bluuebunny/crossref_metadata_2025_split huggingface dataset:
Results of a phase II evaluation of nanoparticle albumin bound paclitaxel (nab-paclitaxel) in platinum-sensitive patients with recurrent ovarian, peritoneal, or fallopian tube cancer
Authors: Teneriello M. G. , Tseng P. C. , Crozier M. , Encarnacion C. , Hancock K. , Messing M. J. , Boehm K. A. , Williams A. , Ilegbodu D. , Asmar L. 
Published: March 2020

5525 Background: Patients (pts) with recurrent ovarian, peritoneal, or fallopian tube cancer generally have a poor outcome with current therapies. There are no reports of albumin-bound paclitaxel (nab-paclitaxel) in pts with platinum sensitive recurrent disease. We are reporting our preliminary efficacy and toxicity results with nab-paclitaxel in this group. Methods: 47 pts were enrolled (44 available for analysis). Main inclusion criteria: histologically or cytologically confirmed epithelial cancer of the ovary, fallopian tube, or peritoneum (any stage, grade 2–3 if stage I) and measurable disease by RECIST or elevated CA-125 (>70 units/mL) in the absence of measurable disease; nonepithelial disease was excluded. Pts received 260 mg/m2 of nab-paclitaxel IV over 30 minutes Day 1 of each 21-day cycle. Pts continued until progressive disease (PD) up to a maximum of 6 cycles. Results: Median age was 65.5 years (range, 42- 84), Stage IIIC (53%) or IV (23%); ECOG PS=0 (87%), and prior surgery (94%). For evaluable pts the overall response rate (ORR) was 50% (13 CR and 9 PR in 44 pts). In pts followed by RECIST only, the ORR was 27% (1 CR and 2 PR in 11 pts). In pts with only CA-125, it was 64% (5 CR and 2 PR in 11 pts). In pts meeting both RECIST and CA-125 criteria, the ORR was 54.5 % (7 CR and 5 PR in 22 pts. Median time to response was 1.8 months (range, 1 to 2.1). The most frequent Grade 3–4 treatment-related toxicities were: neutropenia (8.7%) and fatigue, diarrhea, and dyspepsia (2.2%, each); alopecia (Grades 1–2) occurred in 84.8%. All other adverse events were Grade 1–2. To date, 46 pts are surviving; one death was related to progressive disease. Conclusions: Nab-paclitaxel was very active in this group of pts with recurrent ovarian, peritoneal, or fallopian tube cancer. The ORR was 50%. Toxicities were minimal and manageable. Response and survival analysis and review of the methods of disease assessment are ongoing. Further studies of nab-paclitaxel are warranted. This research was supported, in part, from a research grant from Abraxis BioScience, Inc., Santa Monica, CA. [Table: see text]
Effect of monthly oral ibandronate on anastrozole-induced bone loss during adjuvant treatment for breast cancer: One-year results from the ARIBON study
Authors: Lester J. E. , Gutcher S. A. , Ellis S. P. , Thorpe R. , Horsman J. M. , Brown J. E. , Purohit O. P. , Dodwell D. , Coleman R. E. 
Published: March 2020

553 Background: The aromatase inhibitor anastrozole is a highly effective treatment for breast cancer with superior efficacy and tolerability advantages over tamoxifen. However its use is associated with significant declines in bone mineral density (BMD) with an increase in fracture risk. The ARIBON trial is a double blind, randomised, placebo-controlled study designed to evaluate the impact of bisphosphonate treatment on BMD in women taking anastrozole. The study also aims to explore the relationship between levels of biochemical markers of bone metabolism with longer term changes in BMD as measured by Dual energy Xray Absorptiometry (DXA). Methods: 131 postmenopausal, surgically treated breast cancer patients were recruited from oncology clinics in Leeds and Sheffield, UK. Following consent, baseline bone densitometry showed that 68, 50 and 13 patients were found to be normal (T >-1.0), osteopenic (T -1.0 to -2.5) and osteoporotic (T < -2.5) respectively. All patients were treated with anastrozole 1mg once a day and offered calcium and vitamin D supplementation. In addition, osteopenic patients were randomised on a 1:1 basis to receive either treatment with ibandronate 150 mg orally every month or placebo. Osteoporotic patients were treated with open label ibandronate orally 150mg every month. Results: After I year, osteopenic patients treated with ibandronate gained +2.78% (range -3.8, +15.1) and +1.35% (range -4.1, +5.6) at the lumbar spine and hip respectively. Patients treated with placebo however lost -2.61% (range -11.0, +2.2) at the lumbar spine and -2.34% (range -10.4, +5.2) at the hip. The differences between the two treatment arms were statistically significant at both sites (p<0.001, independent samples t-test). Patients with osteoporosis gained +5.05% (range -8.7, +15.2) at the lumbar spine and +2.62% (range -1.0, +8.6) at the hip after 1 year. Conclusions: Ibandronate 150 mg by mouth once a month prevents anastrozole induced bone loss and results in significant increases in BMD at the hip and lumbar spine in osteopenic and osteoporotic patients. Analysis of the biochemical markers of bone metabolism is underway and relationships between biochemical and BMD changes will be presented. No significant financial relationships to disclose.
Improved overall survival for patients with advanced ovarian, tubal, and primary peritoneal carcinoma as a result of a change in surgical approach: A follow-up study
Authors: Chi D. S. , Eisenhauer E. L. , Sonoda Y. , Abu-Rustum N. R. , Gemignani M. L. , Levine D. A. , Hensley M. L. , Sabbatini P. , Brown C. L. , Barakat R. R. 
Published: March 2020

