tbuckley/cabot-search huggingface dataset:
Value of a serum proteomic signature in the non-invasive evaluation of lung nodules.
Authors: C. V. Pecot, X. Zhang, R. Rajanbabu, M. Li, J. R. Jett, E. Grogan, D. P. Carbone, Y. Shyr, P. P. Massion
Journal: Journal of Clinical Oncology (2010)

10520 Background: The current management of lung nodules leads to futile thoracotomies and a number of missed chances for cure. We hypothesized that a serum proteomic signature may add value to the predictive accuracy of lung cancer derived from combined non-invasive clinical and radiographic data. Methods: Clinical, chest CT imaging and serum-based proteomic data were collected in two prospective cohorts of patients with lung nodules from two institutions. Cohort A included 265 patients (185 all stages NSCLC, 80 controls), and cohort B included 126 patients (44 stage I NSCLCs, 82 controls). All controls were found without a diagnosis of lung cancer at the end of 12 months follow-up. Preset variables were selected on clinical grounds to build multivariable analyses, some of which included age, gender, pack-years of smoking and prior cancer status. CT data included average size, nodule shape, location and presence of calcification. The additive benefit of a previously described 7-peak MALDI MS signature (Yildiz et al, JTO 2007) was determined. Results: The clinical variables were not significantly different between groups in either cohort. The average nodule size in cohorts A and B were 37.83 vs 23.15 mm among the cases and 15.83 vs 16.49 mm among controls, respectively. The serum proteomic signature had an AUC of 0.68 independent of clinical and imaging variables. The signature did not significantly improve the predictive accuracy of the non- invasive diagnostic model of lung cancer in cohort A, but did in cohort B when added to the combined clinical and chest CT data. Conclusions: The results validate the accuracy of the MALDI MS signature in the diagnosis of lung cancer and suggest that, in a population of smaller nodules, the signature may add value to the clinical and radiological evaluation of lung nodules. No significant financial relationships to disclose.
PTU-210 Packing of perianal abscess cavities (PPAC) study: a multi-centre observational feasibility study, interim analysis: Abstract PTU-210 Table 1
Authors: S Smith, L Pearce, K Newton, P Barrow, J Smith, L Hancock
Journal: Gut (2015)

<h3>Introduction</h3> Acute perianal abscess is the seventh most common emergency general surgery condition (18,000 cases/year).<sup>1</sup>This study investigates the current management and health outcomes with the aim of demonstrating feasibility for a randomised controlled trial of packing versus no packing. <h3>Method</h3> Demographic and operative data was collected for all patients. Patients were asked to complete pain score diaries and QoL assessments using VAS and EQL-5D respectively, in addition to 1, 2, 3, 4, 8 week and 6 month follow up. This interim analysis was undertaken 11 months from study inception. <h3>Results</h3> 142 patients were recruited over 10 months at 15 centres. Mean age 39 years, 64% female. At operation, 9% had a fistula identified (no fistulotomies) and 97% were packed. Average number of dressing changes in 21 days was 7.4. Packing causes a double to three-fold increase in pain. Pain intensity halves after a week (Table 1). At 4 weeks, 48% healed. 