tbuckley/cabot-search huggingface dataset:
Herpes simplex virus 2 (HSV-2) is not a co-factor of human papillomavirus (HPV) in adenocarcinoma of the uterine cervix (AUC)
Authors: M. Zereu, C. G. Zettler, A. M. Zelmanowicz, M. E. Canto, E. Cambruzzi
Journal: Journal of Clinical Oncology (2006)

5048 Background: Cervical cancer is an important public health problem worldwide. Following skin and breast carcinoma, cervical cancer is the third most common cancer among Brazilian women, ranking first in some developing countries. AUC occurs in 15–20% of primary cervical neoplasias. Although some etiologic factors for squamous cell carcinoma are well defined, and its relationship with sexually transmitted disease as HPV is established, we still don’t know about the causative factors of most of AUC. The objective of this abstract is to determine the presence of HSV-2 DNA in AUC specimens, and its correlation with HPV infection. Methods: From 1995 to 2003, 229 cases of AUC were diagnosed in a hospital from Brazil. Data was collected retrospectively from medical records. The local ethical committee approved the study. Paraffin embedded tissue was selected and DNA extraction was performed. Samples were first screened for betaglobin DNA sequences. To detect HSV-2 DNA using polymerase chain reaction, a pair of primers that bracket 391 base pair segment of DNA polymerase gene was used as described by Madhavan et al. (2003). The sequences are an upstream primer HSV-5’-ATG GTG AAC ATC GAC ATG TAC GG-3’ and one type specific downstream primer HSV-2–5’- CCT CCT TGT CGA GGC CCC GAA AC-3’ (Invitrogen Custom Primers, Sao Paulo, Brazil). The reaction conditions contained 1microlitre sample DNA. The thermal profile consisted of denaturation 94° for 2” followed by 40 cycles with 45’ of denaturation (94°), annealing (60°) and extension (72°). Analysis with agarose gel electrophoresis with ethidium bromide staining was performed. HSV-2 positive sample was used as control. Results: In our series, patient’s mean age was 53.2 years (from 21 to 94), most of them were multiparous (60.6%) and 42% never used any kind of anticontraception method. In 79.4% of specimes DNA of HPV was identified (51% HPV 18 and 34% HPV 16). All samples were negative for DNA of HVS-2. Conclusion: Although some epidemiologic studies reported an interaction between HPV and HSV-2 in increasing cervical cancer risk, in our series HSV-2 is not found integrated to human genome of adenocarcinoma of the uterine cervix and does not seems to be a co-factor of HPV on the etiology of this cancer subtype. No significant financial relationships to disclose.
Infrastructure to improve together: Fostering palliative care (PC) and quality improvement (QI) learning in oncology through a virtual learning collaborative (VLC).
Authors: Arif Kamal, Ann Alexis Prestrud, Katherine Ast, Julie Bruno, Molly Gavigan, Kristen K. McNiff, Amy Pickar Abernethy, Jamie H. Von Roenn
Journal: Journal of Clinical Oncology (2014)

20 Background: PC and oncology teams can most effectively improve patient experience during cancer when the specialties improve care processes together through collaborative QI activities. To support collaboration ASCO, the American Academy of Hospice and Palliative Medicine, and Duke University developed a partnership to pilot the ASCO VLC. This pilot will develop and test a scalable model for quality improvement and dissemination of best practices, focused on improving palliative care in oncology. Methods: The ASCO VLC integrates lessons learned through the Breakthrough Series, ASCO Quality Training Program, and others. An Advisory Committee representing expertise in medical oncology, palliative care, geriatrics, nursing, social work, survivorship, health services research, and quality improvement oversees the pilot project. Content in the VLC website was refined based on feedback gathered through a needs assessment survey of pilot participants. Results: The online collaborative and learning platform went live in June 2014. The site houses live and recorded educational sessions covering PC and QI topics, includes discussion boards to foster interactions between practices, supports sharing of tools and resources, and allows practices to submit their problems and aims statements, and results of their work for peer review and feedback. 24 practices were recruited to participate; 73% from community/private practice sites. In response to the needs assessment, 85% of participants responded with a high sense of comfort with PC; yet, only 33% had similar comfort with QI. When asked to rank their top preference, respondents were most interested in learning about pain and symptom management (44%), or advance care planning (22%). Ongoing mixed qualitative and quantitative assessments through Spring 2015 will assess feasibility and acceptability of the ASCO VLC model. Conclusions: We are creating an online virtual learning collaborative as a sustainable infrastructure to support and foster clinician education and dissemination of PC best practices in oncology.
Phase 0 pharmacodynamic study of poly (ADP-ribose) polymerase inhibitor ABT-888 in patients with refractory solid tumors and lymphomas: Immunohistochemistry results
Authors: S. X. Yang, S. Kummar, L. Rubinstein, M. Gutierrez, A. J. Murgo, R. E. Parchment, D. Nguyen, A. P. Chen, J. E. Tomaszewski, J. H. Doroshow
Journal: Journal of Clinical Oncology (2008)

