tbuckley/cabot-search huggingface dataset:
Racial disparities in clinical presentation, treatment, and outcome of women with breast cancer: Analysis of national inpatient sample database.
Authors: Ahmed Dehal, Ali Abbas, Samir Johna
Journal: Journal of Clinical Oncology (2012)

66 Background: Despite the established consensus, guidelines, and treatment protocols, there is wide variability in practice patterns among women treated for breast cancer, leading to variable results, with less favorable outcomes among minorities. The objective of this study was to examine racial/ethnic disparities in stage of disease and comorbidities (pre-treatment factors), surgical treatment allocation (breast conserving surgery [BCS] versus mastectomy [MAS]), and postoperative complication and mortality (post-treatment outcomes). Methods: National inpatient sample is a nationwide clinical and administrative database compiled from 44 states representing 95% of all hospital discharges in the Unites States. Patient discharges with primary diagnosis code of breast cancer and coincident procedure code for breast surgery (BCS or MAS) from 2005 to 2009 were identified using International Disease Codes 9th edition. Information about demographics, hospital characteristics, comorbidities, stage, surgical treatment, post-operative complications, and in-patient death was obtained. Multivariate logistic regression analyses were used to examine risk adjusted association between race and the aforementioned outcomes. Results: We identified 75,100 patient discharges with a mean age of 61 years. Overall, 58.3% of women were white, 8.6% black, 5.7% Hispanic, 2.6% Asian, and 24.8% others. Compared to whites, blacks were more likely to present with regional or metastatic disease (1.17, p &lt;0.001) and more likely to present with comorbidities (1.58, p 0.003). Compared to whites, blacks (1.30, p &lt;0.001) and Hispanics (1.20, p &lt;0.001) were more likely to receive BCS whereas Asians were less likely to undergo BCS (0.80, p 0.01). Compared to whites, blacks were more likely to develop postoperative complications (1.35, p&lt;0.001) and in-hospital mortality (1.87, p 0.13). Conclusions: After controlling for potential confounders, we found some racial/ethnic disparities in clinical presentation, treatment, and outcomes. Future researches should examine the underlying factors of these disparities.
Cetuximab plus bevacizumab in patients (pts) with metastatic colorectal cancer (mCRC) who have failed on irinotecan, oxaliplatin and fluoropyrimidines-based chemotherapy
Authors: J. Souglakos, K. Kalbakis, N. Vamvakas, A. Kalykaki, A. Kotsakis, S. Agelaki, A. Karampeazis, J. Gioulbasanis, V. Georgoulias
Journal: Journal of Clinical Oncology (2007)

14576 Background: Bevacizumab (AVASTIN®) and Cetuximab (ERBITUX®) are IgG1 monoclonal antibodies targeting the Vascular Endothelial Growth Factor (VEGF) and Epidermal Growth Factor Receptor (EGFR), respectively. Both are active in mCRC pts as first and/or second line treatment. Preclinical data suggest potentially synergistic effect for the combination of the two antibodies. This phase II trial evaluates the safety and efficacy of cetuximab combined with Bevacizumab in the treatment of mCRC pts who have failed on Irinotecan, Oxaliplatin and Fluoropyrimidines-based chemotherapy. Methods: mCRC pts with ECOG PS = 2 who had refractory disease to all three active chemotherapeutic drugs were enrolled. Determination of EGFR status was not mandatory. Cetuximab was given at an initial dose of 400mg/m 2 , then 250mg/m 2 iv weekly; Bevacizumab was administered at a dose of 10 mg/kg on d 1 every 2 weeks. Results: From June 2005 to November 2006, 14 pts were enrolled. Median age was 65 years, and median PS was 1. Treatment was 3 rd -line in 5 pts, and = 4 th -line for 7 patients. 12 pts had received prior treatment with Cetuximab and 6 were Bevacizumab. Thirty-nine cycles were administered with a median of 3 cycles/patient. All pts were evaluable for toxicity and response. No grade 3–4 hematological toxicity was observed. Non-hematological toxicities included grade 3 fatigue (7.1%), grade 2 diarrhea (7.1%), grade 2 allergic reactions (14.1%). Amongst the 14 patients evaluable for response, there was 1 objective PR (7.1%; 95% CI: 6- 24%), and 2 (14.2%) SD (tumor growth control rate, TGCR: 21.3%). The median time to progression was 2.4 months and the median survival has not yet been reached. The estimated probability for 1-year survival was 65.7%. Conclusions: The combination of Cetuximab plus Bevacizumab in patients with mCRC refractory or resistant all active chemotherapeutic drugs is safe and has promising activity. No significant financial relationships to disclose.
Paclitaxel plus cisplatin in cancer of unknown primary site (CUP)
Authors: Y. H. Park, B.-Y. Ryoo, S.-J. Choi, H. T. Kim
Journal: Journal of Clinical Oncology (2004)

