tbuckley/cabot-search huggingface dataset:
Pejorative factors identification for survival in patients with brain metastases from breast carcinoma treated with whole brain radiation therapy
Authors: R. Le Scodan, C. Massard, E. Fourme, J. Guinebretiere, A. Goupil, B. De Lalande, C. Cohen-Solal, P. Moisson, J. Floiras, A. Labib
Journal: Journal of Clinical Oncology (2006)

10513 Background: To determine overall survival and independent prognostic factors for patients with brain metastases from breast carcinoma treated with whole brain radiation therapy (WBRT). Methods: From January 1998 through December 2003, 132 patients with brain metastases (BM) from breast carcinoma were treated with WBRT (median dose: 3000 cGy/ 10 fractions). We analyzed a number of potential predictors of survival after WBRT: age, presence of other systemic metastases, performance status, RTOG recursive partition analysis (RPA) class (1–2 vs 3), total dose of WBRT, number of brain metastases, interval between primary tumor and brain metastases, SBR score, tumor receptor hormonal (RH) status, lymphocyte count (&lt; 700 vs ≥ 700 G/L), serum lactate dehydrogenase and HER-2 overexpression. The survival time with BM was defined as the time from the date of BM to the date of death or date of last of follow-up. Multivariate analysis was used to determine the effect of prognostic factors on overall survival using the Cox proportional hazard model. Results: One hundred and seventeen patients received exclusive WBRT. Surgery was followed by WBRT in 14 patients and stereotactic radiosurgery was followed by WBRT in 1. The median survival with BM was 6 months (range: 0–52). The 1-year and 2-years survival rates were 31% (CI95%: 23.5–39.8) and 16% (CI95%: 9.8–24.9). In multivariate analysis, RTOG RPA class III, lymphopenia (&lt;700) and negative tumor RH status were independent prognostic factors for poor survival. Moreover, analysis of Her-2 overexpression was performed in 53 patients and 43% BM patients overexpressed Her-2. In preliminary analysis, Her-2 status was not a prognostic factor of survival. A complete analysis is ongoing and will be presented at the meeting. Conclusions: This large study confirms the value of established prognostic factors such as the RTOG RPA score and some less-well recognized factors such as lymphopenia and tumor RH status. No significant financial relationships to disclose.
CRP as predictor as predictor for late treatment failure in hospitalised patients with AECOPD
Authors: Henk-Jan Prins, Hans Daniels, Wim Boersma
Journal: European Respiratory Journal (2013)

Background : 30-day treatment failure rates are high amongst patients admitted with an acute exacerbation of COPD(AECOPD). The aim of this study is to identify whether CRP level measured at day10(CRP-d10) is a risk factor for the development of treatment failure within 30 days.

Methods: 265 hospitalized subjects with AECOPD where enrolled(1). Sixty-six patients where excluded because of early treatment failure(<10 days). Patients received oral doxycycline or placebo for 7 days and systemic corticosteroids. Of 141 subjects CRP-d10 was measured after completing treatment.

Results: 38 subjects had treatment failure at day 30. Median CRP-d10 in the treatment failure group was 2,5 mg/L(IQR:1.0-5.3mg/L) vs 4.0 mg/L(IQR 2.0-8.8mg/L) in the none-treatment failure group(p=0.16). CRP-d10 was influenced by treatment with doxycycline 2,5mg/L (IQR 1,0-4,0mg/L) or placebo 4mg/L (IQR 2.0-12mg/L)(p=0.006). Treatment failure was not influenced by antibiotic treatment: failure rate in doxy vs placebo 51.2% vs 48.8% p=0.984.

