bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of systemic therapy in women with recurrent ovarian cancer—Development of a national clinical practice guideline
Authors: Elit L. , Zitzelberger L. , Fung Kee Fung M. , Brouwers M. , Graham I. D. , Browman G. 
Published: March 2020

16033 Background: To develop a national guideline on the use of systemic therapy for women with recurrent ovarian cancer. Methods: In March 2005, the Society of Gynecologic Oncologists of Canada (GOC) held a workshop with clinicians and methodologists to begin the process of defining specific recommendations for the management of recurrent ovarian cancer in the Canadian context. An adaptation process developed by the Canadian Strategy for Cancer Control (CSCC) Clinical practice Guidelines Action Group (CPG-AG) was used. Guideline adaptation modifies existing guidelines to fit a local organizational and cultural context. A draft guideline was developed and sent to practitioners from across Canada for feedback. Relevant comments were incorporated. Results: A literature review identified seven guidelines which were assessed for quality by six reviewers using the AGREE instrument. Data on guideline quality, currency and content (recommendations) was used by the pan-Canadian panel in an informal consensus process which resulted in the initial draft of a guideline. A sub-panel reviewed the draft and made further edits to ensure the guideline's appropriateness for a national context. Practitioner feedback was requested from 165 health care providers who treat ovarian cancer from across Canada. Overall response rate was 37%. Respondents included gynecologic oncologists (62.5%), medical oncologists (25%), radiation oncologists (3%), internal medicine (3%), gynecologists (1%) and psychosocial oncology (1%). Overall response to the guideline was positive. All comments were reviewed by the sub-panel and the guideline was edited appropriately. Conclusions: This was the first undertaking of the creation of an interdisciplinary guideline in gynecologic oncology with input from health care providers from across Canada. Feedback from the panel and external practitioners indicated that this was a worthwhile process. Our goal was to vet this work in the Canadian context so as to inform provincial decision-makers concerning access to expensive systemic therapy. The guideline has been endorsed by the national organization and will be available to practitioners and decision makers on the organization's website. No significant financial relationships to disclose.
Pilot study of FLT-PET/CT uptake in ovarian cancer patients with biologic correlates
Authors: Deloia J. , Richard S. D. , Edwards R. P. , Elishaev E. , Mason S. , Shinde D. , Mountz J. J. , Bencherif B. 
Published: March 2020

16045 Background: New imaging modalities for ovarian cancer disease burden are needed. Positron emission tomography (PET) with [F-18] fluorodeoxyglucose (FDG) has shown promise for early prediction of outcome and response to therapy when compared to CT alone. Recent studies have suggested that 3’-fluoro-3’ [F-18] deoxythymidine (FLT) has a higher specificity than FDG. The objective of this study was to correlate FLT tracer uptake with different in vitro quantitation of cellular proliferation. Methods: Patients with suspected or know ovarian cancer and an elevated Ca 125 were recruited for this trial. These patients were injected with 5 mCi of [F-18]FLT intravenously as a slow bolus. After an uptake period of 60 minutes, patients were scanned for approximately 36 minutes by CT and then PET, and images were co- registered. Standardized uptake values (SUV) of both hot and cold areas were obtained and these lesions were biopsied at the time of surgery. Tissue was divided and used for Ki-67 proliferation index staining to determine mitotic index, RNA isolation for rt-PCR for thymidine kinase-1 (TK1) levels, and grown ex vivo for cell proliferation analysis. Univariate analysis was preformed using the student's t-test. Results: PET positive lesions were found to have a significantly increased mitotic index when compared to control lesions (0.134 vs. 0.004, p<0.001). There were no significant differences in relative TK1 levels or ex vivo cell proliferation ability between PET positive and control lesions in the initial four patients. Conclusions: Increased mitotic index by Ki-67 staining correlates with increased FLT activity by PET scan, but not TK1 levels or DNA content. We will continue to explore this modality as compared to FDG-PET in patients with ovarian cancer. No significant financial relationships to disclose.
A retrospective review of adenosquamous carcinoma of the uterine cervix
Authors: Kawakami Y. , Takehara K. , Kumagai M. , Hanaoka M. , Akimoto Y. , Mizunoe T. , Saji F. 
Published: March 2020