3580 Background: Poly (ADP-ribose) polymerase 1 (PARP-1) is a nuclear DNA binding protein that has roles in DNA repair and maintenance of genomic stability. A first phase 0 clinical trial was successfully conducted at the National Cancer Institute (NCI) under the FDA Exploratory IND Guidance using a novel PARP inhibitor ABT-888 in patients with refractory solid tumors and lymphomas (Kummar et al, ASCO Ann. Meeting Proc. 25: 142s, 2007). Thirteen patients received oral ABT-888 as a single dose (10, 25, or 50 mg). Tumor biopsies were performed at baseline and 3–24 h after ABT-888 administration in nine patients. Inhibition of the PARP activity (PAR) was detected by a real-time ELISA assay in tumor biopsies. Methods: Immunohistochemical detection of PAR and expression of PARP-1 was performed on paraffin-embedded sections of tumor biopsies using antibodies that were confirmed to detect the PARP activity inhibition in vitro and full size PARP-1 protein. Levels of tumor PAR and PARP-1 were quantitatively analyzed with the assistance of an Automated Cellular Imaging system. Results: Baseline PAR levels were moderate to high in three non-Hodgkin lymphomas, one small cell lung cancer, one squamous cell carcinoma of the head and neck, and one melanoma; low in two cutaneous T cell lymphomas, and one adenocarcinoma of external ear canal. A statistically significant PAR decrease (median 58%, range 41.7 - 90.3%) was achieved after ABT-888 administration (n = 6 pairs, p = 0.02). An increase in PARP-1 expression was observed in five of the six tumors. As a result, there was a significant decrease in the ratio of PAR to PARP-1 in five tumors (> 80%) and a moderate decrease in one tumor (33.5%). Conclusions: ABT-888 reduces the tumor cell PARP activity that is consistent with the previously described ELISA results, and increases the expression of PARP-1 in the majority of tumor samples possibly due to a compensatory or feedback mechanism. Baseline levels of tumor PARP activity vary considerably among patients who entered the NCI phase 0 study. The data underscores a need to study baseline levels of PARP activity in association with response in future preclinical and clinical studies. Funded in part by NCI Contract N01-CO- 12400. No significant financial relationships to disclose.
Treatment (T) guideline (G) development and implementation (I) in community (COMM) practice (P): Experience of the cancer centers of excellence (CCE) network and its clinical quality committee (CQC) in colorectal cancer (CRC)
Authors: F. M. Schnell, L. D. Bosserman, B. Ebrahimi, C. A. Presant, K. Bergstrom
Journal: Journal of Clinical Oncology (2008)

