tbuckley/cabot-search huggingface dataset:
A population-based study evaluating metastatic renal cell cancer (mRCC) patients treated with interferon (IFN) alone, first-line IFN then second-line sunitinib, or sunitinib alone
Authors: C. K. Kollmannsberger, D. Y. Heng, N. Murray, K. N. Chi
Journal: Journal of Clinical Oncology (2007)

15572 Background: Previously, immunotherapy agents such as IFN were the only treatments available for mRCC. Sunitinib has demonstrated prolonged progression free survival in a phase III trial but overall survival benefit has yet to be determined and few patients (pts) with poor MSKCC prognostic profiles were included. Methods: The province-wide BC Cancer Agency Registry was cross-referenced to the central pharmacy database to identify all pts with the diagnosis of mRCC who were treated with IFN and/or sunitinib. Sunitinib became available after October 2005 under an expanded access program or as standard treatment. Three groups of pts were identified: Group A consisted of pts who received IFN alone between January 2003 to October 2005, Group B was all pts who progressed on first-line IFN after October 2005 and subsequently were treated with second-line sunitinib and Group C was all pts treated with first-line sunitinib. Baseline characteristics and overall survival were collected on all patients. Results: A total of 75 patients were identified with 36 patients in Group A, 23 patients in Group B, and 16 patients in Group C. Data are reported from the initiation of IFN in Group A and the initiation of sunitinib in Groups B and C. Median follow-up was 6.0 months in group A, 7.6 months in group B, and 6.2 months in group C. Median age of treatment initiation (62y vs. 60y vs. 62y), number of metastatic sites (&gt;1 site in 63% vs. 61% vs. 56%), and Karnofsky performance status (79 vs. 86 vs. 81) were similar between groups A, B and C, respectively. The MSKCC prognostic profiles were favorable, intermediate and poor in 26%, 51% and 23% in group A, 17%, 65% and 17% in group B and 31%, 38% and 31% in group C, respectively. The estimated 6-month overall survival in groups A, B and C was 56%, 72% and 100%, respectively (log rank A vs C p=0.009; log rank B vs C p=0.042). Conclusion: With the limitations of retrospective analysis and preliminary follow-up, the introduction of sunitinib as standard treatment into the general population of patients with mRCC appears to be associated with a longer overall survival compared to patients treated with IFN alone. Population-based analysis on the impact of the introduction of sunitinib therapy is ongoing. No significant financial relationships to disclose.
BCIRG 007: Serum HER2 levels in women with metastatic HER2-amplified breast cancer
Authors: V. Valero, H. Roche, T. Pienkowski, J. Canon, Y. Zhao, W. Carney, J. Mackey, H. Taupin, M. Buyse, D. Slamon
Journal: Journal of Clinical Oncology (2007)

1020 Background: BCIRG 007 is a multicenter, phase 3 randomized trial comparing docetaxel and trastuzumab (TH) with docetaxel, platinum salt (cisplatin or carboplatin) and trastuzumab (TCH) as first line chemotherapy in women with metastatic breast cancer (MBC). Women enrolled in the study had to have primary breast tumors with HER2 amplification as determined by centralized FISH analysis. Methods: We determined the percentage of subjects with HER2 amplification who had elevated (&gt;15ng/mL) baseline levels of serum HER2 prior to the initiation of trastuzumab-based therapies. Baseline was considered to be the last available determination within 21 days prior to first treatment. Results: The median baseline serum HER2 levels was 75.8 ng/mL (range=8–3,280 ng/mL) for all subjects (n=123), with no statistical difference between subjects randomized to receive TH (median=65.9 ng/mL, n=64) and those randomized to receive TCH (median=89.9 ng/mL, n=59). Overall, 89% of the 123 subjects with HER2-amplified primary tumors had serum HER2 levels &gt;15 ng/mL at the time of metastatic disease (86% in TH vs 92% in TCH). Conclusions: There was no statistical impact of baseline serum HER2 levels on any important clinical event: response to treatment, clinical benefit (response or stable disease for more than 24 weeks), disease progression or death. Conversely, when serum HER2 was measured over time, subjects with higher levels had an elevated risk of experiencing progressive disease (p=.003), even after adjustment for extent of disease (1 or 2 vs 3 or more organs involved) and presence of visceral disease. These analyses suggest that monitoring serum HER2 levels over the course of disease may be a means for detecting progressive disease in women with HER2 amplified breast cancer. Given the long intervals between the serum HER2 measurement and progression (up to 9 months), caution is required in interpreting these results. No significant financial relationships to disclose.
Decreased Radial Function is Associated With Subtle Left Ventricular Remodeling in Type 2 Diabetes Mellitus
Authors: Cyrille Bergerot, Laura Ernande, Ernst Rietzschel, Marc De Buyzere, Michel Ovize, Aurélie Decaudain, Philippe Moulin, Thierry Gillebert, Geneviève Derumeaux
Journal: Circulation (2009)

