tbuckley/cabot-search huggingface dataset:
Prognostication in esophagogastric adenocarcinoma (OGA): Factors influencing overall survival (OS) in REAL3.
Authors: Tom Samuel Waddell, Ian Chau, Clare Peckitt, Bijal Patel, David Gonzalez de Castro, Andrew Wotherspoon, Gary William Middleton, Jonathan Wadsley, David Ferry, Wasat Mansoor, Tom David Lewis Crosby, Fareeda Y. Coxon, David Smith, Justin S. Waters, Timothy Iveson, Stephen Falk, Sarah Slater, Alicia Frances Clare Okines, David Cunningham
Journal: Journal of Clinical Oncology (2014)

91 Background: The REAL3 trial evaluated the addition of panitumumab (P) to epirubicin, oxaliplatin and capecitabine (EOC) in advanced OGA. We previously reported that addition of panitumumab was not associated with improvement in survival endpoints. In this analysis we aimed to explore factors associated with OS in the REAL3 population. Methods: Analysis performed in ITT population (n=553). OS was evaluated in relation to the baseline characteristics displayed in the table below. Cox regression was used to obtain HRs and 95% CIs. Factors with p&lt;0.2 were included in a forward stepwise model and factors with p&lt;0.1 were regarded as significant in the final model. OS was also assessed using the RMH Prognostic Index score which comprises 4 adverse variables: PS 2; liver mets; peritoneal mets; ALP &gt;100 U/L. Results: Results of the univariate analysis are shown in the table below. In multi-variate analysis, the factors which remained statistically significant for OS were: PS (p=0.080): 1 vs 0 HR 1.24 (95% CI 0.99-1.57); 2 vs 0 HR 1.57 (95%CI 0.97-2.54) Disease extent (p=0.054): Met disease vs LA HR 1.42 (95% CI 0.99-2.02) Baseline global health score (p=0.005): Low vs high HR 1.52 (95% CI 1.16-2.00); middle vs high HR 1.45 (95% CI 1.11-1.89) Patients with an RMH Prognostic Index score of 0 (good prognosis) had median OS of 13.1 mo. This compared to 9.5 mo in patients with 1-2 adverse features (intermediate prognosis) (HR 1.37, 95% CI 1.12-1.68; p=0.002) and 4.7 mo in patients with 3-4 adverse features (poor prognosis) (HR 4.02, 95% CI 1.96-8.22; p&lt;0.001). Conclusions: Baseline global quality of life may represent a useful adjunct to clinical parameters to guide prognostication in advanced OGA. These findings also validate the RMH Prognostic Index score in the REAL3 population. Clinical trial information: 2007-005976-15.[Table: see text]
The costs of managing patients with stage 3 and 4 colorectal cancer and the influence of patient factors at presentation
Authors: R. Rajan, A. Noe, J. R. Penrod
Journal: Journal of Clinical Oncology (2004)

3656 Background: The costs of managing stage 3 and 4 colorectal cancer patients were determined and correlated with baseline patient characteristics. Methods: All patients presenting with stage 3 or 4 colorectal cancer at our institution between January 1986 and December 1993 were identified. Patients without pathologic confirmation or treated elsewhere for colorectal cancer were excluded. Ten patients were randomly selected from each of six categories based on disease site and stage, and resource utilization, clinical and demographic data were abstracted for each patient from hospital records. Unit costs obtained from a simultaneous fully allocated costing model and provincial billing data were attached to each resource. Average costs were determined, and univariate and multivariate regression analyses performed to estimate the influence on costs of baseline demographic and clinical variables. Results: Of 573 patients identified, 340 had colon cancer, 111 rectosigmoid cancer, and 122 rectal cancer. Of the 60 patients in the sample, 54% were men, and mean ages at presentation were 67.9 years for men and 69.9 years for women. Overall survival was 39 months for stage 3 and 11 months for stage 4 patients. Patient management in each category was described. Mean total costs per patient in each category varied from $13,075 (Canadian) to $21,853. Most costs were incurred during the first (71.3%) and second (21.1%) years following presentation. The ten most important cost categories were: number of admission days, surgical and operating room charges, clinic visits, medical imaging, inpatient physician charges, radiotherapy, laboratory tests, intensive care, medical specialist consultations, and surgical procedures. A multivariate regression model predicting total costs based on gender, disease site, stage at presentation, age, and comorbidity explained 33% of the variation in costs between patients. Conclusions: The cost components for stage 3 and 4 colorectal cancer were identified, and a multivariate regression model showed that baseline patient characteristics could explain one-third of the variation in health care costs. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pharmacia Hoffmann-La Roche
Clinicopathologic predictors of tertiary gleason pattern 5 in radical prostatectomy specimens
Authors: J. L. Wright, P. H. Lange, W. J. Ellis, L. D. TRUE, D. W. Lin
Journal: Journal of Clinical Oncology (2008)