16049 Background: Adenosquamous carcinoma (ASC) of the uterine cervix is a rare mixture of malignant squamous and glandular epithelial elements. Clinical analyses of this disease were hardly performed independently from those of adenocarcinoma (AC) of the uterine cervix since both of the patients with these diseases show poorer outcome, compared with those with squamous cell carcinoma, which is present in the majority of cervical cancer. In this study, we investigated clinical features including diagnosis and treatment of this disease. Methods: During 1980–2006, total of 270 patients, who were diagnosed as carcinoma of the uterine cervix, were included in our analysis. A retrospective review of patients with ASC were preformed in their age, stage, lymph node metastasis, tumor markers (SCC, CEA, CA125 and CA19–9), treatment, relapse rate and its location, and survival. Results: There were total of 17 and 34 patients, who were histologically confirmed as having ASC (6.3%) and AC (12.6%) of the uterine cervix, respectively. All the ASC patients underwent surgery. The average age of the patients was 45.0 (26–78). The distribution of illness stages among the patients were IA, 4; IB, 8; IIA, 2; IIB, 2; IIIB, 1. Lymph node metastasis was seen in two patients (11.8%). There were no significant difference in these indexes between ASC and AC. Elevation of serum CA125 was observed in two ASC patients but no AC patients. The recurrence rates were 17.6% and 14.7% in ASC and AC, respectively. Five-year survival were 77.8% in ASC and 78.0% in AC, whereas 92.2% in SCC. Conclusions: These analyses indicate that clinical behavior and its outcome of ASC is similar to those of AC. The treatment based on these clinical features may be a useful to improve the prognosis of this disease. No significant financial relationships to disclose.
Anti-tumor activity of ADH-1 in vitro and in vivo in combination with paclitaxel in ovarian cancer cell lines
Authors: Gupta M. , Barnes D. , Losos J. , Spehar G. , Bednarcik M. , Peters W. P. 
Published: March 2020

16050 Background: ADH-1 is a novel N-cadherin (Ncad) antagonist. Ncad is a protein present on certain tumor cells and established tumor blood vessels. Its expression on tumor cells increases as they become more aggressive, invasive and metastatic, making it an important target for anti-cancer therapy. ADH-1 was well tolerated in phase I studies and demonstrated evidence of anti-tumor activity in 7 patients whose tumors expressed Ncad. Patient enrollment in two phase II single agent trials concluded at the end of 2006. We report on the anti-tumor activity of ADH-1 in combination with paclitaxel in cancer cell lines in vitro and in the A2780 (Ncad positive) ovarian xenograft model in vivo. Methods: In vitro cytotoxicity of SKOV-3 (ovarian) cells exposed to a fixed ratio of ADH-1 and paclitaxel simultaneously was evaluated by the WST-1 cell proliferation assay. In vivo anti-tumor activity of ADH-1, paclitaxel, and the combination was evaluated in the A2780 xenograft model. ADH-1 100 mg/kg was administered bid IP for 21 days and paclitaxel was administered qod IV for 5 days. Results: In vitro cytotoxicity assays evaluated for combination effects using CalcuSyn software indicated a strong synergistic effect of ADH-1 in combination with paclitaxel (CI <1). In vivo paclitaxel treatment produced a median Time to Endpoint (TTE) (tumor volume >2gm or study end at 60 day) of 32.1 days and 73% Tumor Growth Delay (TGD), compared to control (p=0.028). For the paclitaxel group, there was only one Tumor Free Survivor (TFS) and one transient Complete Responder (CR). ADH-1 produced a TTE of 16.1 and a -13% TGD (p>0.05). The combination of ADH-1 and paclitaxel produced a median TTE of 48.6 days, corresponding to 161% TGD (p<0.0016 compared to untreated controls, p<0.003 for vehicle treated, and p<0.005 compared to paclitaxel alone). The combination therapy generated durable CR in 5 animals, 1 transient CR and 2 PR. The combination therapy had similar toxicity to paclitaxel alone. Conclusions: In this ovarian cancer model, the combination of ADH-1 with paclitaxel produced a synergistic anti-tumor effect. Based in part on these encouraging pre-clinical results, a clinical program of ADH-1 in combination with chemotherapeutic agents has been initiated. No significant financial relationships to disclose.
Serum biomarker discovery for ovarian serous carcinoma using novel proteomic methods
Authors: Borgia J. A. , Frankenberger C. , Kaiser K. , McCormack S. E. , Usha L. , Rotmensch J. , Coon J. S. 
Published: March 2020