Background: Previous studies have suggested that reduced longitudinal myocardial function might be compensated by increased radial contractility in patients with type 2 diabetes mellitus (DM). 

Aim: To evaluate left ventricular (LV) remodeling in type 2 DM according to radial function assessed by STI. 

Methods: 234 asymptomatic type 2 DM patients with no sign or history of heart disease and normal conventional echo parameters were included. Mean radial strain (SR) was assessed by STI from short-axis view at the midventricular level. Mean longitudinal strain (SL) was calculated from the apical 2- and 4-chamber views. The population was divided into 3 groups according to SR value: group I = SR  60% (n = 57). Differences between groups were tested by ANOVA. 

Results: Clinical, biological and echographic data are shown in table. Age, body mass index (BMI), duration and severity of DM, systolic (sBP) and diastolic (dBP) blood pressure and LV mass index (LVMi) were similar between groups. Conventional systolic parameters (LVEF: LV ejection fraction and FS: fractional shortening) were also similar. However, a lower SR was associated with a significant increase in LV end-diastolic (LVEDD) and end-systolic (LVESD) diameters and a decreased SL. 

Conclusion: These data suggest that an altered radial function might be an indicator of more advanced diabetic cardiomyopathy with altered systolic function and beginning of eccentric LV remodelling.
Determination of expression of platelet derived growth factor receptors (PDGFR) in astrocitic tumors
Authors: C. H. Barrios, F. S. Viola, L. M. Coutinho, E. Paglioli
Journal: Journal of Clinical Oncology (2006)

11518 Background: PDGF and its receptors (α and β) are frequently expressed together in gliomas raising the possibility that an autocrine/paracrine loop could contribute to the pathogenesis of these tumors. Studies with immunohistochemistry (IHC) and in situ hybridization have clarified that PDGF-α receptors (PDGF-R α) are preferentially expressed in tumor cells, whereas PDGF-β receptors (PDGF-R β) are preferentially expressed in proliferating endotelial cells within the tumor vasculature. Objective: Determine the expression of PDGF-R α and β in astrocitic tumors. Methods: Paraffin blocks samples from patients with a diagnosis of low-grade astrocitoma, anaplastic astrocitoma, and glioblastoma were obtained from the Neuro-Oncology Unit at Hospital São Lucas-PUCRS. These patients presented and were treated from 1996 through 2001. We collected a total of 130 cases: 57 Low-grade astrocitomas (LGA), 13 Anaplastic Astrocitomas (AA), and 60 Glioblastomas (GBM). All cases were studied with standard IHC techniques using antibodies for PDGFR α and β (Santa Cruz Biotechnology). Results: See table . Conclusion: The expression of PDGF-R α and β in low-grade tumors reflects the possible role these receptors may have in the evolution of these neoplasms. More importantly we documented that over 60% of high-grade gliomas (61% in AA; 65% in GBM) show expression of PDGF-R β predominantly in the endothelial cell compartment of the tumors. This is consistent with and reflects the extensive angiogenesis observed in these diseases. The level of expression we encountered identifies an attractive molecular target to explore. [Table: see text] No significant financial relationships to disclose.
Aromatase inhibitor (AI)-associated arthralgia (A) and bone pain (BP): Frequency and characterization in clinical practice
Authors: C. A. Presant, C. Kelly, L. Bosserman, G. Upadhyaya, M. Vakil, R. Horns, B. Ebrahimi, C. Yeon, F. Howard, A. Rios
Journal: Journal of Clinical Oncology (2006)