5129 Background: Recent data have shown that prostate cancer patients with tertiary Gleason pattern 5 (TP5) cancers have biochemical recurrence rates similar to those with Gleason sum 8–10 cancers. We evaluate the predictors of having a TP5 identified in radical prostatectomy (RP) specimens. Methods: Patients who underwent RP with Gleason 7 cancer and no neoadjuvant therapy were identified from an institutional database. Demographic and pathologic characteristics were collected. Differences between those with and without TP5 were analyzed with Mann-Whitney rank sum and Chi-squared tests. Predictors of TP5 were determined with multivariate logistic regression analysis adjusting for pathologic stage, surgical margins, preoperative PSA, tumor volume, and prostate gland volume. Results: From 2840 patients undergoing RP, 723 were identified with Gleason 7 cancer of which 92 patients (13%) had a tertiary pattern 5. Patients with TP5 had higher tumor volume (median 4.0cc vs 2.3cc, p < 0.0001). There was no difference in the preoperative PSA or total prostate volume between the two groups. Patients with TP5 more commonly had primary pathologic Gleason pattern 4 (61% vs. 20%, p < 0.001) and extracapsular extension (52% vs. 25%, p < 0.001) than those without TP5. In multivariate analysis, patients with primary Gleason pattern 4 (OR 6.16, 95% CI 3.68–10.3, p < 0.001) and extracapsular extension (OR 2.63, 95% CI 1.52–4.53, p = 0.001) were more likely to have TP5 identified. Additionally, increasing tumor volume was associated with a higher risk of TP5 (p < 0.001). Compared to the tumor volume less than 1cc, the risk of TP5 was 2-fold higher for tumors 1–2.5 cc (OR 1.98, 95% CI 0.77–5.1), almost 3-fold higher for tumors 2.5–4.0cc (OR 2.79, 95% CI 1.05–7.42) and more than 5-fold higher for tumors greater than 4.0cc (OR 5.7, 95% CI 2.15–15.1). Conclusions: Of the associated clinical and pathologic factors, we found that tertiary pattern 5 is more often identified in patients with larger, higher stage tumors with primary Gleason pattern 4, lending insight into why the cancers with tertiary pattern 5 have such aggressive tumor behavior. These data also support the thorough pathologic examination of all cancers with primary Gleason 4 disease in order to identify this important subgroup of high risk patients. No significant financial relationships to disclose.
Is there a benefit to having a clinical oncology pharmacist on staff at a community oncology clinic?
Authors: A. D. Ruder, D. L. Smith, M. T. Madsen, F. H. Kass
Journal: Journal of Clinical Oncology (2007)

19570 Background: The John Marsh Cancer Center is an ambulatory oncology clinic located in Hagerstown, MD. In 2004, an on-site clinical oncology pharmacist was hired to help manage therapies and control cost. The objective was to evaluate the clinical interventions and assess the impact of consultations by the clinical oncology pharmacist to patients during therapy. Methods: This was a retrospective descriptive analysis of previous clinical interventions by the clinical oncology pharmacist from September 4, 2004 to October 27, 2006. This study involved a diverse patient population with different tumor types and/or disease states. The evaluation comprised two different categories: drug related problems (DRPs) and consultations, with several sub-categories. The DRPs included medication reconciliation, dosing, and adverse effect management and prevention. Consultations incorporated drug information questions, patient visits, and patient education sessions. The information was extracted from an online documentation program linked to medical charts and analyzed to determine the impact of a clinical oncology pharmacist on staff at the cancer center. Results: A diverse population of 199 patients was identified. Diagnoses included solid tumors 89%, hematological malignancies (3%), and miscellaneous diseases (8%). The 583 clinical interventions documented totaled 5,705 minutes, at an average of 10 minutes per intervention. Of the 583 interventions, 205 were DRPs, including 22 dosing, 52 medication reconciliations, and 131 adverse events. A total of 378 consultation interventions were documented, including 25 drug information questions, 124 patient visits, 143 patient education sessions, and 86 patient follow-ups. The on-site clinical oncology pharmacist saved $210,000 by admixing chemotherapy. Implementation of a carboplatin skin-testing protocol saved over $3,000 by preventing hypersensitivity reactions. Patient and colleague satisfaction surveys found the pharmacist to be a valuable asset with overall positive ratings of 95% and 98%, respectively. Conclusion: Analysis of clinical interventions, cost-savings, and feedback from patients and colleagues confirmed beneficial services provided by a clinical pharmacist in an outpatient oncology center. No significant financial relationships to disclose.
Randomized phase II trial of nanoparticle albumin-bound paclitaxel in three dosing schedules with bevacizumab as first-line therapy for HER2-negative metastatic breast cancer (MBC)
Authors: A. K. Conlin, C. A. Hudis, A. Bach, M. Moynahan, D. Lake, A. Forero-Torres, G. Wright, M. Hackney, A. Clawson, A. D. Seidman
Journal: Journal of Clinical Oncology (2009)

