bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of sorafenib combined with gemcitabine and 5-fluorouracil in patients with metastatic renal cell carcinoma: Preliminary results
Authors: Hongyun L. , Zhihong C. , Xiangqing Y. , Lu S. , Chuanliang C. , Xinan S. , Lin S. , Jun G. 
Published: August 2020

e16093 Background: The tyrosine kinase inhibitors sorafenib and sunitinib have been approved for use in patients with advanced RCC and have supplanted immunotherapy as first-line therapy. Nevertheless, complete responses have been observed only rarely with these agents and only 10% of patients experience PR. The vast majority of responding patients will ultimately progress despite continued therapy. In order to improve the objective response rate and the durability of those responses in patients, we conducted a single-institution, single-arm phase II trial of gemcitabine and 5-fluorouracil (5-FU) combined with sorafenib in patients with RCC. Methods: Eligibility criteria included advanced, histologically confirmed RCC; age >18 years; ECOG PS ≤ 2, adequate bone marrow, renal and hepatic function; measurable/evaluable lesions. Gemcitabine was administered at 1,000 mg/m2 over 30 min i.v. on days 1 and 8, followed by 5-FU 400 mg/m2 i.v. bolus on day 1 and 1,200 mg/m2/day × 2 days continuous infusion (28-day cycle). From day 1 of cycle 1, 400 mg sorafenib was continuously given twice daily. The sample size of 21 patients was sufficient to provide 80% power to detect an objective response rate that was greater than 10% with significance that 0.05 level. Results were expressed as mean±SD or median ± 95% CI. The primary study endpoint was objective response rate and the secondary were toxicity, progression-free survival and overall survival. Results: Patients (n = 21) were enrolled from May 2006 to Dec. 2007. The rate of objective response and disease control (including stable disease, complete responses and partial responses) were 38% (95% CI, 18–62%) and 86% (95% CI, 64–97%), respectively. Among them, there is 1 complete response and 2 pts occurred completely liquefaction deliquesce in metastatic lesions. The median PFS time is longer than 13 months, with 6/21 patients remaining progression free at 2008.12.26 the data were compiled for this report (three are longer than 26 months and there other three longer than 13 months ). The median OS time have not yet been reached, because of the amount of censoring data. Conclusions: The combination of sorafenib with gemcitabine and 5-FU shows promising activity for patients with metastatic RCC. No significant financial relationships to disclose.
Effect of sorafenib on chemotherapy resistance and refractoriness in castration-resistant prostate cancer (CRPC)
Authors: Nabhan C. , Tolzien K. , Lestingi T. M. , Galvez A. , Bitran J. D. 
Published: August 2020

e16105 Background: There is no standard for CRPC once chemotherapy fails. In studies employing docetaxel (D), 35–39% of pts did not complete therapy due to progression and only 45–50% had a PSA response. This implies that many pts develop resistance to D. Sorafenib is a multi kinase inhibitor with antiangiogenesis properties. We hypothesized that sorafenib could overcome chemotherapy resistance in these pts. Methods: Eligible pts must have progressed while on either D or mitoxantrone (M). They received sorafenib at 400 mg orally twice/daily in addition to the chemotherapy agent they were on. Sorefinib/chemotherapy combination was given for a maximum of 6 cycles followed by sorafenib monotherapy until progression. Primary end point was safety of the sorafenib/chemotherapy combination. Secondary end points included the overall clinical benefit calculated as the sum of complete response (CR), partial response (PR), and stable disease (SD), toxicity, and time to disease progression (TTP). Results: To date, 15 pts have been enrolled; 14 are evaluable. Eleven pts were on D and 4 on M. Median age was 