tbuckley/cabot-search huggingface dataset:
Personalising wound care: A gene expression signature for predicting clinical outcomes of venous leg ulcers
Authors: D. Bosanquet, A. Sanders, E. Cox, F. Ruge, J. Lane, K. Harding, W. Jiang
Journal: International Journal of Surgery (2015)

s / International Journal of Surgery 23 (2015) S15eS134 S20 characteristics on a suitable polymer with ideal bulk properties provides a basis for further research into the effects of PSM on cell behaviour. 0171: PERSONALISING WOUND CARE: A GENE EXPRESSION SIGNATURE FOR PREDICTING CLINICAL OUTCOMES OF VENOUS LEG ULCERS D. Bosanquet, A. Sanders, E. Cox, F. Ruge, J. Lane, K. Harding, W. Jiang. University Hospital of Wales, UK Aim: Despite their widespread occurrence, sensitive prognostic markers of chronic venous leg ulcers VLUs are noticeable by their absence. We describe a novel gene expression signature of wound edge tissue in VLUs which allows accurate personalised outcome modelling, permitting individually tailored treatments. Methods: Sequential refinement and testing of a gene signature was developed utilising three distinct cohorts of humanwound tissue. Over 111 pre-selected candidate genes were first screened using a cohort of acute and chronic wound tissue (n 1⁄4 24) by way of quantitative PCR. Genes showing significant differences were combined and examined as part of a controlled prospective study of 71 patients with VLUs. The final signature was evaluated using a prospective, blinded study comprising 85 consecutive patients with VLUs. Results: The initial gene signature comprised 24 genes (WD24) that allowed distinction between healing wound from non-healing wounds (p < 0.0001, sensitivity: 40%, specificity: 98%). Subsequent refinement excluded 10 genes to create a final 14 gene signature (WD14) which demonstrated significant prognostic power in a prospective, blinded study (p < 0.00001, sensitivity: 84%, specificity: 74%). Conclusion: We report a novel gene signature that can predict wounds at low propensity to heal with current treatment strategies. Advanced wound care products and therapies may be of particular benefit to this population. 0227: AN INCREASED POST-OPERATIVE INFLAMMATORY RESPONSE IS ASSOCIATED WITH REDUCED SURVIVAL FOLLOWING RESECTION OF COLORECTAL LIVER METASTASES O. Sogaolu, H. Shaker, P. Snape, D. O'Reilly. Central Manchester Foundation
Interim analysis of the triplet association cisplatin (P), gemcitabine (G) and vinorelbine(V) for advanced small cell lung cancer (SCLC)
Authors: B. M. Eyll, J. R. Pereira, J. Y. Yamaguchi, M. T. Arruda, F. S. Feio, C. M. Costa, M. A. Melo, J. E. Rangel, A. P. Santana, C. Almeida
Journal: Journal of Clinical Oncology (2006)

17125 Background: Small cell lung cancer (SCLC) is an aggressive disease characterized by rapid growth and early metastasis. Actually, the treatment of choice for advanced SCLC is cisplatin combined with etoposide. For these patients 9 to 12 months are the expected survival, overall response is 61%–78 % and complete response rate is 10%–14%. Despite of these results 5 years overall survival is less than 5% justifying the search for more effective treatment scheme. Methods: Fourteen patients were analyzed between January and October 2005. They received Cisplatin 80 mg/m 2 d1, Gemcitabine 1,500 mg/m 2 d1 and Vinorelbine 30 mg/m 2 d1, every 3 weeks. The response was evaluated by chest X-ray after each cycle. Thorax CT was performed at beginning and end of treatment. Results: Patients received 2–6 cycles (median = 3.78 ); KPS was 50%–90% (median 80%); median age 57 yrs (range 21–75). Thirteen patients had objective response (92.8%), 4 complete response (28.6%) and 9 partial response (64.3%). Non-hematological grade (G) 3–4 toxicity consisted of nausea and vomiting (28.6%); anorexia (42.8%); neurotoxicity (14.5%). Only one patient (7.1%) had neutropenia G3 and another subject (7.1%) had thrombocytopenia G3. There were no febrile neutropenia cases. Conclusions: Although a large study should be performed to confirm these results, PGV association shows promising activity in SCLC patients. Toxicity profile was very favorable too. [Table: see text] No significant financial relationships to disclose.
Patient preference for information about expensive anti-cancer drugs (EACD) that are potential treatment options
Authors: L. R. Mileshkin, E. Agalianos, P. Schofield, M. Levine, J. Savulescu, J. Thomson, M. Jefford, J. Zalcberg
Journal: Journal of Clinical Oncology (2008)