1006 Background: Nanoparticle albumin-bound paclitaxel (nab-P) 260 mg/m 2 is superior to paclitaxel 175 mg/m 2 (P) every 3 weeks (Gradishar et al., J Clin Oncol. 2005). Weekly uninterrupted P is more effective than q3wk P in MBC (Seidman et al., J Clin Oncol. 2008). Bevacizumab (bev) nearly doubles response rate and time to progression (TTP) when added to P as 1st line therapy for MBC (Miller et al., N Engl J Med. 2007). Methods: This open-label, phase II study randomized patients (pts) to nab-P at 260 mg/m 2 q3wk (arm A) versus 260 mg/m 2 q2wk with filgrastim (arm B) versus 130 mg/m 2 weekly uninterrupted, all with bev (15 mg/kg q3wk arm A, 10 mg/kg q2wk arms B and C). Pts were required to have measurable, HER-2-negative MBC and no prior chemotherapy for MBC. The primary endpoints were response rate and toxicity. Results: Accrual is complete, with 25% of pts still on study as of December 1, 2008. Of 208 pts randomized, 202 (72 arm A, 54 arm B, 76 arm C) were treated, with balanced demographics and baseline characteristics. The median age was 56 (range 29–85). 89% had visceral disease and 61% had prior neo-adjuvant or adjuvant chemotherapy. No significant differences in confirmed complete and partial response rates were noted (A: 42%, B: 42%, C: 41%). TTP was longer in arm C (9.2 months) versus both arms B (6.4 months) and A (7.7 months), overall p = 0.028. As per protocol-specified stopping rule, arm B was closed early due to unacceptable safety profile with significantly more grade ≥ 2 fatigue (B:57%, A: 39%, C:39%, p = 0.048) and bone pain (B: 19%, A: 10%, C:4%, p = 0.024). Neurotoxicity grade ≥ 2 was equivalent across all 3 arms (50%); febrile neutropenia occurred in &lt;2% of pts in all arms. Arm C had significantly less arthralgia, myalgia, and nausea compared with arms A and B. Conclusions: Significant antitumor activity was observed in all arms. Weekly nab-P with bev (Arm C) resulted in a significantly longer TTP. Weekly nab-P with bev (Arm C) appears to have the highest therapeutic index, however sensory neuropathy is limiting, suggesting a 3 week on/1 week off schedule could be preferable and should be studied comparatively. [Table: see text]
Pharmacodynamic study of the raf kinase inhibitor BAY 43–9006: Mechanisms of hypertension
Authors: M. L. Veronese, K. T. Flaherty, R. Townsend, A. Mosenkis, R. Zimmer, M. Rosen, M. Gallagher, P. J. O'Dwyer
Journal: Journal of Clinical Oncology (2004)