16058 Background: Ovarian serous carcinoma (OSC) is the most common ovarian cancer sub-type and fourth leading cause of cancer-related deaths for women in the US. Unfortunately, more than two-thirds of women with ovarian cancer present at an advanced stage, when prognosis is poor. Developing methods to detect ovarian cancer at stage I, when it is 90% curable by surgery, or at stage II where survival is 70%, offers the best prospect for changing the clinical course of this dread malignancy. Methods: Serum specimens were collected both before and 3–6 weeks after tumor resection for patients with Stage I/ II high-grade serous carcinoma. None suffered recurrence within 6 months. We collected 98 ‘paired’ (pre- and post operative) serum specimens; including 41 benign paired specimens for comparison. A SELDI-TOF mass spectrometer was used to generate the serum proteomic profiles, optimized for the 2,000–40,000 m/z range. All data analyses were performed in a blinded manner using Bioconductor, an extension of the R-project statistical platform (v2.2.0). Raw spectra were processed as follows: baseline subtraction, spectra normalization, and differential peak detection. Aligned peaks were sorted into groups, based on tumor pathology and pre- vs. post-operative specimen type, and compared using a two tailed homoscedastic t-test. Results: The proteomes of pre- and post-operative serum from 10 patients with OSC were evaluated for significant changes in composition and compared with a set of 8 ‘normal’ specimens (i.e. patients undergoing major surgery for benign disease). We identified 18 serum components common to all OSC pre-op specimens that were extensively reduced or absent (p < 0.05) after tumor resection and 26 components capable of discerning pre-op OSC from pre-op normal specimens (p < 0.05). Most notable of these are components with m/z ratios of 2029.1, 2203.6, 6442.3, and 6851.9, based on level of significance (p < 0.001). Conclusions: These results validate the power of our ‘pre- vs. post- operative’ analysis strategy for the identification of novel serum biomarker candidates. Efforts are currently focused on expanding the scope of our specimen bank and identifying the putative biomarker candidates via mass spectrometry. No significant financial relationships to disclose.
Response to primary chemotherapy (CHT) in advanced epithelial ovarian cancer (EOC) patients (pts) and molecular characterization of CHT-resistant tumor cell populations: Findings from the Arianna 02 Project
Authors: Zamagni C. , Wirtz R. M. , De Iaco P. , Altimari A. , Roth K. , Rosati F. , Rosati M. , Massari F. , Cacciari N. , Martoni A. A. 
Published: March 2020

16059 Background: Despite a high response rate to CHT the prognosis of pts with advanced EOC remains poor. The molecular analysis of pre- and post-CHT tumor specimen may enable the identification of CHT resistant tumor cell populations and thereby lead to adapted treatment options. Methods: Stage III-IV EOC pts diagnosed by laparoscopy and biopsy and not suitable for optimal debulking surgery were eligible. Gene-expression profiles generated from total RNA using the Affymetrix U133A oligonucleotide microarray containing over 22,000 probe sets were obtained at diagnosis and on surgical specimens after 6 courses of primary carboplatin/paclitaxel CHT. Initial comparative analysis focused on proliferative and invasive tumor activity, and on growth factor- and hormone receptors expression. Results: 30 pts were enrolled and data were analyzed according to response to CHT and to time to relapse after surgery. Initial expression analysis results reveal that the quantitative determination of growth factor- and hormone receptors in pre- and post-treatment samples can be used to discriminate responders from non-responders and relates to clinical outcome. Moreover, multiple CHT-resistant tumor cell populations displayed pronounced estrogen receptor expression suggesting a role of hormone receptors in the development of CHT resistance. Conclusions: While hormonal therapies are used in the treatment of other endocrine related tumors, they are not approved for the treatment of EOC. Treatment of EOC cell lines with estrogens down-regulates GnRH activity and promotes cell growth, while tamoxifen has an opposite effect. However, further biological data are lacking in this setting and only few clinical trials have addressed this possibility so far. We have found that the expression of hormone receptors in vivo persists in CHT-resistant tumor cell populations after CHT for EOC. We suggest that hormone receptor activity contributes to the initial development of CHT resistance; hence endocrine therapies particularly in an early setting may be advantageous to a subset of pts and are worth studying. No significant financial relationships to disclose.
A phase II study of irinotecan and docetaxel in patients with platinum-resistant relapsed epithelial ovarian cancer
Authors: Matsumoto T. , Hiura M. , Oshita T. , Hirata E. , Shiroyama Y. , Wroblewski J. , Yokoyama T. , Nogawa T. 
Published: March 2020