20661 Background: Quality care (QC) in oncology depends on physician (PHY) compliance with T G. Although T G have been developed by NCCN and ASCO, methods for I are not widespread. CCE was formed to increase QC and provide increased support for COMM P by extensive network efficiencies. This study evaluated resources required to develop CRC T G in CCE and results with NCCN and ASCO G. Methods: CCE bought 21 COMMP together, developed a CQC committee and formed disease specific user groups to develop evidence-based treatment protocols (ETP) for each disease type and supportive care. Staff provided evidence-based preliminary ETPs by stage and treatment type using NCCN guidelines and updated data. The CQC tee refined the ETPs and added specific quality measures for each ETP. These were then reviewed by the CRC user group, and sent to each CCE COMM P for input and comments. ETP’s were then reevaluated by the user group to incorporate COMM P comments before final CQC approval. The manpower requirements to develop the first 5 ETP’s on colorectal cancer were evaluated, and CCE ETP cost and use in CRC were compared to T G of NCCN. and ASCO. Results: 5 initial ETPs were developed and approved for CRC. Once finalized, the implementation team worked with practices based on their data collection methodologies (specific EMR users or paper based) to develop tools to prompt collection of specific data points and quality measures and data submission and mining. Pilot data was collected from practices on the three major oncology EMR’s and a paper based data collection form. All practices used the LynxMobile system for drug regimen tracking. Results from the first 6 months of pilot 9–12/07 and CCE wide 1–3/08 ETP data on development costs and implementation/treatment details will be presented. These costs will be compared to costs and outcome data available from other guidelines. Conclusions: CRC T G can be developed for COMM P. Costs and resources are reasonable when shared with network efficiencies based on a per PHY or per patient basis. COMM P T G can be defined, delivered and tracked to understand delivered QC in COMM. P. No significant financial relationships to disclose.
Phase I and pharmacokinetic trial of weekly CPT-11.
Authors: M L Rothenberg, J G Kuhn, H A Burris, J Nelson, J R Eckardt, M Tristan-Morales, S G Hilsenbeck, G R Weiss, L S Smith, G I Rodriguez
Journal: Journal of Clinical Oncology (1993)

PURPOSE We conducted a phase I and pharmacokinetic trial of CPT-11 (irinotecan) to characterize the maximum-tolerated dose (MTD), toxicities, pharmacokinetic profile, and antitumor effects in patients with refractory solid malignancies. PATIENTS AND METHODS We treated 32 patients with CPT-11 administered as a 90-minute intravenous infusion every week for 4 consecutive weeks followed by a 2-week rest period. Dose levels ranged from 50 to 180 mg/m2/wk. We determined concentrations of the lactone (active) and total (lactone plus carboxylate) forms of CPT-11 and its metabolite, SN-38, in the plasma and urine of selected patients during and after drug infusion. RESULTS Grade 4 diarrhea was the dose-limiting toxicity (DLT) at the 180-mg/m2/wk dose level. Other toxicities attributed to CPT-11 included dehydration, nausea, vomiting, and asthenia. Hematologic toxicity was mild in most patients. The terminal plasma half-life for CPT-11 (total) was 7.9 +/- 2.8 hours, for CPT-11 (lactone) 6.3 +/- 2.2 hours, for SN-38 (total) 13.0 +/- 5.8 hours, and for SN-38 (lactone) 11.5 +/- 3.8 hours. We observed significant correlations between drug dose and peak plasma concentration (Cpmax) and between drug dose and area under the concentration curve (AUC) for CPT-11, but not for SN-38. CONCLUSION The MTD for CPT-11 in this patient population was 150 mg/m2/wk when administered on a weekly-times-four schedule repeated every 6 weeks. At dose levels greater than 150 mg/m2/wk, diarrhea is dose-limiting.
Phase I pharmacokinetic profile and early clinical evaluation of the PAN-HER inhibitor BMS-599626
Authors: J. C. Soria, J. Cortes, J. P. Armand, A. Taleb, L. van Bree, E. Lopez, S. Song, K. Zeradib, F. Vazquez, R. E. Martell, J. Baselga
Journal: Journal of Clinical Oncology (2005)

