tbuckley/cabot-search huggingface dataset:
Hepatitis C virus-associated membranoproliferative glomerulonephritis in renal allografts.
Authors: J M Cruzado, S Gil-Vernet, G Ercilla, D Seron, M Carrera, J Bas, J Torras, J Alsina, J M Grinyó
Journal: Journal of the American Society of Nephrology (1996)

In renal transplantation, chronic allograft nephropathy is the leading cause of long-term graft losses, transplant glomerulopathy being its glomerular form. Differential diagnosis from recurrent or de novo membranoproliferative glomerulonephritis should be established. Whether hepatitis C virus is associated with cryoglobulinemia and glomerular damage in renal allograft recipients, as in native kidneys, is not known. We identified six hepatitis C virus-infected renal allograft recipients with proteinuria higher than 1.5 g/day, microhematuria, and membranoproliferative glomerulonephritis. Virologic and immunologic studies were conducted. Low serum levels of circulating immune complexes and cryoglobulins were observed, which were type II immunoglobulin G polyclonal-immunoglobulin Mk monoclonal in all six patients. Classical serum complement pathway activation and at least one type of autoantibodies were present in all of them. Hepatitis C virus RNA was found in higher concentrations in cryoprecipitate than in serum (percentage of enrichment ranged from 341 to 18,200%). Hepatitis C virus genotype was 1b in 4 of 6 patients, 1a in 1 of 6 patients, and 2a in 1 of 6 patients. In renal histology prominent parietal diffuse deposition of immunoglobulin M was the rule. Glomerular subendothelial electron-dense deposits with fibrillar appearance were observed in the two patients in which electron microscopy provided information about glomeruli. In renal allograft recipients hepatitis C virus infection may be associated with type II cryoglobulinemia which may lead to membranoproliferative glomerulonephritis. Immunologic and virologic studies may help to differentiate hepatitis C virus-associated membranoproliferative glomerulonephritis from transplant glomerulopathy.
Genetic variants in angiogenesis pathway associated with clinical outcome in NSCLC patients (pts) treated with bevacizumab in combination with carboplatin and paclitaxel: Subset pharmacogenetic analysis of ECOG 4599
Authors: W. Zhang, S. E. Dahlberg, D. Yang, A. B. Sandler, J. R. Brahmer, J. H. Schiller, D. P. Carbone, D. H. Johnson, H. Lenz
Journal: Journal of Clinical Oncology (2009)

8032 Background: E4599 was a randomized phase III study which demonstrated a survival advantage in advanced NSCLC pts treated with bevacizumab (bev) + carboplatin/paclitaxel (BPC) versus carboplatin/paclitaxel alone (PC). Recent studies have shown certain germline polymorphisms (SNPs) are associated with clinical outcome in advanced breast cancer pts treated with paclitaxel plus bev and in advanced colorectal cancer pts treated with first line 5-FU or capecitabine in combination with oxaliplatin and bev. A study also found 2 SNPs in WNK1 gene were associated with bev-induced hypertension. We tested the hypothesis that SNPs involved in angiogenesis pathway (VEGF, EGF, EGFR, IL-8, KDR, ICAM1, FGFR4), DNA repair pathway (ERCC1, XPD, XRCC1, GSTP1) and WNK1 may predict clinical outcome in a subset of pts enrolled on E4599. Methods: Of 878 pts enrolled, samples from 146 pts were available for the current pharmacogenetic study and only 133 of the samples (67 PC, 66 BPC) came from eligible pts. PCR-RFLP assays were performed on genomic DNA extracted from sera of pts. The Kaplan-Meier method was used to estimate time-to-event distributions. Multivariable Cox models adjusted for gender, PS, stage, adrenal, liver and bone mets were separately fitted for each SNP to obtain estimates of hazard ratios. Results: Median OS for the 133 patients was 10.3 mos (8.2–15.6) for PC and 13.0 mos (10.2–16.6) for BPC. Median PFS was 4.6 mos (3.6–5.6) for PC &amp; 6.5 mos (5.4–8.3) for BPC. Pts with mutant homozygote CC genotype for ICAM1 T469C had significantly higher tumor response rate (39%) than heterozygote CT (13%) and homozygote TT (20%) genotype (Fisher's test, p=0.04). Tests for whether treatment effect differs by genotype via interaction terms in the Cox models were statistically significant (p&lt;0.05) for VEGF G-634C, ICAM1 T469C and WNK1-rs11064560 for OS, and for ICAM1 T469C, EGF A-61G and CXCR2 C785T for PFS. Conclusions: Although exploratory, our preliminary results suggest germline SNPs in angiogenesis pathway may predict response, PFS and OS in NSCLC pts treated with BPC. Prospective trials based on these correlative studies are warranted. [Table: see text]
Subgroup analysis and updated results of the randomized study comparing sorafenib (So) plus interleukin-2 (IL-2) versus So alone as first-line treatment in metastatic renal cell carcinoma (mRCC).
