bluuebunny/crossref_metadata_2025_split huggingface dataset:
A validation study of a scoring system to estimate the risk of lymph node metastasis for patients with endometrial carcinoma for tailoring the indication of lymphadenectomy
Authors: Todo Y. , Ebina Y. , Watari H. , Sakuragi N. 
Published: March 2020

5040 Background: The present standard treatment for cases with endometrial cancer is surgical staging including lymphadenectomy. Elimination of lymphadenectomy will not be approved of unless strict condition are met. Our aim is to verify whether a preoperative scoring system to estimate the risk of lymph node metastasis (LNM) in endometrial carcinoma is clinically useful for tailoring the indication of lymphadenectomy. Methods: This study was carried out on 211 patients with endometrial carcinoma for whom volume index, serum CA125 level, tumor grade/histology were preoperatively confirmed. LNM score was set up using these three risk factors as reported in our previous study (Am J Obstet Gynecol 2003). We analyzed whether these factors remain still valid in a different cohort of patients. Based on the LNM score before a validation study was started, the estimated rate of lymph node metastasis (para-aortic lymph node metastasis) in a low risk group was 3.4% (0.0%), an intermediate group 7.7% (5.8%), a high risk group 44.4% (30.6%) and an extremely high risk group 70.0% (50.0%). Results: Volume index, serum CA125 level, and tumor grade/histology, were found to be independent risk factors for LNM in the cohort of this validation study. The actual rate of lymph node metastasis (para-aortic lymph node metastasis) in a low risk group was 3.2% (1.0%), an intermediate group 15.3% (11.9%), a high risk group 30.2% (23.8%) and an extremely high risk group 78.6% (57.1%). Conclusions: LNM frequencies increased in proportion to the impact of the LNM score and the actual rate of lymph node metastasis for each score was quite consistent with the estimated rate of lymph node metastasis.Our LNM score for patients with endometrial carcinoma is useful. No significant financial relationships to disclose.
SUV in pelvic lymph node is a significant prognostic factor in previously untreated squamous carcinoma of the uterine cervix
Authors: Lai C. , Yen T. , Ma S. , Tsai C. , Ng K. , Chang T. 
Published: March 2020

5051 Background: The aim of this prospective study was to identify prognostic factors (including 18F-fluorodeoxyglucose positron emission tomography [FDG-PET] parameters) in previously untreated squamous carcinoma of the uterine cervix with MRI- or CT-defined pelvic or para-aortic lymph node (PLN or PALN) metastasis. Methods: This study included pooled patients selected from two prospective studies who had untreated squamous cell cervical cancer and PLN or PALN metastasis (diagnostic score 3 or 4) by CT-MRI and additional FDG-PET scans were performed for primary staging. Recurrence-free and overall survivals (RFS and OS) were evaluated using the Kaplan-Meier method. Prognostic variables were assessed by the log-rank test and Cox proportional hazards regression method. Optimal cut-offs of standardized uptake value (SUV) in primary tumor, PLN and PALN were determined by receiver operating characteristic and area under the curve analysis. Results: A total of 70 patients were eligible for analysis. The follow-up time ranged 16–59 months (mean ± SD: 38 ± 18). In univariate analyses, FIGO stage ≥ III, PET defined bilateral PLN-positive, PET defined PLN-positive, PET defined PALN-positive and SUV cut-off of 3.04 at PLN and 4.18 at PALN were significant for RFS. FIGO stage ≥ III, SUV cut-offs of 2.94–3.15 at PLN and SUV cut-offs of 2.61–4.91 at PALN were significant for OS. Multivariate analysis showed only SUVmax cut-off of 3.04 at PLN was a significant adverse factors for RFS (RR: 10.1 95% CI 2.2–46.0; P = 0.003) and OS (RR: 11.7 95% CI 1.5–92.6; P = 0.019), while SUVmax cut-off of 4.18 at PALN (P = 0.062) was marginally significant for OS. Conclusions: SUVmax cut-off of 3.04 at PLN was a significant adverse factor for RFS and OS in previously untreated squamous carcinoma of the uterine cervix with MRI- or CT-defined PLN or PALN metastasis. No significant financial relationships to disclose.
Phase I study of irinotecan (Iri) and cisplatin (Cp) in combination with pelvic radiotherapy for the treatment (Tt) of advanced cervical cancer (ACC): A GINECO trial
Authors: Fabbro M. , Gladieff L. , Geay J. F. , Guichard F. , Lemanski C. , Dalenc F. , Paraiso D. , Delannes M. , Pujade-Lauraine E. 
Published: March 2020