8 week fistula rate was 21% and recurrence rate 9% (n = 2) at 6 months. 26 patients withdrew consent or were lost to follow-up. The estimated dressing and community nursing costs are £159.84 per patient, equating to £2,877,120 in England alone (18,000 patients per annum). <h3>Conclusion</h3> Packing is painful. A trial of packing versus no packing, based on pain scores, is feasible. If no packing is shown to be beneficial in terms of reduced pain and safe (no increased fistula or abscess recurrence rates), there could be considerable cost savings to the NHS and to patients, including reduced absence from work. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Hospital Epsiode Statistics. www.hscic.gov.uk/hes
Efficacy of Nab-paclitaxel in patients with poor prognostic factors or with anthracycline-resistant metastatic breast cancer (MBC)
Authors: S. J. Vukelja, J. O'Shaughnessy, D. Krasnojon, S. V. Cheporov, A. Makhson, G. Manikhas, P. Bhar, W. Gradishar
Journal: Journal of Clinical Oncology (2008)

1082 Background: Nanoparticle albumin-bound-paclitaxel (nab-pac) demonstrated significant antitumor activity in patients with MBC compared with solvent-based paclitaxel. This retrospective analysis evaluated the antitumor activity of nab-pac in patients with MBC who were previously treated with anthracycline, had visceral (lung and/or liver) disease, or had ≥ 3 sites of metastases. Methods: Pts (N = 531) were evaluated from a phase II and a phase III study of nab-pac (Gradishar et al. J Clin Oncol. 2005;23:7794–7803). In the phase III study, pts (including first- and second-line pts) received nab-pac 260 mg/m2 q3w (A) or paclitaxel 175 mg/m2 q3w (B). In the phase II study, first-line pts received nab-pac 300 mg/m2 q3w (C), 100 mg/m2 qw (D), 150 mg/m2 qw (E); or docetaxel 100 mg/m2 q3w (F). Results: See Table. Conclusions: Nab-pac, weekly or every 3 weeks, has significant antitumor activity in patients with MBC regardless of baseline factors (eg, anthracycline use, visceral disease, or ≥ 3 sites of metastasis). Prior anthracycline Pts with visceral disease Pts with ≥3 sites of metastasis Nab-pac 77 77 62 Paclitaxel 78 81 52 Nab-pac 24 81 54 Docetaxel 24 88 59 Overall response rate (%) Overall response rate (%) Overall response rate (%) A* 34 34 26 B* 18 19 17 P-value 0.002 0.002 0.092 C 45 45 46 D 53 61 69 E 68 75 70 F 28 37 29 P-value † 0.062 0.003 0.004 Time to progression/Progression-free survival (months) Time to progression/Progression-free survival (months) Time to progression/Progression-free survival (months) A*‡ 5.3 5.0 4.5 B*‡ 3.8 3.8 3.7 P-value 0.004 0.036 0.053 C 7.9 10.9 10.2 D 7.2 7.5 7.4 E 11.4 13.1 12.9 F 5.5 7.8 7.6 P-value † 0.031 0.242 0.557 Overall survival (months) Overall survival (months) Overall survival (months) A* 14.9 13.1 14.2 B* 12.0 12.3 11.0 P-value 0.049 0.945 0.154 C,D,E,F NA NA NA Pts treated 1st- and 2nd-line; † Comparing nab-pac and docetaxel overall; ‡ TTP in the ph III trial Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Abraxis Bioscience Abraxis Abraxis
Comprehensive assessment (CA) of organ function and comorbidities in a large consecutive multiple myeloma patient cohort.
