tbuckley/cabot-search huggingface dataset:
Inhibitor of differentiation-1 (Id1) characterization in poor prognosis (PP) hormone-refractory (HR) metastatic prostate cancer (CaP) primary tumors and matched metastases (MTS) using a new monoclonal antibody (MoAb)
Authors: I. Gil-Bazo, M. Ponz-Sarvisé, J. S. Chen, J. Rodríguez, P. A. Ngwega, C. Reyna, J. L. Pérez-Gracia, J. García- Foncillas, A. Calvo, A. Panizo-Santos
Journal: Journal of Clinical Oncology (2008)

22025 Background: Id1, involved in cell differentiation and tumor angiogenesis, has recently showed to mediate lung MTS from breast cancer. While the importance of Id1 in CaP endothelial cells is well established, its expression (exp.) and role in CaP cells is controversial. Using a new MoAb (195–14) for immunohistochemistry (IHC), Id1 exp. is limited to some PP breast tumors and other non-adenocarcinoma tumor types. A CaP mouse model shows higher Id1 exp. in poorly differentiated tumors. A previous study showed 3% of Id1-expressing CaP in unselected patients (pts). Whether Id1 exp. is a relevant feature in PP CaP tumor cells is still unknown. Therefore, we tested 195–14 in primary high-risk, HR, metastatic CaP samples and matched MTS. Methods: Thirty-three pts were selected. Formalin-fixed and paraffin- embedded prostate biopsy samples of each patient and matched MTS samples of 16 of them were stained and scored for tumor and endothelial cell Id1 exp. Anti-human Id1 rabbit MoAb 195–14 (diluted 1:500), (Biocheck), was used for IHC. Results: Most pts (median age 70) had high-risk (70% T3-T4; 61% Gleason 8 to 10; mean PSA at onset 58 ng/ml), HR, metastatic CaP (79% had 2 or more MTS locations including lymph node, bone or visceral MTS). 94% previously progressed to docetaxel. Median time-to-progression after chemotherapy initiation was 18 weeks and median overall survival 7 months, reflecting PP. Interestingly, 39% of primary CaP and 38% of MTS showed Id1 tumor cell exp. This unexpected higher incidence of Id1 exp. may be due to the selection of high-risk, PP, treatment-refractory pts. Consistently with other reports, 79% of primary neoplasms and 81% of MTS showed endothelial Id1 exp. Size of samples may account for Id1 exp. underestimation. Conclusions: Consistently with preclinical data, in this PP CaP cohort, Id1 exp. seems to be significantly higher than reported in unselected pts. For the first time, using a MoAb against Id1, CaP MTS demonstrate Id1 exp. with similar exp. patterns than primary tumors. Whether Id1 exp. profile is in fact crucial for PP and metastatic initiation of high-risk CaP needs further research. No significant financial relationships to disclose.
F-18 Fluorodeoxyglucose (FDG) PET and Indium-111 SPECT scans to track the biodistribution of macrophage-activated killer (MAK) cells linked with MDX-H210 in patients with epithelial ovarian cancer
Authors: H. M. Prince, L. R. Mileshkin, D. Wall, M. Thompson, J. Wong, D. Rischin, E. Lau, P. Eu, F. Auzelle, R. Hicks
Journal: Journal of Clinical Oncology (2004)

2595 Background: MAK cell immunotherapy has demonstrated activity in Phase I/II trials for patients (pts) with relapsed ovarian cancer. However, little is known about the in vivo distribution of these cells following injection. The aim of this study was to track the destination of MAK cells using PET or SPECT imaging after delivery via intravenous (i.v.) or intraperitoneal (i.p.) injection to pts with recurrent epithelial ovarian cancer. Methods: MAK cells were produced by in vitro culture of autologous monocytes, collected from pts via apheresis. The cells were stimulated by γ interferon plus GM-CSF, and then bound to the anti-HER2/neu antibody (MDX-H210). Prior to injection, the MAK cells were labelled with either F-18 FDG or Indium-111. Pts then underwent serial PET or SPECT scans, respectively to track the destination of injected cells. Results: 13 infusions have been performed in 7 pts, 5 of whom had both i.v. and i.p. (Table 1). In all pts after i.v injection, cells passaged firstly through the lungs and then to liver and spleen. Tracking of cells to sites of peritoneal tumor have been demonstrated after 5 of 7 i.v. injections (in 4 pts), using both PET and SPECT. Following i.p administration, cells distributed throughout the peritoneal cavity in 4 of 5 pts (limited due to adhesions in 1 pt), and tracking to tumor sites was also demonstrated in all 4 pts. Cells were still visible up to 96 hours on serial SPECT. No tracking to tumor was observed in 2 pts, most likely due to poor sensitivity of the method for low-volume disease. Conclusions: We have demonstrated that it is possible to label MAK cells being used for immunotherapy with radiotracers and track their progress in vivo following injection using both PET and SPECT scans. Tracking of cells to the tumour target has been observed after both i.p and i.v injection. No significant financial relationships to disclose.