2123 Cancer of unknown primary site (CUP) consists of a heterogeneous group of tumors that have acquired the capacity to metastasize before the development of a clinically evident primary lesion. They represent about 5–10% of all malignancies. This study was designed to evaluate the efficacy and toxicity of paclitaxel / cisplatin combination chemotherapy in patients with CUP. The rationale for choosing this combination is based on available clinical data that paclitaxel and cisplatin have shown considerable clinical activity in various common malignant tumors including lung, breast, stomach, esophagus, ovary and head/neck cancer. From January 2001 to September 2003, 37 patients with CUP received 21-day cycles of paclitaxel 175 mg/m2 i.v. and cisplatin 60 mg/m2 i.v. on day 1. 31 patients had adenocarcinoma subtypes. The patients received a total of 138 cycles of chemotherapy. The median number of cycles of chemotherapy per patient was 4. The median age of the patients was 53 (range, 21–71) years. The male to female ratio was 1:2.1. Initial presentations were cervical lymphadenopathy, peritoneal carcinomatosis, liver mass, pelvic mass, metastatic bone tumor and pleural effusion. Of these patients, 36 patients were evaluable for efficacy and toxicity. Of the evaluable and measurable 26 patients, complete response was in 1 patient, and partial response was in 10 patients. The overall response rate was 42% (95% C.I., 23–61%). Stable disease was seen in 6 patients, progressive disease in 9 patients. Median time to progression was 4 (95% C.I., 1.3–6.8) months. Median overall survival was 11 (95% C.I., 8.3–13.5) months. No prognostic factor was identified in univariate analysis. However, patients with good performance status and patients with normal CEA level showed marginal progression-free survival benefits (good PS vs poor PS; 5.2 vs 2.7 months, p=0.065) (normal CEA vs abnormal CEA; 5.2 vs 1.9 months, p=0.066). The major toxicities were neuropathy and neutropenia. Grade 4 neutropenia occurred in 10 cases, but febrile neutropenia was seen in 4 cases. Our data suggests that this paclitaxel/cisplatin combination regimen is well tolerated with an encouraging level of activity for patients with CUP. No significant financial relationships to disclose.
Prevalence of inherited and acquired risk factors for venous thromboembolic (VTE) disease among women with breast cancer taking adjuvant tamoxifen (TAM)
Authors: S. Molica, C. Battaglia, R. Santoro, R. Mirabelli, R. Squillace, P. Iannaccaro, F. Iuliano, G. Muleo
Journal: Journal of Clinical Oncology (2004)

802 Background: Information dealing with the association between TAM and risk of developing VTE mainly rely on women included in clinical trials of chemoprevention or adjuvant breast cancer therapy. However, the prevalence of inherited risk factors for VTE and their correlation with acquired ones was never evaluated in detail in women receiving adjuvant TAM in the setting of clinical practice. Methods: Before starting TAM therapy we evaluated the prevalence of either acquired (i.e., hypertension, diabetes, hyperlidemia, previous angina and smoking status) or inherited (i.e., VTE familial history, factor V Leiden and prothrombin G20210A mutations) risk factors for VTE in 48 consecutive operable and estrogen (ER) and/or progesterone (PR) receptor-positive breast cancer women. Median age was 55 years (range, 29–77) and 29 (60.4%) were in postmenopausa. TAM was the sole therapy in 11 out of 48 (22.9%) while it was given after an adjuvant chemotherapy consisting of CMF or antracycline-based regimen to the remaining 37 (77.0%). Results: The factor V Leiden mutation was detected in 3 out of 48 (6.2%) women and the prothrombin G20210A mutation in 4 (8.3%), while no homozygote was observed. When comparison was performed with 181 age- and sex-matched healthy control women used for statistical comparison no difference in the prevalence of either V Leiden (P=0.374) or prothrombin G20210A (P=0.107) mutation was found. Patients carrying V Leiden or prothrombin mutations displayed a trend towards an increase of VTE episodes among first-degree family members (P=0.07), the same did not apply for the patient's thrombotic history (P=0.316). No association was found between V Leiden or prothrombin mutations and the presence of diabetes (P=0.206), hypertension (P=0.560), hyperlipidemia (P=0.280) and smoking status (P=0.652). Conclusions: In conclusion, before starting with TAM screening for inherited VTE risk factors should be offered to women with personal or familial thrombotic history. Asymptomatic patients with heterozigous factor V Leiden or prothrombin mutations should be shifted to aromatase inhibitors. No significant financial relationships to disclose.
Phase IB study of the Src inhibitor dasatinib with FOLFOX and cetuximab in metastatic colorectal cancer.
Authors: C. H. Lieu, R. A. Wolff, C. Eng, M. J. Overman, L. Henry, R. Coulson, C. R. Garrett, J. L. Abbruzzese, G. E. Gallick, S. Kopetz
Journal: Journal of Clinical Oncology (2010)

