bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of docetaxel and gemcitabine in the treatment of recurrent ovarian, peritoneal, and fallopian tube cancer
Authors: Shahin M. S. , Hanjani P. , Nolte S. 
Published: March 2020

15006 Background: The aim of this trial was to investigate the efficacy and toxicity of weekly combination of docetaxel (D) and gemcitabine (G) in the management of recurrent ovarian, peritoneal, or fallopian tube cancer. Methods: D (30 mg/m2) was given as a one-hour IV infusion followed by G (650 mg/m2) as a 30 minute IV infusion on Day 1, 8 & 15 of a 28-day cycle. Results: Thirty pts were enrolled. Mean age was 67.4 (range 47–85). Twelve (40%) pts had Platinum sensitive disease, and 18 (60%) had Platinum resistant disease. One hundred eighteen cycles were evaluable for toxicity. The mean number of cycles was 4 (range 1–7). Twenty-six (22%) of the cycles were incomplete due to toxicity (day # 15 not given in 25 of the incomplete cycles). Dose delay was observed in 4 (13.3%) pts, and a one-dose level reduction was required in 11 (36.7%) pts. Hematologic toxicity included grade 3 neutropenia in 13 (11%) cycles, grade 3 thrombocytopenia in 11 (9.3%) cycles. No grade 4 neutropenia, thrombocytopenia or neutropenic fever was encountered. Bone marrow support with erythropoiten (36.6% pts), and filgrastim (13.3% pts) were utilized. Blood transfusions were given in 10 (8.5%) cycles. Elevated LFT grade 1/2 was seen in 7 (23.3%) pts and 3 (10%) pts, respectively. Nonhematologic grade 3 toxicites occurred in 4 pts (including one seizure). Mean follow-up interval was 19.6 months (mos) (range 1–36.6). To date, 14 (46.6%) pts are alive with disease, and 16 (53.4%) have died of disease. The overall response rate was 32% (1 CR and 8 PR in 28 evaluable pts). Ten pts (33.3%) had SD and 5 had ID. Median progression-free interval (PFI) was 3.8 mos (95% CI: 1.65–5.97). Overall survival was 19.6 mos (95% CI: 14.23–24.96), and no significant differences in PFI and survival between the Platinum-sensitive and resistant pts (P = 0.5, P = 0.08, respectively). Conclusions: Weekly docetaxel plus gemcitabine is an active and tolerable regimen with minimal toxicity in this older population of pts (9 ≥ 80 years of age). No significant difference in response between Platinum sensitive and resistant pts was observed. Overall response rate appears to be better than single agent regimens currently available. Elimination of the third week of treatment may not affect efficacy and will be more acceptable to pts with less toxicity. No significant financial relationships to disclose.
Immunohistochemical staining for XRCC1, XRCC3 and Ku70/80 proteins and their correlation with clinical outcome in locally advanced cervical cancer
Authors: O’Hagan J. E. , Dodson A. , Foster C. S. 
Published: March 2020

15011 Background: Locally advanced cervical cancer can be successfully treated with radiotherapy but the toxicity of this treatment is at the limit of tolerability (5–15% serious late complications). A test of the cancer’s likely response to radiotherapy would be invaluable to clinically individualize treatment. Protein XRCC1 is involved in DNA single strand break repair and sister chromatid exchanges. Protein XRCC3 is involved in homologous recombinational repair forming a heterodimer with RAD51L2. XRCC5 codes for the Ku70/80 heterodimer and is involved in double strand break repair and V(D)J recombination. The objective of this study was to correlate protein expression with the clinical response to treatment, disease free survival (DFS) and overall survival (OS). Methods: The archived paraffin embedded tissue blocks from 122 women with locally advanced cervical cancer previously treated with either radiotherapy or chemoradiotherapy were stained for XRCC1, XRCC3 and Ku70/80 proteins. The slides were reviewed and the intensity of the staining graded from 0 to 3 (none - strong). Clinical data from the patients’ case notes included baseline characteristics, response at the time of brachytherapy, response at 3months, dates of diagnosis, relapse, last clinic visit and death. The χ2 test, log rank test and Kaplan-Meier methods were used for statistical analysis. Results: The median follow up was 31 months (range 1–76 months). Clinical response at 3 months (RECIST criteria) was strongly correlated with both OS and DFS, patients who progressed had a mean OS of 9.5months (CI 4.2–14.7) compared to patients who had a partial response, mean OS 45.2months (32.6–57.8), and patients who had a complete response had 60% OS at 4years. However, no significant relationships were found between staining for XRCC1, XRCC3 or Ku70/80, OS, DFS or clinical response. Conclusions: This study did not find an association between expression of XRCC1, XRCC3 and Ku70/80 proteins and clinical response, OS or DFS in locally advanced cervical cancer. No significant financial relationships to disclose.