Does home antibiotic therapy increase medical risk for patients with low-risk febrile neutropenia? A multi-institutional randomized trial
Authors: J. A. Talcott, B. Yeap, P. A. Godley, C. Lu, R. D. Siegel, J. A. Clark
Journal: Journal of Clinical Oncology (2004)

8113 Background: Home treatment of febrile neutropenia may improve patient quality of life and reduce costs, but new medical problems may remain undetected in outpatients, increasing medical risk. Prior studies have not used sensitive measures of medical risk, measured quality of life or assessed costs directly, including incremental costs to patients and their caregivers. In a multi-institutional randomized trial, we compared hospital care to early discharge to home care in low risk patients. Methods: Patients at low risk for medical complications by validated risk criteria after 24 hours of inpatient observation were randomized to continue their antibiotics in the hospital or receive the same antibiotics at home. Home patients were seen daily by nurses or physicians. The occurrence of subsequent major medical complications was determined by blinded review based on structured clinical summaries. Results: The study was closed after attaining one fourth of its accrual goal. As a result, randomization imbalances between arms occurred, 66 episodes for hospital care and 47 for the home arm were eligible and available for analysis. Although the same age (median: 47 years), patients on the home arm more often had no more than high school education (P= 0.04) and received Medicaid or free care (P= 0.04), and tended to be more often unemployed or disabled (P= 0.07). The two arms had similar initial maximum fever (median: 101°F) and ANC (median: 100/mm3). The median duration of fever was 3 days, of neutropenia 4 days, and of the episode 4 days on both arms. Five patients (11%) on the home arm were readmitted. Complications occurred in 6 episodes (9%) on the hospital arm and in 3 patients (6%) in the home arm, primarily hypotension (P=0.73; 95%CI for increase in home arm complications −13% to 7%). No patient died. Conclusions: In this study, using the same antibiotic regimens as hospital care and under structured daily medical supervision, home care for consenting low risk patients with febrile neutropenia did not worsen medical outcomes, despite adverse socioeconomic characteristics. However, premature study closure limited power. No significant financial relationships to disclose.
