tbuckley/cabot-search huggingface dataset:
Use of x-ray diffraction to detect changes in hair of women with breast cancer
Authors: J. M. Beith, G. Corino, P. French
Journal: Journal of Clinical Oncology (2008)

20732 Background: Mammography has improved survival from breast cancer by earlier detection. This is invasive and uncomfortable for women. Another non-invasive method of diagnosing breast cancer has been reported with the use of synchrotron small angle X-ray scattering of hair fibres. A correlation has been observed in women with breast cancer showing a change in X-ray diffraction in their hair, with a new ring superimposed on the normal diffraction pattern of α-keratin. Some investigators have been unable to reproduce these results. Methods: Women who had been diagnosed with early stage breast cancer within the last 4 weeks or who had advanced breast cancer had at least 10 scalp or pubic hairs cut close to the skin. Women were excluded if they had dyed their hair with in the last 6 weeks. 4 hairs per patient were mounted into the path of the synchrotron X-ray apparatus and the hair fibre centered in the beam using a digital video camera. The beam had an incident wavelength of 1.1168Å and a sample to detector distance of 1032mm. The samples were exposed to the beam for a period of 60 seconds. Diffraction data were collected on a MAR 345 detector. A pattern was deemed to be positive if a ring was present at a Q spacing of 0.132± 0.002 Å-1. Results: Hair was collected from 17 women with early stage breast cancer and from 18 women with metastatic breast cancer. The mean age was 56.5 (range 34–84). Overall 5 samples gave no ring in any hair fibres (2 early, 3 metastatic) and were false negatives. 3 were indeterminate (2 early, 1 metastatic) due to damaged fibres. Of the remaining 27 samples, 15 gave at least 3 positive hair samples. In the early group 12 of 15 (80%) and in the metastatic 14 of 16 (88%) had the presence of the ring for breast cancer in the diffraction pattern in at least one hair. Conclusions: The sensitivity of X-ray diffraction was confirmed in both early and metastatic breast cancer. This is the first report in metastatic breast cancer. This is less sensitive than previously reported 100% in early stage breast cancer. Further assessment of this technique is under investigation in combination with routine screening mammography. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Fermiscan Fermiscan Fermiscan Fermiscan Fermiscan
Prostate cancer with disseminated intravascular coagulation and excessive fibrinolysis (DIC XFL).
Authors: D. M. Hyman, H. I. Scher, L. J. Kampel
Journal: Journal of Clinical Oncology (2010)

e15063 Background: DIC XFL is a potentially life threatening complication of prostate cancer. Most reports are anecdotal involving only a handful of patients. This report describes the clinical findings in 42 patients seen over a 6 year period at Memorial Sloan-Kettering Cancer Center (MSKCC). Methods: Patients with prostate cancer seen at MSKCC between 2000 and 2006 were included if they had a single fibrinogen level < 150 mg/dL and two of the following: a platelet count of less than 150 x 109/L, D-dimer levels of > 0.5 mcg/mL and prolonged PT or aPTT. Patients with comorbid conditions causing coagulopathy were excluded. Results: 42 patients were identified. All had adenocarcinoma of the prostate, including one with neuro-endocrine features. Patients tended to have high-grade disease as defined by Gleason score: 6 (15%), 7 (31%) and 8-10 (54%). One patient developed DIC XFL immediately following prostatectomy. The remainder had advanced metastatic disease: bone (93%), nodes (55%) and viscera (36%). The median platelet count was 45 x 109/L and the median fibrinogen level was 45 mg/dL. These patients were heavily pretreated: 93% were castrate resistant and 50% of the patients had chemotherapy. The following sites of bleeding were observed: skin and soft tissue (26%), hematuria (21%), intracranial (21%), gastrointestinal (17%) and none (21%). Deep vein thromboses were not documented. Management included blood product transfusion, heparin, hormonal and chemotherapy. Overall, patients had a median survival of 4 weeks with a range of 3-14 weeks (25th and 75th percentiles). Hematologic improvement, defined as normalization of fibrinogen, was seen in 20% of the patients. 88% of responders received further hormonal or chemotherapy and all had improvement in PSA with a mean decrease of 65%. Median survival in this group was better at 26 weeks. Conclusions: DIC XFL is a rare complication of advanced stage prostate cancer. Measurement of fibrinogen is essential for diagnosis. Untreated, the risk of hemorrhage is high and the prognosis is poor. Prompt recognition and initiation of active prostate cancer therapy is therefore important. Hematologic responses appear to correlate with PSA decreases. No significant financial relationships to disclose.
Cancer testis antigen (CTAg) expression in early-stage triple negative (TN) breast cancer.
Authors: F. J. Chionh, S. Deb, A. Chakrabarti, J. Seah, J. S. Cebon, S. White
Journal: Journal of Clinical Oncology (2010)