6137 Background: Prior studies of AI have identified A and/or BP as side effects. Reported incidences have varied from 4% (IMPACT) to 35.6% (ATAC). In order to determine the frequency of A or BP in clinical practice, we reviewed a consecutive series of patients (PTs) receiving AI in community cancer centers. Methods: The charts of consecutive PTs receiving AI were reviewed, and PTs were interviewed regarding the occurrence of A or BP (ABP), severity, whether ABP was worse than before AI therapy, preexisting co-morbidities, type of therapy for ABP, and pain characterization. Results: 56 PTs were receiving AI. The type of AI used was anastrazole in 44 PTs, letrozole in 10 PTs, and exemestane in 2 PTs. The age range was 45 to 89 years. All PTs had breast cancer. The duration AI usage was 1 to 44 mo. Worsening of ABP compared to pretreatment ABP was reported in 34 PTs (61%). In 11 Pts (20%), severity was sufficient and control poor enough to result in discontinuation of AI at a median of 2 mo of AI therapy. The median severity of ABP, when present, was 7.5 on a 10 point pain scale. The character of the ABP was continuous in 20 (59%) and intermittent in 14 (41%), affected central/axial bones in 20 (36%), and peripheral bones in 35 (64%). Coexisting conditions possibly contributing to worsening of ABP occurred in 36%, consisting of degenerative joint disease 10, fibromyalgia 1, osteoporosis 4, and degenerative disc disease 1. Therapy associated with amelioration of symptoms included acetaminophen in 26%, NSAIDs in 45%, mild opiates in 11%, strong opiates in 5%, and glucosamine in 13%. The occurrence of ABP was not associated with age (68% in PTs less than 60 versus 57% in PTs over 60). The occurrence of ABP was not associated with duration of use of AI (50% of 16 Pts on AI for 3–6 mo, 75% for 7–12 mo, and 56% for over 12 mo). Conclusions: The occurrence of AI associated ABP is higher in a non-clinical trial population of PTs than reported in most clinical trials. This side effect is severe enough to cause discontinuation of needed AI therapy in 20%. Further studies are warranted to determine the mechanism of AI associated ABP, and optimal therapy. It is reasonable to consider glucosamine as well as standard analgesics in controlling this syndrome. No significant financial relationships to disclose.
Phase I trial of bortezomib (PS-341) in combination with docetaxel in patients with advanced solid tumors
Authors: W. A. Messersmith, S. D. Baker, K. Dinh, L. K. Lassiter, R. A. Akdamar, J. J. Wright, R. C. Donehower, M. A. Carducci, D. K. Armstrong
Journal: Journal of Clinical Oncology (2004)

3052 Background: Bortezomib (PS-341), a first-in-class dipeptidyl boronic acid, is an inhibitor of the 26S proteasome, an ATP-dependent multicatalytic protease central to the ubiquitin-proteasome degradation pathway. The principal mode of bortezomib detoxification is via deboronization involving cytochrome P4503A (CYP3A), which also metabolizes docetaxel. A phase I study combining bortezomib and docetaxel is being performed to determine the MTD/toxicities and pharmacokinetics (PK) of this combination in refractory solid tumor pts. Methods: Pts received escalating doses of weekly docetaxel (d1 and d8) and twice-weekly bortezomib (d2, d5, d9, and d12) in 3-wk cycles. Two pts were enrolled at each dose level, with cohort expansion to 6pts for DLT (occurring in cycles 1 or 2). Dose level 1 (DL1), 2 (DL2), and 3 (DL3) consisted of docetaxel/bortezomib 25/0.8 mg/m2, 25/1.0 mg/m2, and 30/1.0 mg/m2, respectively. CYP3A activity, determined using the erythromycin breath test (ERMBT), and docetaxel PK were evaluated during weeks 1 (docetaxel alone) and 5 (docetaxel + bortezomib). Results: Thirteen pts (10 M/3 F; mean (range) age, 62 (40–76) years; ECOG PS, 0–1) received a total of 31 cycles. DL2 was expanded for DLT which occurred in 2 of 6 pts (febrile neutropenia [1 pt] and thrombocytopenia [1pt]), thus exceeding the MTD. DL1 was then expanded to 6 pts where no DLTs occurred; one additional patient will be enrolled to replace a pt not evaluable for toxicity to define the MTD at DL1. One pt received 2 cycles at DL3 with dose-reduction to DL2; gr 3 thrombocytopenia occurred at cycle 3. Both episodes of gr3 thrombocytopenia were transient (<7d) without clinical sequelae. The ERMBT parameter, 14C-exhaled/h (%), and docetaxel clearance did not change between weeks 1 and 5; mean (SD) values were 1.99 (0.84)% vs 2.31 (0.81)% (P=.44) and 29.2 (13.5) L/h vs 27.0 (14.6) (P = .49), respectively. Conclusions: The MTD of docetaxel given weekly for 2 of 3 weeks with bortezomib twice-weekly (4 doses) has been defined. Bortezomib treatment did not alter CYP3A activity and docetaxel CL demonstrating lack of a drug interaction with this drug combination. Supported by U01 CA70095 and Aventis. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis (Speaker's Bureau) Aventis
Social interaction and stigmatization of cancer patients with orbitofacial disfigurement
Authors: A. Bonanno, B. Esmaeli, D. V. Nelson, M. Fingeret, R. S. Weber
Journal: Journal of Clinical Oncology (2009)