MDX-070, a human anti-plasma antibody, administered as either a single dose or as multiple doses to patients with hormone-refractory prostate cancer
Authors: T. A. Mays, J. Sarantopoulos, A. Tolcher, I. Lowy, G. Preston, E. Levy, M. D. Oslund, E. Manchen, A. Kelly, W. M. Stadler
Journal: Journal of Clinical Oncology (2006)

14549 Background: Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein that is specifically expressed in prostatic epithelial cells and up-regulated in hormone refractory prostate cancer (HRPC). MDX-070 is a HuMAb that recognizes conformational epitopes on PSMA, mediates anti-body-dependent cellular cytotoxicity (ADCC), and is internalized. The primary objective of these studies was to establish the safety and tolerability and maximum tolerated dose (MTD) of MDX070 in patients (pts) with HRPC. Secondary objectives included characterization of the pharmacokinetic (PK) profile and a preliminary assessment of clinical antitumor activity measured by PSA levels and scans. Methods: MDX070 was administered intravenously over 90 minutes to pts with HRPC as either a single dose (Protocol MDX070–01) at dose levels of 0.1 (3 pts), 0.5 (3 pts), 1 (3 pts), 5 (3 pts), or 10 (6 pts) mg/kg/dose or every two weeks for up to 4 doses (Protocol MDX070–02) at dose levels of 1 (9 pts), 5 (6 pts), and 10 (15 pts) mg/kg/dose. Pts with stable disease or better at the end of the treatment period could receive additional treatment cycles until progression in a companion protocol (MDX070–03). Results: There were no Grade 4 toxicities judged to be related to MDX070 administration. One patient experienced Grade 3 anorexia that was possibly drug-related (5 mg/kg). Grade 1 or 2 toxicities (reported in 35 pts in the clinical database- 18 in 01, and 17 in 02) deemed to be related to MDX070 included anorexia (2), fatigue (3), fever (4), nausea (3) and vomiting (2). No significant differences in toxicity were seen between dose groups. No &gt;50% decline in PSA or response according to RECIST criteria occurred in any of the dosing cohorts, but 6 patients had stable disease and received 1 or more additional cycles of treatment at the same dose. Conclusions: MDX-070 as monotherapy, at the dose levels administered, was safe and well tolerated. No objective antitumor activity was observed at the dose levels tested, however, 20% (6/30) had stable disease. Enrollment is continuing at the 10 mg/kg multi-dose cohort. PK analysis is ongoing. [Table: see text]
Early analysis of toxicity and surgery in patients treated with cetuximab single agent followed by 5-fu, cetuximab and pelvic radiotherapy as neo-adjuvant treatment for operable, locally advanced rectal cancer (rc)
Authors: F. Bertolini, S. Zironi, N. Malavasi, C. Dealis, F. Bertoni, L. Losi, S. Chiara, C. Sonaglio, G. Luppi, P. F. Conte
Journal: Journal of Clinical Oncology (2007)

14531 Background: Pre-operative chemo-radiotherapy in locally advanced RC has been used to improve local control and to facilitate sphincter-sparing surgery for distal tumors. Cetuximab, an anti EGFR monoclonal antibody, has proved efficacy in advanced colorectal cancer. Methods: Study design provided: 1) tumor biopsy to confirm diagnosis and to measure tumor biomarkers (EGFR, TS, p53, MAP kinase, Ki 67, p21, bcl-2; immunological cell profile at the tumor level: CD45RO, CD68, CD56 CD4+/CD25+, CD31, HLA-A, -B and -C), 2) Cetuximab single agent (400 mg/sqm loading dose, then 250 mg/sqm weekly) for 3 doses, 3) a second biopsy to evaluate tumor biomarkers, 4) Cetuximab 250 mg/sqm weekly plus 5FU (225 mg/sqm in continuous infusion) concomitantly with RT (50 Gy), 5) surgery. Tumor biomarkers are measured again on tumor specimen in non pCR patients (pts). 66 pts with resectable uT3/uT4 N0/+ RC will enter the study. Primary aim is: toxicity and activity (pathologic complete response). Secondary aim is: evaluation of biological parameters, rates of sphincter sparing surgery and disease free survival. Results: Up to now 29 pts are valuable for toxicity (M/F= 22/5; median age: 61; range: 35–74). Ultrasound staging at diagnosis is: uT3N0: 7; uT3N1: 20; uT4N1: 2. Four pts (14%) withdrew neo-adjuvant treatment after 1 administration of Cetuximab: 2 for hypersensitivity reactions (1 G3; 1 G4), 1 for progression and 1 for purulent arthritis. Twenty-two pts (75%) presented acne-like rash; treatment with Cetuximab was interrupted or reduced in 4 pts (14%): in 2 for acne-like rash grade 3 (NCI-CTC) and in 2 pts for refuse. Grade 1–2 gastro-intestinal toxicity (unrelated to Cetuximab) was observed in 13 pts (proctitis: 4; diarrhoea: 9); in 1 case: diarrhoea G4. Twenty pts are valuable for surgery: 18 pts (90%) underwent conservative surgery. Two pts (10%) experienced post-surgical complications: 1 anastomotic fistula and 1 colonic necrosis. Conclusions: Pre-operative treatment with 5FU, Cetuximab and pelvic RT is well tolerated and does not increase surgical complication rate. An update on efficacy data and biological markers evaluation will be presented at the meeting. No significant financial relationships to disclose.