2035 Background: BAY 43–9006 is an orally available inhibitor of Raf kinase that has also been shown to inhibit angiogenesis in tumor xenografts. In a clinical trial of BAY 43–9006, we observed elevated blood pressure (BP), commonly associated with angiogenesis inhibitors. We investigated the mechanism of BP elevation in patients treated with BAY 43–9006. Methods: Twenty patients (13 males and 7 females, age range 32–83, median 59, PS 0–1) were treated with BAY 43–9006 400 mg orally twice daily. Aldosterone, catecholamines, endothelin, urotensin II, serum VEGF and von Willebrand factor (vWf), all factors shown to be mediators of vascular tone and hypertension, were measured at baseline and after three weeks of therapy. Tumor blood flow and vascular permeability were measured by DCE-MRI, and left ventricular ejection fraction and pulmonary artery systolic pressure by echocardiogram. Aortic pulse wave velocity (PWV), aortic augmentation index (AIX) were performed at baseline and after three weeks of therapy. Results: 19 patients are evaluable for BP, serologic and cardiologic evaluations, and 3 patients are evaluable for response. 11 of 19 (58%) (p<0.001) patients experienced an increase of 20 mmHg or more in systolic BP compared to their baseline value after 3 weeks of beginning BAY 43–9006 and BP remained elevated at 6 weeks. The mean increase of BP for all patients was 20 mmHg (±17, s.d.). Increased serum VEGF was observed in 9 of 13 evaluable patients, but did not correlate with BP elevation. Total catecholamines were decreased in 8 of 11 patients with elevated BP. PWV and AIX increased from 8.7 to 9.6 m/sec and from 21% to 30% respectively (P=NS). All 3 patients evaluable for response achieved PR and 2 of these patients experienced an increase of BP. Conclusions: Mild hypertension occurs with BAY 43–9006 treatment, and may be associated with changes in catecholamines and with indices of vascular stiffness. No significant financial relationships to disclose.
Phase II multicenter trial of the histone deactylase inhibitor (HDACi) belinostat, carboplatin and paclitaxel (BelCaP) in patients (pts) with relapsed epithelial ovarian cancer (EOC)
Authors: N. J. Finkler, D. S. Dizon, P. Braly, J. Micha, U. Lassen, P. Celano, R. Glasspool, E. Crowley, P. Buhl-Jensen, R. T. Penson
Journal: Journal of Clinical Oncology (2008)

5519
Docetaxel in combination with gemcitabine (DG) versus docetaxel (D) as front-line treatment in patients with advanced/metastatic NSCLC: A multicentre, randomized, phase III trial
Authors: V. Georgoulias, K. Syrigos, M. Agelidou, A. Potamianou, A. Polyzos, J. Varthalitis, A. Gerogianni, N. Ziras, D. Mavroudis, N. Androulakis, G. Samonis
Journal: Journal of Clinical Oncology (2005)

7052 Background: To compare the efficacy and toxicity of the DG combination versus D monotherapy in chemotherapy-naïve patients with advanced/metastatic NSCLC. Methods: Patients with histologically or cytologically confirmed NSCLC were randomized to receive either the DG (gemcitabine; 1000mg/m2, d1+d8 and docetaxel; 100mg/m2, d8) regimen (n=186) or single agent D (docetaxel; 100 mg/m2, d1) (n= 186) every 3 weeks. G-CSF support (150μγ/m2 sc) was given in both groups. Results: A total of 925 (DG=475 and D=450) chemotherapy cycles were administered with a median of 3 cycles/pt in each group. The incidence of grade 2–4 anemia and grade 3–4 thrombocytopenia were higher (p=0.011 and 0.028, respectively) in the DG than the D group; there was no difference between the two groups concerning grade 3–4 neutropenia or febrile neutropenia. Other severe toxicities were rare. There were 3 (2.6%) CRs and 26 (22.4%) PRs (ORR=25%; 95% CI: 17.12–32.88%) in the DG arm and 1 (0.8%) CR and 12 (10.2%) PRs (ORR=11%; 95% C.I: 5.37–16.67%) in the D arm (p=0.005). The median response duration was 5 months in each arm (p=0.798) while the median time to tumor progression was 5.7 months in each arm (p=0.609). The overall survival time was 9.1 and 8.3 months in the DG and D arm, respectively (p=0.0305); The 1- and 2-year survival rate was 38.6% and 16.5%, respectively for the DG arm and 32.19% and 7.3%, respectively, for the D arm. Conclusions: The docetaxel/gemcitabine combination is more active in terms of response rate and overall survival than single agent docetaxel and further patients’ accrual was stopped for ethical reasons. No significant financial relationships to disclose.
Safety of long-term administration of capecitabine in metastatic breast cancer patients
Authors: M. Lomas, J. Salvador, M. Ruiz, J. L. Bayo
Journal: Journal of Clinical Oncology (2006)