5530 Background: In January 2001, we initiated a programatic change in our primary surgical approach to advanced ovarian carcinoma utilizing extensive upper abdominal procedures as needed to achieve maximal cytoreduction. The objective of this study was to determine the impact of incorporating these procedures on overall survival in advanced ovarian, fallopian tube, and primary peritoneal carcinomas. Methods: Two groups of patients (pts) with stage IIIC and IV ovarian, tubal, and primary peritoneal carcinoma were identified for comparison. Group 1, the control group, consisted of all 168 pts who underwent primary cytoreduction between 1/96 and 12/99. Group 2, the study group, was composed of all 209 pts who underwent primary surgery between 1/01 and 12/04, during which time a more comprehensive debulking of upper abdominal disease was used, including diaphragm peritonectomy/resection, splenectomy, distal pancreatectomy, liver resection, resection of porta hepatis tumor, and cholecystectomy. Results: Comparison between the 2 groups revealed no significant difference in age, BMI, performance status, stage, tumor grade, proportion with primary ovarian cancer, preoperative CA-125 levels, preoperative platelet counts, percentage with ascites, or type of postoperative primary chemotherapy. The only 2 variables that differed significantly between the 2 groups were percentage of pts who had extensive upper abdominal surgery and percentage of pts cytoreduced to ≤1 cm residual disease (RD). Patients in Group 2 were more likely to have undergone extensive upper abdominal procedure(s) (37% vs. 1%; P <0.001). Cytoreduction to RD ≤1 cm was achieved in 50% of Group 1 pts compared to 80% of Group 2 pts (P <0.01). Overall median survival was significantly improved in Group 2 versus Group 1 pts (58 vs. 43 mos, [P=0.042], respectively). Conclusions: The recent incorporation of extensive upper abdominal surgical procedures to increase the rate of primary cytoreduction to residual disease ≤1 cm resulted in significantly improved overall survival. A paradigm shift toward more complete primary cytoreduction can improve survival for pts with advanced ovarian, fallopian tube, and primary peritoneal carcinomas. No significant financial relationships to disclose.
Chemotherapy and radiation therapy in UPSC
Authors: Viswanathan A. , Horick N. , Tanaka C. , Campos S. , Matulonis U. , Berkowitz R. 
Published: March 2020