Authors: G. Procopio, E. Verzoni, S. Bracarda, S. Ricci, C. Sacco, L. Ridolfi, C. Porta, R. Miceli, N. Zilembo, E. Bajetta
Journal: Journal of Clinical Oncology (2010)

4589 Background: A randomized phase II study showed that in the first line treatment of mRCC, the combination So + IL-2 moderately improves the efficacy when compared to So alone. The subgroup analysis planned in the study design and updated results are reported. Methods: One hundred twenty eight treatment-naïve patients with mRCC were enrolled in the study. Patients were randomized to receive So (given orally at 400 mg twice daily, continuously) and IL-2, 4.5 MIU subcutaneously, five time a week for four consecutive weeks every six (Arm A), or So alone (Arm B).After the first 40 patients enrolled, 20 in each arm, a dose reduction of IL -2 was performed in order to improve the safety profile. Therefore, the remaining 44 patients received IL-2 at 3 MIU for 2 consecutive weeks every four. The study sample size was calculated according to a “phase 2.5 design“ with progression free survival (PFS) as the main endpoint. PFS curves were estimated by the Kaplan-Meier method and compared by means of the one-sided log-rank test.The efficacy and safety analyses will be performed on Intent to treat population. Results: The overall median PFS was 33 weeks for So plus IL-2, compared to 28 weeks for So alone (p=0-123). The 1-year PFS was 31.6 % and 28.9 % in favour of the combination treatment. In patients with good prognosis the median and 1 year PFS were 49 weeks and 47.4 % and 41 weeks and 32.1 % in favour of the combination treatment. When considering the two subgroups of patients receiving full or lower dose of IL-2 separately, the median PFS was 44.5 weeks compared to 31 weeks in favour of the higher dose. Additionally, the 1 year PFS was 45 % and 25.1 % for full and lower dose of IL-2 respectively. The most commonly reported adverse events (AEs) were asthenia, hand foot syndrome, hypertension and diarrhoea. Grade 3-4 AEs were reported in 33% of patients in the combination treatment arm and in 22% in the single agent arm respectively. Conclusions: The combination So + IL-2 was feasible. Subgroup analysis suggest that good prognosis patients could more benefit from the addition of IL-2. The improvement in PFS was meaningful in patients receiving higher doses of IL-2. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer, Novartis, Pfizer, Roche, Wyeth
Second hand smoke exposure among hospital staff in Budapest, Hungary: A case study
Authors: David Laszlo Tarnoki, Adam Domonkos Tarnoki, Mark J. Travers, Andrew Hyland, Katherine Dobson, Laszlo Mechtler, Laszlo Tamas, Ildiko Horvath, K. Michael Cummings
Journal: European Respiratory Journal (2011)

Background:  Hungarian hospitals have been declared smoke free since 2005. However, compliance with this law may not be 100%.   Purpose:  To assess the level of compliance with the smoke-free hospital law by measuring levels of indoor air pollution in different indoor areas of a large public hospital.   Methods:  TSI SidePak AM510 Personal Aerosol Monitor was used to measure the concentration of particulate matter less than 2.5 microns in diameter (PM2.5) observed in the ambient air of 117 locations sampled, containing 16 health care and 6 non-health care departments, in a Hungarian public hospital between January and April 2009.   