Topotecan, paclitaxel, and carboplatin in advanced ovarian cancer: A phase II trial of the Minnie Pearl Cancer Research Network
Authors: Zubkus J. D. , Hainsworth J. D. , Spigel D. R. , Patton J. F. , Shipley D. L. , Baskette M. , Schnell F. , Greco F. A. 
Published: March 2020

15015 Background: Topotecan (T) is standard therapy for patients (pts) with relapsed platinum refractory ovarian cancer (OC). The addition of T to paclitaxel/carboplatin (PC) may improve the first-line therapy for pts with stage III/IV OC. Methods: The primary endpoints were to assess the toxicity and response rate of TPC in previously untreated pts with advanced OC. Pts with previously untreated stage III/IV OC with performance (PS) 0 or 1, normal hematologic and organ function were eligible. Topotecan 1mg/m2 per day IV days 1, 2, and 3; paclitaxel 175mg/m2 IV on day 3 and carboplatin (AUC=5) IV on day 3 were administered at 21-day intervals for 6 cycles with standard dose modifications for toxicities. Responses were assessed clinically after 2 cycles and at completion of therapy. Second look laporatory (SLL) was required for pts without evaluable tumor. Results: 50 pts were enrolled: age range 27–79 (median 63); performance status 0=16, 1=34; suboptimal debulking surgery (tumor > 1 cm) 32; 70% high grade tumors. Intent to treat response rates: complete response (CR) 20 pts (40%); partial response (PR) 12 pts (24%); stable (S) 13 pts (26%); progression 2 pts (4%); not evaluable 3 pts (6%). 13 pts had SLL with 5 CR, 5 PR and 3 S. Toxicities included: grade 3/4 neutropenia/thrombocytopenia 84%/44%; grade 3/4 fatigue/infection 10%/10%; no treatment-related deaths. Median progression-free survival (PFS) for all pts was 13.6 months and 1-, 2-, 3-year PFS 60%, 42%, 36%. Median survival 33.9 months for all pts with 1-, 2-, 3-year survivals 90%, 65%, 49%. Conclusions: The combination of TPC is active and relatively well tolerated with PC given on day 3. The response rates, PFS, and survivals appear similar to standard regimens. Randomized prospective trials will be required to determine the value of T added to PC for first-line therapy of advanced OC. [Table: see text]
Defining the mechanisms by which leptin stimulates proliferation of ovarian cancer cells
Authors: Olawaiye A. B. , Sakamoto H. , Serikawa T. , Friel A. , Kiyama R. , Inoue A. , Drapkin R. , Foster R. , Gonzalez R. R. , Rueda B. R. 