3536 Background: Aberrant activation of the intracellular tyrosine kinase Src has been implicated as a mechanism of acquired chemotherapy resistance in metastatic colorectal cancer (mCRC). Preclinical studies have shown synergistic effects of Src inhibition with both oxaliplatin and cetuximab. Based on these results, a combination study of the oral tyrosine kinase Src inhibitor, dasatinib, was investigated in combination with FOLFOX and cetuximab. Methods: We performed a phase IB study of 30 patients (pts) with previously-treated mCRC. Primary objectives were to determine the maximum tolerated dose, toxicity, and pharmacodynamics of this combination. Using a 3+3 design, cohorts of 3-6 pts received mFOLFOX6 with weekly cetuximab at standard dosing and escalating doses of dasatinib (100, 150, 200 mg PO daily), followed by a 12 pt expansion cohort. Surrogate blood biomarkers of Src inhibition and paired liver biopsies were obtained in all pts in the expansion cohort. Results: Thirty pts were enrolled from 5/07 to 7/09; median age 54 (37-78), 19 females, PS 0/1 in 13/17 pts, and had received a median of 3 prior regimens (2-6). There were 6 pts in each escalation cohort and 12 in the expansion cohort. Twenty-five pts were evaluable for response. The dose-limiting toxicity in both the 100 mg and 150 mg cohorts was gr 4 and 3 fatigue, respectively. Other grade 3-4 toxicities included neutropenia (23%), fatigue (20%), pleural effusions (3%), and thrombocytopenia (3%); delayed myelosuppression was associated with the 200 mg dose. Median PFS was 4.6 months with a 6 month PFS of 23%. Partial response (PR) rate was 24% with a 17% PR rate in pts previously reported to be refractory to FOLFOX and cetuximab. Disease control rate was 56%. Pharmacodynamic data demonstrated modulation of Src expression and activity in peripheral blood mononuclear cells (PBMCs) and paired liver biopsies. Conclusions: The recommended phase II dose of dasatinib in combination with mFOLFOX6 and cetuximab is 150mg daily. There is evidence of clinical activity of this regimen in patients previously reported to be refractory to oxaliplatin. Pharmacodynamic data suggest modulation of Src in both PBMCs and tumor tissue. A two-arm phase II study is being conducted. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis Bristol-Myers Squibb, sanofi-aventis
Cardiac disturbances during the administration of taxol.
Authors: E K Rowinsky, W P McGuire, T Guarnieri, J S Fisherman, M C Christian, R C Donehower
Journal: Journal of Clinical Oncology (1991)

The clinical development of taxol, a new antimicrotubule agent with a unique mechanism of cytotoxic action, has proceeded slowly due to serious hypersensitivity reactions (HSRs) and shortages in its supply. Nevertheless, large-scale phase II trials have been initiated as taxol has recently demonstrated impressive activity in advanced and cisplatin-refractory ovarian carcinoma. Furthermore, the incidence of HSRs has been reduced substantially with premedications and modifications in the administration schedule. However, various manifestations of potential cardiotoxicity have been observed in several patients who participated in four phase I and II studies of taxol. Asymptomatic bradycardia has occurred in a high proportion of patients, including 29% of ovarian cancer patients who were treated with maximally tolerated doses of taxol in a phase II study. More profound cardiac disturbances, including a range of atrioventricular conduction blocks, left bundle branch block, ventricular tachycardia (VT), and manifestations of cardiac ischemia, have been observed in seven of 140 patients (5%) who received taxol. Descriptions of these events are presented in this report to alert investigators to the potential for these adverse effects. Although these disturbances did not result in serious sequelae in most patients, investigators should continue to maintain a high degree of caution until precise risk factors, frequency, and clinical significance of these adverse cardiac effects are determined.
Health care professionals’ practices, perceptions, and awareness regarding breast self-examination.
Authors: Kah Poh Loh, Eng Keong Tan, Owolabi Ogunneye, Jennifer Friderici, Reva Kleppel, Mihaela Stefan, James A. Stewart
Journal: Journal of Clinical Oncology (2014)