Results:  We observed evidence of smoking such as cigarette butts and ashtrays in several indoor areas of the hospital. Air monitory revealed concentrations of respirable suspended particulates ranging from 1 to 336 μg/m 3  depending on the area sampled. Clinical departments averaged 83 μg/m 3  and the non-clinical departments averaged 37 μg/m 3 , respectively. In the rooms where evidence of smoking was not seen the mean PM2.5 level was 6 μg/m 3 . In areas where evidence of smoking was observed the mean PM2.5 level was 138 μg/m 3 . The highest levels of indoor air pollution were found in the radiology (336 μg/m 3 ), intensive care unit (230 μg/m 3 ) and neonatology (163 μg/m 3 ).   Conclusions:  At least in one large public hospital it appears that compliance with the smoke-free law is incomplete resulting in high levels of indoor air pollution which pose a health risk to patients, visitors and staff. The measured levels of indoor fine particle air pollution exceeded the levels in nearly all instances that the WHO and US Environmental Protection Agency have concluded are harmful to human health.
A randomized phase III study comparing paclitaxel-BEP (T-BEP) to standard BEP in patients with in intermediate prognosis germ cell cancer (GCC): An intergroup study of EORTC, German TCSG/AUO, MRC, and Spanish GCC group (EORTC 30983).
Authors: R. De Wit, I. A. Skoneczna, K. Gedske Daugaard, M. de Santis, A. Garin, N. Aass, J. A. Witjes, P. Albers, J. White, J. R. Germa-Lluch, S. Osanto, S. Marreaud, L. Collette
Journal: Journal of Clinical Oncology (2011)

4509 Background: To compare the efficacy of 4 cycles of T-BEP to 4 cycles of BEP in previously untreated patients (pts) with intermediate prognosis GCC. Methods: Pts were randomly assigned to receive either standard BEP (cisplatin 20 mg/m2 d1-5, etoposide100 mg/m2 d1-5, bleomycin 30 mg weekly) or T-BEP (paclitaxel 175 mg/m2 given as a 3-hours infusion on d1, before starting standard BEP. Pts on T-BEP received primary G-CSF prophylaxis. The study was designed as a randomized open-label phase II/III study. To show a 10% improvement in 3-year PFS (2-sided Logrank, α= 5%, 80% power), the study needed 498 patients (98 events planned), but closed with 337 due to slow accrual. Primary analysis is by intent-to-treat (ITT) at α=0.0455 (adjusted for interim). ClinicalTrials.gov id: NCT00003643. Results: Accrual was from 11/1998 to 04/2009. 169 pts were assigned BEP and 168 T-BEP. 13 pts on both arms were ineligible, mainly due to good prognosis GCC (8 on BEP, 6 on T-BEP). Of 5 pts ineligible due to poor risk GCC, 4 had been allocated T-BEP. Relative dose-intensity was > 97.7% for all drugs. T-BEP was well tolerated; 31 episodes of neutropenic fevers were reported on T-BEP (compared to 18 on BEP), but there were only 2 toxic deaths. After a median follow-up of 5.3 years, a total of 84 events occurred. PFS at 3-years (ITT) was 79.4% on T-BEP versus 71.1% on BEP, HR= 0.73 (CI: 0.47-1.13), logrank P = 0.153. PFS at 3-years in all eligible pts was 82.7% versus 70.1%, respectively, HR=0.60 (CI: 0.37-0.97) and statistically significant, logrank P = 0.03. Overall survival was not statistically different. Conclusions: The PFS intent-to-treat (primary efficacy) analysis is not statistically significant, but is negatively influenced by the uneven distribution of ineligible pts amongst the 2 treatment arms. The analysis of all eligible pts, however, shows a 12% superior 3-year PFS with T-BEP, which is statistically significant. This study demonstrates superior efficacy of T-BEP in the management of the intended intermediate prognosis GCC risk group. This is the first study to show superiority over standard BEP in this population.