6533 Background: New developments in cancer have led to many new treatment options, which may only be available at significant personal cost to the patient. We previously reported that up to 41% of medical oncologists do not discuss EACD with patients, primarily because of concern about causing the patient distress. We sought to obtain the views of the general public about this issue. Methods: A cross sectional survey was conducted by telephone of a random sample of adults aged ≥18, stratified by area with quotas controlled by gender and age to be representative of the Australian population. Respondents were asked demographic and financial questions, and about their personal experience of cancer. Their views were sought about a hypothetical scenario in which they were diagnosed with incurable cancer and an EACD (out-of-pocket cost of US$25,000) could prolong median survival by 4–6 months if given with standard chemotherapy. Results: Responses were obtained from 1,255 people (49% male) of whom 47% preferred shared medical decision- making. 137 people (11%) had an existing cancer diagnosis and 686 (54%) had experienced cancer in an immediate family member. 91% wanted to be told by their doctor about the EACD, although only 52% were prepared to pay for it. 68% believed that the government should pay. Cost would be a significant financial burden for a third of those willing to pay. People were significantly more likely to want to be informed if they were younger, employed, tertiary-educated or had higher income levels (p<0.05). People were more willing to pay if the drug could improve quality of life though not survival (71%), or there was no effective standard treatment (76%). Responses did not vary with the person's personal experience of cancer. Of the 9% who did not wish to be informed, half were concerned about distress to themselves or their family (n=70–80 across scenarios). Conclusions: The general public wants to be informed about EACD as potential treatment options, even if they are not willing or readily able to pay for them. Concerns of medical oncologists that people do not want to be told about EACD because such discussions may cause distress apply only to a minority. Discussions related to EACD should occur as part of standard practice. No significant financial relationships to disclose.
ABREAST: A new global registry of adjuvant strategies in patients with early stage breast cancer
Authors: J. de la Garza Salazar, F. Içli, T. Pienkowski, M. Aapro, G. Hortobagyi, M. Martin, M. Piccart, G. Sledge, K. Pritchard, K. Albain
Journal: Journal of Clinical Oncology (2005)

576 Background: There are substantial global variations in BC incidence, diagnosis, treatment, and survival. Prospective data on pt and tumor characteristics, treatment practices, factors impacting treatment decisions, and outcomes are lacking. We report results of a pilot study in 3 countries and the launch of an international registry to provide these data for the pt cohort with early stage BC. Methods: An international panel of experts convened to develop a prospective global BC registry, ABREAST. This was designed to achieve a random sample of pts representative of each country or region and within each participating center. International participation was solicited. A unique case report form (CRF) was designed and tested in a pilot study. Female or male pts with early stage BC were eligible. After obtaining written informed consent, CRFs were completed locally via chart review. Data from the CRFs were assessed for internal consistency, and investigators were asked about the ease of completing the forms. Results: Pilot Study: Contents of the CRF included: pt demographics, BC risk factors, co-morbidities, detection and diagnostic methods, tumor biomarker status, T and N stage, physician’s assessment of 5 year (yr) recurrence, local and systemic therapeutic plan, and outcomes. Thirty-four pts were enrolled in 3 institutions in Mexico, Turkey, and Poland. The CRFs were completed in the first cohort, revised, and validated in a second cohort. Data quality was very good; investigators and research coordinators reported ease in completing the CRFs. ABREAST launch: 36,000 pts will be enrolled over 3 yrs in >60 countries. Accrual began 8 Dec 2004. Data will be collected at entry, 1 yr, and 5 yrs; CRFs will be sent via DataFax to a central data management facility using anonymous identifiers. International Scientific and Steering Committees maintain oversight of this project. Data will be analyzed based on an investigator-driven concept proposal mechanism. Conclusions: The pilot study showed that detailed data on early BC across multiple domains can be accurately collected using a simple tool in diverse countries. Thus, ABREAST was launched globally using these validated CRFs. Accrual status will be updated. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis
Effect of surgical treatment of primary tumor on outcome in stage IV breast cancer.
Authors: M. R. Bower, R. Brown, C. Scoggins, K. M. McMasters, A. B. Chagpar
Journal: Journal of Clinical Oncology (2010)

