tbuckley/cabot-search huggingface dataset:
Colorectal cancer patients’ informational needs about sexuality related issues
Authors: S. Karagiannis, P. Heras, A. Hatzopoulos, A. Georgopoulou, K. Kritikos
Journal: Journal of Clinical Oncology (2006)

18569 The aim of this study was to identify and describe the importance of information for patients about sexuality related issues during hospitalization. 112 patients (87 with colorectal cancer) completed the structural questionnaire. Most colorectal cancer patients (71%) reported that their disease or its treatment had affected their sexuality. Men reported slightly more adverse effects of disease or treatment on their sexuality than did women. Effects on sexuality were reported by 77% of men and 64% of women (p=0,041) having colorectal cancer. Among younger colorectal cancer patients reported more often effects of disease than did older colorectal cancer respondents. Over than half, 75% (n=84) of respondents under 40 and 67% (n= 75) of respondents over 50 years old complained effect on sexuality. Most colorectal cancer patients (72%) stated that it is necessary to discuss about the effect of the disease and of its treatment on sexuality during hospitalization. Most colorectal cancer patients (87%) wanted the health care personnel to take the initiative for the discussion of sexuality related issues. Only 12% expressed the wish that the initiative should come from the patient. It is important that health care professionals provide colorectal cancer patients with an opportunity to discuss sexuality related issues. The caring organization should develop, introduce and evaluate action models to facilitate especially opening discussion for these sensitive issues. No significant financial relationships to disclose.
Effect of follow-up provider source on outcomes of patients with hematologic malignancies receiving hematopoietic stem cell transplantation
Authors: F. R. Loberiza, M. H. Villanueva, M. Devetten, A. K. Ganti, L. J. Maness, P. J. Bierman, R. G. Bociek, J. O. Armitage, J. M. Vose
Journal: Journal of Clinical Oncology (2006)

6112 Background: Studies have shown that involvement of trained physicians is associated with favorable outcomes of patients receiving hematopoietic stem cell transplantation (HSCT). At the University of Nebraska Medical Center (UNMC), most patients are shifted back to the care of their referring physicians in the first 100 days. We evaluated whether the practice of shifting care of patients from specialists to primary care providers (PCP), referred to as patient care oscillation, in HSCT results in optimal outcomes. Methods: Data from 666 patients who underwent HSCT for malignant hematologic disorders between 2000 and 2003 were analyzed. Cox proportional hazards regression analyses were done to compare the relative risk of relapse/progression and mortality at 100-days and 1-year between patients whose care remained with specialists (transplant MDs at UNMC or community oncologist) versus those who were transferred back to the care of referring PCPs while adjusting for patient and disease factors. Results: Rate of patient care oscillation varies according to type of transplant. In allo-HSCT, 50% of patients received follow-up care from PCPs, 30% from community oncologists, while 20% remain at UNMC for follow-up. In auto-HSCT, 70% of patients received follow-up care from PCPs, 20% from community oncologists, while 10% remain at UNMC for follow-up with transplanting physicians. Outcomes after HSCT according to type of transplant is shown in the table. Conclusions: These preliminary findings suggest that in both allogeneic and autologous HSCT, the risk of disease progression/relapse and mortality may be independent of the type of follow-up care provider. However, further studies are needed to determine whether the practice of shifting the care of HSCT patients results in similar medical care utilization, post-transplant complications, re-hospitalizations and patient satisfaction. Patients likely to benefit from specialized versus primary care should be identified. [Table: see text] No significant financial relationships to disclose.
The role of positron emission tomography in the detection of recurrence in symptomatic patients with stage II and III breast cance
Authors: R. M. Wolfort, B. D. L. Li, R. H. Turnage, M. R. Ramaswamy, F. Ampil, G. Burton, Q. D. Chu
Journal: Journal of Clinical Oncology (2004)