Role of p53 mutations in clinical and pathological responses in an open-label study of capecitabine (C) and docetaxel (D) as neoadjuvant treatment for patients with recently diagnosed HER2-neu negative (HER2-) breast cancer (BC)
Authors: S. Truong, N. Patten, D. Tripathy, S. Gluck, C. Moisa, L. Wu
Journal: Journal of Clinical Oncology (2007)

11022 Background: The tumor suppressor gene p53 plays a key role in multiple cellular pathways controlling proliferation, survival, and genomic integrity. Disruption of its function promotes checkpoint defects, genomic instability and inappropriate survival leading to uncontrolled proliferation of damaged cells. The relationship of p53 mutation status to the outcome of patients suggests that p53 mutation status is a potential prognostic and predictive indicator of survival. Immunohistochemical analysis cannot accurately identify p53 mutation status and cannot differentiate between the several functional defects that arise from mutations at specific sites of this multifunctional gene. Methods: The primary objective is to define the rate of pCR in the affected breast after neoadjuvant C+D±T for HER2- or HER2+ BC pts, respectively. Eligibility: infiltrating HER2- or HER2+ stage II/III BC with no evidence of metastases and no prior systemic or local primary treatment. Four 3-week cycles consisted of C 825 mg/m 2 bid on days 1–14 and D 75 mg/m 2 on day 1. HER2+ pts also received T 4 mg/kg x1 on day -1 followed by 2 mg/kg weekly. Enrollment of 99 HER2- patients is planned. The AmpliChip p53 test (Roche Diagnostics, in development), a DNA microarray-based sequencing method, was used to analyze the p53 mutation status. The AmpliChip p53 test is designed to detect all substitution single base changes and single base deletion in all coding regions of the p53 gene. The genomic DNA was extracted from a biopsy sample from each patient and 50–100 ng genomic DNA was used. Results: A total of 47 p53 mutations were found in 44 of 88 (50%) patients, including 32 missense, 6 frameshift, 8 non-sense, and 1 splice site mutation, and were widely distributed in exon 2, 4, 5, 6, 7, 8, 9 and 10. The p53 mutation status including the type and location will be analyzed in relation to clinical and pathological response. Updated data will be presented. Conclusions: The AmpliChip p53 test is a rapid, accurate, and standardized way to detect p53 mutations. These findings suggest that p53 mutations occur in at least 50% of recently diagnosed BC. No significant financial relationships to disclose.
Tolerability and efficacy of indigenously developed nanoparticle paclitaxel in Indian patients
Authors: C. D. Deshmukh, S. S. Hingmire, A. V. Bakshi, D. S. Kelkar
Journal: Journal of Clinical Oncology (2009)

e13533 Background: Nanoparticle paclitaxel ([N]), India's first cremaphor free water-soluble paclitaxel is based on the principles of nanotechnology. The present study evaluates the safety and efficacy of this formulation in an Indian population. Methods: A prospective observational study over 18 months between April 2007 and December 2008 was done using N in a dose of 220 mg/m 2 infused over 1 hour. Safety parameters were based on self reported adverse events while efficacy was monitored as per the RECIST criteria. Results: Fifty-four patients were included. The average age was 56 years (21–72 years). Ten patients (18.52%) had stage III and 23 (42.59%) had stage IV disease. Over 70% of patients were suffering from ovarian cancer, gastric cancer and non small-cell lung cancer (39 of 54 patients). The overall efficacy results across all tumour types were comparable to the published literature with 19 (35.19%) patients showing partial response, 3 (5.56%) showing complete response, stable disease in 11 (20.37%) patients while progressive disease in 12 (22.22%) patients. The efficacy results in the 3 most common tumour types are shown in the table below. In the cohort, 22 (40.74%) patients did not experience any side effects. The most common side effect was body ache (Grade III-NCI CTC v3.0) in 17 (31.5%) patients, neutropenia (Grade II -7, grade III and grade IV -1 each) in 9 (16.67%) cases, 3 (5.56%) cases each experienced neuropathy (Grade III -2 and grade IV-1), nausea, and weakness. Two patients (3.70%) experienced grade III thrombocytopenia and 1 (1.85%) patient developed grade II anemia. Conclusions: Our observations confirm the safety of nanoparticle paclitaxel (N) in an Indian population. This formulation obviates the need for cremaphor thereby allowing shorter infusion duration and eradicating the need of premedication, reduced incidence and severity of adverse effects. Nanoparticle based paclitaxel offers a major advancement in paclitaxel administration. [Table: see text] No significant financial relationships to disclose.