5054 Background: Chemoradiotherapy with weekly Cp has become standard for ACC treatment. Combining Cp with another active drug in ACC such as Ir may increase the activity of Tt. Methods: Treatment consisted of 6 weekly cycles with escalating dose of Ir and fixed dose of Cp (20 mg/m2) administered during pelvic radiotherapy (45–50 Gy). Brachytherapy and/or surgery were allowed after pelvic chemoradiotherapy according to center policy. Cohorts of 3 to 6 pts with FIGO stage IB-IVA newly diagnosed ACC, performance status ECOG 1–2 and adequate major organ function were eligible at each dose level. Results: 15 pts were accrued at dose level I (n = 6), II (n = 3) and Intermediate (Int) (n = 6). Dose levels (DL) for Ir were 30 mg/m2 (I), 40 (II) and 35 (Int). Dose limiting toxicity (DLT) was observed in 2/3 pts at DL II (Gr 3 asthenia in 2/3 pts including Gr 3 diarrhea and abdominal pain in one). DLT was observed in 2/6 pts at DL I (NCI-CTC Gr 3 diarrhea in 2/6 pts including Gr 3 asthenia and abdominal pain in one) and DL Int (Gr 3 asthenia in 2/6 pts including febrile neutropenia in one). However, 3/4 pts without DLT at DL Int did not complete the whole chemotherapy schedule due to pelvic mucositis and skin toxicity (dose reduction: 2pts, early stopping at 3 cycles : 1 pt). In contrast, 5/6 non-progressive pts at DL I completed their scheduled chemo-radiotherapy, with dose reduction in only 1 pt who experienced a DLT. Efficacy evaluation showed complete and partial response in 6 and 5 of the 12 evaluable patients. Conclusions: the recommended dose for future phase II study of chemoradiotherapy in ACC is irinotecan (30mg/m2, weekly) with cisplatin (20 mg/m2, weekly). No significant financial relationships to disclose.
VEGF-A and COX-2 expression correlate with platinum resistance in ovarian cancers
Authors: Engels K. , Moll P. , Harter P. , Du Bois A. , Fisseler-Eckhoff A. , Kommoss F. , Kaufmann M. , Loibl S. 
Published: March 2020

5062 Background: Regulators of angiogenesis such as VEGF-A and cell cycle such as p53 and COX-2 influence tumor behavior and response to chemotherapy. Methods: 114 patients with primary ovarian cancer treated in Frankfurt or Wiesbaden between 1999 and 2004 were examined. Primary surgery was followed by a platinum and taxane based chemotherapy in all patients. Expression of i-NOS, COX-2, VEGF-A, HIF-1 alpha was analyzed immunohistochemically using tissue micro arrays of primary tumor samples. Results were scored according to staining intensity and percentage of positive tumor cells resulting in an immune-reactive score (IRS) from 0 to 12. Vascularity was assessed using the Chalkley-Grid method after highlighting vessels with CD34 antibodies in whole tissue sections. These results were correlated with classical prognostic factors and survival. Non-parametric correlations were done using Spearman’s rho, correlations were significant at the 0,05 level (2-tailed). Results: The median age at the time of surgery was 63y (33–89y). The majority of the patients (85%) had advanced disease (FIGO III-IV). Tumor grading was G1 in 2%, G2 in 37%, and G3 in 61%. Expressions were as follows: i-NOS 60% positive (IRS ≥4); COX-2 50% positive (IRS ≥5); VEGF-A 50% strong (IRS ≥8), 32% moderate (IRS 4–7), 18% weak (IRS ≤4); HIF-1 alpha 37% positive (IRS ≥3), p53 33% weak (IRS ≤4), 67% strong (IRS >4); vascularity 41% low (≤5), 52% moderate (6–9), 7% high (>9). I-NOS correlated positively with COX-2 (p = 0,03), VEGF-A (p = 0,05), and p53 (p = 0,01). Grading correlated positively with HIF-1 alpha (p = 0,02) and vascularity (p = 0,01). Up to now none of the new parameters did show correlations with recurrence free survival (median follow-up 36 months). Platinum resistant tumors (time from primary diagnosis to relapse <12 months) were significantly more often negative for VEGF-A (p = 0,005) and COX-2 (p = 0,02). Conclusions: I-NOS correlates with markers of angiogenesis and cell cycle regulation. VEGF-A and COX-2 expression might predict platinum resistance in ovarian cancers. No significant financial relationships to disclose.
Carboplatin and paclitaxel versus cisplatin, paclitaxel and doxorubicin for frontline chemotherapy of advanced ovarian carcinoma (AOC): A Hellenic Cooperative Oncology Group Study
Authors: Aravantinos G. , Fountzilas G. , Kalofonos H. P. , Skarlos D. V. , Kosmidis P. , Grimani I. , Pavlidis N. , Bafaloukos D. , Pectasides D. , Dimopoulos M. A. 
Published: March 2020