5535 Purpose: To analyze the impact of chemotherapy (Ch) and radiation therapy (RT) on relapse rates in patients with uterine papillary serous carcinoma (UPSC). Materials and Methods: The outcomes of 160 women with UPSC seen between 1980–2005 at the BW/DFCC were analyzed. Exclusion criteria included stage IVB disease, no hysterectomy, unknown stage, or unknown type of RT. Results: The median age was 67 years (range 31–90). FIGO Stage was IA (21), IB (28), IC (13), IIA (7), IIB (10), IIIA (42), IIIB (2), IIIC (21), and IVA (16). Treatment included none (40), Ch alone (20), Ch and whole abdominal radiation (WA) (11), Ch and pelvic radiation (P) (30), Ch and vaginal brachytherapy (VB) (2), WA alone (24), P alone (19), and VB alone (14). The median dose of RT was WA 30 Gy and P 45 Gy. Ch was given to 63 patients; the median number of cycles of Carboplatin, Adriamycin and Paclitaxel was 3. Overall survival (OS) and disease-free survival (DFS) for the entire group were 67% and 57% at 2 years, 62% and 51% at 3 years and 51% and 38% at 5 years. A total of 58 patients relapsed. Among those who received no RT or Ch, 48% (19/40) relapsed; among those treated with Ch only, 50% (10/20) relapsed; in the group treated with RT only, 26% (15/57) relapsed; and, in those treated with Ch and RT, 33% (14/43) relapsed. A significant difference in recurrence rate was seen in patients treated with RT compared to those who received no treatment (OR 0.40, p=0.03). This difference persisted after controlling for Stage, which did significantly affect the relationship between RT treatment and recurrence. Local recurrence (in an RT field) was a component of failure for 14% (14/100) treated with RT, versus 42% (25/59) that received no RT (OR 0.22, p=0.0001). Distant metastases were a component of first failure in 15% (9/61) that received Ch versus 11% (11/97) that did not; there was no significant difference in distant recurrence rate for patients treated with Ch (OR 1.35, p=0.53). Conclusion: This single-institution study represents the largest series of UPSC to date. The use of RT significantly decreases the overall recurrence rate of UPSC in this series and should be considered in patients with stages I-IVA UPSC. Future studies looking at the optimal type, dose and duration of chemotherapy, as well as the use of novel agents, are needed to improve outcomes in this population. No significant financial relationships to disclose.
Markers of angiogenesis in cervical cancer: A Gynecologic Oncology Group study
Authors: Randall-Whitis L. , Monk B. J. , Han E. S. , Darcy K. , Burger R. A. , Liao S. , Peters W. A. , Stock R. J. , Fruehauf J. P. 
Published: March 2020

5536 Background: Extensive tumor angiogenesis has correlated with poorer progression-free and overall survival in cervical cancer; however, specific markers of angiogenesis have not been studied prospectively. Methods: Cervical cancer patients with high-risk features on radical hysterectomy were eligible for randomization to adjuvant pelvic irradiation ± radiosensitizing platinum. Following central pathology review, formalin-fixed, paraffin-embedded tumors were sectioned into 4-micron specimens. Semi-quantitative immunohistochemisty (IHC) was performed using previously validated antibodies against mutant p53 (mp53), vascular endothelial growth factor (VEGF), thrombospondin-1 (TSP-1), and endothelial markers CD 31 and CD 105. Tumoral histoscores (HS) were calculated for mp53 and VEGF using the formula: [% cells positive × (intensity +1)], with a 5% threshold for positivity and intensity ranging 1–4+ (3+ = intensity of positive control). Intensity scores (0–4+) were assigned to TSP-1 specimens referencing the positive control (3+). MVD “hotspots” were counted in a 20X high-power field. HS and MVD counts were considered as continuous variables and TSP-1 intensity as an ordinal variable. Associations between markers were determined by Pearson’s and Spearman’s correlation tests, between markers and clinico-pathologic variables by Wilcoxon rank test, and between markers and survival by Cox regression modeling. Results: One hundred seventy-six specimens were analyzed. Acquisition of mp53 and increased VEGF expression were associated with increased MVD assessed by both CD31 (p=0.08 and p=0.002, respectively) and CD105 (p=0.02 and p=0.012, respectively). Statistically significant associations between markers and high-risk pathologic factors included: low-level TSP-1 and high CD-105 counts with lymph node metastases; high VEGF scores with advanced stage, non-squamous histologic subtype, and depth of tumor invasion; and high CD 31 counts with parametrial metastases. Survival analysis is currently being performed. Conclusions: Angiogenesis occurs early in cervical carcinogenesis, and may be a rational target for biologic therapy in cervical cancer. No significant financial relationships to disclose.
The prognostic factors responsible for survival of women with neuroendocrine small-cell cervical carcinoma—A study of 188 women
Authors: Kapp D. S. , Cohen J. , Shin J. Y. , Husain A. , Teng N. N. , Berek J. S. , Osann K. , Chan J. K. 
Published: March 2020