e21100 Background: There are limited treatment options for TN breast cancer, as there is no role for hormone therapy or trastuzumab. Expression of CTAgs is confined to testis and cancer cells, making them ideal targets for specific vaccine treatment. We examined the expression of 4 CTAgs (MAGE-A3, NY-ESO-1, MAGE-A1, and MAGE-C1) in TN breast cancer to evaluate their potential as targets for vaccine treatment. We also investigated the association between CTAg expression and histopathologic prognostic factors. Methods: 39 patients with histologically confirmed early-stage TN breast cancer resected at Austin Hospital and The Northern Hospital from January 1, 2001 to February 28, 2009 were included. Immunohistochemical staining was performed on tissue microarrays of formalin-fixed paraffin-embedded tissues, with human testis as the positive control. We examined the proportion of tumours expressing CTAgs, percent of tumour area stained, and intensity of staining (semi-quantitative). Associations between CTAg expression and histopathologic prognostic factors were tested using Fisher's exact tests. Results: 82% (32/39; 95% CI 0.69 – 0.95) of tumours expressed one or more CTAg; MAGE-A3 was expressed in 59% (23/39; 95% CI 0.43 – 0.75), NY-ESO-1 in 51% (20/39; 95% CI 0.35 – 0.68), MAGE-A1 in 33% (13/39; 95% CI 0.18 – 0.49), and MAGE-C1 in 33% (13/39; 95% CI 0.18 – 0.49). There was co-expression of ≥2 CTAgs in 59% (23/39; 95% CI 0.43 – 0.75) of tumours. Staining of >50% of tumour area was observed most frequently in tumours expressing MAGE-A3 and NY-ESO-1 (30% and 20% of tumours, respectively); these CTAgs also had higher staining intensity. There was a positive association between CTAg expression and tumour grade (p = 0.02), but no association with T stage, nodal involvement, multifocal tumour, lymphovascular invasion or necrosis. Conclusions: We found that CTAg expression is very common in early-stage TN breast cancer. There was a positive association between CTAg expression and tumour grade. Staining of >50% of tumour area and higher staining intensity was most frequently observed in tumours expressing MAGE-A3 and NY-ESO-1. Development of vaccines against these CTAgs may have potential in TN breast cancer. No significant financial relationships to disclose.
The trifunctional antibody catumaxomab: Correlation between immunological response and clinical outcome—New analysis of a pivotal phase II/III study.
Authors: M. G. Ott, H. Lindhofer, R. G. Linke, M. Hennig, H. Martinius, A. Klein, D. Seimetz
Journal: Journal of Clinical Oncology (2010)

2551 Background: Catumaxomab, a trifunctional anti-EpCAM/anti-CD3 antibody is approved in the EU for intraperitoneal treatment of malignant ascites. In the pivotal study (Parsons et al. J Clin Oncol 2008;26:abst 3000) immunological response (IR) to this murine antibody was monitored. We report here the correlation between IR and clinical outcome. Methods: IR was measured as HAMA (human anti-mouse antibody) by ELISA (Medac) in patient (pt) blood at different time intervals. In a post hoc analysis of the randomized phase II/III pivotal trial the (HAMA +/−) response 8 days after completion of catumaxomab treatment was correlated to clinical outcome. Results: 76% of the tested pts were HAMA-positive. HAMA-positive pts showed a significantly longer puncture-free survival (primary endpoint), time to puncture and overall survival (OS, secondary endpoints) compared with HAMA-negative pts (Table). Of note, median OS in HAMA-positive pts was more than doubled compared with pts in the control group. HAMA-negative pts still benefit in time to first puncture, but do not in terms of OS. Conclusions: HAMA response after catumaxomab therapy is strongly correlated with a better clinical outcome, exemplified by the doubling of overall survival. Patients with a more functional immune system are suggested to induce a better immunological response to the tumor after catumaxomab treatment resulting in improved OS. Control group (n = 50) Median (days) Median (days) PuFs 21 p = 0.0327 p < 0.0001 TTFP 21 p = 0.0002 OS 62 p = 0.0003 Abbreviations: n, number of patients; PuFS, puncture-free survival; TTFP, time to first puncture. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Fresenius Biotech GmbH, TRION Pharma GmbH TRION Pharma GmbH
Inhibition of DNA Synthesis by an Extract From Human Placenta 2
Authors: H. P. Baden
Journal: JNCI Journal of the National Cancer Institute (1973)