Any pathogen found in a sputum culture on day 8 did effect the CRP-d10 levels. A positive culture with any pathogen vs a negative sputum culture resulted in a median CRP level of 4.0mg/L (IQR 2.0-12.0mg/L) vs 2,5mg/L (IQR 1.0-5.3mg/L) in the negative sputum culture(p=0.015). Positive culture vs negative culture failure rate was 24.7% vs 20.7% (p=0.151)

Conclusion: CRP-d10 is not a reliable predictor for treatment failure in a hospitalised AECOPD. Antibiotic treatment resulted in a lower value of CRP-d10, but did not affect the treatment failure rate at day 30. The other factor that seems to play a role in CRP-10 level is bacterial growth although this does not implicate clinical success.
First results from the Patient's Anastrozole Compliance to Therapy (PACT) program evaluating the influence of a standardized information service on compliance in postmenopausal women with early breast cancer (EBC).
Authors: N. Harbeck, P. Hadji, C. Jackisch, M. Landthaler, V. Heilmann, B. Baier, M. Blettner, H. Lück, A. Rexrodt von Fircks, R. Kreienberg
Journal: Journal of Clinical Oncology (2010)

523 Background: Retrospective data show that compliance to adjuvant endocrine therapy for early breast cancer (EBC) may drop below 80% after 1 year and as low as 50% by year 4. PACT aims to increase treatment adherence in postmenopausal women taking adjuvant anastrozole via a standardized information service. Methods: PACT is a prospective, randomised, two-arm parallel group trial with 60 months follow-up. Women on anastrozole for hormone receptor-positive (HR+) EBC were randomized to routine clinical care alone or additional standardized information for the first 12 months of adjuvant therapy. Primary endpoint is the compliance rate after 12 months. Secondary endpoints include reasons for noncompliance, influence of baseline characteristics, and clinical outcome parameters. Compliance is evaluated via patient questionnaires, prescription data and physician recall. Results: 4,924 women were enrolled by November 2008, the average age was 64.7 years. 97.7% were ER+, 8.4% HER2+, mean tumour size 21.4 mm, 74.5% had received breast preserving surgery, 23.5% a mastectomy, 6.7% had had neoadjuvant chemotherapy and almost 40% received adjuvant chemotherapy. 85% were scheduled for adjuvant radiotherapy. Analysis of the primary endpoint compliance at 12 months will be performed after data base lock in February 2010. Conclusions: PACT is the largest prospective trial to date on compliance in HR+ EBC and aims to clarify whether standardized information services throughout year one may improve compliance to adjuvant endocrine treatment and influence outcomes in postmenopausal women with HR+ EBC. Sponsored by AstraZeneca. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca, Roche AstraZeneca
Recurrence of primary renal disease on kidney graft
Authors: M Broyer, N Selwood, F Brunner
Journal: Journal of the American Society of Nephrology (1992)

Of the 4,776 first grafts recorded in the pediatric European Dialysis and Transplant Association (EDTA) registry, 2,113 were reported to have failed and 5.6% of graft failures were related to a recurrence of primary renal disease. Nephrotic syndrome with focal and segmental glomerulosclerosis was the main renal disease prone to recur because recurrence represented 20% of the causes of graft failure in these patients; an even higher proportion was reported in a single-center experience in Europe. Other glomerulonephropathies, such as membranoproliferative glomerulonephritis and Berger's disease, were also reported to be the cause of graft failure by means of recurrence in a proportion similar to focal and segmental glomerulosclerosis. The usual recurrence of primary oxaluria was the cause of close to 50% of graft failure in this disease. Finally, hemolytic uremic syndrome recurred rarely with the graft in the EDTA registry, which is the opposite of what was reported in the United States.
Dual inhibition of aromatase and epidermal growth factor receptor in non-small cell lung cancer
Authors: A. Koutras, I. Kritikou, E. Giannopoulou, K. Dimitropoulos, H. Kalofonos
Journal: Journal of Clinical Oncology (2009)