10755 Background: To evaluate the effectiveness and tolerability of long -term treatment with capecitabine in metastatic breast cancer patients. Capecitabine (C) has been administered offering clinical benefit to women with metastatic breast cancer (MBC) (ORR: 42%). The aim of this trial was to evaluate the efficacy and tolerance of capecitbine in long-term treatment, administered as first, second and third line treatment in MBC. Methods: Patients ≥ 18 years old with MBC, ECOG performance status (PS) ≤2, HER-2 neu negative, non-chemotherapy naive were included in this prospective, multicentre, non-randomized. To date, twenty-two ambulatory patients were evaluable for toxicity and response. Median age 59.2 years (37–81). All of patients had previously received adjuvant treatment. Hormonal therapy were allowed as clinically required. They received three weekly cycles of oral capecitabine 1000–1250 mg/m 2 twice daily, days 1–14, followed one week rest until progression or relapse. Results: The overall response rate (ORR) is including PR, CR, and EE 78%. The median treatment duration was 14 months, median range (3–32). Median progression-free and overall survival have not yet been reached. The most common grade ½ (NCIC CTC) treatment related adverse events were /23, hand foot syndrome 4/23, diarrea 1/23. Conclusions: These preliminary data confirm that the treatment with capecitabine (C) is an effective and well tolerated regiment in metastatic breast cancer patients. No significant financial relationships to disclose.
Tumor budding as a useful prognostic marker in esophageal squamous cell carcinoma
Authors: M. S. Roh, J. I. K. Lee, P. J. Choi, H.-C. Kwon, H. K. Kim
Journal: Journal of Clinical Oncology (2004)

4199 Background: Tumor budding along the invasive margin was reported to be associated with greater malignant potential in colorectal adenocarcinoma. We examined the prognostic significance of tumor budding in patients with esophageal squamous cell carcinoma (ESCC), particularly in comparison to other routine pathological findings. Methods: Fifty-six cases who underwent an esophagectomy were reviewed. We defined tumor budding as an isolated single cancer cell or a cluster composed of fewer than five cancer cells and divided these into two grades; low-grade (<5 budding foci) and high-grade (≥5 budding foci) within a microscopic field of x200. Results: There were 22 (39.3%) and 34 (60.7%) cases with low- and high-grade budding, respectively. There were significant differences in the patients with low- and high-grade budding in relation to tumor size, pT stage, lymphovascular invasion, perineural invasion, circumferential resection margin involvement, and AJCC stage (p<0.05). The 3-year survivals of the patients with low- and high-grade budding were 72.3% and 30.7%, respectively (p=0.04). Conclusions: We propose that tumor budding may be a pathological marker suggesting high malignant potential and decreased postoperative survival in patients with ESCC. No significant financial relationships to disclose.
Long-term outcome of bacilles Calmette-Guerin perfusion therapy for upper urinary tract urothelial carcinoma in situ.
Authors: Takahiro Yoneyama, Naoki Sugiyama, Yuuichirou Suzuki, Akiko Okamoto, Hayato Yamamoto, Atsushi Imai, Shingo Hatakeyama, Yasuhiro Hashimoto, Takuya Koie, Chikara Ohyama
Journal: Journal of Clinical Oncology (2013)

265 Background: Bacillus Calmette-Guerin (BCG) therapy has already been established as a treatment for muscle noninvasive bladder cancer. Although there are several reports indicating the effectiveness of BCG perfusion therapy for the upper urinary tract urothelial carcinoma in situ (CIS), it is not well established yet. We conducted a retrospective study to assess the long-term outcome of BCG perfusion therapy for the upper urinary tract CIS. Methods: Twenty-six subjects (20 male, 6 female) who received BCG perfusion therapy for the upper urinary tract CIS from December 1997 to December 2011 were enrolled. Ten subjects had the entire urinary tract CIS, seven had bilateral, nine had unilateral CIS of the urinary tract. The average period of observation was 52.6 months (ranging from 5 to 156 months), and the average subject age was 73.6 years (ranging from 56 to 90 years). We used a double-J catheter for 17 cases, a transvesical single-J catheter whose curl was positions in an upper calyx for eight cases, and a straight ureteral catheter inserted for ureterocutaneostomy for one case. We used 80 mg of BCG for the first five cases, 40 mg for the late twenty-one cases. Urine cytology was performed to assess the treatment validity. Results: Of the 26 cases, the treatment protocol was completed in 21 cases. Urine cytology tests became negative in 22 of the 26 subjects (84.6%) who underwent upper urinary tract perfusion. Among these 22 subjects who had negative tests, five subjects had a recurrence in their upper urinary tracts. Side effects were observed in 25 subjects (96.5%), and the most common side effect was bladder irritation. Localized renal tuberculosis which was successfully treated with conservative therapy was seen in two cases. Conclusions: BCG perfusion therapy for the upper urinary tract CIS is active. However, severe side effects are possible, and careful observation is essential while using this therapy.