5539 Background: To determine the clinical and pathological factors associated with survival in women with neuroendocrine small-cell cervical carcinoma. Methods: A review of the literature identified 136 patients with neuroendocrine small-cell carcinoma and an additional 52 patients identified from tumor registry databases at four hospitals. Survival analyses and predictors of outcome were analyzed using Kaplan-Meier method and Cox regression analysis. Results: Of 188 patients, the median age was 41.5 years (range: 20–87 years); 135 had stages I-IIA, 45 IIB-IVA, and 8 had stage IVB disease. Of all patients, 55.3% underwent primary surgery, 16.0% had chemoradiation therapy, 12.8% primary radiation therapy, 3.2% chemotherapy alone, and 12.8% had unknown or no primary treatment. Of the women who had initial surgery, 46.8% patients underwent a radical hysterectomy, and 6.4% had a simple hysterectomy. 49.5% of patients with nodal information had lymph node metastases. After initial surgery, 15.4% of all patients had adjuvant radiation therapy, 13.8% chemoradiation, 6.9% chemotherapy, and 2.1% had neoadjuvant chemoradiation. Of the 81 patients who received chemotherapy, 51.9% had etoposide and cisplatin combinations, 25.9% other cisplatin combinations, and 7.4% had cisplatin alone. The 5-year disease-specific survivals for those stage I-IIA, IIB-IVA, and IVB were 36.8%, 9.8%, and 0.0%, respectively (p<0.001). Those with tumors <2 cm showed a trend toward better survival (67.4% vs. 34.4%) compared to those with larger tumors (p=0.057). Women with stage I-IIA disease who underwent a radical hysterectomy had a survival of 42.5% vs. 38.4% without radical surgery. Chemotherapy (adjuvant or radiation sensitizer) was associated with improved survival in patients with stages IIB-IVA disease compared to those who did not receive chemotherapy (17.8% vs. 6.0%; p=0.043). On multivariable analysis, early stage of disease and chemotherapy were independent prognostic factors for improved survival. Conclusions: Advanced stage of disease is a poor prognostic factor for survival in neuroendocrine small-cell cancer of the cervix. Chemotherapy appears to offer a survival advantage, particularly in patients with stage IIB-IVA disease. No significant financial relationships to disclose.
Cardiotoxicity after doxorubicin and AZD2171, an oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor, in patients (pts) with breast cancer
Authors: Denduluri N. , Berman A. W. , Vatas U. , Chow C. K. , Rosing D. R. , Swain S. M. 
Published: March 2020

554 Background: AZD2171 selectively inhibits VEGFR 1,2,3. This trial examined the safety and efficacy of AZD2171 with anthracycline-containing therapy. Methods: Pts with previously untreated Stage IIB and III breast cancer received neoadjuvant AZD2171 (30mg) alone for one cycle (1 week) followed by daily AZD2171 and TAC chemotherapy with docetaxel (T), doxorubicin 50 mg/m2 (A) cyclophosphamide (C) for 6 cycles (Cy) every 3 weeks. Pts underwent breast surgery after completing neoadjuvant therapy. Eligible pts had left ventricular ejection fraction (EF) = 50%, and no uncontrolled HTN or cardiac history. Pts underwent electrocardiogram (EKG), and troponin first day (D) of every Cy and 24 hours after TAC as well as serial echocardiograms (echo). Cardiac stress MRI with dipyridamole was performed when pts had decreases in EF by echo. Results: Two pts received 2 Cy of AZD2171 alone, 9 Cy with TAC and AZD2171, and 1 Cy with TAC alone. Pt 1 and Pt 2 developed hypertension requiring medical therapy Cy4, D1 (148/97 mm Hg) and Cy2, D2 (169/93 mm Hg) respectively. Pt 1 had asymptomatic decrease in EF from 65% to 40% (grade 2) with global hypokinesis pre-Cy5 by echo. Troponin and EKG were negative for acute ischemia. Cardiac stress MRI was normal and EF returned to 60% within 48 hours. The pt continued therapy and pre-Cy7 EF was 51% by echo. Cumulative A dose received was 250mg/m2 pre-Cy7. AZD2171 was held while Cy7 TAC was continued. EF was 57% by echo 1 month after Cy7 TAC. Pt 2 had asymptomatic decrease in EF from 65% to 50% pre-Cy4 by echo with mild global hypokinesis. Troponin and EKG were negative for acute ischemia. Cardiac stress MRI showed EF of 56% with no ischemia. She continued AZD2171 and TAC. Pre-Cy5 EF was 35–40% (grade 3) with global hypokinesis. Troponin and EKG were negative. Cumulative dose of A received was 150mg/m2. AZD2171 and A were stopped; T and C were continued. EF normalized to 55% by cardiac stress MRI and echo within 21 days. Conclusion: Due to the systolic dysfunction that occurred with concurrent AZD2171 and doxorubicin administration, the study is closed. Future trials should administer AZD2171 and anthracyclines sequentially with stringent monitoring of blood pressure and ejection fraction. No significant financial relationships to disclose.
Impact of physical activity on insulin levels in breast cancer survivors
Authors: Ligibel J. A. , Campbell N. , Chen H. , Salinardi T. , Chen W. , Partridge A. , Mantzoros C. , Winer E. 
Published: March 2020