Published: March 2020

15017 Background: Ovarian cancer (OvCa) ranks fourth as the cause of death related to cancer in women in the U.S. The vast majority (>90%) of OvCa originates from the ovarian surface epithelium. There is sufficient evidence to suggest that hormones, especially estrogen, may be involved in the etiopathogenesis of epithelial OvCa. Recent studies indicate that leptin participates either directly or indirectly to promote carcinogenesis in both breast and endometrial cancers. Furthermore it has been proposed that leptin may elicit its action via an estrogen related pathway. Leptin can stimulate proliferation of some OvCa cell lines and has been implicated as a potential biomarker for OvCa. However the mechanism(s) by which leptin contributes to the growth of OvCa has yet to be defined. We hypothesize that leptin’s effect will be mediated in part by estrogen receptor (ER) pathways. Methods: Three epithelial OvCa cell lines (IGROV1, OVCAR5 and TOV21G) and one benign human ovarian surface epithelial cell line (HOSE) were evaluated. Enzyme linked immunosorbent assay (ELISA) and Western blotting were used to assess leptin and leptin receptor (ObR), respectively. Leptin (0.06 nM–6.25 nM) induced effects on cell proliferation were assessed in the presence or absence of an aromatase enzyme inhibitor (Anastrozole) or the ER antagonist (ICI182780). Further, we explored leptin-induced effects on ERα promoter activity as evidenced by change in fluorescence via a dual luciferase promoter reporter. All experiments were conducted in triplicate. All data were subjected to ANOVA followed by Tukey’s post hoc test (p < 0.05). Results: All ovarian cell lines expressed ObR; whereas, no measurable amounts of leptin were detected in conditioned media. Leptin stimulated cell proliferation in both the benign and malignant lines. Leptin-induced cell proliferation was inhibited by Anastrozole and ICI182780. Furthermore, leptin stimulated luciferase activity of the ERα promoter/reporter. Conclusions: Leptin promotes proliferation of benign and malignant ovarian epithelial cells and appears to be mediated, at least in part, via aromatase and ER which may have therapeutic implications. This work was supported by the Vincent Memorial Hospital, SG Komen Foundation and the Advanced Medical Research Foundation. No significant financial relationships to disclose.
Concurrent chemoradiotherapy using high-dose-rate intracavitary brachytherapy with a modified dose schedule: Retrospective analysis of a single institutional experience
Authors: Toita T. , Tamaki W. , Maehama T. , Ogawa K. , Nagai Y. , Iraha S. , Kakinohana Y. , Moromizato H. , Kanazawa K. , Murayama S. 
Published: March 2020

15019 Background: The purpose of this study was to assess the effectiveness of concurrent chemoradiotherapy (CCRT) using high-dose-rate intracavitary brachytherapy (HDR-ICBT) with a dose schedule modified from the American Brachytherapy Society (ABS) recommendation. Methods: 68 consecutive patients (IB2: 3, IIA: 2, IIB: 32, and IIIB: 31) with cervical squamous cell carcinoma consecutively treated with CCRT using HDR-ICBT were retrospectively analyzed. Patients with para-aortic lymphadenopathy (greater than 10mm in minimum diameter assessed by CT) were excluded. The median tumor size (assessed by MRI) was 60mm (range: 40–86mm). Cisplatin (20 mg/m2/day) was concurrently administered with radiotherapy (RT) for 5 days at 21-day intervals for a median of 2 courses (range: 1–5). The planned RT schedule consisted of pelvic external beam RT (EBRT) with 40Gy/20 fractions followed by HDR-ICBT with 18Gy/3 fractions and pelvic EBRT with 10Gy/5 fractions using a midline block (MB). The cumulative biologically effective dose (BED) at point A of this schedule was 77Gy10. 60 patients (88%) were treated with this schedule. In the remaining 8 patients, pelvic EBRT was delivered without MB (up to 50Gy), and/or additional HDR-ICBT (up to 24Gy) was given. The actual BED for all 68 patients thus ranged from 77 to 89 Gy10. Median follow-up of the surviving 54 patients was 46 months (range: 8–91 months). Late complications were graded by the RTOG/EORTC criteria. Results: The actuarial overall survival rate, disease-free survival rate, and pelvic control rate at 4 years were 78% (95% CI, 68–90%), 74% (95% CI, 63–85%), and 90% (95% CI, 83–97%), respectively. Only one patient suffered a grade 3 complication (enterocolitis). The actuarial late complication (Grade 1or higher) rates at 4 years were 12% (95% CI, 3–20%) for proctitis, 2% (95% CI, 0–5%) for cystitis, and 21% (95% CI, 10–33%) for enterocolitis. Conclusions: This retrospective analysis suggests that CCRT using HDR-ICBT with a modified dose schedule was able to achieve favorable pelvic disease control without severe late complications for patients with cervical cancer. No significant financial relationships to disclose.