16062 Background: Patients with epithelial ovarian cancer are often diagnosed with advanced-stage disease. Although clinical complete remissions are obtained in the majority of patients through a combination of cytoreductive surgery and chemotherapy, relapse is common. Relapsed patients with a short treatment-free interval (TFI) after prior chemotherapy have a poor prognosis. We conducted a pilot study of irinotecan (CPT-11) and docetaxel (DTX) in patients with platinum-resistant relapsed epithelial ovarian cancer. Methods: Eligible patients must have at least one platinum and paclitaxel-containing regimen, and recur with a TFI of less than 6 months. CPT-11 60 mg/m2 and DTX 30 mg/m2 were administrated on days 1, 8, 15 of a 28-day cycle. Eligibility included preserved organ function, aged 20–75, and ECOG performance status 0 or 1. The primary endpoint was response rate, and secondary objectives were duration of response, time to progression (TTP) and safety. Toxicity was assessed using NCI-CTCAE ver.2.0. Results: Between 12/2000 and 4/2005, 26 patients were enrolled, 24 of whom were eligible. The median age was 57.5 years (range 35–75). A total of 99 cycles were analyzed, median number of cycles was 3 (range 1–12). Grade 3/4 hematologic toxicities occurred in 33.3% for anemia, 4.2% for thrombocytopenia, 50.0% for leucopenia, and 62.5% for neutropenia. Non-hematologic grade 3/4 toxicities were not observed. Efficacy based on RECIST criteria was available for 20 patients, and the overall response rate was 10% (2 PR) with SD in 40%. In addition, of 4 patients with no measurable diseases, 2 patients had a confirmed PR by CA125 criteria (GCIG). Over all, clinical benefit (PR, SD) was seen in 63.6% of patients. The median duration of response was 17 weeks (range 2–49). The median TTP was 31 weeks (range 7–86). Conclusions: These results suggest that weekly treatment with CPT-11 and DTX is feasible and effective chemotherapy regimen for platinum-resistant relapsed ovarian cancer. No significant financial relationships to disclose.
A phase II trial of radiation therapy with concurrent paclitaxel chemotherapy in high-risk endometrial cancer patients after staging operation: An interim analysis of a prospective multicenter trial (KGOG2001)
Authors: Kim J. , Jeong J. , Nam B. , Kim S. , Cho C. , Kim B. , Lee J. , Kim Y. , Bae D. , Kang S. 
Published: March 2020

16069 Background: This is an interim report of a prospective multicenter phase II trial to evaluate 2-year disease free survival rate, toxicity, overall survival rate and recurrence rate in high-risk endometrial cancer patients who received concurrent chemoradiotherapy after staging operation. Methods: Thirty four patients with endometrial cancer from 17 medical centers in Korea have enrolled the study. The cell types were all endometrioid type and they had no prior chemotherapy. They were in either stage III or IV and all received staging operation including total hysterectomy, bilateral salpingo-oophorectomy, pelvic and paraaortic lymph node dissection and washing cytology. Concurrent chemoradiotherapy was performed with paclitaxel (60 mg/m2/weekly, 6 cycles) and external field irradiation (5 fractions/week, total 4,500–5,040 cGy). Primary end point was 2-year disease free survival rate. Overall survival rate and recurrence rate were secondary end points. Toxicity of the treatment was also evaluated. Results: The expected number of subjects to complete the trial is 56. The trial was activated on 5th June 2005 and median follow up period is 5.8 (0–11) months until December 2006. 19 patients (55.8%) have completed treatment regimen and 14 patients (41.1%) are still receiving treatment. 1 patient (2.9%) died during treatment of the disease and 1 patient (2.9%) was lost during the follow up period. Disease free survival is 94.1% (32/34) and no recurrence has occurred so far. Toxicities have occurred in 52.9% (18/34) with gastrointestinal symptoms (13/34, 38.2%) such as diarrhea and constipation being the most common ones. Conclusions: This interim report suggest a possibility that a concurrent chemoradiotherapy for high-risk endometrial cancer may be an optimal treatment option to improve disease free survival rate. [Table: see text]
Toxicity of adjuvant sequential chemo- and radiotherapy of high-risk endometrial carcinoma (HREC)—Results of a phase II multicenter feasibility NOGGO study
Authors: Koehler G. , Sehouli J. , Sommer H. , Blohmer J. , Bartz K. , Belau A. 
Published: March 2020