5074 Background: Carboplatin combined with paclitaxel are considered treatment of choice as initial chemotherapy for AOC. We compared this combination with a regimen combining cisplatin plus paclitaxel and doxorubicin. In the pre-taxane era the addition of doxorubicin to the cisplatin-based regimens appeared to improve survival. Therefore, there was a significant interest in assessing the role of a taxane/platinum/ anthracycline combination therapy in a randomized study. Methods: Patients with AOC after the initial cytoreductive surgery were stratified according to the FIGO stage and the presence of residual disease and randomized to either 6 courses of paclitaxel 175 mg/m2 as 3h infusion plus carboplatin 7AUC (group A) or paclitaxel at the same dose plus cisplatin 75 mg/m2 plus doxorubicin 40 mg/m2 and G-CSF (Lenograsim) 0.263 mg sc from day 7 to day 11 (group B). Primary endpoint was overall survival (OS). At alpha = 5%, 400 patients were required, to detect with power of 80%, a ±15% difference to a baseline survival rate of 50% at the 3-year time point. Results: Intent to treat analysis was performed on 432 patients (group A: 210, B: 222). The treatment groups were well balanced in terms of major patient and tumor characteristics. 70% of the patients had stage III and 23% stage IV disease. Significantly more patients developed febrile neutropenia in group B (p = 0.01). No other significant differences were observed in terms of severe toxicity and no difference was found between the two groups in complete and overall response rate. With a median follow up of 44 months, median survival was 37.2 months in group A and 45.2 months in group B (p = 0.33). Conclusions: Both regimens are well tolerated and effective as first line chemotherapy of AOC. Combination of cisplatin, paclitaxel and doxorubicin does not seem to improve survival as compared with the standard carboplatin/paclitaxel regimen. No significant financial relationships to disclose.
Final follow up survey of the randomized Pbo-controlled study of oregovomab (Ov) as a consolidation treatment for advanced ovarian cancer (OC): Insights into surveillance approaches
Authors: Nicodemus C. F. , Berek J. S. , Schultes B. C. , Balser J. P. , Taylor P. T. 
Published: March 2020

5079 Background: Ov is a monoclonal antibody specific for CA125 currently in two phase III studies as a consolidation immunotherapy for OC. A five year outcome follow up for patients participating in the prior randomized phase II study used to design the current pivotal trials has been completed. An assessment of survival post relapse (SPR) as a function of identifiable risk factors, and implications for long term survival survey methodology were reviewed. Methods: OC patients with no evaluable disease post front-line chemotherapy were randomized to IV infusions of OV or Pbo Q4 wks × 3, then Q12 wks. At relapse, therapy was stopped and second-line Rx was initiated without restriction. All patients were surveyed quarterly for long term outcomes for a pre-specified 5 years from initial randomization. A Kaplan-Meier (KM) analysis of overall survival and Cox multivariate analysis of SPR was completed. Results: 145 randomized participants were followed, including 67 designated as the successful front-line (SFLT) subpopulation identified to have characteristics favorable for intervention with immunotherapy (basis of ongoing phase III program). At five years, 47% of Ov (n = 73) and 37% of Pbo (n = 72) patients were alive overall, and 56% of Ov (n = 34) and 32% of Pbo (n = 33) were alive in the SFLT population. KM estimates of median survival are 57.5 mo [44.5-non-estimable (ne)] for Ov and 48.6 mo [30.9-ne] for Pbo in the overall population and ne mo [50.5-ne] for Ov and 48.6 mo [24-ne] for Pbo (p = 0.11) in the subpopulation. For relapsed patients, improved survival post relapse was most associated (Cox regression p < 0.10) with lower CA125 velocity at relapse, treatment (Ov), and longer time to relapse. Conclusions: Survival data was consistent with previously reported time to relapse data in this study. For the SFLT, the 5 yr duration of survival survey and sample size were insufficient for a definitive outcome. However, results support the hypothesis that treatment with OvaRex may provide clinical benefit. The ongoing phase III studies will include a 10 year survival survey of 354 patients to definitively assess the impact of this treatment on long term survival. [Table: see text]
Pegylated liposomal doxorubicin (PLD) and gemcitabine (GEM) in combination in the salvage treatment of epithelial ovarian cancer (OC)—a Danish Gynaecologic Cancer Group (DGC) study
Authors: Mirza M. R. , Lund B. , Bertelsen K. , Lindegaard J. , Keldsen N. , Mellemgaard A. , Depont R. 
Published: March 2020