14 Background: In 2009, the United States Preventive Services Task Force (USPSTF) published the revised guidelines for breast cancer screening which recommended against teaching breast self-examination (BSE).The objective of this study was to assess healthcare professionals' practices, perceptions and knowledge in BSE as well as their adherence to the newly revised USPSTF guideline for BSE. Methods: A cross-sectional survey study was carried out in five medical and gynecological practices affiliated with a large academic teaching hospital in western Massachusetts. The survey was sent to all attending- and resident-physicians, nurse practitioners (NPs), physician assistants (PAs), and registered nurses (RNs) working in these medical practices.The survey collected demographic data and inquired about practitioners’ awareness and perceptions of the 2009 USPSTF guidelines. Results: The survey completion rate was 50.7%. Fewer than half of respondents correctly identified the 2009 USPSTF guidelines recommendations for BSE (41.4%). However, among 35 respondents who stated they were aware of USPSTF guidelines, only 37.1% adhered to them. Overall, 70% (95% CI 61.3%, 79.1%) stated that they do teach patients to perform BSE. The most frequent reasons cited for teaching BSE were: “early detection of cancer” (48.0%), and to “empower women”, (37.0%). In univariable analyses, female practitioners were significantly more likely than male practitioners to report teaching BSE (OR 2.64, 95% CI 1.11, 6.29). Other characteristics which showed an association without reaching statistical significance were: ≥ 5 years of practice (OR 1.67, 95% CI 0.70, 3.98); non-physician practitioner (OR 3.5, 95% CI 0.82, 14.93); US Med School (OR 2.20, 95% CI 0.84, 5.75); ever detecting a lump in a patient (OR 2.95, 95% CI 0.80, 10.87), and belief that BSE reduces morbidity and mortality (OR 2.12, 95% CI 0.84, 5.37). Conclusions: Knowledge of, and adherence to, the 2009 USPSTF guidelines related to BSE are relatively low. Despite being aware of the guidelines, some health professionals still taught BSE. Greater efforts should be made to educate healthcare professionals about the 2009 USPSTF guidelines on BSE.
Analysis of skeletal morbidity in breast cancer (BC) patients treated with zoledronic acid (Zol) or placebo: Time to first pathologic fracture
Authors: N. Sauter, H. Minami, N. Kohno, K. Aogi, S. Takashima
Journal: Journal of Clinical Oncology (2006)

10639 Background: We have previously reported that Zol significantly delayed time to first skeletal-related event (SRE) compared with placebo in BC patients with bone metastases in a multicenter randomized trial conducted in Japan. Patients with bone metastases from BC suffer from a range of skeletal complications, including pathologic fractures that can dramatically decrease mobility and adversely affect patient autonomy and quality of life. Methods: 228 women with bone metastases were randomized to 4 mg Zol (n = 114) or placebo (n = 114) every 4 weeks for 1 year. Time to first skeletal event was estimated using the Kaplan-Meier method for all individual types of event. Median time to individual skeletal events was not reached in either treatment group; therefore, data are presented as the incidence at 1 year, and the log-rank P value is from the Kaplan-Meier estimate of time to first event. Results: Median time to first SRE (including hypercalcemia) was not reached in the Zol group versus 360 days in the placebo group (P = .002). Time to first pathologic fracture (P = .022), spinal cord compression (P = .022), need for radiation therapy to palliate bone pain (P = .054), and hypercalcemia (P = .040) were all reduced in the Zol group compared with the placebo group. The incidence of each of these events at 1 year is shown in the table . Cox regression analysis (adjusting for stratification factors) also showed that treatment with Zol significantly reduced the risk of pathologic fractures by 39% compared with placebo (hazard ratio = 0.61; P = .041). Conclusions: This prospective analysis of time to first skeletal event demonstrates that treatment of BC patients with Zol significantly delays the onset and reduces the risk of skeletal complications, including pathologic fractures, which may help preserve independence and quality of life. [Table: see text] [Table: see text]
BIK (Bcl2-Interacting Killer) CpG methylation status as a potential predictive biomarker of relapsed/refractory multiple myeloma disease.
Authors: E. Hatzimichael, A. Dasoula, G. Dranitsaris, A. Vassou, A. Papoudou-Bai, J. Stebbing, K. Bourantas, T. Crook
Journal: Journal of Clinical Oncology (2010)