720 Background: Imaging modalities such as CT scans, bone scans, and MRI have been used as an adjunct to detect recurrence in high-risk breast cancer patients. The role of positron emission tomography (PET) for patients with Stage II and Stage III breast cancers who present with signs and symptoms suggestive of recurrence is evolving. We report our experience with PET scans for detecting recurrence in this population. Methods: Between January 2000 to November 2003, 22 patients with stage II and III breast cancer who present with signs and symptoms of recurrent disease underwent PET scans. These patients also underwent other imaging modalities as part of their work-ups. Patients were staged according to the 2001 AJCC staging system. The PET scan results were correlated with other imaging modalities and/or confirmed by tissue biopsy of suspicious lesions. Results: Of the 22 patients studied, three patients were excluded for the following reasons: 2 patients had incomplete data, 1 patient had a primary breast sarcoma. There were six patients with stage II breast cancer and thirteen patients who had stage III breast cancer. Overall, there were 11 true positives, five true negatives, and three false negatives. Since there were no false positives, the specificity and positive predictive values were therefore all 100%. The overall sensitivity was 78.6% with an overall negative predictive value of 62.5%. For stage II cancers, PET scan had a sensitivity of 75% and a negative predictive value of 75%. For stage III cancers, PET scan had a sensitivity of 80% and a negative predictive value of 50% (Table 1). Conclusion: Positron emission tomography is an effective modality to detect recurrent breast cancer in symptomatic patients with stage II and III disease. No significant financial relationships to disclose.
Tuberculosis as Complication of Diabetes Mellitus
Authors: W. R. Gauld, A. Lyall
Journal: BMJ (1947)

During the nineteenth century, when the incidence of and the mortality from pulmonary tuberculosis were much greater than at present, a large percentage of sufferers from diabetes mellitus died of coma, and most of those who survived this died of pulmonary tuberculosis.Publications towards the end of that century indicate that 50% of diabetics succumbed to pulmonary tuberculosis.For example, Windle (1883) reported that of 333 diabetic cases coming to necropsy half had active tuberculous lesions.Naunyn (1906) found pulmonary tuberculosis in 264 out patients suffering from diabetes over the period 1932-46.Among these were 60 deaths-11 from pulmonary tuber- culosis after 1936, with eight such deaths during the war years.A review in 1945 showed that of 657 patients alive at that time 239 were males and 418 females; 12 were under 15 years and 236 between 15 and 45 years of age; and 387 were under insulin treatment.The cases con- sidered here are summarized in Table I.In all cases the patients were definitely diabetic, and the diagnosis of tuberculosis was verified by isolation of the tubercle bacillus.In 11 cases the diabetes preceded the onset of tuberculosis by periods of up to 13 years, while in the other six cases the diagnoses were made simultaneously.Fourteen patients were males and three females.The diabetic condition was detected on an average at 40.18 years of age, and the tuberculosis at 44.23 years.In the greater percentage of cases the tuberculosis made its appearance in the fifth decade, whereas the majority of cases of tuberculosis in the general population occur in the second or third decade.This suggests that tuberculosis
Das28 responses in patients with active rheumatoid arthritis who received golimumab and methotrexate: A randomized, double-blind, placebo-controlled phase 2 trial
Authors: J. Kay, E. L. Matteson, B. Dasgupta, P. Nash, P. Durezs, S. Hall, J. Han, M. U. Rahman
Journal: Annals of the Rheumatic Diseases (2006)
Circulating CD68 positive (+) leukocytes in blood samples from patients (pts) with breast cancer (BC).
Authors: Maryam B. Lustberg, Brandon L. Miller, Yongqi Wu, Wei Xue, Clayton Deighan, Sarah Carothers, Michael J. Berger, Charles L. Shapiro, Jeffrey J. Chalmers
Journal: Journal of Clinical Oncology (2012)

172 Background: Several different CD45 + leukocyte populations are present in primary breast tumors and stroma (Coussens et al, 2011). These include CD4+/CD8+ T cells and myeloid derived cells such tumor associated macrophages/monocytes (TAMs). TAMs are under investigation as prognostic and predictive markers during chemotherapy (CX). The detection of TAMs has been restricted thus far to tumor tissue. We hypothesized that we can detect changes in CD45+ leukocyte populations in blood samples obtained before and during CX from pts with early and advanced BC. Methods: Venous blood samples from BC patients were collected, and were either directly analyzed or further processed using previously described immunomagnetic negative depletion. Multistep, sequential labeling was performed to first label and fix cell surface markers followed by permeablization for cytokeratins, before and after negative depletion, followed by multiparameter flow cytometry analysis for the following basic markers: CD45, cytokeratins, and EpCAM, and for a subset of patients additional markers including: CD13, CD14, CD68, and CD133. Results: Forty blood samples were analyzed and study is ongoing. Different CD45+ subpopulations were observed in peripheral blood including: a) CD45+, CK+, CD68 negative (-), b) CD45+, CK+, CD68+, c) CD45+, CK+, CD68+, CD14+, and CD16+. In addition, there was a trend in increasing CD 68+ leukocytes after 1 cycle of CX in pts with poor response to therapy or progression of disease. No abnormal cell subpopulations were present blood samples from healthy volunteers. Conclusions: This is the first study to report various peripheral blood leukocyte populations in BC that are similar to those observed in primary breast tumor stroma. The precise origin of these CD45 + cells is under investigation, including additional phenotypic characterization for TAMs. Results will be correlated to patient stage, tumor subtype and response to therapy.
Inducing mammaglobin-A (mamA) specific HLA class I tetramer positive CD8+cytotoxic T-lymphocytes (CTL) against breast cancer by DNA vaccination
Authors: A. Bharat, K. Narayanan, N. Benshoff, J. Dietz, W. Gillanders, T. Fleming, T. Mohanakumar
Journal: Journal of Clinical Oncology (2006)