1103 Background: It has been suggested that surgical resection of the primary tumor in patients with breast cancer with metastatic disease may improve survival. The aim of this study was to determine whether surgery influences survival in patients with metastatic breast cancer. Methods: A single institution, IRB-approved, database of patients with breast cancer was reviewed for patients presenting with metastatic breast cancer. The survival interval was measured from the time of initial diagnosis until death or most recent follow up. Patient age, race, tumor grade, hormone receptor status, site of metastasis, and type of treatment were analyzed. Survival was estimated using the Kaplan-Meier method and groups were compared using the log-rank test. Multivariate analysis was carried out using a Cox proportional hazards model. Results: Of the 1,906 patients with breast cancer treated between January 1996 and December 2007, 78 patients were identified who presented with stage IV disease (4%). The metastatic sites included bone only (n=20; 26%), lung only (n=8; 10%), liver only (n=2; 3%), brain only (n=3; 4%), multiple sites (n=10; 13%), or other sites (n= 5; 6%). On univariate analysis, race was significantly correlated with survival with a median survival of 12 months in African American patients (n=21, 27%) vs. 23 months for White patients (n=57, 73%) (p=.004). Patients treated with chemotherapy (n=47, 60%) showed better survival (22 vs. 13 months, p=0.008), as did patients treated with surgery of the primary tumor (32 vs. 15 months p=0.019). Age, site of metastasis (bone vs. visceral), hormone receptor status, radiation treatment, and tumor grade were not significant predictors of survival on univariate analysis. On multivariate analysis, performance of mastectomy (OR: 1.8; 95% CI: 1.03-3.8, p=0.040) and chemotherapy (OR: 2.2; 95% CI: 1.3- 3.8, p=0.003), remained as independent significant factors predicting survival. Conclusions: Surgical treatment of the primary tumor potentially is associated with prolonged survival of patients who present with stage IV breast cancer. Further studies are warranted to establish whether or not resection of the primary tumor improves survival in such patients. No significant financial relationships to disclose.
Clinical and pathological correlations in male breast cancer (MBC): Intratumoral aromatase expression (ITA) via tissue microarray (TMA)
Authors: S. Gray, K. A. Dakin-Hache, P. J. Barnes, R. Dewar, T. Younis, D. Rayson
Journal: Journal of Clinical Oncology (2006)

10553 Background: Most cases of MBC are hormone-receptor (HR) positive and there is anecdotal evidence of disease response to aromatase inhibitors in the metastatic setting. Study objectives were to (i) assess clinical-pathologic characteristics in a cohort of MBC, (ii) evaluate intratumoral aromatase expression and (iii) assess its’ prognostic impact. Methods: A retrospective chart review was conducted for all cases of MBC seen at the Nova Scotia Cancer Centre between 1985–2005. Data abstracted included disease stage, tumor grade, HR status (ER/PR), HER2-neu and ITA expression as well as dates of disease recurrence and death. Tumor blocks were incorporated into 3 TMA’s with control specimens (gynecomastia, benign breast tissue, liver). Four 1.0 mm cores were taken of each tumor. Immunohistochemistry (IHC) was performed with the following antibodies; 6F11 ER primary Ab (Ventana, USA), 1A6 PR primary Ab (Ventana, USA), TAB250 monoclonal mouse anti-HER2 (Zymed, USA), DAKO 0185 rabbit anti-human c-erbB2 (DAKO, Canada), mouse anti-human p450 aromatase Ab (Cedarlane, Canada). ITA staining intensity and distribution was compared to benign hepatic tissue and if &gt; or = to liver was called ’strong’ while &lt; liver was called ’weak’. The log-rank test was used for survival comparisons. Kaplan-Meyer curves were used to estimate 5year disease-free (DFS) and overall (OS) survival probabilities. Results: 54 cases were identified with median age at diagnosis of 64 (31–85 yrs). Median tumor size was 2.6 cms (0.9–8cms) and 22 (41%) had nodal metastases. 45 cases had tissue available for IHC. Of these, 40 (89%) were ER and 33 (73%) were PR positive. HER2-neu was overexpressed in 4/42 (9.5%) and 12/45 (27%) had strong ITA expression. 5 yr DFS was 71% and OS was 64%. In univariate analysis strong (vs weak) ITA expression was associated with improved 5 yr OS (92% vs 49%, p = 0.038) but not DFS (82% vs 76%, p = 0.44) rates. Conclusion: The suggestion of improved OS but not DFS for those tumors with strong ITA expression may imply that these were more responsive to hormonal therapy in the metastatic setting or had a more indolent pace of progression. It is suggested that further investigation of ITA and response to hormonal therapy in MBC is warranted. No significant financial relationships to disclose.
A phase 1 study of oral navelbine in patients with advanced solid tumors
Authors: L. Rajdev, Q. Dai, G. Goldberg, S. Hoschander, C. Baker, K. Miller, J. A. Sparano
Journal: Journal of Clinical Oncology (2006)