8118 Background: BIK (bcl2-interacting killer) is the founding member of the BH3-only family proapoptotic proteins. Genomic deletions, epigenetic silencing or post-transcriptional downregulation of BIK by the proteasome and induction of apoptosis upon BIK re-expression reinforce the notion that BIK is a tumor suppressor. Although it has been shown that BIK is a target of epigenetic silencing in cell lines, no studies exist regarding the CpG methylation status of BIK in MM patients. Methods: Bone marrow aspirate samples from MM patients were obtained at diagnosis. Methylation-specific PCR (MSP) was employed to study methylation in the BIK CpG island. Genomic DNA was isolated and bisulphite modification performed using commercially available kits. Control methylated and unmethylated genomic DNAs were included in each experiment. Logistic regression analysis was used to measure the association between gene methylation and age, ISS stage, ECOG performance status, extramedullary disease, bone disease, anemia (Hb <10 g/dl), serum albumin and beta 2 microglobulin levels and relapsed/refractory disease. Results: Methylation in the BIK CpG island was studied in 40 MM patients (21 male, 19 female, mean age 66). Methylation of the BIK CpG island was found in 16 patients (40%) and men were more likely to be methylated (OR=3.08, p=0.01) than women. No correlation was found between BIK CpG methylation and age, ECOG performance status, ISS staging, anemia, beta 2 microglobulin levels, albumin levels, and overall survival. Patients methylated for BIK had a 2-fold tendency to have bone disease (p=0.35) and a 3-fold tendency to have extramedullary disease (p=0.14). Notably, patients with methylated BIK had a significantly higher risk of relapsed/refractory disease (OR=5.4, p=0.033). Conclusions: To the best of our knowledge, this is the first demonstration of aberrant methylation in the BIK CpG island in MM patients. BIK CpG methylation in this series of patients was found to be strongly associated with relapsed/refractory disease. Patients with refractory/relapsed disease could possibly benefit from agents enhancing BIK expression, such as proteasome inhibitors. No significant financial relationships to disclose.
Understanding the use of breast reconstruction after mastectomy.
Authors: A. K. Alderman, S. J. Katz
Journal: Journal of Clinical Oncology (2010)

e11011 Background: The opportunity for postmastectomy breast reconstruction is an important component of breast cancer care but few receive it at the time of the mastectomy. Virtually nothing is known about the receipt of reconstruction after initial cancer therapy or the reasons why receipt of treatment might be delayed. Methods: A 5-year follow-up survey was mailed to a population-based cohort of breast cancer patients diagnosed 2002 and reported to the Los Angeles and Detroit SEER registries. Patients who completed a baseline survey shortly after diagnosis and who received mastectomy were enrolled in the follow-up study (N = 645, response rate 60%). Outcomes were receipt of reconstruction (immediate [IR], delayed [DR], or no recon) and patient decision appraisal. Results: About one third (35.9%) had IR; 11.5% had DR; and 52.6% had no recon. Common reasons for recon delay were concerns about pain (52.3%), complications (48.8%), and interference with cancer surveillance (48.8%). One-third delayed the decision because they focused more on other cancer interventions. Among those without recon at time of follow-up, two-thirds said that the procedure was not important to them but one-fifth said that they did not know it was an option. Common reasons for having IR or DR included wanting to feel whole again (89.8% and 97.6%, respectively); wanting to feel attractive (94.9% and 90.7%, respectively); wanting to avoid breast prostheses (97.0% and 100.0%, respectively); and wanting to feel less self-conscious during sexual activity (94.1% and 81.4%, respectively). A large proportion of all patients were satisfied with their decision about recon (89.8% IR, 79.1% DR, 81.7% no recon, p = NS). However, only 58.2% of those without reconstruction felt that they were adequately informed about their reconstructive options (vs. 83.3% IR and 79.1% DR, p < 0.0001). Conclusions: There was modest uptake of breast reconstruction after initial cancer diagnosis and treatment. Factors associated with DR were primarily related to uncertainty about the procedure, concern about cancer surveillance, and low priority. Those without reconstruction demonstrated significant informational needs, which should be addressed with future research efforts. No significant financial relationships to disclose.