5094 Background: Ovarian cancer patients (pts) recurring with a short treatment-free interval (TFI) after prior chemotherapy (PCT) have a bad prognosis. DGC has conducted a phase II study of PLD-GEM in combination in OC pts recurring with a TFI of less than 12 months (mo). Methods: All pts must have received at least one platinum-paclitaxel containing regimen; no PCT with GEM or anthracyclines. Regimen: GEM 800mg/m2 day 1+8 and PLD 25mg/m2 day 1, q 21 days. GEM dose escalation to 1g/m2 day 1+8 from 2. cycle in the absence of grade 3–4 toxicity. Primary end point: OS, secondary: PFS, response and toxicity. Pts were grouped according to their response to PCT. Group 1: pts with CR on PCT and TFI 3–12 mo; group 2: pts with CR on PCT and TFI 0–3 mo; group 3: pts with PR/SD on PCT and TFI 0–12 mo. 35 pts with ≥2 prior number of treatments. Results: 82 pts were enrolled (May 2003-Aug 2005); the median age was 59 yrs (range 31 to 77 yrs); 15 pts were entered with rising CA125 only (GCIG criteria). Groups according to their response to PCT: group 1: 44 pts; group 2: 5 pts; group 3: 33 pts. TFI ≤ 6 mo 33 pts, TFI > 6 to ≤ 12 mo 49 pts. To date data on 330 cycles (mean 4.7 cycles) is available; 45 pts are evaluable for PFS and OS; 62 pts are evaluable for response and 71 pts for toxicity. Grade 3–4 toxicity: PPE 6/330 cycles; mucosites 8/330 cycles; febrile neutropenia 4%; treatment delay 9%. No dose reductions performed for PLD. GEM dose escalation to 1000 mg/m2 in 31 pts; dose reduction to 650 mg/m2 at any time in 21 pts; skipped dose day 8 in 44 cycles. Response (RESIST): CR 3 pts; PR 17 pts (CR+PR 32%); SD 39 pts; PD 2 pts. Median PFS 212 days, Median OS 234 days. Conclusions: PLD-GEM in combination in the salvage setting is well tolerated, with acceptable toxicity and clear activity. No significant financial relationships to disclose.
Prediction of long-term survival using expression of FOXA1, a determinant of estrogen response domains in breast cancer
Authors: Badve S. , Turbin D. , Morimiya A. , Nielsen T. , Perou C. , Dunn S. , Huntsman D. , Nakshatri H. 
Published: March 2020

539 Background: Recent studies have demonstrated cofactor dependency of estrogen receptor alpha (ERα) in defining specific pattern of estrogen (E2) response in breast cancer. FOXA1, also called HNF3α, a forkhead family transcription factor, has emerged as a major cofactor that is essential for optimum transcription of ∼50% of ERα:E2 responsive genes. FOXA1 is expressed in breast cancer cells and in cDNA microarray cluster analysis segregates with genes that characterize the luminal A subtype such as ERα, GATA3, and XBP-1. Detailed expression analysis of FOXA1 in human breast tumors has not been previously performed and it is not known whether it is an independent prognostic factor in breast cancer. Methods: A tissue microarray comprising tumors from 438 patients with 20 years follow-up was analyzed for FOXA1 expression using goat-anti-human FOXA1 antibody by immunohistochemistry. Percentage (P) and intensity (I) of expression was analyzed to generate numerical score (S= P × I). FOXA1 expression was correlated with tumor grade, nodal status, disease free survival, and expression of ER, PR, GATA3, HER2, p27kip1, phospho-AKT, and luminal A subtype (defined as ER &/or PR+, bcl-2+ and Her-2-neg). Results: FOXA1 expression (score greater than 100) was seen in 187 of 438 breast cancers and correlated with greater likelihood of survival at 20 year (p=0.0114). A significant positive correlation was observed between FOXA1 expression and expression of ERα (p= 0.000001), GATA3 (p= 0.000001), PR (p= 0.00001), phospho-AKT (p= 0.00001). Similarly, a significant correlation was noted with luminal A subtype. An inverse correlation was noted with tumor grade and mdm-2 expression (p=0.00001). HER2 or p27kip1 expression and nodal status showed no correlation with FOXA1. Conclusions: FOXA1 is good prognostic marker predicting disease free survival in patients with breast cancer. Since its expression correlates well with breast cancer of luminal A subtype, it can also be used to identify these good prognosis tumors from the rest of the ER positive breast cancers in archival paraffin embedded breast tissues. No significant financial relationships to disclose.
Updated analysis of NCIC CTG MA.17 (letrozole vs. placebo to letrozole vs placebo) post unblinding
Authors: Robert N. J. , Goss P. E. , Ingle J. N. , Tu D. , Shepherd L. , Palmer M. , Pater J. 
Published: March 2020