e22189 Background: Recent evidence suggests that estrogen signaling is important in the progression of cancers expressing estrogen receptors (ERs) and may also be involved in the pathogenesis of non-small cell lung cancer (NSCLC). Aromatase is an enzyme complex that catalyses the final step in estrogen synthesis and is present in several tissues, including the lung. In view of a possible functional interaction between the ER and the epidermal growth factor receptor (EGFR) pathways in NSCLC, we investigated the dual inhibition of aromatase and EGFR in NSCLC cell lines. Methods: In the current study we used exemestane, an irreversible steroidal aromatase inactivator, and erlotinib, an EGFR tyrosine kinase inhibitor. The in vitroexperiments were performed using H23 and A549, two NSCLC cell lines with low and high levels of aromatase, respectively. Cell proliferation was measured by MTT assay. Metalloproteinase (MMP) levels were detected by zymography and cell migration was determined by boyden chamber assay. EGFR protein levels detection was performed by immunofluorescense assay. Results: Exemestane and erlotinib inhibited H23 and A549 cell proliferation either alone or in combination, 48 hours after their application. However, the combination of exemestane and erlotinib was more effective than each agent alone, in H23 cells. Furthermore, exemestane decreased MMP-2 and MMP- 9 levels in H23 cells, whereas erlotinib did not. The combination of exemestane and erlotinib had the same effect on MMPs, as exemestane alone. The effect on cell migration was in line with the results in MMPs levels. In A549 cells, no changes in MMPs levels or cell migration were demonstrated. In addition, exemestane altered the location of EGFR protein in H23 cells, but not in A549 cells. Conclusions: Our findings suggest an antiproliferative effect of exemestane and erlotinib in both cell lines, as well as synergy for the combination in H23 cells. The activity of the combination in these cells with low levels of aromatase might involve an additional effect of exemestane on EGFR protein location. Erlotinib did not enhance the effect of exemestane on MMPs secretion and migration in H23 cells. No significant financial relationships to disclose.
A multicenter, randomized phase II study of neoadjuvant chemotherapy including trastuzumab with cyclophosphamide with docetaxel in patients with operable HER2-positive breast cancer (JBCRG-10 study).
Authors: N. Masuda, M. Toi, T. Ueno, K. Aogi, H. Iwata, S. Ohno, K. Kuroi, N. Sato, S. Nakamura
Journal: Journal of Clinical Oncology (2010)

TPS105 Background: Japan Breast Cancer Research Group (JBCRG) is collaborating with Breast International Group (BIG) to develop new evidence for breast cancer treatments in Japan. Combination regimens of anthracyclines and taxanes have been widely used as preoperative systemic therapy (PST) in patients with operable breast cancer. However, we have several clinical questions related to PST: (1) additional effect of cyclophosphamide (CPA) to standard regimen (anthracycline and taxane) to identify preferred regimen for PST, (2) preferable order of anthracycline and taxane, (3) relation between the order of anthracycline and taxane and cardiac toxicity and (4) effect and safety of anthracycline-free regimen. To answer to these questions, we conduct this JBCRG 10 study. Methods: One hundred eighty HER2-positive breast cancer patients (T1C-3, N0-1, M0) are planned to be enrolled. Patients will receive the following treatment: (1)FEC-TCH group, 4 cycles of 5-fluorouracil (5-FU; 500 mg/m2, q3w) + epirubicin (EPI; 100 mg/m2, q3w) + CPA (500 mg/m2, q3w) (FEC regimen) followed by 4 cycles of docetaxel (75 mg/m2, q3w) + CPA (600 mg/m2, q3w) + trastuzumab (H; 2 mg/kg, weekly with loading 4 mg/kg or 6 mg/kg, q3w with loading 8 mg/kg) (TCH regimen); (2) TCH-FEC group, 4 cycles of TCH followed by 4 cycles of FEC and (3) TCH group, 6 cycles of TCH. The primary endpoint is pathological complete response (pCR) rate. Secondary endpoints include safety, cardiac toxicity rate, overall response rate, disease-free survival, overall survival, breast cancer conserving rate and nondissection rate of axillary lymph nodes. Translational research is also planned. In summary, JBCRG-10 will evaluate the efficacy and safety of FEC-TCH, TCH-FEC and TCH as PST in Japanese patients with operable HER2-positive breast cancer and will also answer to the question on regimen order and a power of anthracycline-free regimen. No significant financial relationships to disclose.
The expression of Fibroblast Activation Protein in human colon carcinoma
Authors: L. Henry, J. Lee, A. Klein-Szanto, W.-T. Chen, C. Renner, P. Watts, E. Ross, J. Cheng
Journal: Journal of Clinical Oncology (2005)