e20659 Background: Advances in cancer treatment extend the survival of orbitofacial cancer patients who undergo orbital exenteration. Survivorship creates social problems as facial deformities potentially engender social stigma (a mark of social disgrace). Stigmatization is created through social interaction and depends on reactions of “others” to disfigured patients and patients’ postures toward others. In this qualitative study, we investigated a) patterns of stigmatization in interaction with acquaintances and friends in small and large groups and b) whether interactions with family members is always positive and non-stigmatizing and interaction with strangers is always stigmatizing. Methods: In-depth interviews with 12 patients and 12 family members (8 spouses, 4 offspring and siblings) were carried out with an open-ended questionnaire. Cancer diagnoses included lacrimal gland adenoid cystic ca. (n=3), conjunctival SCCA(n=3), and 1 each of conjunctival melanoma, eyelid sebaceous gland ca., lacrimal sac transitional cell ca., orbital adenoca., orbital neuroendocrine ca., and eyelid basal cell ca. The median time from orbital exenteration to interview was 44 months. None were receiving active cancer therapy and none had cancer recurrence at interview time. Results: Patients were comfortable in interactions with friends and family members as they respond in supportive and non-stigmatizing ways. Interaction with acquaintances and strangers engender varying outcomes. In large groups, actions toward patients characterized by “benign neglect” (n=3) - kind indifference toward patients - generate non-stigmatizing outcomes. Actions characterized by sympathy (n=5) - overt support for patients - generate inconsistent patterns of interaction. “Intrusion” - unsolicited attention paid to patients - (n=4) leads to feelings of stigmatization. In small groups, intrusion creates stigmatization. Sympathy creates positive outcomes, while interaction characterized by benign neglect generates varying patterns. Conclusions: Patients should be warned about possible difficulties interacting in large and small groups. Health care professionals should be trained to address these problems through programs of social intervention for head and neck cancer survivors. No significant financial relationships to disclose.
Enhanced Inflammatory response in cancer patients with end stage renal disease. Implications in thrombotic risk stratification
Authors: O. Iqbal, M. Tobu, V. Bansal, D. Hoppensteadt, C. Patel, R. Wahi, J. Fareed
Journal: Journal of Clinical Oncology (2005)

8238 Background: Upregulation of inflammatory cytokines in patients with cancer is known to mediate hypercoagulopathy. Cancer patients who harbor other inflammatory conditions such as end stage renal disease (ESRD), Diabetes mellitus (DM) and hypertension (HT) may be at a higher risk of thrombotic complications. Methods: Baseline plasma samples from patients with cancer and ESRD were collected. The samples were analyzed for various inflammatory parameters such as monocyte chemotactic protein-1 (MCP-1), C-reactive protein (CRP), nitric oxide (NO), beta-2 microglobulin (beta-2 micro), tissue factor pathway inhibitor (TFPI), CD40 ligand (CD40L), thrombomodulin(TM) and p-selectin (P-select) using ELISA methods. Results: Parameters such as MCP-1, CRP, NO, beta-2 microgolulin, TFPI, CD40L,TM and p-selectin were markedly increased (see table). The increased levels of these inflammatory markers may result in increased thrombotic risk. Conclusions: Marked upregulation of inflammatory response is seen in cancer patients. This inflammatory response is enhanced in the presence of ESRD. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis, Pfizer
A randomized, multicenter phase III trial of bevacizumab plus capecitabine as maintenance treatment after initial treatment with bevacizumab plus XELOX in previously untreated metastatic colorectal cancer.
Authors: S. Yalcin, R. Uslu, F. Dane, U. Yilmaz, N. Zengin, E. Buyukunal, S. Buyukberber, C. Camci, O. Sencan, S. Kilickap
Journal: Journal of Clinical Oncology (2011)