Clinical outcome of atypical uterine smooth muscle tumors
Authors: Pothuri B. , Kehoe S. M. , Wright T. , Herzog T. 
Published: March 2020

15028 Background: Smooth muscle tumors of uncertain malignant potential (STUMP) and atypical leiomyomas have increased mitotic activity, cellular atypia and necrosis but the degree is less than that used to define uterine leiomyosarcomas. Our objective is to evaluate the clinical outcome of patients with uterine masses histologically defined as smooth muscle tumors of uncertain malignant potential or atypical leiomyomas. Methods: A thorough search of our institution’s pathology database from 1990 to 2005 was performed. A retrospective chart review was performed to obtain initial and subsequent treatments, documented recurrences and clinical outcomes. Pathology reports and slides were reviewed and the presence of atypia, necrosis and number of mitosis was recorded. Statistical analysis was performed by Student’s T-test. Results: Eighteen patients with a histologic diagnosis of atypical leiomyoma were identified with 14 STUMP, 2 bizarre leiomyomas, 1 myxoid and 1 mitotically active leiomyoma. The mean age of these patients was 41.8 years (range: 25–77) and was significantly younger than those with leiomyosarcoma (mean age was 54 years, p < 0.001). The histologic characteristics of the tumors included the presence of atypia at 50%, necrosis at 82% and mitoses at 94%. The rate of necrosis and number of mitosis was significantly less in the atypical group as compared to the leiomyosarcoma group (p values < 0.05). However the rate of cellular atypia was not statistically different between the two groups. The median follow-up period was 25 months, range 1–138 months. One of the eighteen patients developed a pelvic and pulmonary recurrence at which time a low grade leiomyosarcoma was diagnosed. The recurrence occurred 32 months after the initial diagnosis of a mitotically active leiomyoma. Sixteen patients demonstrated no recurrence or metastatic disease at the time of follow-up. Conclusions: Atypical leiomyomas appear to be diagnosed in younger women which leads to challenging treatment issues involving fertility preservation. While these tumors generally behave in a benign fashion, they have histologic characteristics that may allow for progression or recurrence. Close follow-up is warranted for patients who are diagnosed with atypical leiomyomas and smooth muscle tumors of uncertain malignant potential. No significant financial relationships to disclose.
Ovarian cancer treatment patterns and outcomes in the United States: A National Program of Cancer Registries (NPCR) study
Authors: Stewart S. L. , Wike J. M. , Cress R. , O’Malley C. , Neloms S. , Kahn A. R. , Schymura M. J. 
Published: March 2020

15031 Background: Ovarian cancer (ovca) is the fifth leading cause of cancer death among women in the United States. In 2001, the NPCR program (administered by the Centers for Disease Control and Prevention) initiated a multi-year study to determine the first course of treatment for ovca patients in order to assess whether the ovca standard of care (as defined by the NIH Physician Data Query) was met. Methods: Population-based cancer registries in Maryland, New York, and Northern California were funded to collect patient, tumor, provider, and treatment data on patients diagnosed in these areas between 1997 and 2000. Information was collected through a retrospective medical record abstraction; all ovca records in Northern California and Maryland were included in the study, a simple random sample of ovca medical records in New York was included. Data on over 3000 patients from Northern California and New York were obtained (about 1500 patients each); data on about 1000 patients from Maryland was obtained. Patient vital status was followed through 2002. Results: Most patients were non-Hispanic white and between the ages of 50 and 79. About 30% of the tumors were papillary serous cystadenocarcinomas and almost 40% were poorly differentiated; about 66% of tumors were distant stage at diagnosis. The percentage of distant stage diagnoses increased with increasing age through age 79. Over half of patients were treated by gynecologic oncologists; obstetrician/gynecologists treated a little over 10% of patients. Overall, over 80% of patients underwent cancer directed surgery; about 50% were treated with carboplatin and about 55% were treated with paclitaxel. Patients ages 70 and older received cancer-directed surgery less often than younger patients. Overall, about 50% of patients were alive at the end of the follow-up period, with the percentage alive within age categories decreasing with increasing age. Conclusions: Age remains a negative factor in ovca presentation, treatment, and survival. Continued assessment of ovca patterns of care will enhance ovca knowledge and may aid clinicians in determining appropriate treatments for their ovca patients. No significant financial relationships to disclose.