2522 Background: We recently reported that DNA vaccination using MamA, a highly expressed human (hu) breast cancer specific protein, leads to immunity against breast cancer. Here we demonstrate that the induction of breast cancer immunity following MamA DNA vaccination occurs through the expansion of CD8 + CTL by using HLA class I MamA peptide tetramers. Methods: HLA-A2 + huCD8 + double transgenic mice received four (100μg) two-weekly IM injections of PCI-neo vector cloned with hu MamA gene. HLA-A2 tetramers (tet) carrying an immunodominant Mam 2 .1 peptide (LIYDSSLCDL) were used to monitor development of mam-A specific CD8 + T cells. Specificity of tetramers was tested against CD8 + CTL lines developed in vitro by stimulation of normal hu HLA-A2 + peripheral blood lymphocytes with TAP-2 deficient T2 cells pulsed with pooled MamA HLA-A2 binding peptides. Results: There was a sequential expansion of Mam 2 .1 tet + CD8 + T cells during stimulation of hu PBLs with MamA peptides in vitro (&lt;1% pre-stimulation to &gt;15% after six stimulations). These Mam 2 .1 tet + CD8 + T cells were HLA-A2 restricted and MamA specific since they revealed cytotoxicity only towards UACC-822 (HLA-A2 + MamA + , 75% lysis) but not MCF-7 (A2 + MamA − ) or DU-4475 (A2 − MamA + ) breast cancer cell lines. In contrast, there was no binding of MamA peptide tetramers to control Flu-specific CD8 + CTL lines (&lt;1%). MamA DNA vaccination, but not PCI-neo vector alone, of HLA-A2 + huCD8 + mice lead to the expansion of Mam 2 .1 tet + CD8 + T cells (&lt;0.7% pre-vaccination to &gt;2.5% post-vaccination) in the peripheral blood that revealed in vitro cytotoxicity against UACC-822 (70% lysis) but not against DU-4475 or MCF-7 breast cancer cell lines. Adoptive transfer of both whole splenocytes or fractionated CD8 + T cells from vaccinated mice into immunodeficient SCID-beige mice with previously established subcutaneous hu breast cancer colonies lead to tumor infiltration of tet + CD8 + CTLs and, at 4-weeks, at least 80% tumor regression of UACC-822 but not DU4475 or MCF-7 colonies. Conclusions: MamA DNA vaccination resulted in the expansion of CD8 + CTL. The CD8 + CTL were HLA class I MamA peptide tetramer positive, HLA class I restricted and specifically lysed mamA + human breast cancer cells both in vitro and in vivo. No significant financial relationships to disclose.
Clinical development of CX-3543, a novel multi-targeting antitumor agent
Authors: J. K. C. Lim, W. G. Rice, M. K. Schwaebe, A. Siddiqui-Jain, K. B. Trent, J. P. Whitten, L. H. Hurley, D. D. von Hoff
Journal: Journal of Clinical Oncology (2005)