3109 Background: BMS-599626 is an orally bioavailable inhibitor of HER1 (EGFR), HER2 (ErbB2) and to a lesser extent HER4. Methods: This is a phase I dose escalation study of BMS-599626 administered by daily oral dosing. Patients: ≥18 yrs with metastatic solid tumors, refractory to standard therapies and whose tumors expressed HER1 or HER2 by IHC (FISH for breast). A large translational ancillary study included skin biopsies (baseline and Day 8) and analysis of biomarkers of HER1 and HER2. Dosing was initiated at 100mg/d and escalated in subsequent cohorts based on a modified Fibonacci scheme. Data from a prior healthy volunteer study, which evaluated single dose PK in 18 subjects, 6 at each dose level (10mg, 30mg and 100mg) is also included. Results: Between May and November 2004, 13 patients have been enrolled; cohort level 5 has reached a dose level of 660 mg. Adverse events at least possibly related to BMS-599626 of 24 Nov 2004 include diarrhea (3), anorexia (1), dyspnea (1), sweating (1) and rash (2); all grades 1 or 2. All 3 patients at 480mg developed grade 1 skin-rash (not yet in database). The healthy volunteer study had one AE: transient grade 2 ALT elevation. Three out of 13 patients allowed fresh tumor sampling before and during treatment. Plasma pharmacokinetics of BMS-599626 for the 100 and 200mg dose were available at the time of abstract submission. For the 100mg dose, the Tmax ranged from 1 to 8h (median 4h), somewhat delayed compared to the healthy volunteer study (median 2 hr). Following a single 100mg dose, the geomean Cmax=62 ng/mL, mean AUC0-∞=1570 ng/mL hr, relatively low compared to the healthy volunteer study, which revealed 120 ng/mL and 2610 ng/mL hr respectively. PK on day 8 and day 29 revealed similar findings, with respective geomean values of Cmax =167 and 210 ng/mL and AUC0-∞=2340 and 2545 ng/mL hr, suggesting no significant accumulation in exposure over time. Terminal half life was about 17 hrs. Exposure increase with the 200 mg dose was linear from the 100 mg dose. Conclusions: BMS-599626 has been well tolerated, with mild target-related AEs. The maximum tolerated dose has not yet been reached. Additional clinical, pharmacological and translational data will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb
Surgical Diseases of the Chest
Journal: JAMA (1935)

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Diffusely Increased Bone Marrow 18F-FDG Uptake Is an Independent Predictor of Focal Bone Lesions in Patients with Newly Diagnosed Classical Hodgkin Lymphoma
Authors: Lars C. Gormsen, Cecilia Wassberg, Daniel Molin, Peter Kamper, Gunilla Enblad, Francesco d'Amore
Journal: Blood (2014)
Steroids related tuberculosis: Does a subgroup require a more cautious approach?
Authors: Amin Afridi, Maria Labrador, Cathy O'Rourke, Jacqui Nation, Nazim Nathani
Journal: European Respiratory Journal (2011)

Background:  Increased use of steroids for treatment of autoimmune and other respiratory disorders poses a danger of reactivation of tuberculosis. Patients receiving immunosuppression (non-antiTNF) are generally offered a baseline CXR only. This potential susceptibility was investigated further.   Results:  Our TB service treats 250 patients/year. Over 24 months, 4 patients requiring steroid therapy for primary lung pathology developed TB. 24 patients with no lung pathology were matched.  Only 2 cases of TB have been detected in patients given steroids for a non-pulmonary cause.   Discussion:  A previous meta-analysis had concluded TB occurred more frequently in patients receiving steroids but wasnt statistically significant.[J Intern Med 1994;236:619]. Specifically a prospective study in steroids for lung disease had commented on an incidence of 4.9%. [J Ass Phys Ind 2000;48:881].  In our centre, reactivation was limited to patients with underlying chronic lung pathology, of ethnic origin not born in UK.   Conclusion:  The incidence of TB among patients on steroids for lung pathology, born in areas of high incidence is unacceptably high and it seems prudent to investigate and treat them for latent tuberculosis before embarking on steroid therapy. This is particularly relevant for respiratory departments who deal with a high proportion of ethnic population. Further case controlled propective evidence is required to define this relationship.
Bereaved family members' perceptions of end-of-life cancer care in nursing homes, hospices with home care, and acute care hospitals
Authors: D. Brandoff, T. Wetle, M. Bourbonnaire, V. Mor, F. Schiffman, J. Teno
Journal: Journal of Clinical Oncology (2004)