Authors: D. De Pasquale, M. Kleber, G. Ihorst, M. Terhorst, B. Deschler, M. M. Engelhardt
Journal: Journal of Clinical Oncology (2010)

e18523 Background: MM is a frequent hematological cancer, typically affecting elderly patients. Individualized disease management has substantially improved MM-outcome. The prognostic importance of comorbidities is increasingly recognized. We aimed to define which comorbidities substantially affect PFS and OS and which of various comorbidity scores is most valuable. Methods: We retrospectively assessed 466 consecutive MM patients treated in our department between 2003-2009. Comorbidity was scored via Kaplan Feinstein (KF), HCT-CI and KLeber-score (Karnofsky-index, lung function and eGFR). Treatment was given according to institutional/international guidelines with SCT in transplant-eligible patients, and standard-therapy plus novel agents in elderly patients. Results: Patients showed a median age of 62 years (range; 27-90). Increasing CKD stages (1->5) were associated with increased age (58->63years), increased D&S and ISS-stages (median ISS 2->3), reduced KI (90->70%), impaired organ- function, anemia (11.8->9.6g/dl) and hypoalbuminemia (3.8->3.2g/dl), whereas ß2-MG (3.2->23.6mg/dl), LDH (217->292U/l), HCT-CI (1->5) and KLeber-indices (1->2) increased. Univariate analysis determined moderate or severe pulmonary disease, RF, decreased KI, age >59years, secondary neoplasms (SN), adverse cytogenetics, ß2-MG, albumin, hemoglobin and LDH to significantly diminish PFS and OS. The KF-, HCT-CI- and KLeber-score led to significantly different OS rates of not reached (nr) vs. 57 months (ms; KF with 2 vs. 3 risk factors [rfs]), 135 vs. 53ms (HCT-CI with <1 vs. >1 rfs) and nr vs. 86 and 39ms (KLeber with 0, 1 vs. 2 or 3 rfs; log-rank test), respectively. Conclusions: Comorbidities in MM are frequent. Important prognostic determinants for diminished PFS and OS are pulmonary disease, impaired RF, decreased KI, age >59years, SN, adverse cytogenetics, ß2-MG, albumin, hemoglobin and LDH. With only 1-point-score difference, the KF, HCT-CI and KLeber-indices induced significant OS changes. Our results highlight the debate on CA which seems vastly useful to implement into future analyses and clinical trials. Our defined risk factors and comorbidity scores should prove decidedly valuable. No significant financial relationships to disclose.
A randomised multi-centre phase-II trial to assess the effect of dose splitting of carboplatin (CARBO) in comparison to a single application of carboplatin in a gemcitabine (GEM)/carboplatin regime for stage IIIB and IV non small cell lung cancer (NSCLC)
Authors: W. Schuette, S. Nagel, S. Guetz, H. Reichardt, L. Fischer, V. Weikersthal, C.-P. Schneider, G. Laier-Groenefeld, T. Fink, M. Reck
Journal: Journal of Clinical Oncology (2005)

7130 Background: Gem/Carbo is an active regime in the treatment of stage IIIB and IV NSCLC without relevant non hematological toxicity. The main hematological toxicity is thrombocytopenia. The aim of the study is the reduction of thrombocytopenia in the Gem/Carbo regime by splitting the dose of carbo. Methods: A multi-centre randomised phase II trial in NSCLC comparing Gem (1250 mg/m2 day 1 and 8) and Carbo (AUC 5 day 1) (armA) vs Gem and Carbo (AUC 2,5 day 1 and 8) (armB) every 3 weeks for 4 cycles has been completed. Eligibility included ECOG-PS 0–2; locally advanced or metastatic disease; no prior chemotherapy. Patients (pts) were randomised in an 1:1 ratio. Treatment continued until disease progression or intolerable toxicity. Primary endpoint was thrombocytopenia and secondary endpoints were response rate, time to progression and survival. Results: 160 pts were randomised between 05/03 and 08/04. Pretreatment characteristics were well balanced between the two groups; median age 62.4 years, WHO PS 0–1 81%, stage IV 78% of pts. Preliminary data are available; response rate and stable disease rate were 45%/36% in arm A and 38%/46% in arm B respectively. WHO grade 3/4 thrombocytopenia is significantly reduced in arm B (Chi-square p = 0.026). Conclusions: Preliminary data show a reduction of severe thrombocytopenia in arm B (splitted dose). Data on primary and secondary endpoints will be available for presentation at the ASCO meeting. No significant financial relationships to disclose.