A water extract of human placental membranes inhibited DNA synthesis and cell division in fibroblasts, lymphocytes, and epidermis. The effect occurred rapidly and was abolished by heating at 60°C. Gel filtration studies indicated the inhibitor had a molecular weight of about 70,000. Storage in aqueous solutions and treatment with trypsin resulted in marked loss of activity. No significant inhibition of RNA or protein synthesis could be demonstrated. The inhibitor did not exhibit cytotoxicity as judged by cytologic criteria and uptake of trypan blue, but cell death did occur after prolonged exposure.
Phase I study of cetuximab in combination with cisplatin or carboplatin and 5-fluorouracil (5-FU) in patients (pts) with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN)
Authors: Y. Humblet, E. Vega-Villegas, R. Mesia, A. Awada, L. Geoffrois, C. Borel, R. Hitt, N. Amellal, E.-H. Bessa, J. Bourhis
Journal: Journal of Clinical Oncology (2004)

5513 Background: The goal of this study was to investigate the safety and efficacy of cetuximab (Erbitux), an IgG1 monoclonal antibody targeting the EGFR, given in combination with platinum and various doses of 5-FU in pts with recurrent and/or metastatic SCCHN and to evaluate the pharmacokinetic profile of cisplatin and cetuximab. Methods: Main eligibility criteria: Stage III/IV recurrent and/or metastatic SCCHN not suitable for local therapy, no prior palliative chemotherapy (CT) except as part of a multimodal treatment for locally advanced SCCHN, adequate hematologic and biologic functions, and Karnofsky performance status (KPS) ≥ 70. Cetuximab was given at an initial dose of 400 mg/m2, followed by 250 mg/m2 weekly. Pts were randomized to receive either cisplatin 100 mg/m2 (day 2) or carboplatin AUC=5 (day 1). 5-FU was administered as continuous infusion on days 1 during 120 hours at the dose levels of 600, 800 and 1000 mg/m2/day. CT cycles were repeated every 3 weeks. Results: 52 pts (47 male, 5 female) were enrolled (12 pts in 5-FU low dose, 16 pts in medium dose and 24 pts in high dose), median age 55.5 years (33–77) and median KPS 80 (70–100). Typical grade 3/4 adverse events of 5-FU in combination with cisplatin and cetuximab (27 pts), regardless of relationship to the study medication, included neutropenia (48%), asthenia (30%), nausea/vomiting (30%), mucositis (15%), arrhythmia/myocardial infarction (15%), thrombopenia (11%), and dyspnea (11%); in the carboplatin group (25 pts), the most frequent grade 3/4 side effects were neutropenia (36%), asthenia (20%), dyspnea (12%), and thrombopenia (12%). Preliminary efficacy results are available for 47 patients: 2 CR, 21 PR, 16 SD, 7 PD, 1 not assessable. Overall response rate was 48.9% (95% CI: 34.6%–63.2%) disease control rate was 83.0%, (95%CI: 72.2%–93.7%). Conclusions: Cetuximab can be safely combined with therapeutic doses of cis-/carboplatin plus 5-FU. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck KGaA
Phase I clinical pharmacokinetics of RTA 744: A blood brain barrier penetrating anthracycline active against high-grade glioma
Authors: R. Kazerooni, C. Conrad, C. Baud, M. Johansen, N. Thapar, C. Meyer, W. Priebe, T. Madden
Journal: Journal of Clinical Oncology (2007)

2045 Background: Preclinical studies demonstrated that RTA 744, a 4’-O benzyl anthracycline designed to circumvent P-gp and MRP1-mediated efflux, effectively crosses the BBB, is retained in brain &amp; brain tumor tissue for &gt;24 hrs, and has demonstrated in vivo activity against glioblastoma multiforme (GBM) in an orthotopic model. Methods: We designed a multicenter, phase I dose- escalation study of RTA 744 administered as a short intravenous infusion for 3 consecutive days, every 3 weeks. Patients enrolled in the study were adult patients with recurrent or refractory GBM, anaplastic astrocytoma, or other primary brain tumors. Peripheral blood samples for PK analysis were collected prior to and at selected timepoints from 5 min to 96 hrs after drug administration, and quantified by LC/MS/MS. PK parameters describing RTA 744 disposition were determined by fitting compartmental models to individual patient plasma concentration-time data. Results: Twenty patients have been enrolled at daily doses ranging from 1.2 to 9.6 mg/m 2 . Mean (range) population terminal half-life was 34.6 (20.5–89.2) hrs, plasma drug clearance was 45.0 (27.4–86.9) L/hr/m 2 , and V ss was 1942 (684.9–4721.7) L/m 2 ; population PK values reported for doxorubicin are 20–32 hrs, 24–35 L/hr/m 2 , and 700–1100 L/m 2 , respectively. Regimen related toxicity has been minimal with the most common adverse event being myelosuppression. Percentage of unchanged parent drug renally eliminated was 2.4% (0.42–6.03%). Several partial responses and one complete response have been noted, even at dose levels below the observed MTD of 7.5 mg/m 2 /day. Conclusions: These results are similar to what we have observed in our preclinical studies, demonstrating increased lipophillicity and enhanced biodistribution of RTA 744 when compared to doxorubicin. Direct confirmation of drug penetration into the CNS has not been determined in this study, however this is the focus of an ongoing trial in patients with leptomenigeal malignancies. No significant financial relationships to disclose.
Identification of factors predicting loss of renal differential function on the operated kidney after laparoscopic partial nephrectomy
Authors: F. Pouliot, A. J. Pantuck, B. Calimlim, T. Dujardin
Journal: Journal of Clinical Oncology (2009)

