017)

561 Background: Bridging disparities to increase colorectal cancer (CRC) screening and treatment can be expensive and time consuming. This insurmountable cost often limits care; however, for every $1 spent on cancer screening $22.37 is saved on treatment costs and economic benefits. By finding cancer through free screening initiatives for the public, a new problem arises of how to fund further treatment. Methods: Project goals are to increase screening rates and knowledge about CRC and screening in our medically underserved region. The project provides screening at no cost, but these unfunded patients do not have coverage to treat their cancer diagnosis. By establishing partnerships with home health organizations, hospital CEOs, federally qualified health centers, locally elected officials, department of public health employees, and healthcare professionals our project has navigated patients through screening and treatment free of charge by encouraging community sharing of resources. Community relationships have been nurtured by utilizing quarterly program meetings, educational outreach for providers with CME credit, and cancer symposiums. This outreach provides an open forum to ask for feedback and coordinate care for the community with a primary focus on population healthcare management. Results: In addition to the many precancerous lesions removed, two cases were identified that needed further cancer treatment. The first patient did not qualify for county indigent clinic care. One private hospital waived the facility fees and we waived the surgeon fees, and the local cancer center agreed to cover adjuvant chemotherapy costs. Another patient was navigated to a local indigent care clinic, with CT scans paid by another nonprofit organization. This patient received surgery at no cost from the surgeon or hospital. These illustrations reflect community involvement in sharing cost for the uninsured. Conclusions: Utilizing cost and resource sharing through patient navigation can lessen the financial burden of caring for uninsured patients. By focusing on community relationships, our project is overcoming limitations to provide comprehensive care for patients.