3206 Background: The targeting of cell signaling pathways as an effective therapeutic strategy has been validated by the emergence of new anticancer drugs such as the tyrosine kinase inhibitors. In a novel therapeutic approach, a G-quadruplex DNA motif found in the promoter regions of many well characterized oncogenes has been targeted by a synthetic small molecule, CX-3543. Methods: Medicinal chemistry efforts introduced drug-like moieties to achieve desirable DNA recognition and ADMET properties, and customized screening and molecular selectivity assays were used to confirm that CX-3543 selectively targets the parallel-type quadruplex with significant preference over other types of quadruplex conformations, or single stranded or duplex DNA. Results: Molecular selectivity assays have shown that CX-3543 targets the quadruplex structures found in the promoter regions of several major oncogenes, including VEGF, PDGF-Α, HIF-1α, H-Ras, c-Myc and others. In vitro tests conducted with CX-3543 have demonstrated no significant inhibition of liver cytochrome P450 enzymes, very low metabolism when incubated with human hepatocytes, and no mutagenic effects in the Ames bacterial mutagenicity assay. CX-3543 displays favorable pharmacokinetic properties in mice, rats and dogs, and is well tolerated in murine xenograft models dosed at levels substantially higher than needed for an antitumor effect. Moreover, in vivo tests have shown that CX-3543 inhibits xenograft tumor growth in murine models of pancreatic cancer (MiaPaCa), refractory prostate cancer (PC3), and colorectal cancer (HCT-116). Conclusions: Phase I clinical testing of CX-3543 is planned for early 2005. Eligible cancer patients will be enrolled with tumors that are likely to be driven by the relevant oncogenes including certain lymphomas and colorectal, renal, lung, prostate, ovarian, pancreatic and breast cancers. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cylene Cylene Cylene
Final results of a phase I study of daily PI-88 as a single agent and in combination with dacarbazine (D) in patients with metastatic melanoma
Authors: M. Millward, A. Hamilton, D. Thomson, A. Gautam, E. Wilson
Journal: Journal of Clinical Oncology (2007)

8532 Background: PI-88 is a heparan sulfate mimetic that inhibits angiogenesis and metastasis directly and via release of tissue factor pathway inhibitor (TFPI). PI-88 has shown some efficacy in an intermittent dosage regimen (250 mg/day 4 days/week) in melanoma (Thomson et al, ASCO 2005). This study tested PI-88 7 days per week alone (group 1) and in combination with 3 weekly D (group 2). Methods: Eligibility included inoperable metastatic melanoma, no prior chemotherapy, PS 0–1, adequate organ function, no recent use of heparin, negative anti-heparin antibody (AHA), no concurrent use of anti-coagulants or anti-platelet agents, no history of GI bleeding. Group 1 cohorts received daily PI-88 in doses of 140 mg, 190 mg and 250 mg. Group 2 received PI-88 commencing at the level below the single agent MTD plus D 1,000 mg/m 2 every 21 days. Group 1 pts who had PD could continue PI-88 with the addition of D. FDG-PET scans were performed prior to and after 6 weeks PI-88 in Group 1. Free TFPI was measured in serum prior to and up to 2hr post first dose PI-88 in group 1. Results: Group 1 - DLT occurred in 0/3 (140 mg), 0/3 (190 mg) and 2/3 (250 mg) pts. Group 2 - DLT occurred in 1/6 (140 mg) and 0/4 (190 mg) pts. All DLTs were AHA positive grade III/IV thrombocytopenia with in 1 pt (250 mg) cerebral venous sinus thrombosis. No other major toxicities and no increase in expected DTIC toxicities were observed. 4 group 1 pts had pre/post PET scans. One pt had 50% fall in SUV max with radiologic SD for 4 months. No radiologic responses occurred with PI-88 alone. 3/9 pts in group 2 had radiologic PR. 2/5 group1 pts who had D added to PI-88 had PR. Free TFPI increased from 6.9 ± 1.9 ng/ml just prior PI-88 to 56.1 ± 19.4 30 min post PI-88. The elevated levels were maintained at 60 and 120 min. Elevation of free TFPI did not correlate with PI-88 dose. Conclusion: The recommended phase II dose of continuous daily PI-88 is 190mg alone and in combination with D 1,000 mg/m 2 every 3 weeks. An ongoing randomised study is comparing D 1,000 mg/m 2 plus PI-88 190mg/day to single-agent D. No significant financial relationships to disclose.
Induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone for unresectable stage III non-small cell lung cancer (NSCLC): Randomized phase III trial
Authors: S. Kim, M. Kim, E. Choi, H. Sohn, D. Lee, C. Suh, J. Lee, H. Yang, J. Hong, W. Kim
Journal: Journal of Clinical Oncology (2007)