Induction chemotherapy + gefitinib followed by concurrent chemotherapy/radiation therapy/gefitinib for patients (pts) with locally advanced squamous carcinoma of the head and neck: A phase I/II trial of the Minnie Pearl Cancer Research Network
Authors: H. H. Doss, F. A. Greco, A. A. Meluch, J. R. Gray, D. R. Spigel, D. L. Shipley, J. H. Barton, M. E. Kuzur, S. Ramsey, S. D. Lunin, J. D. Hainsworth
Journal: Journal of Clinical Oncology (2006)

5543 Background: Concurrent chemotherapy/radiation therapy (RT) improves treatment outcome in pts with locally advanced unresectable squamous cancers of the head and neck. We previously reported a 51% 3-year disease-free survival with induction paclitaxel/carboplatin/5-FU followed by concurrent paclitaxel/carboplatin/RT. In this phase II trial, we added gefitinib, an EGFR inhibitor, to a similar chemoradiation regimen. Methods: All pts had squamous carcinoma of the head and neck, with at least one of the following: N 1 -N 3 disease, T 3 or T 4 primary lesion, nasopharynx primary (except T 1 N 0 M 0 ). Additional eligibility: no previous therapy, ECOG PS 0 or 1, adequate bone marrow, kidney, liver function; informed consent. All pts received initial docetaxel 60mg/m 2 D1, 22; carboplatin AUC 5.0 D1, 22; 5-FU 200mg/m 2 , 24-hour CI, D1–43; gefitinib 250mg PO qd, D1–43. Beginning week 8, pts received RT, 1.8Gy single daily dose to total 68.4 Gy, and concurrent docetaxel 20mg/m 2 weekly × 6 doses + gefitinib 250mg PO daily. At completion of therapy, pts were reevaluated with CT scans and endoscopy. Results: 45 pts entered this trial between 8/04 and 8/05. Pertinent clinical characteristics: clinical T 3 /T 4 , 17; N 2 /N 3 , 23. 42 pts (93%) completed induction chemotherapy. 34 pts (76%) have completed combined modality therapy and have been restaged. Response to treatment: 11 CR (32%); 18 PR (53%); 5 stable/progression (15%). After median follow-up 7 months, 9 patients (20%) have developed progressive cancer. Actuarial PFS and OS at 1 year are 68% and 86%, respectively. Grade 3/4 myelosuppression was common, and grade 3/4 mucositis occurred in all pts during combined modality therapy. One pt had a treatment-related death during combined modality therapy. The addition of gefitinib did not substantially increase toxicity. Conclusions: This combined modality regimen was feasible and produced high response rates in pts with locally advanced head and neck cancer. Toxicity was consistent with other effective combined modality regimens for these pts. Further follow-up is needed to better assess the benefit of this approach. [Table: see text]
A pilot study of weekly docetaxel and daily trofosfamide as metronomic second-line chemotherapy in the treatment of metastatic non-small cell lung cancer (NSCLC)
Authors: M. Gorn, C. Habermann, I. Thom, G. Schuch, B. Andritzky, S. Brandl, I. Burkholder, D. K. Hossfeld, C. Bokemeyer, E. Laack
Journal: Journal of Clinical Oncology (2007)

18105 Background: An emerging notion for the treatment of advanced solid malignancies in adults is to manage it as a chronic disease and aim to keep tumor burden and associated symptoms at the lowest possible level. One of the most promising strategies to achieve this is to target the tumor vasculature using modified, “metronomic”, dosing schedules. We conducted a pilot study of weekly docetaxel in combination with daily trofosfamide as a metronomic second-line regimen in patients (pts) with metastatic non-small cell lung cancer (NSCLC). Methods: From March 2003 to November 2005, 21 pts with stage IV disease who had one prior chemotherapy were enrolled. Pts received docetaxel 25 mg/m 2 on days 1, 8 and 15, every 4 weeks plus trofosfamide 50mg per day. Results: Median age: 60 years; gender: 18 male (85.7%), 3 female (14.3%); median Karnofsky PS: 80%; histologic subtypes: 8 squamous cell carcinomas (38.1%), 7 adenocarcinomas (33.3%), 6 large cell carcinomas (28.6%); previous chemotherapy: platinum-based in 15 pts (71.4%), platinum-free in 6 pts (28.6%). A total of 62 chemotherapy cycles were administered. The median number of cycles per pt was 3 (range 1 - 8). The intent-to-treat overall response rate was 19% (95% CI 5.5 - 41.9) 1 CR (4.8%), 2 PR (14.3%), 9 SD (42.9%), 8 PD (38.1%). The median overall survival from onset of second-line therapy was 6.9 months (95% CI 5.0 - 13.9 months), the median progression-free survival 2.9 months (95% CI 1.58 - 6.28 months), the 1-year survival rate 28.6% (95% CI 14.5 - 56.2%), and the 2-year survival rate 7.1% (95% CI 1.26 - 40.6%). Hematological and non-hematological toxicities were mild. No grade 4 toxicity was observed. Conclusions: To the best of our knowledge, this is the first trial that combines docetaxel and trofosfamide for the treatment of NSCLC. Our results suggest that the concept of metronomic chemotherapy is a valuable addition to the treatment of NSCLC. The combination of docetaxel and trofosfamide is active and well tolerated as second-line therapy in pts with metastatic NSCLC. No significant financial relationships to disclose.
The Yale Gastrointestinal Cancer Biorepository: A comprehensive biospecimen and data resource for studying determinants of pancreatic ductal adenocarcinoma prognosis following curative-intent pancreaticoduodenectomy.
Authors: Bonnie Elyssa Gould Rothberg, Carol Deminie, Heather Lazowski, Joanna A Gibson, Charles Cha, Jill Lacy, Howard S. Hochster, Ronald R Salem
Journal: Journal of Clinical Oncology (2015)

272 Background: Although surgical resection can be curative for pancreatic ductal adenocarcinoma (PDAC), only 20% of patients qualify and, of these, only 20% survive for 5 or more years. Because tumor biology, germline genetics, environmental exposures and lifestyle factors all contribute, we designed the Yale Gastrointestinal (GI) Cancer Biorepository to partner biospecimen science best practices with comprehensive clinico-epidemiologic annotations evaluate determinants of outcome for PDAC and other GI cancers. Methods: Adult patients presenting to Yale GI Oncology Clinics with incident cancers who consent are interviewed using a validated instrument to capture demographics, medical comorbidities, family history of cancer, employment history and lifestyle choices including tobacco, alcohol, diet and physical activity. Buffy coat and 20 mL of plasma are collected pre-operatively. Surgical Pathology provides three 3 mm tissue cores to be stored in RNALater at -190°C in addition to formalin-fixed tissue blocks with time to fixation at ≤30 minutes. Confirmatory touch-preparations are required for all RNALater-preserved specimens. Periodic medical record abstraction documents recurrence, progression, treatment and vital status. Quality-of-life and lifestyle reassessments occur at 6 and 12 months post-diagnosis then annually thereafter. Results: Since our March 2012 launch, we consented 388 individuals including 57 PDAC patients undergoing pancreaticoduodenectomy with 16 (28%) having received FOLFIRINOX-based neoadjuvant therapy prior to surgery. Median follow-up is 7.9 months with 11 PDAC recurrences and 7 PDAC-related deaths confirmed. Receipt of neoadjuvant therapy trended towards downstaged cancers upon resection (p=0.08). Women (n=20) were more likely to be older (p=0.02) and trended towards less advanced cancers (p=0.06) but smoked, used aspirin similarly and have BMIs comparable with men (n=37). Exome and transcriptome analysis of tumor and germline are ongoing. Conclusions: Determinants of early-stage PDAC prognosis will emerge as this cohort matures.