9668 Background: Human Fibroblast Activation Protein (FAP)/seprase is a 97-kd surface glycoprotein with dipeptidyl peptidase and gelatinolytic activity expressed on tumor associated fibroblasts in the majority of epithelial cancers including colon adenocarcinomas. FAP overexpression has been shown to promote tumor growth in animal models, and clinical trials targeting FAP enzymatic activity have been initiated. The primary objective of this study was to evaluate expression levels of FAP in human colon cancers by immunohistochemisty and relate its expression to clinical outcome. Methods: Sections of paraffin-embedded resected primary human colon cancer specimens from 1996 through 2001 within the Fox Chase Cancer Center tumor bank were stained with D8 antibody directed against FAP/seprase. Grading of staining was performed by assessment of FAP staining intensity (none, light, medium, dark) and overall percent of stromal staining (0, 1–10%, 11–50%, 51%+) as previously established. Survival time and time to recurrence data were analyzed using Kaplan-Meier plots, log-rank tests and Cox proportional hazards models. Results: 138 patients with resected specimens were available for study (mean follow-up 1050 days) with 6 patients (4%) stage I, 52 (38%) stage II, 43 (31%) stage III, and 37 (27%) stage IV. FAP was detected in over 93% of specimens and semiquantitative staining was scored as 1+ in 28 (20%), 2+ in 52 (38%) and 3+ in 49 (35%). FAP staining was graded as light in 45 (33%), medium in 48 (35%), and dark in 36 (26%). Overall survival was higher in patients with medium or dark staining intensity (median days not yet achieved) versus those with no or light staining intensity (median = 1415 days, p= .02). However, the impact of FAP intensity on overall survival was lost when analyzed with stage within a multivariate model. Thus, FAP staining intensity correlated inversely with stage. Conclusion: Patients whose colon cancers intensely express FAP are more likely to have early stage disease. This suggests that clinical trials utilizing FAP as a therapeutic target to disrupt FAP-driven tumor growth may have greater potential efficacy prior to the establishment of metastatic disease. No significant financial relationships to disclose.
Response of mouse proximal straight tubule and medullary thick ascending limb to beta-agonist.
Authors: N S Morgunov, Y D You, D J Hirsch
Journal: Journal of the American Society of Nephrology (1993)

Scatchard analysis of (3H)CGP-12177 and (125I)cyanopindolol (CYP) radioligand binding data revealed the presence of specific beta-adrenergic receptor-binding sites on microdissected mouse proximal straight and medullary thick ascending limb (mTAL) tubules. beta-Receptor (10(-6) M isoproterenol) stimulation of isolated perfused mTAL tubules produced a consistent hyperpolarization of the transepithelial potential that was blocked by propranolol (10(-6) M), a beta-receptor antagonist, and furosemide (10(-4) M), an inhibitor of the Na+/K+/2 Cl- triporter. In contrast, there was no electrogenic response to isoproterenol stimulation in isolated perfused proximal straight tubules. In summary, radioligand binding data show that both proximal straight and mTAL tubules possess beta-receptor-binding sites. Electrogenic transport in the mTAL can be modulated by beta-agonists, but there was no detectable electrogenic response to beta-receptor stimulation in proximal straight tubules.
NIH Funds Cooperative Robot Research Projects
Authors: Julie A. Jacob
Journal: JAMA (2016)

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Single-agent pemetrexed or sequentially administered pemetrexed/gemcitabine as first-line chemotherapy for advanced non-small cell lung cancer (NSCLC) in elderly patients or patients ineligible for platinum-based chemotherapy: Preliminary results of a phase II randomized trial
Authors: C. Gridelli, M. Reck, V. Gregorc, M.-R. Migliorino, T. R. Muller, C. Manegold, A. Favaretto, E. Crucitta, A. Rossi, G. Koschel
Journal: Journal of Clinical Oncology (2005)