7528 Background: We conducted a prospective randomized phase III trial comparing induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) versus immediate CCRT to evaluate whether the addition of induction chemotherapy would result in improved survival. Methods: Patients with unresectable stage III NSCLC, ECOG PS 0–1, and weight loss up to 10% were eligible. They were randomized to receive either induction chemotherapy followed by CCRT (arm A) or immediate CCRT (arm B) after stratification for stage (T4N0–2, T1–3N3, T4N3, and stage IIIA), histology (squamous vs non-squamous), and SCLN positivity. Induction chemotherapy consisted of two cycles of gemcitabine (1,000 mg/m 2 D1, D8) and cisplatin (70 mg/m 2 D1) q 21days. Chemotherapy during CCRT consisted of 6 cycles of weekly paclitaxel (50 mg/m 2 ) and cisplatin (20 mg/m 2 ). Radiation therapy performed with hypofractionated scheme (2.2 Gy/fraction, once a day) and total dose was 66 Gy. Irradiated volume encompassed gross tumor plus 1.0 cm margin. Results: Between March 2003 and June 2006, 134 patients were enrolled. 92% of patients were male and 60% were age 60 or older. Objective tumor response was obtained in 38% after induction chemotherapy. Response rates after completion of CCRT were 72% (95% CI, 61%–83%) on arm A and 79% (95% CI, 69%–89%) on arm B. Grade 3/4 toxicities during induction chemotherapy consisted mainly of neutropenia (11%/3%). During CCRT, grade 3/4 neutropenia was noted in 8%/5% (arm A) versus in 8%/0% (arm B), grade 3 anemia was 8% vs 0%, grade 3 thrombocytopenia 5% vs 0%, and grade 3 esophagitis 16% vs 16%. At median follow-up of 28 months, median survival was 12.6 months (95% CI, 8.6–16.7 months) on arm A versus 18.2 months (95% CI, 11.7–24.8 months) on arm B (P=0.18). Two year survival estimates was 25% (15%–35%) and 43% (31%–55%), respectively. Median progression free survival was 7.5 months (95% CI, 5.6–9.4 months) on arm A and 11.6 months (95% CI, 9.6–13.6 months) on arm B (P=0.04). Conclusions: The addition of induction chemotherapy to CCRT failed to increase the survival of unresectable stage III NSCLC over immediate CCRT. Moreover, the progression free survival was inferior to immediate CCRT. No significant financial relationships to disclose.
Phase II trial of ixabepilone (BMS-247550) in children and young adults with refractory solid tumors: A report from the Children’s Oncology Group
Authors: S. Jacobs, B. Fox, M. D. Krailo, G. Hartley, F. Navid, L. Wexler, S. M. Blaney, B. Frank, P. C. Adamson, B. C. Widemann
Journal: Journal of Clinical Oncology (2008)

10026 Background: The epothilone B analog ixabepilone (IXB) is a non-taxane microtubule-stabilizing agent with activity in adult solid tumors and in vivo activity - q 4 days (d) × 3- in pediatric tumor xenografts de novo resistant to paclitaxel. The maximum tolerated dose in adults and children was 6 and 8 mg/m2/d IV over 1 hour × 5 d q 21d, respectively, and the prominent dose-limiting toxicity (DLT) was neutropenia. Methods: We performed a phase II trial of IXB (8 mg/m2/d × 5d q21d) in taxane naïve children and young adults. Using a two-stage design (stage 1: 10 pts/stratum) we evaluated six independent strata: rhabdomyosarcoma, Ewing family tumors, neuroblastoma, Wilms tumor, osteosarcoma, and synovial sarcoma or malignant peripheral nerve sheath tumor. DLT was ≥ grade 3 IXB related non-hematologic toxicity, grade 4 thrombocytopenia, or grade 4 neutropenia for ≥5 d. Results: 61 eligible pts (64 pts total) (male 36/female 25) were enrolled. Median age (range) at entry was 13 yrs (3–36 yrs), 8 pts ≥ 21 yo, and the number of prior regimens was 2 (1–6). 59 pts were evaluable for toxicity and response. DLT developed in 10/59 pts (16× <12 yo; 18× ≥12 yo) during cycle 1: pain (n=3), neutropenia (n=5), and one each developed sensory neuropathy, anorexia, fatigue, thrombocytopenia, dehydration, and CNS hemorrhage. In subsequent cycles, 6 pts developed DLT: anorexia (n=3), neutropenia (n=2), and one each thrombocytopenia, pain, sensory neuropathy, febrile neutropenia, lipase, hypertension. 13 pts (22×) had ≥ grade 2 pain related to IXB. No partial or complete responses (RECIST) were observed. The median number of cycles was 2 (range 1–18). 7 pts received ≥ 3 cycles, with 2 having prolonged stable disease (Wilms tumor 18+ cycles, synovial sarcoma 8 cycles). Conclusions: IXB was well tolerated at 8 mg/m2/d in children and adults, but did not demonstrate significant clinical activity in the pediatric tumors evaluated. The pediatric xenograft model was thus not predictive of IXB activity in these heavily pre-treated patients. No significant financial relationships to disclose.