e16015 Background: Partial nephrectomy (PN) is now the gold standard for small renal mass of less than 4 cm since it prevents renal insufficiency that may occur with radical nephrectomy. The impact of warm ischemis time (WIT) on the operated kidney's renal differential function (RDF) have been poorly studied in the litterature, especially when WIT is less than 30 minutes. We evaluated the effect of WIT and other perioperative factors on RDF function assessed by pre- and post-operative renal scintigraphy. Methods: Between 2003 and 2008, 182 laparoscopic PN were performed by a single surgeon on patients with two kidneys. Among those, 56 had a MAG3-lasix renal scintigraphy pre- and post-operatively between 7 and 14 days. Data were collected prospectively. Loss in RDF is calculated as follow: Loss in RDF=(RDF preoperatively-RDF postoperatively/RDF preoperatively) × 100. Results: Medians for age, pre- op creatinine, pre-op GFR (Cockroft formula) and tumor CT-size were 61 years, 83 μM, 83,2 ml/min and 26 mm, respectively. Median WIT and pre-operative RDF were 30 minutes and 50%. Median loss of RDF after surgery was 24%. In multivariate analysis, low pre-operative RDF, WIT and intrarenal location of the tumor were associated with a statistically significant loss of RDF (p&lt;0.05). Age, pre-op GFR, tumor CT-size, diabetes and HTN did not predict loss in RDF. Fitting the relative RDF loss versus WIT to a polynomial curve suggests that the rate of loss in RDF increase with WIT. The point of inflection of the polynomial curve (reflecting the maximal change in rates of loss in RDF) was estimated to be at 32 minutes. Linear regression curves show that loss in RDF rate is 0.8% per minute when WIT is less than 32 minutes and 1.3 % per minute when WIT is more or equal to 32 minutes. Conclusions: We show that a WIT of less than 32 minutes optimizes the chances of preserving RDF of the operated kidney and that the rate of loss in RDF is higher above 32 minutes. Finally, higher loss in RDF must be expected if the patient has a low pre-operative RDF and intrarenal location of the tumor. No significant financial relationships to disclose.
Phase I/II trial of capecitabine (C), dacarbazine (D) and imatinib (I) (CDI) for patients (pts) metastatic medullary thyroid carcinomas (MTC)
Authors: P. M. Hoff, A. O. Hoff, A. T. Phan, S. I. Sherman, J. Yao, N. White, L. Phan, J. L. Abbruzzese, R. F. Gagel
Journal: Journal of Clinical Oncology (2006)