Phase II study of nab-paclitaxel plus carboplatin in patients with recurrent platinum-sensitive ovarian or primary peritoneal cancer
Authors: Benigno B. B. , Hines J. F. 
Published: March 2020

15033 Background: This open-label, non-randomized study was designed to determine the efficacy and safety of nab-paclitaxel (a 130-nm albumin-bound particle form of paclitaxel) plus carboplatin in patients with metastatic ovarian or primary peritoneal carcinoma following platinum-based chemotherapy. Methods: Eligible patients had to have either measurable disease (based on RECIST criteria) or pretreatment CA-125 levels ≥2 times the upper limit of normal in the absence of measurable disease. Patients also had to have good performance status, adequate hepatic/renal function, peripheral neuropathy ≤ grade 1, and life expectancy ≥6 months. Patients may have received prior chemotherapy for ovarian cancer, including taxane-containing regimens, provided the treatment was completed at least 6 months before enrollment. nab-Paclitaxel 100 mg/m2 was administered IV over 30 minutes on days 1, 8, and 15 every 28 days. Carboplatin AUC6 was administered IV over 1−2 hours on day 1 every 28 days. Treatment continued for 6 cycles (or longer in the absence of unacceptable toxicity). Planned sample size was 43 patients (39 evaluable). Efficacy was determined by changes in tumor size for patients with measurable disease or changes in CA-125 levels for those with non-measurable disease. Results: To date, 10 patients have been enrolled, 2 of whom completed 2 treatment cycles; both patients had a 50% reduction in their disease (partial response). One patient had grade 4 neutropenia; grade 3 hematologic events were neutropenia (2 patients), thrombocytopenia (3), and anemia (1). Severe headache and severe nausea were reported for 2 patients each; all 4 events required medication. Conclusions: Preliminary results suggest that nab-paclitaxel 100 mg/m2 plus carboplatin AUC6 will have antitumor activity in patients with recurrent platinum-sensitive ovarian or primary peritoneal cancer and that treatment appears to be well tolerated. Updated response and toxicity data from this study will be presented. No significant financial relationships to disclose.
The significance of the ratio of metastatic to examined lymph nodes in endometrioid uterine cancer
Authors: Teng N. N. , Cheung M. K. , Husain A. , Osann K. , Berek J. S. , Kapp D. S. , Chan J. K. 