68 (range 61–83), median PSA was 111.2 ng/ml (13.6–1703.9). Nine pts (60%) had visceral and bone disease. Median PSA-DT pre-study was 2 months (0.5–6) and median time from last chemotherapy to starting study was 4 weeks. Median number of given cycles was 6.5 (2–12). Six pts did not require dose reduction, 2 others were re-escalated to the full dose. Sorafenib was safely combined with chemotherapy with 6 pts experiencing grade 3 fatigue, 3 developing grade 3 hand/foot syndrome, and 1 experiening grade 3 diarrhea. Eleven pts (73%) had SD radiographically that lasted a median of 6.7 months. In all, 6 out of 14 pts (42%) had a PSA decline after adding sorafenib and 3 (21%) had stable PSA. Of these 9 pts (PR+SD), 2 never doubled their PSA. Two pts had PSA decline after withdrawing sorafenib. Median TTP for PSA was 3.75 months. PSA responses did not correlate with radiographic changes or clinical benefit. With a median follow-up of 8 months, 5 pts (33%) remain alive with 1 continuing on therapy without progression. Conclusions: Sorafenib overcomes chemotherapy-refractoriness and failures in CRPC. [Table: see text]
Risk factors for thromboembolic events in testicular cancer patients receiving chemotherapy
Authors: Shim K. , Potvin K. R. , Mills K. , Whiston F. , Stitt L. , Winquist E. 
Published: August 2020

e16109 Background: Cancer patients are at increased risk for thromboembolic events (TTEs), and those receiving chemotherapy are at even greater risk. Clinical experience and the literature have suggested that men receiving cisplatin-based chemotherapy for metastatic germ cell tumors are at particularly high risk. As TTEs can be fatal and treatment is curative, the stakes are high. Despite this, prophylactic anticoagulation (PA) is not routinely used. Methods: All men treated with cisplatin-based chemotherapy for metastatic germ cell cancer at the London Regional Cancer Program from January 1978 to December 2007 were identified from electronic databases. Data including type and timing of TTEs were extracted by retrospective chart review. Multivariable analyses were used to identify predictors of TTEs. Results: 196 eligible patients were identified with median age 31 years (range, 15–75). No patients received PA. Thirty-two TTEs were identified in 29 patients for an overall incidence of 14.8% (95% CI, 9.8–19.8%). The majority of events were deep venous thromboses, and five patients died due to TTE or its complications. Sixteen of the patients with TTE (55.2%) were diagnosed while on treatment (defined as TTE within 6 months of chemotherapy initiation); 8 (27.6%) had their TTE prior to, and 5 (17.2%) after this time period. Age greater than 30 years (OR = 3.02; 95% CI, 1.10–8.33; p = 0.033) and elevated LDH (OR = 1.93; 95% CI, 1.07–3.48; p = 0.029) were independently associated with an increased risk of TTE. If both adverse risk factors were present, the risk of TTE on treatment was 21.7% (95% CI, 9.8–33.7%). If neither were present, the negative predictive value was 97% (95% CI, 92–100%). Conclusions: The overall TTE incidence rate of 14.8% is consistent with prior reports (8.4–19%). The risk of TTE appears greatest during chemotherapy and shortly thereafter, and nearly one in 10 patients in this group had a TTE. These data support the concept of PA for selected patients starting chemotherapy for metastatic germ cell cancer. However, the efficacy of PA and risk of hemorrhage in this group is unknown. In this cohort, patients under 30 with normal LDH were at very low risk for TTE. Confirmation of these findings to help guide the study and optimal use of PA should be pursued. No significant financial relationships to disclose.
The value of PET/CT with 18F-FLT and 18F-FDG in the management of metastatic germ cell tumors (GCT): A pilot study
Authors: Hartmann J. T. , Aschoff P. , Dittmann H. , Lichy M. , Mayer F. , Reischl G. , von Weyhern C. , Kanz L. , Claussen C. D. , Pfannenberg C. 