13048 Background: MTC is a rare tumor that responds poorly to conventional chemotherapy. 5-FU and D are frequently used, with an expected response rate of around 15%. MTC is often associated with multiple endocrine neoplasia type 2, an autosomal dominant syndrome caused by a mutation in the RET proto-oncogene which encodes RET, a tyrosine kinase receptor. I is a tyrosine kinase inhibitor with activity against c-Kit, PDGF and possibly RET, and we postulated that its addition to chemotherapy would increase its efficacy against this disease. Methods: We designed a phase I/II trial combining escalating doses of oral C, IV D and oral I. Pts with any advanced solid tumors were eligible for the phase I part of the trial. Results: 13 pts were entered and 12 were eligible (7 MTC, 2 adrenocortical, 1 islet-cell, 1 insular thyroid and 1 small cell). 4 pts did not complete one cycle (1 pt withdrew after 5 days and 2 pts progressed in less than 10 days and were replaced for toxicity analysis, 1 had a DLT and is included). 3 patients were entered in dose level 1, without DLT. 2 out of 6 pts developed DLT at the second dose level (1 G 3 fatigue and 1 G3 hypokalemia). Three additional pts are being entered on dose level 1. The first one had PD after 7 days and is being replaced. For the 11 pts who were evaluable, best response was 3 SD (range 3 to 9 + months) and 8 PD. Conclusions: The combination of CDI is feasible but has resulted in an unexpected pattern of toxicity in this patient population, with fatigue and hypokalemia as the DLT. No significant diarrhea or hand-foot syndrome was seen. Only G1 and 2 fluid retention and neutropenia have been encountered. Only minor reduction in tumor size has been seen among these heavily pretreated pts. Once the phase I is complete, the trial will continue in a phase II setting for untreated MTC pts. [Table: see text] [Table: see text]
Imprint cytology of biopsied samples and rinse fluid cytology of forceps and brush improve the diagnostic power of fiberoptic bronchoscopy for peripheral lung cancer
Authors: K. Nishii, K. Masashi, K. Gemba, H. Ueoka, K. Kiura, T. Kodani, M. Tabata, M. Tanimoto
Journal: Journal of Clinical Oncology (2004)

7185 Background: Fiberoptic bronchoscopy is now routinely used for obtaining specimens to diagnose peripheral lung cancer. To improve the efficacy of fiberoptic bronchoscopy in the diagnosis of peripheral lung cancer, we evaluated the effectiveness of various techniques for obtaining samples for cytological examination. Methods: Between January 1984 and December 2000, flexible fiberoptic bronchoscopy under fluoroscopic guidance was performed in 1372 patients with lung cancer having no visible endoscopic findings. Histological examination of specimens obtained by forceps biopsy and cytological examinations of imprints of biopsy specimens, brushing, selective bronchial lavage, curettage, transbronchial needle aspiration, rinse fluids of the forceps, brush, curette, and aspiration needle, and all fluids aspirated during the bronchoscopic examinations were evaluated for diagnostic power. Results: Using these techniques, the overall diagnostic rate with bronchoscopy was 93.4%. The sensitivity of the histological examination was 76.9%, additional imprint cytology increased the sensitivity to 84.8% (p<0.0001), while additional cytology on the rinse fluid of the forceps increased the sensitivity to 83.8% (p<0.0001). The addition of both imprint cytology and cytology on the rinse fluid of the forceps increased the diagnostic rate to 86.2% (p<0.0001). Conclusions: Our results indicate that cytological examinations of the imprints of biopsy samples and the rinse fluids of the forceps and the brush improve the efficacy of fiberoptic bronchoscopy in the diagnosis of peripheral lung cancer. No significant financial relationships to disclose.
Treatment with temozolomide for malignant gliomas: Is rechallenge with alternative dosing regimens successful?
Authors: C. Balmaceda, S. Pannullo, J. Serventi, M. Sisti, J. Bruce, G. McKhann, R. Lai, S. Rosenfeld, R. Fine
Journal: Journal of Clinical Oncology (2006)

11514 Background: Temozolomide (TMZ) is an alkylating agent with activity against malignant gliomas. A variety of dosing schedules has been used including: 5 days on/21 days off (200 mg/m 2 /d), bid dosing (initial bolus of 200 mg/m 2 followed by bid dosing of 90 mg/m 2 × 9 doses), and 7 days on/7 days off (150 mg/m 2 /d). It is not known which regimens are the most effective. Furthermore, it is not known whether patients failing one schedule will respond to alternative ones. Materials and Methods: We report on a retrospective series of 8 patients (7 M, 1 F), who were treated with TMZ at least twice. Mean age at recurrence was 48 (26–58). Pathology revealed GBM (3), AA (4), and AO (1). 7 patients had received prior XRT. 7 patients had a local (L) recurrence at the time of retreatment with TMZ, and one patient had leptomeningeal (LM) and L recurrence. 7 pts received TMZ alone both at the time of the first recurrence and at the time of rechallenge. One patient had received TMZ concommitant with XRT and TMZ alone at the time of rechallenge. Results: See Table . Toxicity was mild and not different than that seen in patients treated with the first course of TMZ. Conclusions: While the number of patients is limited, some observations can be made: 1) patients can respond to TMZ at rechallenge, particularly if a prior response to TMZ had been observed. 2) Some patients who fail or respond modestly to one regimen may achieve a better response to alternative dosing schedules. Further studies need to address whether one regimen of TMZ given at rechallenge allows an improved survival as compared with other regimens without sacrificing safety. [Table: see text] [Table: see text]