Published: March 2020

15043 Background: To determine the impact benign to positive lymph node ratio (LNR) on the disease-specific survival of women with advanced endometrioid corpus cancer. Methods: Demographic and clinico-pathologic information were obtained from the Surveillance, Epidemiology and End Results Program from 1988–2001 and analyzed using Kaplan-Meier methods and Cox proportional hazards regression. Results: Of the 1,222 women diagnosed with stage IIIC-IV endometrioid uterine cancer with nodal disease, the median age was 64 (range: 28–93). 1,025 (83.9%) were White, 75 (6.1%) Black, 91 (7.5%) were Asian and 31 (2.5%) were Other. All patients underwent surgical staging including a lymph node assessment and were found to have nodal metastases. 639 (52.3%) had stage IIIC, 24 (2.0%) IVA, and 559 (45.7%) IVB disease. Furthermore, 123 (10.1%), 466 (38.1%), and 581 (47.6%) women had grade 1, 2, and 3 disease, respectively. Grade information was unavailable for 51 (4.2%) patients. The benign to positive lymph node ratios (LNR) were divided in four subgroups: ≤5%, >5% to ≤10%, >10% to ≤20%, and >20% to determine impact of LNR on disease-specific survival. Increasing LNR (≤5%, >5% to ≤10%, >10% to ≤20%, and >20%) was associated with a decrease in disease-specific survival at 83.8%, 73.2%, 62.4%, and 50.8%, respectively (p < 0.0001). More specifically, LNR was an important factor only in patients with 11–20 and >20 lymph nodes removed but not for those with less than 10 nodes resected. Women with higher (LNR) received significantly more adjuvant radiotherapy at 72.0%, 69.7%, 61.1%, and 52.6%, respectively. On multivariate analysis, age, stage, grade, and lymph node ratio were significant independent prognostic factors for survival. Adjuvant radiation was not an important independent prognostic factor in multivariate analysis. Conclusion: The ratio of metastatic to examined lymph nodes in endometrioid uterine cancer is an important prognostic factor. Clinical trials on adjuvant therapy should be designed with consideration of this significant prognosticator. No significant financial relationships to disclose.
A preclinical study of cellular immunotherapy redirected by bispecific antibodies in uterine cell lines and primary cancer cells
Authors: Hamilton C. A. , Zhang M. M. , Chan J. K. , Cheung M. K. , Thorne S. H. , Baker J. , Contag C. H. , Negrin R. S. 
Published: March 2020

15044 Background: Cytokine induced killer cells (CIKs) are ex-vivo activated and expanded CD8+ natural killer T cells that have been shown to have cytotoxic activity against cancers in randomized clinical trials. We determined the cytotoxic activity of CIK cells against endometrioid and serous papillary (UPSC) uterine cancer cell lines and evaluated the ability of Trastuzumab and Her2xCD3 bispecific antibodies to enhance CIK-mediated cytotoxicity in Her2/neu expressing uterine cancer cells. Methods: The cytotoxicity of CIKs was quantified by 4-hour 51Cr release assays against uterine cell lines HEC-1A (endometrioid) and SPEC-2 (UPSC). Bispecific antibodies against Her2/neu (BSAbHer2) were designed using chemical conjugation methods. Results: Using FACS analysis, we found that the population of CD3+ CD8+ T cells increased from 24% to 56% over 21 days, while the CD3+ CD56+ T cells increased from 7% to 14%. Immunofluorescence microscopy revealed that both cell lines overexpressed Her2/neu. Cytotoxicity assays were performed at effector to target (E:T) ratios of 10:1, 20:1, 40:1 and 100:1 with increasing E:T ratio correlating directly with mean percent specific lysis. At the 100:1 E:T ratio, the mean percent lysis of CIKs against HEC-1A and SPEC-2 cells was 38.8% (±0.21) and 35% (±3.4), respectively. Trastuzumab did not affect the cytotoxic activity of CIKs. However, BSAbHer2 redirection significantly enhanced the cytotoxicity of CIKs against HEC-1A and SPEC-2 cells with a mean percent lysis of 66.3% (±1.0) and 50% (±2.7), respectively. Anti-NKG2D antibodies significantly reduced CIK activity by 49% and 47% in HEC-1A and SPEC-2 cells, respectively. The effects of CIK on advanced uterine cancers were demonstrated using our in vivo bioluminescence imaging system. Conclusion: CIK cells have cytotoxic activity both endometriod and UPSC cell lines. Redirection by BSAbHer2 significantly increased CIK-cell mediated cytotoxicity against Her2/neu expressing cell lines. The mechanism of CIK cytotoxicity appears to be partly mediated by the NKG2D receptor. No significant financial relationships to disclose.