Residual cancer burden (RCB) is practical and may be more informative than pathological response following neoadjuvant chemotherapy (NC) for locally advanced breast cancer (LABC)
Authors: D. Sivasubramaniam, R. Komrokji, S. Dhaliwal, V. Sundarajan, Z. Nahleh
Journal: Journal of Clinical Oncology (2007)

21103 Background: Complete pathological response (pCR) has been considered a reliable endpoint to assess the benefit of NC. However, different pathological responses ranging from near complete response to resistance would likely indicate different prognostic groups. Method: We studied patients with locally advanced breast cancer (LABC) who received NC between 2001–2006 at the University of Cincinnati. Pathological response to therapy was evaluated. In addition, RCB was quantified according to MD Anderson RCB Calculator index that combines pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size). We examined the correlation between pCR, RCB, event-free survival (EFS) and over all survival (OS) by Cox regression analyses. Result: Pathological slides of 32 patients were analyzed. Median age 52, 38% white and 62% African American. Stage IIB 12% , Stage IIIA 19%, Stage IIIB 53% and Stage IIIC 16% . 72% invasive ducal, 6% invasive lobular and 22% inflammatory cancer. Forty seven percent of tumors were ER +/or PR+ , 53% ER-/PR-, 28% HER-2 /neu + ( IHC 3+ or FISH HER2 gene to chromosome 17 ration &gt; 2.2). Tumor response was as follows: 22% (n=7) achieved pCR , RCB scores ranged between 0- 4.87. By univariate Cox regression analysis, RCB correlated with EFS {Hazard ratio (HR) 1.57 (95% CI 1.04–2.38), p-value 0.018}, and with OS {HR 1.74 (95% CI 0.91 -3.32), p value-0.09}. However, pCR did not seem to correlate with EFS {HR 0 .24 (95%CI 0.03 -1.86–2.38), p-value .172} or OS {HR 0.03 (95% CI 0–89),p value-0.40}. By multivariate Cox regression analysis, RCB was noted to be an independent predictive variable for EFS {HR 1.59 (95% CI 1.04–2.43), p value-0.033} while pCR was not {HR 0.90 (95% CI 0.52–1.57), p value-0.7. Conclusion: RCB was easily quantifiable and appears to be a better predictor of outcome following neoadjuvant chemotherapy in LABC compared to pCR. Higher RCB scores were associated with higher EFS and lower rate of OS. Prospective trials are needed to further evaluate the role of RCB as an endpoint following NC. No significant financial relationships to disclose.