Phase I analysis of systemic interferon alpha utilized with gliadel in adults with recurrent glioblastoma multiforme (GBM)
Authors: D. H. Lawson, S. Phuphanich, E. McKenzie, K. Greiner, K. Shires, J. J. Olson
Journal: Journal of Clinical Oncology (2006)

11508 Background: Local therapy with Gliadel was found to increases median survival at recurrence from 23 to 31 weeks when compared to placebo wafers. Brain tumor specimens have been observed to have a 40–50% rate of deletion of the IFNα interferon a gene. Previous clinical studies have demonstrated response rates to IFN-α in the range of 0–41% in the treatment of recurrent primary malignant glioma, either alone, or in combination with other modalities. This study assess the safety and toxicity of Interferon α-2b (IFN-α) and 3.85% BCNU-permeated wafers (Gliadel ® ). Methods: This is a phase I dose escalation assessment of the toxicity of IFN-α utilized in conjunction with Gliadel ® in patients with recurrent GBM, who failed previous radiation and chemotherapy. Ten patients were enrolled in this dose escalation trial. Three dose levels were studied were with the starting dosage of was IFN-α 3 Mu/m 2 (n = 3), 6 Mu/m 2 (n = 3) and 9 Mu/m 2 (n = 4) subcutaneously injection 3 times a week for a total period of 8 weeks with the first dose being initiated 1 week following craniotomy and Gliadel placement. Results: There were 10 patients, 5 males and 5 females with a median age of 46 yrs (range 35–55). At re-operation, all histology revealed 10 GBM. At dose 3 Mu/m 2 , 2/3 pts developed grade 2 fatigue, myalgia and depression, but completed treatment with 1 PR (109 + wks) and 1 CR (91 + wks) and 1 PD (6 wks). Another patient was off study because of progressive disease (PD). At dose 6 Mu/m 2 , all 3 had PD with 2 pts having Grade 2 received a dose reduction because of diarrhea and 1 patient withdrawing early for PD finished only 1 cycle (4 wks). At dose 9 Mu/m 2 , 2 patients developed grade 3 toxicity fatigue/malaise and one patient completed therapy with dose reduction and but progressed, another patient stopped treatment after first 3 doses due to progression. There were overall response of 20% (1 PR and 1 CR) with duration of 109+ and 91+ wks. Clinical response with IFNα gene is being analyzed. Conclusions: This study defined MTD at 6 Mu/m 2 with a DLT at 9 Mu/m 2 and recommended a Phase II dose in this population. Since interestingly, the responses occurred at the lowest dose, suggesting a portion of the effect may be anti-angiogenic in nature. No significant financial relationships to disclose.
Metastatic sarcoma to the brain: Case series and literature review.
Authors: N. N. Hawk, B. Mathew, C. Hadjipanayis, K. Goddette, G. Z. D'Amato
Journal: Journal of Clinical Oncology (2010)

e20505 Background: Sarcomas are rare, constituting <1% of all adult cancer cases. They are a group of malignant tumors originating from the connective tissues. When considering metastatic brain disease, metastatic sarcoma to the brain is also a relatively rare phenomenon. Methods: A hospital-based tumor registry was searched to find all patients with sarcomas metastatic to the brain, between 1990 and 2009. The medical records of all patients were reviewed. Results: Among the 2,000 patients with sarcomas, eight metastatic sarcoma to the brain were found: four leiomyosarcomas, one Ewing sarcoma, two alveolar soft parts sarcoma (ASPS), and one malignant peripheral nerve sheath tumor (MPNST). The patients presented with symptoms such as new visual field defects, headaches, nausea and vomiting. The mean age of patients was 42 (21-60). All patients had stage IV at the time the brain metastases occurred. Some of the patients with metastatic sarcoma to the brain still remain alive up to one year after development of brain metastasis. Conclusions: Most patients present with visual field defects, headaches, nausea and vomiting. While the optimal management of these tumors is uncertain, aggressive treatment of the brain metastases with resection and stereotactic radiosurgery along with chemotherapy can result in prolonged survival. In patients with leiomyosarcoma, the median survival after aggressive treatment of brain metastases was better than those of other sarcoma types. No significant financial relationships to disclose.