13095 Background: Anti-tubulin agents have potent anti-angiogenic effects (Blood 94: 4143–4155, 1999). Recent evidence suggests that “metronomic” drug schedules employing doses sufficient to inhibit angiogenesis yet low enough to allow more frequent administration may enhance the effectiveness of antiangiogenic therapy (J Clin Invest 105: 1045–7, 2000). We therefore performed a phase I trial to determine feasibility and safety of administering and oral navelbine (ON) preparation that is 40% bioavailable thrice weekly (TIW). Methods: ON was given TIW (eg, Monday-Wednesday-Friday) using the dosing escalation schema outlined below with 3–6 patients/cohort. Dose limiting toxicity (DLT) during cycle 1 was defined as a) neutrophil nadir &lt; 500/uL, b) platelet nadir &lt; 50,000/uL, c) febrile neutropenia, or d) grade 3–4 non-hematologic toxicity. One patient was not evaluable (NE) due to urosepsis unrelated to treatment. No patient had a DLT. The most common toxicities were grade 2 nausea (n = 1), dyspepsia (n = 1) and abdominal cramping (n = 2), and grade 3 neutropenia (N = 1). One patient with renal cell carcinoma had stable disease for 19 months; a second with prostate cancer had a greater than 50% PSA response that lasted 18 weeks. Results and Conclusions: The recommended phase II dose of ON is at least 50 mg TIW. Further dose escalation was not possible due to cessation of the drug supply by the manufacturer. Correlative studies of surrogate angiogenesis markers (urine VEGF and serum VCAM-1 and Tie2in serum by ELISA) are currently being analyzed and will be presented. [Table: see text] No significant financial relationships to disclose.
Phase I/II study of sequential combination with irinotecan and S-1 in patients with metastatic colorectal cancer
Authors: T. Yoshioka, S. Kato, M. Gamoh, T. Suzuki, H. Shibata, H. Shimodaira, K. Otsuka, Y. Kakudo, S. Takahashi, C. Ishioka
Journal: Journal of Clinical Oncology (2008)

4107 Background: Both irinotecan (CPT-11) and S-1 are active against colorectal cancer, however, S-1 is a prodrug of 5- fluorouracil (5-FU), which suggests that 5-FU and its metabolites might inhibit the antitumor effect of CPT-11. Therefore, we designed sequential combination with CPT-11 and S-1. The aim of this phase I/II study was to determine the maximum tolerated dose (MTD) and the recommended dose (RD), and to evaluate the toxicity and efficacy of our regimen. Methods: Twelve patients entered the phase I part, and 36 patients entered the phase II part. CPT-11 infusion was administrated on day 1 and S-1 was administrated orally at 40 mg/m2 daily on day 3 to 16 every 3 weeks. Results: In the phase I part, MTD was not reached and we determined the highest level, which represented a CPT-11 dose of 150 mg/m2 and a S-1 dose of 80 mg/m2, to be the RD. In the phase II part, a total 215 courses of treatment were administrated to 36 patients. Four patients had complete responses, and 16 had partial responses. The overall response rate was 55.6% (95% confidence interval, 38.1 to 72.1 %). Median progression-free survival was 7.2 months (95 % confidence interval, 4.1 to 11.6 months). Grade 3 neutropenia was the most common hematological toxicity and occurred in 6.5 % of 215 treatment courses. Grade 3 nonhematological toxicities were anorexia (1.4%), diarrhea (0.9 %), nausea (0.5 %), vomiting (0.5 %), obstruction of the gastrointestinal tract (0.5 %) and general fatigue (0.5 %). There was no hematological or nonhematological grade 4 toxicity. Conclusions: The RD of CPT-11 and S-1 in our sequential regimen was 150 and 80 mg/m2, respectively. This sequential therapy is effective, well tolerated and appears to be a promising choice for patients with metastatic colorectal cancer. No significant financial relationships to disclose.
A phase II trial of the novel oral camptothecin gimatecan (G) in women with anthracycline (A) and taxane (T) pre-treated advanced breast cancer
Authors: P. Mariani, A. Moliterni, G. Da Prada, D. Hess, T. Gamucci, A. Zaniboni, A. Malossi, P. Barbieri, S. Marsoni, L. Gianni
Journal: Journal of Clinical Oncology (2006)