550 Background: 5187 postmenopausal women were originally randomized to NCIC CTG MA.17 to receive letrozole (LET) or placebo (PLAC) after 5 years of tamoxifen. The hazard ratio (HR) for disease-free survival (DFS) was 0.58 (0.450.76, p=0.00004) after a median follow-up of 30 months (mo). The trial was unblinded in October 2003 after the first interim analysis. Women randomized to PLAC were offered LET at the time of unblinding. The goal of this analysis was to determine whether women switching from PLAC to LET benefit in terms of disease outcome and to evaluate treatment related toxicities. Methods: LET and PLAC-LET have been compared to PLAC, based on the hazard ratio and adjusting for baseline patient and disease variables including, among others, tumor size, nodal status and prior adjuvant chemotherapy. Results: Information about their follow-up treatment after unblinding was available on 2268 women originally assigned to PLAC and who were free of recurrence and alive at the time of unblinding. Among them, 1655 crossed over from PLAC to LET while 613 elected no treatment. With 54 mo f/up the HR for DFS was 0.31 (0.18, 0.55: p<0.0001) favoring patients who crossed over to LET compared to those who stayed on no treatment. The treatment switch was well tolerated with no significant difference in bone fractures or cardiovascular events. An updated analysis of DFS, DDFS and OS by nodal and tumor receptor status, prior chemotherapy, menopausal status at the start of tamoxifen, and duration of prior tamoxifen therapy will be presented at the meeting. Conclusion: Women with hormone dependent breast cancer prescribed LET after a prolonged delay from completing tamoxifen experienced a significant improvement in outcome (DFS, DDFS, OS) and should be considered for this therapy. [Table: see text]
Gene expression profiling for prediction of distant metastasis and survival in primary nasopharyngeal carcinoma
Authors: Kao K. J. , Cheng S. H. , Huang A. T. 
Published: March 2020

5503 Background: Distant metastasis is the major cause of treatment failure for nasopharyngeal carcinoma (NPC). An accurate means to predict potential of distant metastasis before therapy could allow optimization and further improvement of treatment. Gene expression profiling was performed to identify such predictors. Methods: mRNA transcript profiling was performed using Affymetrix U133A GeneChips on 138 biopsy specimens of primary NPC obtained before therapy and stored in liquid nitrogen. The specimens represented two groups of patients: distant metastasis <3 years after initial therapy (high risk group, n = 47) vs no distant metastasis after >3 years of follow-up (low risk group, n = 91). Two thirds of cases in each risk group were randomized to a training set and 1/3 to an independent test set. Supervised analyses were conducted to discover gene expression signatures associated with metastasis in the training set (n = 96). Genes were selected by Kruskal-Wallis test, grouped by self-organizing-map and further selected by logistic regression. Predictive models were established using logistic regression and k-nearest neighbors (kNN). The predictors thus discovered were validated using independent test set (n = 42). Results: Two molecular predictors were established for identification of patients with high or low risk of developing distant metastasis. The first predictor was based on 52 genes and kNN. The second predictor was based on 12 genes and logistic regression. The specificity, the sensitivity and the accuracy determined on the independent test set were 86%, 69% and 81% for the 52-genes predictor, and 72%, 85% and 77% for the 12-genes predictor. The accuracy increased to 85% and the estimated hazard ratio between predicted high and low risk was 11.1 (95% CI=2.4 to 52.4, p = 0.002), when both molecular predictors were used in combination. Log rank test showed significant difference in overall survival between patients predicted with low and high risk for distant metastasis in the test set (p = 0.003). Conclusions: mRNA transcript profiling of primary tumors of NPC can be used to determine the risk of distant metastasis. The method can be used to identify NPC patients at high metastatic risk to undergo trials of new modalities of treatment at the time of diagnosis. No significant financial relationships to disclose.