Efficacy and safety of single agent pertuzumab (rhuMAb 2C4), a HER dimerization inhibitor, in hormone refractory prostate cancer after failure of taxane-based therapy
Authors: D. B. Agus, C. J. Sweeney, M. Morris, D. Mendelson, D. G. McNeel, F. Ahmann, J. Wang, M. K. Derynck, M. W. Kattan, H. I. Scher
Journal: Journal of Clinical Oncology (2005)

4624 Background: Pertuzumab (P), a humanized HER2 antibody, inhibits dimerization of HER2 with other HER kinase family members (EGFR, HER3 and HER4), thereby inhibiting signaling through MAP and PI3 kinase. A phase I trial demonstrated safety and activity in prostate cancer. This single agent, multicenter phase II trial assessed P activity in prostate cancer pts that had progressed on or after hormone and taxane therapy. Methods: 42 pts were enrolled. 41 were treated with a loading of 840mg P followed by 420mg every 3 weeks. Primary objectives were best overall response, time to progression and safety. Response assessments by CT, bone scan and PSA were obtained after 4, 8, and 12 cycles. Results: The median age was 68 years. 52% had responded to primary hormonal therapy for less than one year and 36% had obtained a response to prior taxane-based therapy. There were no PSA or objective radiographic responses to P. Of 41 treated pts, 5 (12%) pts had stable disease beyond cycle 4 - 1 for 36 weeks and 2 each for 24 and 23 weeks. 20 (49%) progressed at or prior to cycle 4, and 16 (39%) came off therapy for other reasons. Under separate protocols, survival data was retrospectively analyzed with predicted survival based on a validated nomogram used to determine probability of survival based on prognostic factors. Actual overall survival (median >16 months) was better than predicted based on historical controls (10.1 months) with similar prognostic features. The major toxicity was diarrhea (61%) and rash. Conclusions: P is well tolerated. No responses were observed; stabilization of disease was observed in a small number of pts with taxane-resistant HRPC. In spite of these findings, preliminary analysis suggests that P may have an impact on survival compared to predicted survival based on prognostic factors; randomized studies would be necessary to confirm this finding. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech unknown, dollar range unknown Genentech Genentech, unknown, dollar range unknown
Factors contributing to delays in breast cancer management.
Authors: E. Barlow, S. Verma, F. Kanji, S. Hopkins, L. Paquet
Journal: Journal of Clinical Oncology (2010)

6070 Background: Patients with breast cancer (BC) often face delays in diagnosis, surgery, and onset of systemic or loco-regional treatment. While there is considerable literature on this third component, especially regarding delays in onset of radiation therapy, it is relevant to examine the entire continuum. We set out to quantify each component for both adjuvant and neoadjuvant patients, including potential factors for delay: hospital class, availability of prognostic markers, and the use of pre-operative MRI. Methods: We conducted a retrospective review of 949 BC patients referred to The Ottawa Hospital Cancer Centre (TOHCC) in 2008, of which 794 of which were included in this analysis. Dates of screening procedures (S), biopsies (B), marker reports (M), MRI scans, surgeries (Sx), and treatment initiation (chemotherapy [CT], radiation therapy [RT], and hormone therapy [HT]) were obtained and time intervals were calculated for all patients where data was available. Patients were stratified by referring hospital class (academic, nonacademic, or peripheral) and use of preoperative MRI. Analysis was carried out using chi-squared tests, and confirmed with ANOVA, Wilcoxon-Mann-Whitney, and Kruskal-Wallis tests, where appropriate. Results: The results are shown in the Table. Wait time intervals were compared between academic, nonacademic, and peripheral referring hospitals, and were significantly different. Approximately 35 percent of patients had a preoperative MRI. Impact of MRI was highly significant in terms of the number of mastectomies performed: 46.1% with MRI, 53.9% without (p=0.000), as well as the length of time to surgery: 54 days with MRI, 43 days without (p=0.000). Conclusions: Diagnostic and therapeutic delays have been identified in the care of women with early BC. The effect of these delays on outcome has not been determined but need to be considered in the overall management of these patients. S to B B to M B to MRI B to CT B to HT B to Sx Sx to M Sx to CT Sx to RT Sx to HT CT/HT to Sx Neoadjuvant Median 11 35 23 29 48 180 80th %ile 16 54 38 42 129 193 Adjuvant Median 18 48 24 55 74 58 80th %ile 32 67 34 68 95 97 No significant financial relationships to disclose.