Published: August 2020

e16142 Background: The purpose is to assess the ability of [F-18]-3’-Fluoro-3’-deoxythymidin (FLT), a cell proliferation marker, for early response monitoring and prediction of histology of residual tumor masses in patients (pts) with metastatic GCT in comparison to the standard tracer F-18-FDG, CT-scans and tumor markers. Methods: 11 male pts, age 23–48 yrs, with metastatic GCT were evaluated with both FDG- and FLT-PET/CT prior to chemotherapy (CTh), after the first cycle (early response) and 3 weeks after completion of induction CTh. PET was analyzed visually and quantitatively. The results were validated by histopathology of resected residual masses after CTh in 7 pts or by clinical follow-up for at least 6 mos in 4 pts. Presence of necrosis was judged as responder, as well as CR/PRm- within a minimum progression-free interval (PFI) of 6 mos. In case of multiple resections, the worse histology was taken into account. Regarding early tumor response EORTC criterias were used. Results: 8 out of 11 pts had a PFI > 6 mos (range, 206–1337 days). Examination of resected masses revealed necrosis in 3/7, teratoma in 2/7 as well as 2/7 pts with viable tumors. Prior to CTh the reference lesions showed increased FDG uptake (SUVrange/mean, 2.9–15.0/8.8) in all pts but moderate FLT uptake (SUVrange/mean, 1.7–9.7/3.7) in 10 out of 11 pts. SUVavg decrease in early response FDG monitoring was 64% in responders and 60% in non-responders (p = 0.8), as well as 57% vs. 48% for FLT (p = 0.5), respectively, and 85% vs. 72% (FDG, p = 0.1) and 67% vs. 65% (FLT, p = 0.8) in the final monitoring. Results of early and final response were inconsistent in 6/11 pts in FDG and in 4/10 pts in FLT-PET. In 2 pts with teratoma false negative results in both FDG- and FLT-PET have been seen. The sensitivities, specificities, positive and negative predictive values (%) of FDG and FLT-PET for early and final response monitoring were 60/33/43/50, 60/80/75/67, 20/100/100/60, and 0/100/0/50, respectively. Conclusions: PET negative residual masses after CTh of metastatic GCT still require resection, since the low negative predictive value of FDG-PET cannot be improved by application of the proliferation marker FLT. No significant financial relationships to disclose.
Expression and circulating levels of lymphangiogenic parameters in renal cell cancer: Implication for antiangiogenic treatments
Authors: Mouawad R. , Comperat E. , Spano J. P. , Izzedine H. , Cajfinger F. , Deray G. , Capron F. , Khayat D. 
Published: August 2020

e16144 Background: Vascular endothelial growth factors C, VEGF-D and VEGFR-2, R-3, are overexpressed in different malignancies and associated with lymph node metastasis and poor prognosis. In renal cell cancer (RCC) lymphatic tumor spread exist but data focusing on lymphangiogenesis are rare. Since the VEGF-C/VEGF-D/VEGFR-2, R-3 axis appears to be the signaling pathway for tumor-induced lymphangiogenesis and an attractive target for therapeutic intervention; we analyzed the expression and the presence of the soluble forms in 30 RCC patients and results were correlated with clinicopathological parameters. Methods: Tumor and sera from 30 RCC patients (20 clear cell (ccRCC)&10 papillary (pRCC) were included in this study. The expressions of VEGFR-2,R-3 &VEGF-C,-D expressions on tumor were evaluated by immunohistochemestry. Using ELISA assays, sVEGFR-2, R-3 &sVEGF-C,-D were measured in sera of RCC patients in comparison to 20 healthy controls. Results: In overall patients, a high expression of VEGF-C,-D and their receptors were observed in more than 55%of the patients as compared to the negative control. Regarding circulating VEGF-C,-D, R2, R-3 they were variable in all samples from either patients or healthy donors. Only median sVEGF- R3 level was significantly higher (p=0.005) in RCC patients as compared to healthy donors. VEGF-C and VEGF-D expression was significantly correlated (r’=0.43, p=0.02) with each other but not with the expression of its receptors. An inverse correlation between Flt-4 expression & its soluble form was noted (r=-0.33 p=0.040). The expression of VEGF-C, VECF-D and sVEGFR-3 were significantly higher in pRCC than ccRCC (p=0.02, 0.01 and 0.035 respectively). The expression of VEGFR-2,VEGFR-3 were not different between the subgroups (p=0.11). Furthermore, no correlation with clinicopathological parameters was shown in either overall patients or in the two subgroups. Conclusions: we showed that in RCC the lymphangiogenic factors are expressed or present as soluble form, a different expression pattern in ccRCC and pRCC existe. Therefore, further studies are necessary to determine if lymphangiogenesis can play a role as a prognostic tool or a target for therapeutic intervention in renal cell carcinoma. No significant financial relationships to disclose.