Dose, Response, and Survival in Metastatic Mammary Cancer
Authors: A. Robert Kagan
Journal: Journal of Clinical Oncology (1985)

To the Editor: Congratulations to Hryniuk and Bush in their effort to make sense out of many different chemotherapy regimens. However, in my opinion, I think they interpret their results too narrowly. For example, in Fig 2 and especially Fig 4, a straight line parallel to the ordinate at 0.6 fits the data as well as a line with a slope. In Fig 5, I am led by the discussion to accept a line from a median survival time (MST) of 10 months to an MST of 20 months, as the CR plus PR percent is increased from 20% to 80%. A line parallel to the abscissa at an MST of 15 months fits the data as well. If the lines drawn through the data have slopes, then the authors are correct in postulating increased dose intensity from 0.6 to 1.0+ indicates increased responses and increased survival. On the other hand, parallel lines drawn through the data give an alternate conclusion, namely that a threshold must be reached to achieve maximum benefit and doses above the threshold dose achieve very little. Accepting the data points by Hryniuk and Bush without criticism, how do we know what line best fits their compilation of data, a straight line or a line with a slope?
Gene expression patterns identify patients with non-small cell lung cancer (NSCLC) who are at increased risk for venous thromboembolism (VTE)
Authors: V. S. Ramiah, A. Potti, H. Dressman, A. Bild, R. Peterson, M. Moore, D. Conlon, D. Harpole, J. R. Nevins, T. L. Ortel
Journal: Journal of Clinical Oncology (2006)

8535 Background: VTE is the leading cause of death in patients with cancer. The 1 year survival rate in patients diagnosed with cancer at time of VTE is 12% compared to 36% in cancer patients who are free of VTE .Also, a thrombotic event in a hospitalized cancer patient leads to higher in-hospital mortality.Thus,VTE in cancer patients may indicate a more aggressive phenotype. Methods: With the overarching goal of testing the ability of genomic profiling to detect biologically and clinically significant differences in patients with cancer and VTE, using NSCLC as a proof of principle, we expanded on previous work wherein we have shown the ability of multiple gene expression patterns (‘metagenes’) to predict a thrombotic event .96 patients with NSCLC were enrolled in this study. RNA was extracted and gene array data obtained using an Affymetrix U133 2.0 plus GeneChip. The clinical history of all 96 patients was reviewed to identify patients with a definitive VTE episode after the initial diagnosis of cancer and not within six weeks of surgery.14/96 (14.5%) patients met these criteria. We then identified 14 additional patients with NSCLC matched by age, gender and clinical stage patients who did not have VTE for at least 2 years following the diagnosis of cancer. Gene expression data was analyzed using a binary regression analysis. Results: Using the metagene approach, a discriminator gene set (n = 45) that differentiated patients with NSCLC and VTE from patients with NSCLC without VTE was identified. A leave-one-out cross validation performed to further assess the reliability of the discriminator metagene set was more than 85% accurate in identifying patients with NSCLC and VTE. Also, significant biologically relevant differences were seen between the comparison groups, to include genes such as P53, VEGFC, E2F4, TFPI and EPHB2 Conclusions: Our data suggests that a genomic approach can be used to identify with NSCLC that develop VTE, while also providing information important to an understanding of the underlying biology of the association between cancer and thrombosis. We are in the process of validating these results in a prospective trial. No significant financial relationships to disclose.