Recurrent alveolar abscesses by bisphosphonates
Authors: R. Ratti, G. Farina, K. Borgonovo, N. La Verde, D. Pedretti, R. Rovej, S. Cobelli, C. Mantica, M. Dimaiuta, A. Scanni
Journal: Journal of Clinical Oncology (2005)

3211 Background: Cancer patients (pts) with bone metastases could have pain, pathological fractures, hypercalcemia. Bisphosphonates (B) are used in the management of disease, inhibiting osteoclastic function and decreasing bone turnover. Pancytopenia, fever, bradycardia and arthralgia are frequent. B. associated with chemotherapy (CT), ameliorate the response rate having also antiangiogenetic effects. Recently were reported dental complications related to treatment. Methods: We evaluated the onset of recurrent alveolar abscesses during treatment with B. in pts. with bone metastases by clinical features, radiologic images and hystologic samples. Results: From 10/2003 to 11/2004 we treated 101 pts. (61 females, 40 males) with bone metastases by zoledronic acid (ZA) 4 mg/monthly alone or with CT. Primary tumors sided: 44 breast, 18 prostate, 11 lung, 3 gastrointestinal tract, 5 urinary tract, 5 haematological disease, 15 other sites. Recurrent alveolar abscesses were present in 9 pts, median age 65,2 years (range 51–77), 4 females, 5 males. They were treated with total 246 cycles of ZA, median cycle for pts 27,3 (range 6–71); 7/9 were also treated with CT. One patient had been submitted to encephalic radiotherapy (RT) for brain metastases. No other RT was administered in head and neck region. Recurrent alveolar abscesses had been complicated by osteonecrosis of the jaw in 4 pts. Lesions were resistant to antibiotic and conservative treatment; odontojatric surgery with hystologic samples from the jaw was performed in 7/9 pts. resulting 2 aseptic osteonecrosis, 2 osteonecrosis with acute inflammation, 1 chronic osteitis, 1 osteomyelitis. Conclusions: It’s unclear the relationship between therapy with B. and the onset of osteonecrosis, probably due to modified bone homeostasis caused by cumulative effects and duration of treatment, as it was observed after a median of 27,3 cycles. Furher studies are needed. No significant financial relationships to disclose.
Clinical features and course of brain metastases in colorectal cancer: Experience from a single institution.
Authors: M. A. Tehfe, K. Damiens, J. M. Ayoub, B. Lemieux, D. Charpentier, M. Campeau
Journal: Journal of Clinical Oncology (2010)

e14124 Background: Brain metastases (BM) from colorectal cancer (CRC) are quite rare, with reported percentages of patients developing BM ranging from 2% to 12%. This is a review of patient characteristics, presentation and clinical course at our institution. Methods: We reviewed retrospectively the medical records of all patients with BM from CRC treated from 2000 to 2009 at our institution. Associations between patient and tumor characteristics, treatment modality and survival were assessed using the Kaplan-Meier method. The log-rank test was used to assess the impact on survival of individual factors. Results: Forty-eight patients (25 men and 23 women) who developed BM from CRC were identified. The median age at diagnosis of BM was 63 years (range 37 to 84 yr). Twenty-three patients (48%) had a tumor in the rectum. Forty-three patients (90%) had other systemic metastases (mainly pulmonary and hepatic metastases) upon diagnosis. The median interval between the diagnosis of the primary tumor and the development of BM was 24 months. Single BM were diagnosed in 31 patients (63%), and the presenting symptom was neurologic deficit in 31patients (65%), headache in 8 patients (16%) and alteration of consciousness in 9 patients (19%). The median survival after a diagnosis of BM from CRC was 4 months (range 2.5 to 5.5 months). Survival of patients treated by surgery followed by whole-brain radiotherapy (WBRT) was significantly associated with better survival (13 months, p < 0.001) compared to radiotherapy alone, or surgery alone. Sex, age (< 70 vs. ≥ 70), location (infratentorial vs. supratentorial vs both) and number of BM (1 vs. 2-3 vs. ≥ 4), timing of diagnosis (synchronous vs metachronous) did not have an impact on survival. Conclusions: BM from CRC are rare and develop late, as the majority of patients had other secondary lesions. Patients have a poor overall survival, those treated with surgery plus WBRT having the best survival. Early detection and treatment of BM associated with new systemic therapies may contribute to better outcome. No significant financial relationships to disclose.