Molecular profiling in the diagnosis of synchronous primary cancers of the endometrium and ovary
Authors: Soliman P. T. , Celestino J. , Finklelstein S. , Broaddus R. , Westin S. , Schmeler K. M. , Lu K. H. , Coleman R. L. 
Published: August 2020

e16500 Background: Synchronous primary cancers of the endometrium and ovary (SYNCH) have a better prognosis than either primary endometrial or ovarian cancer with metastasis (MET). Distinguishing SYNCH from MET can be a challenge when the neoplasms share similar histologic features. To date, histologic characteristics are used to make this distinction and guide treatment decisions. The purpose of this study was to determine if objective discrimination using an integrated molecular approach can assist in making this distinction. Methods: Paired tumor samples from 16 SYNCH and 11 MET were sent for mutational profiling. 13 samples were sent as blinded duplicates for internal validation. The mutational profile for each neoplasm was determined using PCR and quantitative genotyping for a panel of LOH markers targeting 1p,3p,5q,9p,10q,17p,17q,21q,22q and k-ras-2 exon 1 DNA sequencing for point mutational change. The paired samples were then re-defined as SYNCH versus MET based on the profile results. Survival was compared using Kaplan-Meier. Results: The results are in the table. All of the duplicate samples had the same molecular profile results. Median survival based on pathologic diagnosis was 106 months in SYNCH versus 37 months in MET (p=0.07). The median survival was 110 months in both groups based on molecular profiling results. For patients with a diagnosis of SYNCH by both pathology and molecular profiling median survival was 117 months. For those with a pathologic diagnosis of SYNCH but metastasis on molecular profiling survival was 129 months. Conclusions: Molecular profiling to distinguish synchronous primary cancers from either primary endometrial or ovarian cancer with metastasis, is currently being evaluated. In this study, the pathologic diagnosis was a better indicator of survival than a diagnosis based on molecular profiling alone. Further studies are being performed to determine the role of molecular profiling in women who are thought to have synchronous primary cancers of the endometrium and ovary. [Table: see text] [Table: see text]
A Gynecologic Oncology Group study of frequent copy number aberrations in DNA repair genes and other genomic regions in stage I serous ovarian cancers
Authors: Pejovic T. , Gaile D. P. , Darcy K. M. , Liu S. , Shepherd L. , Rodgers W. H. , Kohn E. , Mannel R. , Birrer M. J. , Nowak N. 