A randomized phase III trial comparing mitomycin-C plus short-term doxifluridine (Mf) versus mitomycin-C plus long-term doxifluridine plus cisplatin (MFP) after curative resection of advanced gastric cancer (AMC 0201) (NCT00296335)
Authors: H. Chang, Y. Kang, Y. Min, D. Zang, G. Kim, D. Yang, S. Jang, J. Yook, S. Oh, B. Kim
Journal: Journal of Clinical Oncology (2008)

4531 Background: Despite a continuing debate on the role of adjuvant chemotherapy, several studies have suggested that mitomycin-C (M) plus fluoropyrimidine (f) could improve the outcome of curatively resected advanced gastric cancer (AGC) patients (pts). To improve further the adjuvant Mf chemotherapy, we have prolonged the administration of oral fluoropyrimidine (F) and added cisplatin (P) to Mf (MFP) and performed a phase III randomized trial to determine whether this strategy could improve the 3 year relapse free survival rate (3yRFSR) in curatively resected AGC pts (HR=0.63, α=0.05, β=0.1). Methods: Three to 6 wks after R0 resection, the pts who had postoperative stage II-IV were randomized to receive either Mf or MFP adjuvant chemotherapy. For Mf group, 20 mg/m2 of M was iv injected and 4 wks later, 460–600 mg/m2/day of doxifluridine was administered orally for 3 months. For MFP group, the administration of doxifluridine was extended for a total of 12 months and 6 shots of monthly 60 mg/m2 of cisplatin were added to Mf. Results: Between Feb 2002 and Aug 2006, a total of 871 pts were randomized (435 in Mf, 436 in MFP). Sixteen pts were excluded because of ineligibility (11 in Mf, 5 in MFP). Postoperative stages were II in 51.0%, IIIA in 31.1%, IIIB in 9.4%, and IV in 8.5% of pts. In Nov. 2007 after a median follow up of 3.2 yrs, there was no difference in 3yRFSR between the two groups (67.0% in Mf and 64.9% in MFP). Difference in overall survival (OS) was also insignificant; 3yOSR was 75.8% in Mf and 72.5% in MFP. The treatments were well tolerated in both groups. And, 92.9% of Mf and 71.6% in MFP could complete the planned schedule of treatment. Grade 3/4 neutropenia was more common in MFP (34%) than in Mf (9%). Grade 3/4 thrombocytopenia was rare and similar in both arms (3.6% in both groups). Vomiting of grade ≥2 was more common in MFP (23.2%) than in Mf (12.2%). There was no treatment-related death. Conclusions: Prolongation of doxifluridine administration and addition of cisplatin to adjuvant chemotherapy with mitomycin-C plus 3 months of doxifluridine could be safely performed but did not improve the treatment outcome in curatively resected AGC pts. No significant financial relationships to disclose.
Polycomb repressive complex PRC1 spatially constrains the mouse embryonic stem cell genome
Authors: Stefan Schoenfelder, Robert Sugar, Andrew Dimond, Biola-Maria Javierre, Harry Armstrong, Borbala Mifsud, Emilia Dimitrova, Louise Matheson, Filipe Tavares-Cadete, Mayra Furlan-Magaril, Anne Segonds-Pichon, Wiktor Jurkowski, Steven W Wingett, Kristina Tabbada, Simon Andrews, Bram Herman, Emily LeProust, Cameron S Osborne, Haruhiko Koseki, Peter Fraser, Nicholas M Luscombe, Sarah Elderkin
Journal: Nature Genetics (2015)