8052 Background: Nursing homes (NH) are increasingly the last place of care (LPOC) and site of death for persons with cancer. Little is known about the quality of care in NH for terminally ill cancer patients. Based upon a study of dying experiences, we examined the quality of end-of-life cancer care (EOLCC) for patients in NH, at home with hospice, and in acute care hospitals. Methods: A national mortality follow-back survey was conducted via telephone interviews with a family member or knowledgeable informant of the decedent (n=1578, 65% cooperation rate). Interviewers asked if health care workers provided the desired physical comfort and emotional support to the dying person, treated the dying person with respect, supported shared decision-making, coordinated care, and provided emotional support to the family. Chi-Square test was used to examine bereaved family members' perceptions of the LPOC. Results: 427 of 1578 patients (27.1%) died from cancer. For the LPOC, 19.3% died at a NH (41.8% home with hospice, 38.9% hospitals). Decedents in NH had greater unmet needs with pain and anxiety (p<0.1). 29.8% of respondents felt that NH staff had insufficient knowledge of the patient's medical history to provide highest quality EOLCC (7.2% home with hospice, 10.1% hospitals, p<.01). 32% of respondents stated that NH staff did not treat the patient with respect (2.6% home with hospice, 20.6% hospitals, p<.01). About 50% of respondents for both NH and hospitalized patients felt they were inadequately educated by staff about the dying process (30.6% home with hospice, p=.01). Respondents' overall satisfaction was lowest for NH (44% “excellent”) compared to home with hospice and hospitals (67.0%, 58.4%, p<.01). Conclusions: NH were consistently rated less favorably by bereaved family members than were home with hospice services and acute care hospitals for providing quality EOLCC. While challenging, opportunities to improve EOLCC should be sought, recognized and pursued in all settings. Oncologists have an important and central role in coordinating these efforts. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Robert Wood Johnson Foundation
Serum proteomics guided discovery of predictive biomarkers of response to androgen ablation (AA) in prostate cancer.
Authors: Manish Kohli, Ann L. Oberg, Douglas W. Mahoney, Shaun M Riska, Roman M Zenka, Deepak M. Sahasrabudhe, Sheng Zhang
Journal: Journal of Clinical Oncology (2012)

104 Background: Currently there are no serum predictive markers of response to AA. We used a proteomic based analytic approach to identify candidates. Methods: Serum from three non-localized prostate cancer cohorts was analyzed. The first included15 paired untreated hormone-sensitive “pre-AA” and 3-month “post-AA” specimens; the second included 10 “early AA failure” (median time to AA failure:11 months) and the third included 10 “late AA failure” specimens (median time to AA failure: 95 months). Proteomic analysis was performed with isobaric mass tags for relative and absolute quanititation (iTRAQ) analyzed by reverse-phase liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS). Differentially expressed candidate proteins were identified by comparisons of (i) paired pre/post-AA proteomes and (ii) post-AA proteome with the combined AA failure cohorts at a False Discovery Rate of 0.2. ELISA assays were used to verify candidate markers in a second stored aliquot of first cohort specimens. This cohort was followed for AA failure. Association of post-AA ELISA levels of candidate markers with time to AA failure was performed using Cox proportional hazards regression, summarized as relative risk (RR) for AA failure. Results: Median PSA in pre/post-AA first cohort were 3.15 ng/ml and 0.29 ng/ml. Median PSA in the second and third cohorts were 27.3 and 4.3 ng/ml. Between post-AA and AA failure cohorts, 149 proteins were differentially expressed. Between early and late AA failure 98 proteins were differentially expressed; 47 proteins were common in both comparisons. ELISA assays verified expression levels of 2/47 proteins in the first cohort; zinc alpha-2 macroglobulin (ZAG), and Neuropilin-2 (NPL2). Median change in ZAG decreased by 2073.5 ng/ml (post versus pre-AA) while median change in NPL2 levels increased by 2.9 ng/ml. After a median follow-up of 43 months from the post-AA time-point, 4/15 first cohort subjects had failed AA. The RR of AA failure for ZAG levels below the median change was 3.8 (95% CI: 0.4-37) and 3.0 (95% CI: 0.3-29) for NPL2. Conclusions: A global proteomic analysis identified ZAG and NPL2 as candidate serum predictive markers of AA response which needs further validation.