662 Background: Gimatecan (G) is a new oral camptothecin with a favourable therapeutic index in several tumor xenograft models and with documented antitumor activity in breast, endometrial and NSCLC cancer in Phase I. A Phase II trial was implemented to determine the antitumor activity of G in women with pre-treated metastatic breast cancer (MBC). Methods: A Simon 2-step design was used: patients with MBC who failed A &amp; T were eligible. Treatment failure was defined as disease progressing after receiving both A and T (adjuvant or metastatic setting). All patients had ECOG 0–1. Baseline neuropathy &gt; gr 1 or CNS metastases were criteria of exclusion. G was administered for 5 days every week on weeks 1 &amp; 2 q4weeks at 4–5 mg/m 2 total dose per cycle. Results: To date, 21 patients have received 67 cycles of G (median 3); 18 are evaluable for the 1 st step analysis. Median age was 53 years (range, 32–70), all had received A &amp; T prior treatment. The initial dose of 5 mg/m 2 was reduced to 4 mg/m 2 after treating the first 7 cases due to hematological toxicity (thrombocytopenia G3 30% and neutropenia G3–4 40%) that prevented the planned monthly retreatment. The toxicity at 4 mg/m 2 included thrombocytopenia (% of cycles with any grade: 36%, G3 9%); neutropenia (G3 18%), diarrhea (1 case), nausea (81%, G3 18%), vomiting (G1 18%), and asthenia (G1 36%). To date, three confirmed partial responses (PR) lasting respectively 5.5, 5.7+, and 9.4+ months and two unconfirmed PR were observed in visceral and nodal sites. Accrual into step 2 is proceeding. Conclusions: Gimatecan at a dose of 4 mg/m 2 is well tolerated and active. The antitumor activity of 27% observed in the first step of the study is unusual for camptothecins and prompted to continue to the second step and complete the ongoing enrolment of 43 patients overall. [Table: see text]
Six Months of Hydroxyurea Reduces Albuminuria in Patients with Sickle Cell Disease
Authors: Pablo Bartolucci, Anoosha Habibi, Thomas Stehlé, Gaetana Di Liberto, Marie Georgine Rakotoson, Justine Gellen-Dautremer, Sylvain Loric, Stéphane Moutereau, Dil Sahali, Orianne Wagner-Ballon, Philippe Remy, Philippe Lang, Philippe Grimbert, Etienne Audureau, Bertrand Godeau, Frédéric Galacteros, Vincent Audard
Journal: Journal of the American Society of Nephrology (2015)

The earliest symptom of glomerular injury in patients with sickle cell disease (SCD) is microalbuminuria. The effect of hydroxyurea (HU) on urine albumin-to-creatinine ratio (ACR) is unclear and should be determined, because increasing numbers of patients with SCD take this drug to improve red blood cell function. In this cohort study of 58 SS-homozygous adults with SCD who initiated HU therapy, we evaluated ACR changes and relationships of these changes with demographic, clinical, and biologic parameters at HU initiation (baseline) and 6 months later (follow-up). Between baseline and follow-up, ACR declined significantly for the entire population (3.0-1.7 mg/mmol; P<0.01), but this was primarily driven by the ACR reduction in the microalbuminuria subgroup (8.1-2.3 mg/mmol; P=0.03; n=23). According to bivariate analyses on 39 patients who did not receive a blood transfusion during the study period, the baseline to follow-up ACR decline was strongly associated with decreases in levels of hemolysis markers, percentage of dense red blood cells, and systolic BP. Bivariate analysis also revealed a close association between the ACR decrease and high baseline levels of hemolysis markers and percentage of dense red blood cells. These results show that urine ACR decreased significantly after 6 months of HU and confirm a close relationship between ACR and hemolysis evolution in patients with SCD.
Preoperative chemoradiation (CRT) with concurrent capecitabine and irinotecan in MRI-defined locally advanced rectal cancer: Relationship of histologic downstaging to long-term survival end points.
Authors: S. W. Gollins, S. Myint, S. Susnerwala, M. Wise, B. J. Haylock, M. P. Saunders, R. Neupane, C. Topham, L. M. Samuel, E. L. Levine
Journal: Journal of Clinical Oncology (2010)

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