474 Background: Colorectal cancer is one of the most frequent malignancies, second to breast cancer in women and third to lung cancer and prostate cancer in men. The aim of this study in first-line metastatic colorectal cancer (mCRC) was to achieve a better progression-free survival (PFS) and less risk of toxicity by administrating bevacizumab (BEV) + capecitabine + oxaliplatin (XELOX) for 6 cycles, stop oxaliplatin and go with maintenance therapy (BEV + capecitabine) until progression. Methods: BEV (7.5 mg/kg) + XELOX (capecitabine 1,000 mg/m 2 bid d1–14 + oxaliplatin 130 mg/m 2 d1 q3w) were administered until progression (Arm A) or 6 cycles of BEV + XELOX followed by BEV + capecitabine were administered until progression (Arm B). PFS was the primary endpoint; secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. A sample size of 118 patients (pts) was calculated to achieve 80% power to detect an increase of 1.5 months in median PFS between Arm A (9.5 months) and Arm B (11.0 months) with a standard deviation of 3.9 months and significance level of 0.05 using a 10% drop-out rate. Results: A total of 122 pts were randomized. No significant differences were found in demographic characteristics between the two arms. Median treatment period was 6.1 (range 0.7–13.4) and 6.8 (range 0.7–12.4) months in Arms A and B, respectively. Interim analysis showed no statistically significant differences in median PFS and ORR between arms (see table). Tolerability was also acceptable in both arms with grade 3/4 diarrhoea in 7.7% vs. 8.2%, weakness in 15.2% vs. 8.4%, hand-foot syndrome in 6.3% vs. 9.4%, and neuropathy in 2.8% vs. 4.6% of pts in Arms A and B, respectively. Conclusions: BEV + capecitabine as maintenance therapy following induction BEV + XELOX is non-inferior to continuous BEV + XELOX until progression. While this study is ongoing, these interim findings suggest that maintenance therapy with BEV + capecitabine is an appropriate option following induction BEV + XELOX in pts with mCRC. [Table: see text] [Table: see text]
Should palpable DCIS be treated as IDC? A retrospective audit.
Authors: N. S. Nair, N. Pandey, V. Vanmali, T. Shet, R. Hawaldar, V. Parmar, R. A. Badwe
Journal: Journal of Clinical Oncology (2011)

146 Background: Ductal carcinoma in situ (DCIS) identified by screening mammography accounts for 20% of breast cancer diagnoses, and microinvasion (DCIS-M) is found in 5%-10%. There are no defined treatment guidelines for palpable DCIS or DCIS-M. In the developing world wherein screening mammography is controversial due to a predominantly premenopausal population, most women with DCIS present with a palpable lump in the breast. The objective of this study was to evaluate whether disease in these patients with palpable DCIS have been treated differently from screen detected DCIS. Methods: Annually we register 3,000 new cases of breast cancer of which DCIS constitute a small fraction. Over a period of 12 years (1998-2010) we registered 71 cases of DCIS for treatment. A retrospective analysis of these was performed. Results: Of the 71 patients reviewed, 35 (49.2%) had foci of microinvasion. The median age of presentation was 49 years and mean tumor size was 2.3 cm; all presented with palpable breast lumps. Of the 36 women with DCIS alone Tsize was &gt; 2 cm in 26 (72.2%), 14 (38.9%) had presence of comedo necrosis and 1 (2.7%) had positive lymph nodes on histopathology. Adjuvant chemotherapy was given to 4 (11.11%). Of the 35 women with DCIS-M Tsize was &gt; 2 cm in 23 (66%), 10 (29%) had comedo necrosis (compared to 38.9% in pure DCIS p=0.45), 3 (8.5%) had positive lymph nodes, and 17 (48.6%) received chemotherapy. We compared this data to that of women treated for invasive ductal carcinoma with pTsize &lt;2cm, at a median follow-up of 60 months, DFS for the women with DCIS was 82% (95% CI 0. 67- 0.98), for DCIS-M was 78% (95% CI 0. 59 -0.98), and that for IDC &lt; 2cm was 83% (95% CI 0.70-0.95). Conclusions: DCIS presenting in these palpable lesions poses a clinical dilemma for the use of adjuvant therapy. Over 49.2% of the palpable DCIS showed evidence of microinvasion. We thus need to consider the role of adjuvant chemotherapy when treating women with palpable DCIS.