Published: August 2020

e16504 Background: A proof of principle array-based comparative genomic hybridization (aCGH) analysis was performed in archival formalin-fixed and paraffin-embedded (FFPE) stage I ovarian cancers (EOC) to determine if frequent (>40%) copy number aberrations (CNAs) can be detected in DNA repair genes including the Fanconi anemia complementation group (FANC) and RAD51 families compared with the rest of the genome. Methods: Tumor DNA was isolated from 22 serous cancers from the GOG-175 virtual tissue bank. RPCI 19K BAC arrays were hybridized (GeneTAC HybStation) and scanned (Gene Pix 4200AL Laser Scanner). Spot fluorescence values were quantified using ImaGene, vetted for quality and loess corrected with adjustments for chip-specific spatial effects. The genome was segmented to identify regions with common copy number means (DNAcopy software). Posterior aberration probabilities for the regions were obtained using CGHcall and data was visualized and annotated using iGenomicViewer in R. Results: Several genes associated with the Fanconi DNA-damage response pathway were frequently altered in stage I serous ovarian carcinomas. A RAD51 homology DMC1 was amplified in 55% of the specimens. Genomic losses were observed in FANC-D1 (BRCA2), and RAD51L3 in 41%, and 27% of specimens, respectively. In contrast, frequent genomic losses or gains involved 13q33.1; 13 q21.31; 17p12; 17q22; 18q12.3; 9p11.2; 9p22.2–22.3; 9q33.1; 8p23.2; 21q21.3; and 5q14.2; or 8q24.3; 3q29; 12p11.1; 17q25.1; 17q25.3; 20q13.33; 20q11.21; 20q11.23; 19p13.13; and 19p13.2, respectively. Conclusions: The GOG-0175 virtual tissue bank yielded high quality DNA for detecting and mapping CNAs in archival FFPE specimens with high resolution. Frequent genomic losses and gains were observed in DNA repair genes and other genomic regions in stage I serous ovarian cancer which may promote genomic instability, resistance, metastasis and aggressiveness of this disease. No significant financial relationships to disclose.
Use of amplification of the 8q24 and 20q11–13 loci to predict progression-free survival of advanced epithelial ovarian cancer patients receiving standard therapy
Authors: Tominaga E. , Tsuda H. , Arao T. , Nishimura S. , Chiyoda T. , Nomura H. , Kataoka F. , Susumu N. , Aoki D. , Nishio K. 
Published: August 2020

e16526 Background: The purpose of this study was to identify genes that predict the progression free survival (PFS) of advanced epithelial ovarian cancer (aEOC) receiving standard therapy. Methods: We performed expression analysis using GeneChip (Human Genome U133 plus 2.0 Array) in aEOC cells produced by laser-based microdissection. Thirty three aEOC patients (stage IIc: 4, III: 19, IV: 10; serous adenocarcinoma: 21, endometrioid adenocarcinoma: 5, undifferentiated: 7) were included in this array study. All cases received staging laparotomy, cytoreductive surgery, and adjuvant chemotherapy (carboplatin + paclitaxel) as primary therapy. Results: Class comparison analysis between groups of NED (no evidence of disease) and non-NED identified 46 genes that exhibited significant differences (p < 0.001). Among them, 6 (13%) genes are located in 8q24 and 9 (19.6%) genes are located in 20q11–13. Finally, we focused on 8q24 and 20q11–13 loci, and confirmed array data using real-time quantitative PCR in 94 validation sets. The validation showed that ZNF7, MAF1, ADRM1, and GNAS amplification was related with PFS (p < 0.05, respectively). Conclusions: The amplification of 8q24 and 20q11–13 can predict the PFS of aEOC and these genes may be new biomarkers for aEOC. No significant financial relationships to disclose.
Extent of cervical involvement in endometrial cancer as a predictor of outcome
Authors: Ferriss J. S. , Brix W. , Henretta M. , Hanley K. , Stoler M. , Duska L. , Modesitt S. 