555 Background: Accumulating data suggest that body weight and physical activity may affect breast cancer risk and outcomes. Biological mechanisms underlying these relationships are not clear. Studies have demonstrated that high levels of insulin, often seen in obese and sedentary individuals, are also associated with an increased risk of breast cancer recurrence and breast cancer-related death. We sought to analyze whether exercise lowers insulin levels in a population of breast cancer survivors. Methods: Inactive women with early stage breast cancer who had completed adjuvant treatment were randomized to a 16 week, mixed cardiovascular and strength training exercise intervention, or to a normal care control group. Target exercise goals included 2 supervised strength training sessions and 90 minutes of unsupervised cardiovascular exercise each week. Fasting insulin and glucose levels, as well as measurement of weight, body composition, and circumference at the waist and hip, were collected at baseline and after 16 weeks in both groups, and changes in these measures were assessed. Results: One hundred and one women were randomized. Comparison of changes in anthropometric measures are presented in Table 1 . Baseline insulin levels were similar in the 2 groups. After the 16-week exercise or control period, insulin levels decreased by 2.86 μIU/ml in the exercise group (p=0.03), and by 0.27 μIU/ml in the control group (p=0.65). A comparison of the change in insulin levels across time in the 2 groups approached statistical significance (p=0.07). There was also a trend toward improvements in insulin sensitivity in the exercise group (p=0.09), with no change seen in fasting glucose levels. Conclusions: Physical activity was associated with a decrease in insulin levels and in hip circumference in breast cancer survivors. The relationship between physical activity and breast cancer prognosis may be mediated, at least partially, through changes in insulin levels and/or changes in fat mass or deposition. [Table: see text] No significant financial relationships to disclose.
Molecular correlates (EGFR status) and plasma VEGF levels associated with a phase II study of bevacizumab plus erlotinib (BE) for patients with recurrent ovarian cancer (OC) and fallopian tube (FT) cancer
Authors: Nimeiri H. S. , Faoro L. , Oza A. M. , Morgan R. J. , Gandara D. , Janamanchi V. , Salgia R. , Stadler W. M. , Vokes E. E. , Fleming G. F. 
Published: March 2020

5554 Background: The epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are commonly over- expressed in OC and may correlate with poor prognosis. EGFR mutations, although rare, have recently been reported in ovarian cancer. We examined these factors for prognostic value in the setting of treatment with BE. Results of a phase II trial of BE in recurrent OC pts have previously been reported; there were 1 CR and 1 PR among 13 patients. The trial was closed to accrual due to 2 bowel perforations. Methods: Pretreatment plasma VEGF, urine VEGF, and serum VEGFR2 levels are available on 9, 8, and 8 pts to date. VEGF levels were determined using an ELISA (R& D Systems, Minneapolis, MN). Tumor from 8 pts: 1(CR), 1 (PR), 5 (SD), 1 (PD) was available for immunohistochemical analysis for EGFR. Genomic DNA was successfully isolated from 6 paraffin embedded tumor specimens. EGFR exons 18 to 21 were amplified by PCR using primary and secondary PCR primer pairs. PCR products were purified and submitted for DNA sequencing against forward and reverse primers (analyzed with Sequencher). Results: Mean baseline plasma VEGF level was 107.6 pg/ml (range, 52–198 pg/ml). For analysis, we combined CR+PR+SD versus PD. Wilcoxon rank-sum test was used to compare baseline plasma VEGF levels, urine VEGF and serum VEGFR2 between the two response groups. There were no significant differences between response and baseline VEGF levels (p=0.39), urine VEGF (p=0.56), and VEGFR2 (p=0.56) respectively. The pt with prolonged CR (18 mos) had the highest baseline VEGF level. Cox proportional hazards regression models was used to look at the association between overall survival (OS) and VEGF levels. There was no significant relationship between (OS) and baseline plasma VEGF (p= 0.38), urine VEGF (p=0.33) or serum VEGFR2 (p=0.63) respectively. No EGFR mutations were found in exon 19 (n=4) or exon 21 (n=6). EGFR expression is being evaluated. Conclusions: Our results indicate that there were no significant relationship between response or OS and baseline VEGF or VEGFR2 levels in our treated pts. The study was supported by NCI Grant N01-CM-17102. [Table: see text]