16074 Background: Isolated adjuvant radio- or chemotherapy (CHT) only reduces local or distant relapses in HREC without impact on overall-survival. Therefore a multicenter feasibility study on adjuvant sequential chemo- and radiotherapy of HREC was initiated in order to evaluate safety and toxicity. Planned number of patients was 40, if after 17 pts. no termination of therapy because of toxicity was necessary, study can be closed and a phase III-study can be initiated. The data on toxicity are presented. Methods: Eligibility criteria: adenocarcinomas G1/G2 stage IC or G3 stage IA-IC or all stages II and IIIA (histological), all tumours with more than 2 cm diameter in size or non endometrioid cancers stage IA-C, II and IIIA and all cases with vessel invasion. Surgery: abdominal hysterectomy with bilateral adnexectomy without lymphadenectomy or with pelvic and para-aortic lymphadenectomy and positive lymph nodes. Further: Karnofsky-Index > 70, normal bone marrow, kidney, and liver function with laboratory tests not higher than 1.5 times of the normal local reference values. CHT: 175 mg/m2 paclitaxel plus carboplatin AUC 5, q 3 weeks for 4 cycles beginning latest 6 weeks after surgery. Within 6 further weeks after CHT an external beam irradiation (total dose 50.4 Gy, 28 fractions with 1.8 GY/d) plus 3 intracavitary HDR-iridium-192- brachytherapy courses with 3 x 5 GY were performed. Results: To date 17 pts (mean 64.1 years) completed 68 cycles CHT and following radiotherapy. There was no termination of therapy. Grade III leucopenia was observed in 9 % with 2 pts. requiring prolongation of treatment interval. There were 3 and 1 % grade II anemia and thrombocytopenia respectively. Further grade II toxicity: alopecia 38, fatigue 12, nausea/emesis 3, sensory neuropathy 12 %. Administration of G-CSF (pegfilgrastim) and epoitin (darbepoetin) was necessary in 2 and 6 % of cycles. Conclusions: Adjuvant sequential chemo- and radiotherapy of HREC is feasible by safety and toxicity and a phase III study can be initiated. No significant financial relationships to disclose.
Radical surgery (RS) plus intraperitoneal hyperthermic perfusion (IPHP) with oxaliplatin followed by intravenous docetaxel in the treatment of peritoneal carcinosis from platinum-sensitive recurrent ovarian cancer (OC): A pilot study
Authors: Fagotti A. , Ferrandina G. , Paris I. , Mari A. , Legge F. , Fanfani F. , Facchini G. , Scambia G. 
Published: March 2020

16077 Background: Much attention has been focused on the efficacy of radical surgery (RS) plus intraperitoneal hyperthermic perfusion (IPHP) in peritoneal carcinosis from recurrent OC. Methods: A pilot study aimed at analyzing the feasibility, morbidity, and toxicity of RS/IPHP and adjuvant chemotherapy has been carried out. Patients with recurrent, platinum-sensitive OC (PFI->6 months), have been enrolled. RS has been performed with peritonectomy procedures. The perfusion of the abdominal cavity has been achieved using 2 liters/m2 of 5% dextrose solution with oxaliplatin 460 mg/m2, preheated (41.5°C), and infused through the closed abdomen technique. After RS/IPHP, patients have received systemic chemotherapy with docetaxel (75 mg/mq), day 1, every 21 days, for 6 cycles. Results: As of December 2006, 14 patients underwent RS/IPHP: median age was 48.5 yrs (range 34–62). Ten (71.4%) patients had an ECOG PS=0. Median PFI was 24 months (range 7–72). TMedian value of PCI was 6 (range 2–10). Completeness of cytoreduction was 0 in 12 cases and 1 in 2 cases. Median EBL was 700 cc (range 400–1,600) and median number of blood transfusion was 3 (range 0–11). Median length of hospitalization was 15.5 days (range 8–27). We documented 3 cases of sepsis, 1 case of wound dehiscence requiring surgical intervention, 1 case of pleural effusion requiring thoracentesis, and 6 cases of post-operative haemorrhage, treated with surgical re-intervention (n=1), endoscopic cauterization (n=3), or blood transfusions (n=2). Ten patients underwent chemotherapy (total number of cycles= 49): grade 3 and 4 leukopenia occurred in 1, and 2 cases. Three patients (21.4%) experienced severe onicolysis and conjunctivitis. No deaths from this regimen was registered. With a median follow up of 7 months (range 1–18), 2 progressions of disease were observed. Conclusions: RS/IPHP utilizing intraperitoneal oxaliplatin followed by i.v. adjuvant docetaxel was shown to be a feasible approach to peritoneal recurrence of ovarian cancer. No significant financial relationships to disclose.