Published: August 2020

e16566 Background: Endometrial cancer will affect 40,000 women this year. Extent of myometrial invasion and presence of cervical stromal disease are risk-factors for metastasis and recurrence. Uterine cervical involvement is often not known in advance of surgery, and superficial involvement may not be seen at frozen section. The objective of this study was to determine if the extent of cervical invasion is a predictor of outcome. Methods: The institutional cancer registry was searched for cases of stage II uterine cancer from 1996–2006. Inclusion criteria were endometrioid histology and clinical data and pathology available for evaluation. Demographics, extent of surgery, tumor grade, depth of myometrial invasion, presence of lymph-vascular space invasion (LVSI), and last follow up were collected. In addition, a gynecologic pathologist evaluated all slides to determine depth of cervical stromal invasion. Statistical analysis to compare predictors of outcome was performed. Results: There were 800 cases of endometrial cancer diagnosed from 1996–2006, 75 (9%) were stage II. Fifty two cases met all inclusion criteria. Mean age at diagnosis was 63.4 years. Mean BMI was 31.6. Ninety four percent were white, 4% black, and 2% Asian. All patients had a hysterectomy, 6 (11.5%) had a radical hysterectomy and 36 (69%) had lymphadenectomy performed. Eighteen (34.6%) were stage IIA and 32 (61.5%) were IIB. LVSI was seen in 15 (28.8%) cases. On pathologic review, 37.5% had no cervical stromal invasion, 42.5% had invasion of less than half and 20% had invasion of more than half of the cervical stroma. Forty patients (77%) received adjuvant radiation. There were 8 recurrences and 6 disease-related deaths. The mean follow up period was 30 months. Extent of cervical invasion did not correlate with recurrence or survival. Factors associated with increased risk of recurrence were: LVSI (p = 0.017), lack of lymph node sampling (p = 0.035), and age >55 years (p = 0.027). Women with and without recurrence were compared and did not significantly differ. Conclusions: In this study with pathologic review, extent of cervical involvement in stage II endometrial cancer was not associated with increased risk of recurrence or death. Age >55 years, lack of node sampling and presence of LVSI were predictors of recurrent disease. No significant financial relationships to disclose.
Current management of borderline ovarian tumors: A multicenter survey of 323 clinics in Germany, on behalf of the North-Eastern German Society of Gynecological Oncology (NOGGO)
Authors: Chekerov R. , Coumbos A. , Sehouli J. , Schaedel D. , Oskay-Oezcelik G. , Lichtenegger W. , Kuehn W. 
Published: August 2020

e16568 Background: The aim of this survey was to analyze the standard of care in diagnostic, surgery, chemotherapy and aftercare management of patients with Borderline tumor of the ovary (BOT) in Germany. Methods: A structured questionnaire comprising different dimensions of treatment of BOT was sent to all 1,114 gynecological departments in Germany. The questionnaire could be returned anonymously. Results: The overall response rate was 29.0% (323 departments). The most departments were on secondary care (71.8%), tertiary care (23.2%) or university hospital (5.0%) level. The most clinicians performed not more than 5 BOT operations (89.2%) per year. 93.2% of the gynecological departments used additional preoperative diagnostic procedures to the classical bimanual examination and vaginal ultrasound in a case of unclear ovarian tumor: CA-125 or CEA detection (95%), CT-scan (76%), Doppler ultrasound (66%), MRI (36%), or PET-CT (1.7%) techniques. In university hospitals (87%), tertiary care (80%), secondary care (68%) and most of the general practitioners’ hospitals (64%) a regular fresh frozen section was the intraoperative diagnostic standard. For diagnosis of BOT mostly laparotomy (48%) and laparoscopy (15%) were performed, whereas 19% used a diagnostic laparoscopy, followed by laparotomy for completion in a second intervention or switch from laparoscopy to laparotomy in the primary surgical session (18%). In young women with desire to preserve fertility clinicians performed much seldom unilateral salpingo-oophorectomy (92%) and only in 53% biopsies of the contra lateral ovary and in 67% peritoneal biopsies. Generally biopsies of the contra lateral ovary were performed in 4% to 53% of all patients. Chemotherapy was the second therapy option (64%) after surgery (97%) for BOT, mostly favored in “high-risk” patients with tumor residual, micro invasion or invasive implants. Conclusions: These data demonstrate a high clinical unsureness in the clinical management of borderline tumors of the ovary. No significant financial relationships to disclose.