7156 Background: Because elderly patients (pts) may tolerate combination chemotherapy poorly, single-agent chemotherapy is often the preferred treatment. This study evaluated the efficacy (primary objective: time to progressive disease [TTPD]) and toxicity of single-agent pemetrexed (P), and sequential pemetrexed/gemcitabine (P/G) for the treatment of advanced NSCLC in elderly pts (≥70 years) or pts ineligible for platinum-based chemotherapy. Methods: Chemonaive pts with stage IIIB/IV NSCLC and an ECOG PS of 0–2 were randomized to P 500 mg/m2 on day 1 every 3 weeks for 8 cycles (P arm), or P 500 mg/m2 for cycles 1 and 2 followed by G 1200 mg/m2 on days 1 and 8 of cycles 3 and 4 (P/G arm); this 4-cycle schedule was repeated once for a total of 8 cycles. Vitamin B12 and folic acid supplementation were required on both study arms. Results: A total of 92 pts were enrolled: 46 pts (7 with stage IIIB, 39 with stage IV) on the P arm and 46 pts (8 with stage IIIB, 38 with stage IV) on the P/G arm. Of the 92 pts, 81 (40 P, 41 P/G) were evaluable for efficacy and toxicity. The median TTPD was similar for both arms (4.2 and 4.1 months for P and P/G, respectively). Partial response was observed in 5 (12.5%) pts (3 unconfirmed after 1 month) treated with P and 5 (12.2%) pts (2 unconfirmed) treated with P/G. Nine (22.5%) pts on the P arm and 8 (19.5%) on the P/G arm had stable disease. Hematologic toxicity was mild: grade 3 neutropenia in 3 (7.5%) pts on the P arm (2 pts with febrile neutropenia); grade 3/4 thrombocytopenia in 1 pt per arm (2.5% and 2.4%, respectively); and grade 3/4 anemia in 3 (7.5%) and 2 (4.9%) pts on the P and P/G arm, respectively. Grade 3/4 allergic reaction, diarrhea, melena, gastritis, and anorexia occurred in 1 (2.5%) pt each treated with P. Grade 3/4 fatigue and abdominal pain occurred in 1 (2.4%) pt and rash in 2 (4.9%) pts treated with P/G. Conclusions: Preliminary results show that single-agent P and sequential P/G are active and well tolerated in this subset of pts with advanced NSCLC. The overall survival analysis is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly Eli Lilly Eli Lilly
The referential survival data of borderline resectable pancreatic cancer (BRPC) patients who are candidate for neoajuvant chemotherapy followed by surgery.
Authors: Kei Saito, Hiroshi Ishii, Masato Ozaka, Hiroki Osumi, Ikuhiro Yamada, Takashi Sasaki, Masato Matsuyama, Kouichi Takano, Naoki Sasahira
Journal: Journal of Clinical Oncology (2015)

434 Background: The aim of this study is to clarify referential survival data of BRPC patients who are candidate for neoajuvant chemotherapy followed by surgery. Methods: This retrospective study included data from all consecutive patients who were diagnosed as having invasive ductal pancreatic cancer at our hospital between January 2008 and December 2013. Selection criteria were as follows: patients who 1) had histologically confirmed pancreatic adenocarcinoma, 2) were diagnosed as having non-metastatic disease by dynamic CT before treatment, 3) had received anti-cancer treatment, and had been observed for 3 months or longer. We reviewed CT stage (UICC) and treatment modality, and analyzed their survival data. Results: There were 428 patients who met the selection criteria. Among them, clinical CT stage I/II (Group A; potentially respectable) and stage III (Group B; locally advanced) were documented in 170 (40%) and 131, respectively. Laparotomy was performed in all patients in Group A. Of the 170 in Group A, 166 (98%) received resection with curative intent, and the remaining 4 did not received resection because of discovery of occult metastasis at laparotomy. Of the 131 in Group B, 36 (27%; Group B-1) received resection with curative intent, 7 did not received resection because of occult metastasis, and the remaining 88 did not receive laparotomy because they were diagnosed as having locally advanced unresectable disease by CT. Among Group B, patients other than Group B-1 received gemcitabine-based chemotherapy (Group B-2; N=95). The median survival time, 1-yr, 2-yr, and 3-yr survival rate were 28.7 months, 78.6%, 55.5%, and 38.9% in Group A, 16.8 months, 63.8%, 31.8%, and 19.8% in Group B-1, and 13.8 months, 60.1%, 21.7%, and 5.9% in Group B-2, respectively. Conclusions: Based on our historical data, we suppose that 16.8 months of median survival time or survival rate of 19.8 at 3-yr, i.e, Group B-1 survival data, may be an appropriate threshold value in the single-arm phase 2 BRPC study.